1 of 998 DOCUMENTS US Fed News January 25, 2012 Wednesday 2:06 PM EST GRANT WILL FUND STUDY OF COGNITION AND SCHIZOPHRENIA LENGTH: 927 words SACRAMENTO, Calif., Jan. 25 -- The University of California issued the following press release: Michael Minzenberg, a UC Davis psychiatry researcher, has been awarded a prestigious three-year, $200,000 seed grant from the Dana Foundation to study the brains of patients being treated for schizophrenia to determine how additional treatment to improve cognition interacts with antipsychotic medication. "Cognition is very important in schizophrenia because it is a strong predictor of outcome. It determines whether a person can be a contributing member of a community, stay out of the hospital and live independently," said Minzenberg, associate professor in the Department of Psychiatry and Behavioral Sciences and a faculty member of the UC Davis Imaging Research Center. Schizophrenia is a chronic mental disorder characterized by decline in thought processes and loss of emotional responsiveness. It affects 3.2 million Americans, the majority of whom are not receiving treatment. It can lead to auditory hallucinations, paranoia and delusions. Despite the importance of cognition in the rehabilitation of those with schizophrenia, there are no U.S. Food and Drug Administration (FDA)-approved drugs for the improvement of cognition in this patient population. "Dr. Minzenberg is at the forefront of trying to develop therapies for impaired cognition in schizophrenia, using powerful new non-invasive brain imaging to measure the effects of drugs and other treatments on functional networks in the brain," said Cameron Carter, director of the Center for Neuroscience and the Imaging Research Center at UC Davis. "His work is suggesting that some of the other medications that patients are taking may interfere with the procognitive effects of some of the newer more promising therapies. If this proves to be true then it will be important to 'fine tune' patients' medications to optimize cognitive outcomes in people with schizophrenia and other brain disorders." Modafinil is a drug approved by the FDA for the treatment of narcolepsy. It is also known by the brand name Provigil. Narcolepsy is a chronic neurological disease characterized by sudden urges to sleep, episodes of loss of voluntary muscle tone, vivid dreams while falling asleep or upon awakening, and brief episodes of total paralysis while waking up from sleep. Both genetic and environmental factors appear to contribute to narcolepsy. Although no cure exists, medications can often help restore a patient's quality of life. Like other stimulants, Modafinil's side effects are relatively mild. It is used off-label to combat the effects of sedatives. Currently, it is not prescribed on a long-term basis to schizophrenia patients. However, Minzenberg and his colleagues conducted a small, unpublished pilot study that showed Modafinil can improve cognition in patients being treated for schizophrenia. "What we understand about how Modafinil works in the brain leads us to believe that it might be good for improving cognition deficits of our patients," Minzenberg said. Because the cause of schizophrenia is unknown, treatment focuses on eliminating symptoms. Antipsychotic drugs are effective at reducing its most serious symptoms: delusions and hallucinations. Any treatment to improve cognition cannot interact with these drugs in a negative way. "The use of antipsychotic medications is the standard of care in patients with schizophrenia. So, before we can move forward with a large clinical trial involving Modafinil's impact on cognition, we need to know how it interacts with these drugs." Cognition refers to a range of high-level brain functions, including the abilities to learn, remember information, organize, plan, problem-solve and understand and use language. It is thought to be controlled by an area of the brain called the locus coeruleus, which controls the body's physiological responses to stress and panic, commonly referred to as the "fight or flight" response. "This area of the brain also serves to coordinate activity in the entire brain as it performs almost any type of task or behavior," Minzenberg said. Minzenberg and his colleagues will conduct the study at the UC Davis Early Diagnosis and Preventive Treatment of Psychosis (EDAPT) Clinic. Researchers will enroll 60 patients newly diagnosed with schizophrenia. These patients will have a specialized brain scan performed, called functional magnetic resonance imaging or fMRI, and will be randomly assigned to an FDA-approved treatment for schizophrenia. After eight weeks of treatment, another fMRI scan will be conducted. The patients, who also will have been assigned to either a control or study group, will undergo a third scan while performing a cognitive task. Functional magnetic resonance imaging allows researchers to see changes in blood flow related to neural activity. Minzenberg and his colleagues will examine whether patients being treated with Modafinil perform better or worse, as measured by the changes in activity in locus coeruleus, depending on which antipsychotic medication they receive. "We are hoping to find evidence that using Modafinil we can improve brain function in stable schizophrenia patients," Minzenberg said. The New York-based Dana Foundation is a private philanthropic organization that supports clinical research in neuroscience and neuroimmunology and their interrelationship in human health and disease. For further information, visit www.dana.org. For any query with respect to this article or any other content requirement, please contact Editor at htsyndication@hindustantimes.com LOAD-DATE: January 26, 2012 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2012 HT Media Ltd. All Rights Reserved 2 of 998 DOCUMENTS CNS Drug News November 29, 2011 Modiodal approved for additional indication in Japan SECTION: NEWS LENGTH: 154 words Alfresa Pharma (Alfresa Holdings) has received approval in Japan of a partial change in the indications of Modiodal (modafinil) Tablets 100mg, a sleep disorder treatment that has been jointly developed in the country with Mitsubishi Tanabe Pharma. Since March 2007, Modiodal has been jointly marketed by the companies as a treatment for excessive daytime sleepiness associated with narcolepsy. The new indication, approved for the first time in Japan, is "excessive diurnal sleepiness accompanied with obstructive sleep apnoea syndrome under treatment for airway obstruction by continuous positive airway pressure therapy and the like". Modafinil is a wakefulness-enhancing agent to which Alfresa acquired the right to develop, manufacture and market in Japan from Cephalon in June 1998. The drug is currently approved in more than 30 countries, and in seven, including the US, it is marketed with approval for the new indication. LOAD-DATE: November 29, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter JOURNAL-CODE: CNS Drug News Copyright 2011 Espicom Business Intelligence All Rights Reserved 3 of 998 DOCUMENTS CNS Drug News November 29, 2011 Modiodal approved for additional indication in Japan SECTION: NEWS LENGTH: 154 words Alfresa Pharma (Alfresa Holdings) has received approval in Japan of a partial change in the indications of Modiodal (modafinil) Tablets 100mg, a sleep disorder treatment that has been jointly developed in the country with Mitsubishi Tanabe Pharma. Since March 2007, Modiodal has been jointly marketed by the companies as a treatment for excessive daytime sleepiness associated with narcolepsy. The new indication, approved for the first time in Japan, is "excessive diurnal sleepiness accompanied with obstructive sleep apnoea syndrome under treatment for airway obstruction by continuous positive airway pressure therapy and the like". Modafinil is a wakefulness-enhancing agent to which Alfresa acquired the right to develop, manufacture and market in Japan from Cephalon in June 1998. The drug is currently approved in more than 30 countries, and in seven, including the US, it is marketed with approval for the new indication. LOAD-DATE: January 6, 2012 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter JOURNAL-CODE: CNS Drug News Copyright 2011 Espicom Business Intelligence All Rights Reserved 4 of 998 DOCUMENTS The Pharmaceutical Journal November 29, 2011 Tuesday Modafinil indication and dosage error in BNF 62 LENGTH: 80 words HIGHLIGHT: An error is included under the indications and dosage information for modafinil that are printed in the British National Formulary 62... An error is included under the indications and dosage information for modafinil that are printed in the British National Formulary 62 (section 4.4, pp250-251). Modafinil is listed as indicated for the treatment of daytime sleepiness associated with narcolepsy, obstructive sleep apnoea syndrome and chronic shift work sleep disorder. The entry should list daytime sleepiness associated with narcolepsy only. Corrected indication and dosage information is available on the BNF website. LOAD-DATE: November 29, 2011 Tuesday LANGUAGE: ENGLISH PUBLICATION-TYPE: Journal Copyright 2011 PJ Online All Rights Reserved 5 of 998 DOCUMENTS IPR November 25, 2011 Friday 3:11 PM EST India Tender Notice: South Central Railway Seeks "Modafinil 100 Mg Tablets" LENGTH: 87 words DATELINE: SECUNDERABAD, Andhra Pradesh SECUNDERABAD, Andhra Pradesh, Dec. 5 -- South Central Railway has a requirement for "Modafinil 100 Mg Tablets." Tender Bidding Type: Domestic Competitive Bidding According to the description: "Tenders are invited for Supply of Modafinil 100 Mg Tab - 7500 Nos" The tender ref. no. is L-883/2011-2012. Project Location: India The expression of interest should be received by Dec. 5 till 1:00 p.m. For any query with respect to this article or any other content requirement, please contact Editor at htsyndication@hindustantimes.com LOAD-DATE: November 25, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2011 HT Media Ltd. All Rights Reserved 6 of 998 DOCUMENTS Targeted News Service November 7, 2011 Monday 10:51 PM EST Teva Pharmaceutical Industries Assigned Patent BYLINE: Targeted News Service LENGTH: 238 words DATELINE: Alexandria, Va. ALEXANDRIA, Va., Nov. 7 -- Teva Pharmaceutical Industries, Petah Tiqva, Israel, has been assigned a patent (8,048,222) developed by Arina Ceausu, Rishon Lezion, Israel, Anita Lieberman, Ramat Aviv, Israel, and Judith Aronhime, Rechovot, Israel, for a highly pure modafinil. The abstract of the patent published by the U.S. Patent and Trademark Office states: "The present invention provides an improved process for preparing modafinil, whereby it may be isolated in high purity by a single crystallization. The process produces modafinil free of sulphone products of over-oxidation and other byproducts. The invention further provides new crystalline Forms II-VI of modafinil and processes for preparing them. Each of the new forms is differentiated by a unique powder X-ray diffraction pattern. The invention further provides pharmaceutical compositions containing novel modafinil Forms II-IV and VI." The patent application was filed on Sept. 23, 2004 (10/947,228). The full-text of the patent can be found at http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetah tml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=8,048,222&OS=8,048,2 22&RS=8,048,222 Written by Satyaban Rath; edited by Hemanta Panigrahi. For more information about Targeted News Service federal patent awards please contact: Myron Struck, Editor, Direct: 703/866-4708, Cell: 703/304-1897, Myron@targetednews.com SR1107HP1107-666772 LOAD-DATE: November 7, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Targeted News Service LLC All Rights Reserved 7 of 998 DOCUMENTS Health Daily Digest November 4, 2011 Friday Modafinil may not affect Operating Skills of Weary Surgeons LENGTH: 164 words DATELINE: U.S. U.S., Nov. 4 -- Weary surgeons may benefit with the intake of sleep-fighting medication modafinil by having an enhanced brain power but it may not bring any changes in their operating skills, according to a new study. The research was carried out on 39 young surgeons. They were made to be awake throughout the night. As many as 50 percent of doctors were given a modafinil pill and the remaining were provided with a dummy pill. The doctors went through some psychological tests and did a virtual surgery on a simulator as early as 6 a.m in the morning. It was observed that having a sleep-fighting medication modafinil improved the brain power of weary surgeons but it was of no use as far as enhancing their operating skills in a simulator is concerned. Written by Manishika Miglani Published by HT Syndication with permission from Health Daily Digest. For any query with respect to this article or any other content requirement, please contact Editor at htsyndication@hindustantimes.com LOAD-DATE: November 15, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2011 HT Media Ltd. All Rights Reserved 8 of 998 DOCUMENTS Indian Patents News October 22, 2011 Saturday 6:30 AM EST Cephalon Inc Receives Patent for a Pharmaceutical Composition LENGTH: 262 words New Delhi, Oct. 22 -- Cephalon Inc received patent for a pharmaceutical composition on April 11, 2008. The patent number issued by the Indian Patent Office is 218719. Cephalon Inc had filed patent application number IN/PCT/2002/128/KOL for a pharmaceutical composition on Jan. 25, 2002. The inventors of the patent are Miller Matthew S and Scammell Thomas E. The International classification number is A61K31/165. The PCT International application number of the patent is PCT/US00/22338 and the application was filed on Aug. 16, 2000. According to the Controller General of Patents, Designs & Trade Marks, " Modafinil is effective in improving symptoms of attention deficit hyperactivity disorder and symptoms of multiple sclerosis fatigue. The administration of modafinil is also shown to activate the tuberomamillary neurons of the posterior hypothalamus, and thus exhibits activity in an area of the brain associated with normal wakefulness functions. A method of identifying a compound that selectively modulates activity of the tuberomamillary nucleus of the posterior hypothalamus is also disclosed." About the Company Cephalon, Inc. (NASDAQ: CEPH) is a U.S. biopharmaceutical company co-founded in 1987 by Dr. Frank Baldino, Jr., a pharmacologist and former scientist with the DuPont Company, who served as the company's chairman and chief executive officer until his death in December 2010.[2] The company's name comes from the adjective "cephalic" meaning "related to the head or brain," and it was established primarily to pursue treatments for neurodegenerative diseases. LOAD-DATE: October 22, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Indian Patents News, distributed by Contify.com All Rights Reserved 9 of 998 DOCUMENTS World Generic Market October 21, 2011 Teva completes Cephalon acquisition SECTION: NEWS LENGTH: 967 words Teva Pharmaceutical Industries announced on 14th October 2011 that it had completed its acquisition of Cephalon. The firm had initially announced it had acquired all of Cephalon's outstanding shares for US $81.50 per share in cash in May 2011; the deal amounted to a total enterprise value of some US $6.8 billion. With the acquisition of Cephalon now completed, Teva commented that the combined company would have a significant presence in over 60 countries and generated around US $20 billion in revenues on a pro-forma basis for the year ended June 2011. The completion of the deal came after two hurdles were cleared. On 7th October 2011, Teva reported that the US Federal Trade Commission had accepted a proposed consent order in connection with the transaction and granted early termination of the Hart-Scott-Rodino waiting period. The FTC had complained that the acquisition as originally proposed would have violated US antitrust law by reducing competition in three markets: transmucosal fentanyl citrate lozenges used to treat cancer pain; extended-release cyclobenzaprine hydrochloride used as a muscle relaxant; and modafinil tablets used to improve wakefulness. The FTC commented that transmucosal fentanyl citrate lozenges are versions of a cancer pain drug developed by Cephalon and marketed under the brand name Actiq. Three generic versions of the drug, manufactured and marketed by Teva, Cephalon / Watson Pharmaceuticals and Covidien, currently exist in the US. Teva's acquisition of Cephalon would have reduced this to two, and would have given Teva a more than 80% share of the sales of generic Actiq. Extended-release cyclobenzaprine hydrochloride is the generic form of Amrix. The FTC noted that Cephalon had acquired the rights to the branded version, which was approved by the FDA in 2007. Currently, no generic versions of the drug are marketed in the US, but the FTC argued that Teva and Cephalon were two of only a limited number of suppliers that could enter the market quickly with a generic version. As a result, combining the two firms would reduce competition in the future. Modafinil tablets are generic versions of the brand drug Provigil, marketed by Cephalon and used to treat excessive sleepiness caused by narcolepsy or shift work disorder. The FTC noted again that no companies currently market a generic version of the product, which had sales worth US $1 billion in 2010. Teva, Ranbaxy Pharmaceuticals, Mylan Pharmaceutical and Barr Laboratories (another Teva company) have all taken steps to enter the market, and are all eligible to seek the 180-days marketing exclusivity allowed under the Hatch-Waxman Act for being the first to file an ANDA. However, the FTC noted that each company had also signed an agreement with Cephalon to refrain from marketing a generic version until April 2012. The FTC contended that without the proposed settlement, Teva and Cephalon would have been two of only a limited number of suppliers of generic Provigil during the 180-day period. In order to replace the competition potentially lost through the acquisition, the FTC proposed a settlement order which would require Teva to sell all of its rights and assets related to generic Actiq or transmucosal fentanyl citrate lozenges, Actiq or generic extended-release cyclobenzaprine hydrochloride capsules, to Par Pharmaceutical Companies. With regard to modafinil, the FTC's proposed order required Teva to enter into a supply agreement to provide Par with generic modafinil tablets in the US for one year. This would allow Par to compete with a generic modafinil product during the 180-day exclusivity period. In addition, Par may extend the agreement for another year. Across the Atlantic The second hurdle to the transaction had been in Europe. In April 2011, before Teva had announced its acquisition agreement, the European Commission reported that it had opened a formal antitrust investigation regarding an agreement between Teva and Cephalon that was unconnected with the acquisition. The EC had reported that in December 2005, the two firms had settled patent infringement disputes in the US and UK concerning modafinil, with Teva undertaking as part of the agreement not to sell its generic version in the European Economic Area markets before October 2012. The EC was investigating whether this agreement may have had the object or effect of hindering generic competition for the drug in the EEA. On 14th October 2011, the EC formally announced that it had cleared the proposed acquisition of Cephalon under the EU Merger Regulation. However, the decision was conditional upon the divestment of Cephalon's generic version of its Provigil product. The Commission commented that it had examined the effects of the proposed transaction on the market for modafinil drugs, having had concerns that the acquisition, as originally proposed, would have significantly reduced generic competition. The Commission determined that the divestment of Cephalon's generic pipeline modafinil product, as was offered by the company, would allow a competitor to emerge and compete effectively with the Teva / Cephalon combined company. The investigation did not reveal any other significant modification to the competitive situation and dynamics of other relevant markets, as a number of significant and credible competitors would continue to exercise a competitive constraint on the merged entity. Consequently, the Commission was happy with the modified transaction proposal. Teva noted that it was required to divest Cephalon's marketing authorisation of generic modafinil in France and grant to the purchaser of the marketing authorisation certain additional rights with respect to the entire EEA, including a covenant not to sue effective as of October 2012. LOAD-DATE: October 21, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter JOURNAL-CODE: World Generic Markets Copyright 2011 Espicom Business Intelligence All Rights Reserved 10 of 998 DOCUMENTS World Generic Market October 21, 2011 Teva completes Cephalon acquisition SECTION: NEWS LENGTH: 967 words Teva Pharmaceutical Industries announced on 14th October 2011 that it had completed its acquisition of Cephalon. The firm had initially announced it had acquired all of Cephalon's outstanding shares for US $81.50 per share in cash in May 2011; the deal amounted to a total enterprise value of some US $6.8 billion. With the acquisition of Cephalon now completed, Teva commented that the combined company would have a significant presence in over 60 countries and generated around US $20 billion in revenues on a pro-forma basis for the year ended June 2011. The completion of the deal came after two hurdles were cleared. On 7th October 2011, Teva reported that the US Federal Trade Commission had accepted a proposed consent order in connection with the transaction and granted early termination of the Hart-Scott-Rodino waiting period. The FTC had complained that the acquisition as originally proposed would have violated US antitrust law by reducing competition in three markets: transmucosal fentanyl citrate lozenges used to treat cancer pain; extended-release cyclobenzaprine hydrochloride used as a muscle relaxant; and modafinil tablets used to improve wakefulness. The FTC commented that transmucosal fentanyl citrate lozenges are versions of a cancer pain drug developed by Cephalon and marketed under the brand name Actiq. Three generic versions of the drug, manufactured and marketed by Teva, Cephalon / Watson Pharmaceuticals and Covidien, currently exist in the US. Teva's acquisition of Cephalon would have reduced this to two, and would have given Teva a more than 80% share of the sales of generic Actiq. Extended-release cyclobenzaprine hydrochloride is the generic form of Amrix. The FTC noted that Cephalon had acquired the rights to the branded version, which was approved by the FDA in 2007. Currently, no generic versions of the drug are marketed in the US, but the FTC argued that Teva and Cephalon were two of only a limited number of suppliers that could enter the market quickly with a generic version. As a result, combining the two firms would reduce competition in the future. Modafinil tablets are generic versions of the brand drug Provigil, marketed by Cephalon and used to treat excessive sleepiness caused by narcolepsy or shift work disorder. The FTC noted again that no companies currently market a generic version of the product, which had sales worth US $1 billion in 2010. Teva, Ranbaxy Pharmaceuticals, Mylan Pharmaceutical and Barr Laboratories (another Teva company) have all taken steps to enter the market, and are all eligible to seek the 180-days marketing exclusivity allowed under the Hatch-Waxman Act for being the first to file an ANDA. However, the FTC noted that each company had also signed an agreement with Cephalon to refrain from marketing a generic version until April 2012. The FTC contended that without the proposed settlement, Teva and Cephalon would have been two of only a limited number of suppliers of generic Provigil during the 180-day period. In order to replace the competition potentially lost through the acquisition, the FTC proposed a settlement order which would require Teva to sell all of its rights and assets related to generic Actiq or transmucosal fentanyl citrate lozenges, Actiq or generic extended-release cyclobenzaprine hydrochloride capsules, to Par Pharmaceutical Companies. With regard to modafinil, the FTC's proposed order required Teva to enter into a supply agreement to provide Par with generic modafinil tablets in the US for one year. This would allow Par to compete with a generic modafinil product during the 180-day exclusivity period. In addition, Par may extend the agreement for another year. Across the Atlantic The second hurdle to the transaction had been in Europe. In April 2011, before Teva had announced its acquisition agreement, the European Commission reported that it had opened a formal antitrust investigation regarding an agreement between Teva and Cephalon that was unconnected with the acquisition. The EC had reported that in December 2005, the two firms had settled patent infringement disputes in the US and UK concerning modafinil, with Teva undertaking as part of the agreement not to sell its generic version in the European Economic Area markets before October 2012. The EC was investigating whether this agreement may have had the object or effect of hindering generic competition for the drug in the EEA. On 14th October 2011, the EC formally announced that it had cleared the proposed acquisition of Cephalon under the EU Merger Regulation. However, the decision was conditional upon the divestment of Cephalon's generic version of its Provigil product. The Commission commented that it had examined the effects of the proposed transaction on the market for modafinil drugs, having had concerns that the acquisition, as originally proposed, would have significantly reduced generic competition. The Commission determined that the divestment of Cephalon's generic pipeline modafinil product, as was offered by the company, would allow a competitor to emerge and compete effectively with the Teva / Cephalon combined company. The investigation did not reveal any other significant modification to the competitive situation and dynamics of other relevant markets, as a number of significant and credible competitors would continue to exercise a competitive constraint on the merged entity. Consequently, the Commission was happy with the modified transaction proposal. Teva noted that it was required to divest Cephalon's marketing authorisation of generic modafinil in France and grant to the purchaser of the marketing authorisation certain additional rights with respect to the entire EEA, including a covenant not to sue effective as of October 2012. LOAD-DATE: January 6, 2012 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter JOURNAL-CODE: World Generic Markets Copyright 2011 Espicom Business Intelligence All Rights Reserved 11 of 998 DOCUMENTS Global Insight October 19, 2011 Teva Sells Three Generic Products Rights to Par Pharma BYLINE: Georgette Calnan SECTION: In Brief LENGTH: 242 words US firm Par Pharmaceutical yesterday (18 October) announced the ownership of the rights to three products from Teva (Israel) as a result of the terms attached by the US Federal Trade Commission (FTC) to the latter's acquisition of Cephalon (US). Under the terms of the agreement, Par will now own the Abbreviated New Drug Applications (ANDAs) of the generic versions of Actiq (fentanyl citrate lozenges), Amriz (cyclobenzaprine extended-release--ER--capsules), as well as the US rights to market the generic version of Provigil (modafinil). According to Par's press release, citing IMS data, Actiq, Provigil and Amrix achieved annual sales in the US of USD173 million, USD1.1 billion and USD125 million respectively. Par will begin immediate shipment of all strengths of fentanyl citrate lozenges which were previously available from Teva. Cyclobenzaprine ER capsules and modafinil tablets are not yet available. Significance:The deal was part of the US Federal Trade Commission (FTC)'s conditional nod of Teva's acquisition of Cephalon. The sale of the ANDAs allowed Teva to complete its acquisition of Cephalon by its targeted deadline of 14 October. Par's acquisition of the three products preserves competition in all relevant markets. This will boost the US firm's generic drug portfolio which in turn could result in increased revenues. The acquisition of Amrix and Provigil ANDAs will allow Par to enter the generic market for both products next year. LOAD-DATE: October 19, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Web Publication Copyright 2011 World Markets Research Limited All Rights Reserved 12 of 998 DOCUMENTS India Investment News October 18, 2011 Tuesday 6:30 AM EST Par Pharmaceutical Acquires Three Generic Products from Teva Pharmaceuticals LENGTH: 173 words New Delhi, Oct. 18 -- Par Pharmaceutical Companies Inc. issued the following news release: Par Pharmaceutical Companies, Inc. (NYSE: PRX) announced today that it acquired rights to three products from Teva Pharmaceuticals in connection with Teva's acquisition of Cephalon. Under terms of the agreement, Par will own the ANDAs of fentanyl citrate lozenges, a generic version of Actiq, and cyclobenzaprine ER capsules, the generic version of Amrix, as well as the U.S. rights to market modafinil tablets, the generic version of Provigil. According to IMS Health data, annual sales in the U.S. for Actiq and the equivalent generic products are $173 million. Annual sales in the U.S. for Provigil and Amrix are approximately $1.1 billion and $125 million, respectively. Par is currently shipping to the trade all strengths of fentanyl citrate lozenges that were previously available from Teva. Cyclobenzaprine ER capsules and modafinil tablets were not previously marketed by Teva and are not yet available. Source: Par Pharmaceutical Companies Inc. LOAD-DATE: January 3, 2012 LANGUAGE: ENGLISH PUBLICATION-TYPE: Web Publication Copyright 2011 Contify.com All Rights Reserved 13 of 998 DOCUMENTS Key Pharma News October 18, 2011 Tuesday Par acquires three generic products from Teva SECTION: NEWS LENGTH: 177 words Par Pharmaceutical Companies has acquired rights to three products from Teva Pharmaceutical Industries in connection with the latter's acquisition of Cephalon. Under terms of the agreement, Par will own the ANDAs for fentanyl citrate lozenges, a generic version of Actiq, which is indicated for the management of breakthrough cancer pain in patients aged >=16 years with malignancies who are already receiving and tolerant to around-the-clock opioid therapy for their underlying persistent cancer pain, and cyclobenzaprine extended-release (ER) capsules, a generic version of Amrix, indicated as an adjunct to rest and physical therapy for the relief of muscle spasm associated with acute, painful musculoskeletal conditions, as well as the US rights to market modafinil tablets, a generic version of Provigil, a wakefulness-promoting agent. Par is currently shipping all strengths of fentanyl citrate lozenges that were previously available from Teva. Cyclobenzaprine ER capsules and modafinil tablets were not previously marketed by Teva, and are not yet available. LOAD-DATE: October 18, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter JOURNAL-CODE: Pharma Company Insight Copyright 2011 Espicom Business Intelligence All Rights Reserved 14 of 998 DOCUMENTS Key Pharma News October 18, 2011 Tuesday Par acquires three generic products from Teva SECTION: NEWS LENGTH: 177 words Par Pharmaceutical Companies has acquired rights to three products from Teva Pharmaceutical Industries in connection with the latter's acquisition of Cephalon. Under terms of the agreement, Par will own the ANDAs for fentanyl citrate lozenges, a generic version of Actiq, which is indicated for the management of breakthrough cancer pain in patients aged >=16 years with malignancies who are already receiving and tolerant to around-the-clock opioid therapy for their underlying persistent cancer pain, and cyclobenzaprine extended-release (ER) capsules, a generic version of Amrix, indicated as an adjunct to rest and physical therapy for the relief of muscle spasm associated with acute, painful musculoskeletal conditions, as well as the US rights to market modafinil tablets, a generic version of Provigil, a wakefulness-promoting agent. Par is currently shipping all strengths of fentanyl citrate lozenges that were previously available from Teva. Cyclobenzaprine ER capsules and modafinil tablets were not previously marketed by Teva, and are not yet available. LOAD-DATE: January 6, 2012 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter JOURNAL-CODE: Pharma Company Insight Copyright 2011 Espicom Business Intelligence All Rights Reserved 15 of 998 DOCUMENTS PR Newswire October 18, 2011 Tuesday 9:00 AM EST Par Pharmaceutical Acquires Three Generic Products From Teva Pharmaceuticals; Par Begins Shipping Fentanyl Citrate Lozenges to the Trade Immediately LENGTH: 453 words DATELINE: WOODCLIFF LAKE, N.J., Oct. 18, 2011 Par Pharmaceutical Companies, Inc. (NYSE: PRX) announced today that it acquired rights to three products from Teva Pharmaceuticals in connection with Teva's acquisition of Cephalon. Under terms of the agreement, Par will own the ANDAs of fentanyl citrate lozenges, a generic version of Actiq®, and cyclobenzaprine ER capsules, the generic version of Amrix®, as well as the U.S. rights to market modafinil tablets, the generic version of Provigil®. According to IMS Health data, annual sales in the U.S. for Actiq® and the equivalent generic products are $173 million. Annual sales in the U.S. for Provigil® and Amrix® are approximately $1.1 billion and $125 million, respectively. Par is currently shipping to the trade all strengths of fentanyl citrate lozenges that were previously available from Teva. Cyclobenzaprine ER capsules and modafinil tablets were not previously marketed by Teva and are not yet available. About Par Pharmaceutical Companies, Inc. Par Pharmaceutical Companies, Inc. is a US-based specialty pharmaceutical company. Through its wholly-owned subsidiary's two operating divisions, Par Pharmaceutical and Strativa Pharmaceuticals, it develops, manufactures and markets high barrier-to-entry generic drugs and niche, innovative proprietary pharmaceuticals. For press release and other company information, visit www.parpharm.com. Safe Harbor Statement Certain statements in this news release constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. To the extent any statements made in this news release contain information that is not historical, these statements are essentially forward-looking and, as such, are subject to known and unknown risks, uncertainties and contingencies, many of which are beyond the control of the Company, which could cause actual results and outcomes to differ materially from those expressed herein. Risk factors that might affect such forward-looking statements include those set forth in Item 1A of the Company's most recent Annual Report on Form 10-K, in other of the Company's filings with the SEC from time to time, including Quarterly Reports on Form 10-Q and Current Reports on Form 8-K, and on general industry and economic conditions. Any forward-looking statements included in this news release are made as of the date hereof only, based on information available to the Company as of the date hereof, and, subject to any applicable law to the contrary, the Company assumes no obligation to update any forward-looking statements. SOURCE Par Pharmaceutical Companies, Inc. CONTACT:Allison Wey, Vice President, Investor Relations and Corporate Affairs, Par Pharmaceutical Companies, Inc., +1-201-802-4000 URL: http://www.prnewswire.com LOAD-DATE: October 19, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 PR Newswire Association LLC All Rights Reserved 16 of 998 DOCUMENTS Europolitics (daily in English) October 17, 2011 Monday MERGERS : ISRAEL'S TEVA CLEARED TO BUY CEPHALON, SUBJECT TO CONDITIONS BYLINE: Sophie Mosca SECTION: No. 4286 LENGTH: 246 words The world's number one generic pharmaceutical company, Teva, obtained the European Commission's green light, on 13 October, to buy its American competitor, Cephalon, which is primarily an originator company. The EU executive nevertheless makes the EUR4.5 billion merger contingent on Cephalon's sale of its generic version of Provigil, a medicine used to treat excessive daytime sleepiness. The Commission determined that the two groups have a similar generic drug based on the same active ingredient as Provigil, namely modafinil, and that competition on the generic drug markets where modafinil is sold could be hampered. The commitment on the "divestment of Cephalon's generic pipeline modafinil product, as offered by the company, will allow a competitor to emerge and compete effectively with the merged entity," explains the EU executive. The investigation did not reveal any other significant modifications to the competitive situation and dynamics of other relevant markets, as a number of credible and significant competitors will continue to exercise a competitive constraint on the merged entity. The Commission concluded that the proposed transaction, as modified by the commitment, would not significantly impede effective competition in the European Economic Area. The US trade regulator, the Federal Trade Commission, made the merger conditional on Teva's divestment of its Provigil generic, its Actiq generic used to treat cancer and Amrix, a muscle relaxant. LOAD-DATE: October 14, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: EURE Copyright 2011 Europolitique All Rights Reserved 17 of 998 DOCUMENTS The Sunday Times (London) October 16, 2011 Sunday Edition 1; National Edition Doctors given drug perform better surgery; Tests of the brain-stimulant modafinil on exhausted surgeons produced remarkable results, says Jonathan Leake BYLINE: Jonathan Leake SECTION: NEWS; Pg. 15 LENGTH: 673 words IS your doctor on drugs? If not, perhaps they should be. A new study suggests that surgeons given "smart drugs" perform better, safer operations. Researchers gave sleepdeprived surgeons a brain stimulant called modafinil, known to boost memory and brain power, and then tested how good they were at thinking clearly, solving problems and carrying out simulated operations. The results were so convincing that scientists believe the medical profession could even be weaned off its current drug of choice: caffeine. The study, led by Lord Darzi, professor of surgery at Imperial College London and a junior health minister in the previous Labour government, suggests that doctors whose brains have been sharpened by the drug will perform better under pressure. What is more, he says, their extra brain power means they would think faster and react more decisively if something went wrong. "We found that when surgeons had taken modafinil they saw sharp improvements in their ability to solve problems and think flexibly. In fact, their performance was very good," said Barbara Sahakian, professor of psychiatry at Cambridge University. The sight of bleary-eyed doctors scrubbing up for surgery after sleepless nights in hospital has caused widespread concern over the risk to patients. But the usual remedy of strong coffee, taken orally in large quantities, can cause hand tremors, the last thing a surgeon needs during a tricky procedure. Sahakian suggests that modafinil could be a superior substitute for caffeine. Sahakian and Charlotte Housden, her research colleague, worked with Darzi and his surgical team in conducting the tests. Housden said: "Sleep deprivation is like being legally drunk - it causes problems with learning, memory and increased impulsiveness. This is particularly important for people with critical jobs like surgeons, pilots and drivers. "Imaging studies show that the pre-frontal cortex, which is where you do your thinking, undergoes changes in people who lack sleep." In the study, Housden and her colleagues tested 39 tired doctors who had worked all day and then stayed up all night. They were divided into two groups: one was given 200mg of modafinil while the other took a placebo. Then, from 6am to 8am, the doctors were subjected to a battery of tests to measure their cognitive skills, including carrying out virtual operations using a surgical training system. Compared with those who received modafinil, the doctors given a placebo achieved much lower scores on memory tasks, were more impatient, less able to solve problems and to think flexibly. Housden said: "Doctors who are deprived of sleep lose their ability to solve problems and think flexibly. It means that if they encounter a surgical problem they will find it harder to solve. "However, when they took modafinil they regained their ability to solve problems and think flexibly." Modafinil is currently available only on prescription but it has been approved in America for shift workers suffering from sleeping problems while at work. It is, however, widely available from online pharmacies for about 50p a tablet. One key concern is that modafinil has not been subjected to long-term safety tests. Sahakian suggests, however, that, subject to safety approval, modafinil could even be offered over the counter. In other jobs, the use of modafinil has already become widespread - if hidden. The military in Britain and America use the drug to keep soldiers and pilots awake on long missions and in recent years it has become popular with students and, increasingly, with business executives and other groups. Darzi says in his paper, published in the Annals of Surgery: "The continuing discourse over work hours, service provisions, graduate education, fatigue and patient safety strongly suggests that novel solutions might ultimately be required." If modafinil can make even the most exhausted of doctors bright-eyed and cheerful, then that is a problem solved. Of course, they could just cut the working hours instead. Additional reporting: Jan Piotrowski LOAD-DATE: October 16, 2011 LANGUAGE: ENGLISH GRAPHIC: Smart drugs might have benefited the medics in Carry on Doctor ALLSTAR PUBLICATION-TYPE: Newspaper JOURNAL-CODE: STS Copyright 2011 Times Newspapers Limited All Rights Reserved 18 of 998 DOCUMENTS Tendersinfo News October 15, 2011 Saturday 6:30 AM EST BELGIUM : Mergers: Commission approves the acquisition of Cephalon by Teva, subject to conditions LENGTH: 338 words The European Commission has cleared under the EU Merger Regulation the proposed acquisition of US-based pharmaceutical company Cephalon by the generic pharmaceutical company Teva of Israel. The decision is conditional upon the divestment of Cephalon's generic version of its "Provigil" drug. Provigil is indicated for the treatment of excessive daytime sleepiness associated with narcolepsy. Teva has also developed a generic version of the drug. In light of the commitments, the Commission concluded that the transaction does not raise competition concerns. The Commission examined the effects of the proposed transaction on the market for drugs based on Modafinil, the main active pharmaceutical ingredient of Provigil and the generic version developed by Teva as well as the one Cephalon has in the pipeline. The Commission was concerned that the proposed transaction, as initially notified, would have significantly reduced generic competition in the markets where Modafinil is sold. The Commission's investigation showed that the divestment of Cephalon's generic pipeline Modafinil product, as offered by the company, will allow a competitor to emerge and compete effectively with the merged entity. The investigation did not reveal any other significant modification to the competitive situation and dynamics of other relevant markets, as a number of credible and significant competitors will d continue to exercise a competitive constraint on the merged entity. The Commission therefore concluded that the proposed transaction, as modified by the commitment, would not significantly impede effective competition in the European Economic Area (EEA)1 or a substantial part of it. Teva is the world s largest generic pharmaceutical company. Cephalon is a primarily originator company, but also supplies generic pharmaceuticals in the EEA. The transaction was notified to the Commission on 25 August 2011. LOAD-DATE: October 15, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Web Publication Copyright 2011 Tendersinfo News, distributed by Contify.com All Rights Reserved 19 of 998 DOCUMENTS Globes (Tel Aviv, Israel) Distributed by McClatchy-Tribune Business News October 14, 2011 Friday Teva receives European approval for Cephalon acquisition BYLINE: Guy Katsovitch, Globes, Tel Aviv, Israel SECTION: BUSINESS AND FINANCIAL NEWS LENGTH: 272 words Oct. 14--Teva Pharmaceutical Industries Ltd. (Nasdaq: TEVA; TASE: TEVA) and Cephalon Inc. (Nasdaq: CEPH ) announced today that they received approval from the European Commission to proceed with Teva's $7 billion acquisition of innovative drugs company Cephalon. A condition of the approval is that Teva must divest Cephalon's marketing authorization of generic modafinil in France and grant to the purchaser of this marketing authorization certain additional rights with respect to the entire European Economic Area, including a covenant not to sue effective as of October 2012. Teva received approval for the US authorities for the merger at the beginning of the week. Under that approval, Teva is required to divest two ANDAs for fentanyl citrate lozenges, a generic version of Actiq, and cyclobenzaprine ER capsules, the generic version of Amrix. Teva will also grant non-exclusive U.S. rights to an undisclosed company to market modafinil tablets, the generic version of Provigil, which had annual brand sales in the US of approximately $1.1 billion. With the European Commission approval, the parties have now obtained all regulatory approvals required to close the transaction and, accordingly, have scheduled a closing date of October 14, 2011. Teva projects that the deal will be accretive on a non-GAAP basis as soon as it is completed, and on a GAAP basis within four quarters. Teva also expects synergies of $500 million in the third year after completion. ___ (c)2011 the Globes (Tel Aviv, Israel) Visit the Globes (Tel Aviv, Israel) at www.globes.co.il/serveen/globes/nodeview.asp?fid=942 Distributed by MCT Information Services LOAD-DATE: October 15, 2011 LANGUAGE: ENGLISH ACC-NO: 20111014-TL-Teva-receives-European-approval-for-Cephalon-acquisition-1014-201110 14 PUBLICATION-TYPE: Newspaper JOURNAL-CODE: TL Copyright 2011 Globes (Tel Aviv, Israel) 20 of 998 DOCUMENTS States News Service October 14, 2011 Friday MERGERS: COMMISSION APPROVES THE ACQUISITION OF CEPHALON BY TEVA, SUBJECT TO CONDITIONS BYLINE: States News Service LENGTH: 459 words DATELINE: BRUSSELS The following information was released by the European Union: The European Commission has cleared under the EU Merger Regulation the proposed acquisition of US-based pharmaceutical company Cephalon by the generic pharmaceutical company Teva of Israel. The decision is conditional upon the divestment of Cephalon's generic version of its "Provigil" drug. Provigil is indicated for the treatment of excessive daytime sleepiness associated with narcolepsy. Teva has also developed a generic version of the drug. In light of the commitments, the Commission concluded that the transaction does not raise competition concerns. The Commission examined the effects of the proposed transaction on the market for drugs based on Modafinil, the main active pharmaceutical ingredient of Provigil and the generic version developed by Teva as well as the one Cephalon has in the pipeline. The Commission was concerned that the proposed transaction, as initially notified, would have significantly reduced generic competition in the markets where Modafinil is sold. The Commission's investigation showed that the divestment of Cephalon's generic pipeline Modafinil product, as offered by the company, will allow a competitor to emerge and compete effectively with the merged entity. The investigation did not reveal any other significant modification to the competitive situation and dynamics of other relevant markets, as a number of credible and significant competitors will d continue to exercise a competitive constraint on the merged entity. The Commission therefore concluded that the proposed transaction, as modified by the commitment, would not significantly impede effective competition in the European Economic Area (EEA)1 or a substantial part of it. Teva is the world's largest generic pharmaceutical company. Cephalon is a primarily originator company, but also supplies generic pharmaceuticals in the EEA. The transaction was notified to the Commission on 25 August 2011. Merger control rules and procedures The Commission, in 1989, was given the power to assess mergers and acquisitions involving companies with a turnover above certain thresholds (see Article 1 of the Merger Regulation). Its duty is to prevent concentrations that would significantly impede effective competition in the EEA or any substantial part of it. The vast majority of mergers do not pose competition problems and are cleared after a routine review. From the moment a transaction is notified, the Commission generally has a total of 25 working days to decide whether to grant approval (Phase I) or to start an in-depth investigation (Phase II). A non-confidential version of today's decision will be available at: http://ec.europa.eu/competition/elojade/isef/case_details.cfm?proc_code=2_M_6258 LOAD-DATE: October 14, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 States News Service 21 of 998 DOCUMENTS States News Service October 14, 2011 Friday PRELIMINARY STUDY EXAMINES EFFECTS OF 'COGNITIVE ENHANCEMENT' DRUG ON SLEEP-DEPRIVED DOCTORS BYLINE: States News Service LENGTH: 919 words DATELINE: LONDON The following information was released by Imperial College London: Researchers have carried out a preliminary study looking at the effects of the 'cognitive enhancement' drug modafinil on the performance of doctors who had been deprived of sleep for one night. Modafinil, discovered in the 1970s, is currently prescribed in the UK for the treatment of sleepiness associated with narcolepsy, sleep apnoea, and shift work sleep disorder, a condition that affects people who frequently have to work at night. In the new study of 39 people, published today in the Annals of Surgery by researchers from Imperial College London and the University of Cambridge, modafinil improved performance in a series of mental tasks when compared with placebo, but had no effect on the performance of a surgical motor skills task. The doctors did not interact with any patients during the exercise. See also: Annals of Surgery Imperial College London is not responsible for the content of external internet sites Department of Surgery and Cancer Faculty of Medicine Long periods without sleep are known to increase doctors' risk of making poor judgements and committing medical errors. The study was designed as a preliminary investigation into whether certain drugs might be effective at reversing some of the effects of fatigue. Colin Sugden, Clinical Lecturer in Surgery, Department of Surgery and Cancer at Imperial College London, who led the study, said: "This study set out to explore whether modafinil, a wakefulness-promoting drug, might help doctors to perform more effectively under conditions of fatigue when their performance might otherwise be compromised." In this randomised double-blind trial, 20 healthy male doctors took modafinil and 19 took a placebo after one night of sleep deprivation. All were asked to complete both a series of tasks that are commonly used in psychology research and a virtual reality surgical motor skills task. In the psychological tasks, the group that had taken modafinil performed better in tests of working memory and planning, were less impulsive decision-makers, and were more responsive to changing demands during a task. However, there was no significant difference between the two groups on the surgical motor skills task. Mr Sugden said: "Participants in the modafinil group were less impulsive, displayed greater flexibility and solved working memory and planning problems more efficiently than those in the placebo group. However, no benefit was seen in the performance of a basic motor skills task. This was a small, short-term study so we have to be very cautious about how the results are interpreted. Most importantly, it is not clear how performance on tests of mental function relate to how someone performs as a doctor." The researchers stress that these results remain to be confirmed with a larger sample size and ideally in a longer term study. The research explored the effects of one dose of modafinil over a short term and it was not designed to investigate the effects of repeated use, either on a person's physical and mental health or on their performance. Mr Sugden said: "Larger studies looking at the performance effects and safety of longer term use of the drug would need to be performed before we could draw conclusions about whether or not sleep-deprived doctors might benefit from taking it. There are also many challenging ethical considerations which will need to be thought through very carefully. "We should continue to do everything we can to ensure that doctors aren't in a situation where fatigue might impact upon their performance. We don't suggest that anyone should take modafinil to combat sleep deprivation, unless it has been prescribed by a doctor. The study was funded by Imperial College London. -ENDS- For further information please contact: Simon Levey Research Media Officer Imperial College London e-mail: s.levey@imperial.ac.uk Telephone: +44 (0)207 594 6702 or ext. 46702 Out of hours duty Press Officer: +44 (0)7803 886 248 Notes to editors: 1. Journal reference: C. Sugden et al. Effect of pharmacological enhancement on the cognitive and clinical psychomotor performance of sleep deprived doctors. Annals of Surgery, 2011 DOI: 10.1097/SLA.0b013e3182306c99 2. About Imperial College London Consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 14,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture. Since its foundation in 1907, Imperial's contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve global health, tackle climate change, develop sustainable sources of energy and address security challenges. In 2007, Imperial College London and Imperial College Healthcare NHS Trust formed the UK's first Academic Health Science Centre. This unique partnership aims to improve the quality of life of patients and populations by taking new discoveries and translating them into new therapies as quickly as possible. Website: www.imperial.ac.uk LOAD-DATE: October 14, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 States News Service 22 of 998 DOCUMENTS Globes [online] - Israel's Business Arena October 13, 2011 Thursday Teva receives European approval for Cephalon acquisition; The deal will be closed Friday. BYLINE: Guy Katsovitch LENGTH: 267 words Teva Pharmaceutical Industries Ltd. (Nasdaq: TEVA; TASE: TEVA) and Cephalon Inc. (Nasdaq: CEPH ) announced today that they received approval from the European Commission to proceed with Teva's $7 billion acquisition of innovative drugs company Cephalon. A condition of the approval is that Teva must divest Cephalon's marketing authorization of generic modafinil in France and grant to the purchaser of this marketing authorization certain additional rights with respect to the entire European Economic Area, including a covenant not to sue effective as of October 2012. Teva received approval for the US authorities for the merger at the beginning of the week. Under that approval, Teva is required to divest two ANDAs for fentanyl citrate lozenges, a generic version of Actiq, and cyclobenzaprine ER capsules, the generic version of Amrix. Teva will also grant non-exclusive U.S. rights to an undisclosed company to market modafinil tablets, the generic version of Provigil, which had annual brand sales in the US of approximately $1.1 billion. With the European Commission approval, the parties have now obtained all regulatory approvals required to close the transaction and, accordingly, have scheduled a closing date of October 14, 2011. Teva projects that the deal will be accretive on a non-GAAP basis as soon as it is completed, and on a GAAP basis within four quarters. Teva also expects synergies of $500 million in the third year after completion. Published by Globes [online], Israel business news - www.globes-online.com - on October 13, 2011 © Copyright of Globes Publisher Itonut (1983) Ltd. 2011 LOAD-DATE: October 14, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2011 Globes Publisher Itonut (1983) Ltd. All Rights Reserved 23 of 998 DOCUMENTS Globes [online] - Israel's Business Arena October 13, 2011 Thursday Teva receives European approval for Cephalon acquisition; The deal will be closed Friday. BYLINE: Guy Katsovitch LENGTH: 267 words Teva Pharmaceutical Industries Ltd. (Nasdaq: TEVA; TASE: TEVA) and Cephalon Inc. (Nasdaq: CEPH ) announced today that they received approval from the European Commission to proceed with Teva's $7 billion acquisition of innovative drugs company Cephalon. A condition of the approval is that Teva must divest Cephalon's marketing authorization of generic modafinil in France and grant to the purchaser of this marketing authorization certain additional rights with respect to the entire European Economic Area, including a covenant not to sue effective as of October 2012. Teva received approval for the US authorities for the merger at the beginning of the week. Under that approval, Teva is required to divest two ANDAs for fentanyl citrate lozenges, a generic version of Actiq, and cyclobenzaprine ER capsules, the generic version of Amrix. Teva will also grant non-exclusive U.S. rights to an undisclosed company to market modafinil tablets, the generic version of Provigil, which had annual brand sales in the US of approximately $1.1 billion. With the European Commission approval, the parties have now obtained all regulatory approvals required to close the transaction and, accordingly, have scheduled a closing date of October 14, 2011. Teva projects that the deal will be accretive on a non-GAAP basis as soon as it is completed, and on a GAAP basis within four quarters. Teva also expects synergies of $500 million in the third year after completion. Published by Globes [online], Israel business news - www.globes-online.com - on October 13, 2011 © Copyright of Globes Publisher Itonut (1983) Ltd. 2011 LOAD-DATE: October 14, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2011 Globes Publisher Itonut (1983) Ltd. All Rights Reserved 24 of 998 DOCUMENTS Federal Trade Commission Documents and Publications October 7, 2011 FTC Requires Sale of Generic Cancer Pain Drug and Muscle Relaxant as Conditions of Teva's $6.8 Billion Acquisition of Cephalon SECTION: OFFICE OF PUBLIC AFFAIRS LENGTH: 1052 words For Release: 10/07/2011 FTC Requires Sale of Generic Cancer Pain Drug and Muscle Relaxant as Conditions of Teva's $6.8 Billion Acquisition of Cephalon Par Pharmaceuticals Will Acquire Drug Assets, Enter Agreement To Make Generic Provigil To protect competition in the market for prescription drugs, the Federal Trade Commission will require Teva Pharmaceutical Industries Ltd. to sell the rights and assets related to a generic cancer pain drug and a generic muscle relaxant, as a condition of its proposed $6.8 billion acquisition of rival drug firm Cephalon, Inc. In addition, the proposed settlement requires Teva to enter into a supply agreement that will allow a competing firm to sell a generic version of Cephalon's wakefulness drug Provigil in 2012. "This settlement preserves competitive markets for current generic drugs, which are key to holding down the cost of health care for consumers. It also ensures there will be competition among generic drugs introduced in the future," said Richard Feinstein, Director of the FTC's Bureau of Competition. According to the FTC's complaint (http://www.ftc.gov/os/caselist/1110166/111007tevacephaloncmpt.pdf), the acquisition as originally proposed would violate U.S. antitrust law by reducing competition in three markets: transmucosal fentanyl citrate lozenges used to treat cancer pain; extended release cyclobenzaprine hydrochloride used as a muscle relaxant; and modafinil tablets used to improve wakefulness. The markets for each of these drugs is described below. Transmucosal fentanyl citrate lozenges are versions of the cancer pain drug developed by Cephalon and marketed under the brand name Actiq. Three generic versions of the drug, manufactured and marketed by Teva, Cephalon/Watson Pharmaceuticals, and Covidien, currently exist in the United States; this number would be reduced to two after Teva's acquisition of Cephalon. As originally proposed, the deal would have given Teva more than an 80 percent share of the sales of the generic Actiq product. Extended release cyclobenzaprine hydrochloride is an extended release version of the muscle relaxant Flexeril. Cephalon acquired the rights to the branded version of the drug, called Amrix, which was approved by the FDA in 2007. While no companies currently make or market a generic version of Amrix, Teva and Cephalon are two of only a limited number of suppliers that may be able to enter the market quickly with a generic product. Combining the two companies would result in less competition in the future. Modafinil tablets are versions of the brand name drug Provigil marketed by Cephalon and used to treat excessive sleepiness caused by narcolepsy or shift work disorder. No companies currently market a generic version of Provigil, which had sales of $1 billion in 2010. Teva, Ranbaxy Pharmaceuticals, Inc., Mylan Pharmaceutical Inc., and Barr Laboratories, Inc. - which Teva now owns - all have taken steps toward entering the market, and all are eligible to seek a 180-day marketing exclusivity provided under federal law. However, each company also has signed an agreement with Cephalon to refrain from marketing generic Provigil until April 2012. The FTC contends that without the proposed settlement, Teva and Cephalon would have been two of only a limited number of suppliers of generic Provigil during the 180-day exclusivity period. In each of the three markets, Teva's acquisition of Cephalon would harm consumers by significantly reducing competition, leading to higher prices, the FTC contends. The proposed settlement order is designed to replace the competition lost through Teva's acquisition of Cephalon. First, it requires Teva to sell all of its rights and assets related to generic Actiq or transmucosal fentanyl citrate lozenges, and Actiq or generic extended release cyclobenzaprine hydrochloride capsules, to Par Pharmaceuticals, Inc., a generic drug manufacturer based in New Jersey. This divestiture must be completed within 10 days of the acquisition. Next, to remedy the consolidation of marketers of modafinil drugs during the 180-day exclusivity period, the proposed order requires Teva to enter into a supply agreement to provide Par with generic modafinil tablets in the United States for one year. This will allow Par to compete with a generic modafinil product during the 180-day exclusivity period. In addition, Par may extend the modafinil supply agreement for another year. The Commission vote approving the complaint and proposed consent order was 4-0. The order will be published in the Federal Register shortly and will be subject to public comment for 30 days, until November 7, 2011, after which the Commission will decide whether to make it final. Comments can be submitted electronically here (https://ftcpublic.commentworks.com/ftc/tevacephalonconsent). NOTE: The Commission issues a complaint when it has "reason to believe" that the law has been or is being violated, and it appears to the Commission that a proceeding is in the public interest. The issuance of a complaint is not a finding or ruling that the respondent has violated the law. A consent order is for settlement purposes only and does not constitute an admission of a law violation. When the Commission issues a consent order on a final basis, it carries the force of law with respect to future actions. Each violation of such an order may result in a civil penalty of up to $16,000. The FTC's Bureau of Competition works with the Bureau of Economics to investigate alleged anticompetitive business practices and, when appropriate, recommends that the Commission take law enforcement action. To inform the Bureau about particular business practices, call 202-326-3300, send an e-mail to antitrust@ftc.gov, or write to the Office of Policy and Coordination, Bureau of Competition, Federal Trade Commission, 601 New Jersey Ave., Room 7117, Washington, DC 20580. To learn more about the Bureau of Competition, read Competition Counts (http://www.ftc.gov/competitioncounts). Like the FTC on Facebook (http://www.ftc.gov/leaving/facebook/index.shtml) and follow us on Twitter (http://www.ftc.gov/leaving/twitter/index.shtm). MEDIA CONTACT: Mitchell J. Katz, Office of Public Affairs 202-326-2161 STAFF CONTACT: Kari Wallace, Bureau of Competition 202-326-3085 (FTC File No. 111-0166) (Teva-Cephalon.final) LOAD-DATE: October 7, 2011 LANGUAGE: ENGLISH JOURNAL-CODE: FTDA Copyright 2011 Federal Information and News Dispatch, Inc. 25 of 998 DOCUMENTS States News Service October 7, 2011 Friday FTC REQUIRES SALE OF GENERIC CANCER PAIN DRUG AND MUSCLE RELAXANT AS CONDITIONS OF TEVA'S $6.8 BILLION ACQUISITION OF CEPHALON PAR PHARMACEUTICALS WILL ACQUIRE DRUG ASSETS, ENTER AGREEMENT TO MAKE GENERIC PROVIGIL BYLINE: States News Service LENGTH: 970 words DATELINE: WASHINGTON The following information was released by the Federal Trade Commission: To protect competition in the market for prescription drugs, the Federal Trade Commission will require Teva Pharmaceutical Industries Ltd. to sell the rights and assets related to a generic cancer pain drug and a generic muscle relaxant, as a condition of its proposed $6.8 billion acquisition of rival drug firm Cephalon, Inc. In addition, the proposed settlement requires Teva to enter into a supply agreement that will allow a competing firm to sell a generic version of Cephalons wakefulness drug Provigil in 2012. This settlement preserves competitive markets for current generic drugs, which are key to holding down the cost of health care for consumers. It also ensures there will be competition among generic drugs introduced in the future, said Richard Feinstein, Director of the FTCs Bureau of Competition. According to the FTCs complaint, the acquisition as originally proposed would violate U.S. antitrust law by reducing competition in three markets: transmucosal fentanyl citrate lozenges used to treat cancer pain; extended release cyclobenzaprine hydrochloride used as a muscle relaxant; and modafinil tablets used to improve wakefulness. The markets for each of these drugs is described below. Transmucosal fentanyl citrate lozenges are versions of the cancer pain drug developed by Cephalon and marketed under the brand name Actiq. Three generic versions of the drug, manufactured and marketed by Teva, Cephalon/Watson Pharmaceuticals, and Covidien, currently exist in the United States; this number would be reduced to two after Tevas acquisition of Cephalon. As originally proposed, the deal would have given Teva more than an 80 percent share of the sales of the generic Actiq product. Extended release cyclobenzaprine hydrochloride is an extended release version of the muscle relaxant Flexeril. Cephalon acquired the rights to the branded version of the drug, called Amrix, which was approved by the FDA in 2007. While no companies currently make or market a generic version of Amrix, Teva and Cephalon are two of only a limited number of suppliers that may be able to enter the market quickly with a generic product. Combining the two companies would result in less competition in the future. Modafinil tablets are versions of the brand name drug Provigil marketed by Cephalon and used to treat excessive sleepiness caused by narcolepsy or shift work disorder. No companies currently market a generic version of Provigil, which had sales of $1 billion in 2010. Teva, Ranbaxy Pharmaceuticals, Inc., Mylan Pharmaceutical Inc., and Barr Laboratories, Inc. which Teva now owns all have taken steps toward entering the market, and all are eligible to seek a 180-day marketing exclusivity provided under federal law. However, each company also has signed an agreement with Cephalon to refrain from marketing generic Provigil until April 2012. The FTC contends that without the proposed settlement, Teva and Cephalon would have been two of only a limited number of suppliers of generic Provigil during the 180-day exclusivity period. In each of the three markets, Tevas acquisition of Cephalon would harm consumers by significantly reducing competition, leading to higher prices, the FTC contends. The proposed settlement order is designed to replace the competition lost through Tevas acquisition of Cephalon. First, it requires Teva to sell all of its rights and assets related to generic Actiq or transmucosal fentanyl citrate lozenges, and Actiq or generic extended release cyclobenzaprine hydrochloride capsules, to Par Pharmaceuticals, Inc., a generic drug manufacturer based in New Jersey. This divestiture must be completed within 10 days of the acquisition. Next, to remedy the consolidation of marketers of modafinil drugs during the 180-day exclusivity period, the proposed order requires Teva to enter into a supply agreement to provide Par with generic modafinil tablets in the United States for one year. This will allow Par to compete with a generic modafinil product during the 180-day exclusivity period. In addition, Par may extend the modafinil supply agreement for another year. The Commission vote approving the complaint and proposed consent order was 4-0. The order will be published in the Federal Register shortly and will be subject to public comment for 30 days, until November 7, 2011, after which the Commission will decide whether to make it final. Comments can be submitted electronically here. NOTE: The Commission issues a complaint when it has reason to believe that the law has been or is being violated, and it appears to the Commission that a proceeding is in the public interest. The issuance of a complaint is not a finding or ruling that the respondent has violated the law. A consent order is for settlement purposes only and does not constitute an admission of a law violation. When the Commission issues a consent order on a final basis, it carries the force of law with respect to future actions. Each violation of such an order may result in a civil penalty of up to $16,000. The FTCs Bureau of Competition works with the Bureau of Economics to investigate alleged anticompetitive business practices and, when appropriate, recommends that the Commission take law enforcement action. To inform the Bureau about particular business practices, call 202-326-3300, send an e-mail to antitrust@ftc.gov, or write to the Office of Policy and Coordination, Bureau of Competition, Federal Trade Commission, 601 New Jersey Ave., Room 7117, Washington, DC 20580. To learn more about the Bureau of Competition, read Competition Counts. Like the FTC on Facebook and follow us on Twitter. MEDIA CONTACT: Mitchell J. Katz, Office of Public Affairs 202-326-2161 STAFF CONTACT: Kari Wallace, Bureau of Competition 202-326-3085 LOAD-DATE: October 8, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 States News Service 26 of 998 DOCUMENTS Targeted News Service October 7, 2011 Friday 2:16 AM EST FTC Requires Sale of Generic Cancer Pain Drug and Muscle Relaxant as Conditions of Teva's $6.8 Billion Acquisition of Cephalon BYLINE: Targeted News Service LENGTH: 968 words DATELINE: WASHINGTON The Federal Trade Commission issued the following news release: To protect competition in the market for prescription drugs, the Federal Trade Commission will require Teva Pharmaceutical Industries Ltd. to sell the rights and assets related to a generic cancer pain drug and a generic muscle relaxant, as a condition of its proposed $6.8 billion acquisition of rival drug firm Cephalon, Inc. In addition, the proposed settlement requires Teva to enter into a supply agreement that will allow a competing firm to sell a generic version of Cephalon's wakefulness drug Provigil in 2012. "This settlement preserves competitive markets for current generic drugs, which are key to holding down the cost of health care for consumers. It also ensures there will be competition among generic drugs introduced in the future," said Richard Feinstein, Director of the FTC's Bureau of Competition. According to the FTC's complaint, the acquisition as originally proposed would violate U.S. antitrust law by reducing competition in three markets: transmucosal fentanyl citrate lozenges used to treat cancer pain; extended release cyclobenzaprine hydrochloride used as a muscle relaxant; and modafinil tablets used to improve wakefulness. The markets for each of these drugs is described below. Transmucosal fentanyl citrate lozenges are versions of the cancer pain drug developed by Cephalon and marketed under the brand name Actiq. Three generic versions of the drug, manufactured and marketed by Teva, Cephalon/Watson Pharmaceuticals, and Covidien, currently exist in the United States; this number would be reduced to two after Teva's acquisition of Cephalon. As originally proposed, the deal would have given Teva more than an 80 percent share of the sales of the generic Actiq product. Extended release cyclobenzaprine hydrochloride is an extended release version of the muscle relaxant Flexeril. Cephalon acquired the rights to the branded version of the drug, called Amrix, which was approved by the FDA in 2007. While no companies currently make or market a generic version of Amrix, Teva and Cephalon are two of only a limited number of suppliers that may be able to enter the market quickly with a generic product. Combining the two companies would result in less competition in the future. Modafinil tablets are versions of the brand name drug Provigil marketed by Cephalon and used to treat excessive sleepiness caused by narcolepsy or shift work disorder. No companies currently market a generic version of Provigil, which had sales of $1 billion in 2010. Teva, Ranbaxy Pharmaceuticals, Inc., Mylan Pharmaceutical Inc., and Barr Laboratories, Inc. - which Teva now owns - all have taken steps toward entering the market, and all are eligible to seek a 180-day marketing exclusivity provided under federal law. However, each company also has signed an agreement with Cephalon to refrain from marketing generic Provigil until April 2012. The FTC contends that without the proposed settlement, Teva and Cephalon would have been two of only a limited number of suppliers of generic Provigil during the 180-day exclusivity period. In each of the three markets, Teva's acquisition of Cephalon would harm consumers by significantly reducing competition, leading to higher prices, the FTC contends. The proposed settlement order is designed to replace the competition lost through Teva's acquisition of Cephalon. First, it requires Teva to sell all of its rights and assets related to generic Actiq or transmucosal fentanyl citrate lozenges, and Actiq or generic extended release cyclobenzaprine hydrochloride capsules, to Par Pharmaceuticals, Inc., a generic drug manufacturer based in New Jersey. This divestiture must be completed within 10 days of the acquisition. Next, to remedy the consolidation of marketers of modafinil drugs during the 180-day exclusivity period, the proposed order requires Teva to enter into a supply agreement to provide Par with generic modafinil tablets in the United States for one year. This will allow Par to compete with a generic modafinil product during the 180-day exclusivity period. In addition, Par may extend the modafinil supply agreement for another year. The Commission vote approving the complaint and proposed consent order was 4-0. The order will be published in the Federal Register shortly and will be subject to public comment for 30 days, until November 7, 2011, after which the Commission will decide whether to make it final. Comments can be submitted electronically here. NOTE: The Commission issues a complaint when it has "reason to believe" that the law has been or is being violated, and it appears to the Commission that a proceeding is in the public interest. The issuance of a complaint is not a finding or ruling that the respondent has violated the law. A consent order is for settlement purposes only and does not constitute an admission of a law violation. When the Commission issues a consent order on a final basis, it carries the force of law with respect to future actions. Each violation of such an order may result in a civil penalty of up to $16,000. The FTC's Bureau of Competition works with the Bureau of Economics to investigate alleged anticompetitive business practices and, when appropriate, recommends that the Commission take law enforcement action. To inform the Bureau about particular business practices, call 202-326-3300, send an e-mail to antitrust@ftc.gov, or write to the Office of Policy and Coordination, Bureau of Competition, Federal Trade Commission, 601 New Jersey Ave., Room 7117, Washington, DC 20580. To learn more about the Bureau of Competition, read Competition Counts. Like the FTC on Facebook and follow us on Twitter. Contact: Mitchell J. Katz, 202/326-2161 Copyright Targeted News Services TNS MT93 111008-3622578 61MarlizTagarum LOAD-DATE: October 8, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Targeted News Service LLC All Rights Reserved 27 of 998 DOCUMENTS US Fed News October 7, 2011 Friday 2:07 PM EST FTC REQUIRES SALE OF GENERIC CANCER PAIN DRUG AND MUSCLE RELAXANT AS CONDITIONS OF TEVA'S $6.8B ACQUISITION OF CEPHALON LENGTH: 788 words WASHINGTON, Oct. 7 -- The Federal Trade Commission issued the following press release: To protect competition in the market for prescription drugs, the Federal Trade Commission will require Teva Pharmaceutical Industries Ltd. to sell the rights and assets related to a generic cancer pain drug and a generic muscle relaxant, as a condition of its proposed $6.8 billion acquisition of rival drug firm Cephalon, Inc. In addition, the proposed settlement requires Teva to enter into a supply agreement that will allow a competing firm to sell a generic version of Cephalon's wakefulness drug Provigil in 2012. "This settlement preserves competitive markets for current generic drugs, which are key to holding down the cost of health care for consumers. It also ensures there will be competition among generic drugs introduced in the future," said Richard Feinstein, Director of the FTC's Bureau of Competition. According to the FTC's complaint, the acquisition as originally proposed would violate U.S. antitrust law by reducing competition in three markets: transmucosal fentanyl citrate lozenges used to treat cancer pain; extended release cyclobenzaprine hydrochloride used as a muscle relaxant; and modafinil tablets used to improve wakefulness. The markets for each of these drugs is described below. Transmucosal fentanyl citrate lozenges are versions of the cancer pain drug developed by Cephalon and marketed under the brand name Actiq. Three generic versions of the drug, manufactured and marketed by Teva, Cephalon/Watson Pharmaceuticals, and Covidien, currently exist in the United States; this number would be reduced to two after Teva's acquisition of Cephalon. As originally proposed, the deal would have given Teva more than an 80 percent share of the sales of the generic Actiq product. Extended release cyclobenzaprine hydrochloride is an extended release version of the muscle relaxant Flexeril. Cephalon acquired the rights to the branded version of the drug, called Amrix, which was approved by the FDA in 2007. While no companies currently make or market a generic version of Amrix, Teva and Cephalon are two of only a limited number of suppliers that may be able to enter the market quickly with a generic product. Combining the two companies would result in less competition in the future. Modafinil tablets are versions of the brand name drug Provigil marketed by Cephalon and used to treat excessive sleepiness caused by narcolepsy or shift work disorder. No companies currently market a generic version of Provigil, which had sales of $1 billion in 2010. Teva, Ranbaxy Pharmaceuticals, Inc., Mylan Pharmaceutical Inc., and Barr Laboratories, Inc. - which Teva now owns - all have taken steps toward entering the market, and all are eligible to seek a 180-day marketing exclusivity provided under federal law. However, each company also has signed an agreement with Cephalon to refrain from marketing generic Provigil until April 2012. The FTC contends that without the proposed settlement, Teva and Cephalon would have been two of only a limited number of suppliers of generic Provigil during the 180-day exclusivity period. In each of the three markets, Teva's acquisition of Cephalon would harm consumers by significantly reducing competition, leading to higher prices, the FTC contends. The proposed settlement order is designed to replace the competition lost through Teva's acquisition of Cephalon. First, it requires Teva to sell all of its rights and assets related to generic Actiq or transmucosal fentanyl citrate lozenges, and Actiq or generic extended release cyclobenzaprine hydrochloride capsules, to Par Pharmaceuticals, Inc., a generic drug manufacturer based in New Jersey. This divestiture must be completed within 10 days of the acquisition. Next, to remedy the consolidation of marketers of modafinil drugs during the 180-day exclusivity period, the proposed order requires Teva to enter into a supply agreement to provide Par with generic modafinil tablets in the United States for one year. This will allow Par to compete with a generic modafinil product during the 180-day exclusivity period. In addition, Par may extend the modafinil supply agreement for another year. The Commission vote approving the complaint and proposed consent order was 4-0. The order will be published in the Federal Register shortly and will be subject to public comment for 30 days, until November 7, 2011, after which the Commission will decide whether to make it final. Comments can be submitted electronically here (https://ftcpublic.commentworks.com/ftc/tevacephalonconsent). For any query with respect to this article or any other content requirement, please contact Editor at htsyndication@hindustantimes.com LOAD-DATE: October 10, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 HT Media Ltd. All Rights Reserved 28 of 998 DOCUMENTS Indian Patents News September 13, 2011 Tuesday 6:30 AM EST Cephalon Inc Receives Patent for Novel Pharmaceutical Formulations of Modafinil LENGTH: 262 words New Delhi, Sept. 13 -- Cephalon Inc received patent for novel pharmaceutical formulations of modafinil on Dec. 14, 2007. The patent number issued by the Indian Patent Office is 212727. Cephalon Inc had filed patent application number 633/KOLNP/2005 for novel pharmaceutical formulations of modafinil on April 13, 2005. The inventors of the patent are Vincent Corvari, George Grandolfi and Alpa Parikh. The International classification number is A61K7/28. The PCT International application number of the patent is PCT/US03/028528 and the application was filed on Sept. 11, 2003. According to the Controller General of Patents, Designs & Trade Marks, "A composition comprising modafinil, wherein modafinil comprises about 90% by weight of the composition; a lactose monohydrate which comprises about 3-10% of the composition by weight; a cross-linked sodium carboxymethyl cellulose, which comprises about 2-5% of the composition by weight; a polyvinyl pyrrolidone, which comprises about 2-5% of the composition by weight; and magnesium stearate, which comprises about 0.2-2.0% of the composition by weight." About the Company Cephalon, Inc. (NASDAQ: CEPH) is a U.S. biopharmaceutical company co-founded in 1987 by Dr. Frank Baldino, Jr., a pharmacologist and former scientist with the DuPont Company, who served as the company's chairman and chief executive officer until his death in December 2010. The company's name comes from the adjective "cephalic" meaning "related to the head or brain," and it was established primarily to pursue treatments for neurodegenerative diseases. LOAD-DATE: September 13, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Indian Patents News, distributed by Contify.com All Rights Reserved 29 of 998 DOCUMENTS Indian Patents News August 18, 2011 Thursday 6:30 AM EST Cephalon Inc Files Patent Application for Modafinil Pharmaceutical Compositions LENGTH: 275 words New Delhi, Aug. 18 -- USA based Cephalon Inc filed patent application for modafinil pharmaceutical compositions. The inventors are Heacock Craig, Parikh Alpa and Patel Piyush R. Cephalon Inc filed the patent application on Feb. 11, 2005. The patent application number is 00172/KOLNP/2005 A. The international classification number is A61K31/165. According to the Controller General of Patents, Designs & Trade Marks, "Pharmaceutical compositions comprising modafinil in the form of particles of defined size. The particle size of modafinil can have a significant effect on the potency and safety profile of the drug." About the Company Cephalon, Inc. (Public, NASDAQ:CEPH) is an international biopharmaceutical company engaged in the discovery, development and commercialization of products in four core therapeutic areas: central nervous system (CNS), pain, oncology and inflammatory disease. In addition to conducting an active research and development program, it markets seven products in the United States and numerous products in various countries throughout Europe and the world. Its principal product are its wakefulness products, PROVIGIL (modafinil) Tablets [C-IV] and NUVIGIL (armodafinil) Tablets [C-IV], which comprised 51% of its total consolidated net sales during the year ended December 31, 2009. During 2009, Cephalon, Inc. acquired an exclusive, worldwide license to the ImmuPharma investigational compound, LUPUZOR, which is in Phase IIb development for the treatment of systemic lupus erythematosus. In August 2009, Cephalon, Inc. acquired Arana Therapeutics Limited. In April 2010, the Company acquired Mepha, a pharmaceutical company. LOAD-DATE: August 18, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Indian Patents News, distributed by Contify.com All Rights Reserved 30 of 998 DOCUMENTS Indian Patents News August 18, 2011 Thursday 6:30 AM EST Alembic Limited Files Patent Application for Process for the Preparation of 2-[(diphenylmethyl) Thio] Acetamide LENGTH: 342 words New Delhi, Aug. 18 -- India based Alembic Limited filed patent application for process for the preparation of 2-[(diphenylmethyl) thio] acetamide. The inventors are Bhatt Surendra B, Patel Jiten R, Panchasara Dinesh, Shah Hetal R, Deo Keshav and Kansal Vinod Kumar. Alembic Limited filed the patent application on Jan. 31, 2003. The patent application number is 130/MUM/2003. The international classification numbers are A61K31/165, C07C317/44 and C07C323/29. According to the Controller General of Patents, Designs & Trade Marks, "Process for the preparation of 2-[(diphenylmethyl) thioacetamide, an intermediate for the preparation of Modafinil which is a CNS stimulant and used for the treatment of narcolepsia. The process comprises reacting 2-[dipenylmethyl) thio] acetic acid with alcohols, in presence of catalytic amount of inorganic acid or organic acid at reflux temperature of alcohol to obtain corresponding ester which is reacted with ammonia to give 2- [(diphenylmethyl)thio]acetamide. If desired 2- [(diphenylmethyl) thioacetamide thus produced is reacted with hydrogen peroxide to produce Modafinil." About the Company Alembic Limited (Public, BOM:506235) is engaged in manufacturing synthetic active pharmaceutical ingredients (APIs), consisting of independent manufacturing blocks for Macrolides, non-steroidal anti-inflammatory drugs (NSAIDs) and other drugs. The Company's veterinary products include antibiotics/anti-microbials injectables/orals, speciality injectables, endectocides, boli, feed supplements and poultry. The Company's therapeutic category includes anti-infectives, caphalosporins, anti-protozoal, musculo skeletal, erectile dtsfunction, anti-parkinsons, anti-depressants, anti-epileptics, CNS stimulant, anti anziety and cardiovascular. Its basket of formulation products contain 150 products in several forms belonging to diverse therapeutic segments, including anti-infective, cough and cold products to cardiovascular and oral anti-diabetics. The wholly owned subsidiary of the Company is Alembic Global Holding SA. LOAD-DATE: August 18, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Indian Patents News, distributed by Contify.com All Rights Reserved 31 of 998 DOCUMENTS Targeted News Service August 6, 2011 Saturday 3:52 AM EST SRI International, HealthPartners Research Foundation Assigned Patent BYLINE: Targeted News Service LENGTH: 267 words DATELINE: Alexandria, Va. ALEXANDRIA, Va., Aug. 6 -- SRI International, Menlo Park, Calif., and HealthPartners Research Foundation, Minneapolis, have been assigned a patent (7,989,502) developed by five co-inventors for an "intranasal delivery of modafinil." The co-inventors are Mary Ann Katherine Greco, San Francisco, William Howard Frey II, White Bear Lake, Minn., Jacqueline DeRose, Santa Clara, Calif., Rachel Beth Matthews, Dayton, Minn., and Leah Ranae Bresin Hanson, Vadnais Heights, Minn. The abstract of the patent published by the U.S. Patent and Trademark Office states: "Modafinil is selectively delivered to the brain, minimizing delivery to the blood, of a person in need thereof by administering to the person a therapeutically-effective dosage of modafinil, wherein the dosage is less than 1 mg, formulated in a lipid microemulsion (LME) and selectively delivered to the upper third of the nasal cavity. The method may be implemented with an intranasal pharmaceutical delivery device loaded with a modafinil composition and adapted to deliver the dosage to the upper third of the nasal cavity." The patent application was filed on Feb. 6, 2009 (12/367,496). The full-text of the patent can be found at http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=% 2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=7,989,502.PN.&OS=PN/7,989,502&RS= PN/7,989,502 Written by Shabnam Sheikh; edited by Jaya Anand. For more information about Targeted News Service federal patent awards please contact: Myron Struck, Editor, Direct: 703/866-4708, Cell: 703/304-1897, Myron@targetednews.com SH0806JA0806-604728 LOAD-DATE: September 22, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Targeted News Service LLC All Rights Reserved 32 of 998 DOCUMENTS Indian Patents News July 31, 2011 Sunday 6:30 AM EST Alembic Limited Files Patent Application for Process for the Preparation of Modafinil of Formula II LENGTH: 314 words New Delhi, July 31 -- India based Alembic Limited filed patent application for process for the preparation of Modafinil of formula II. The inventors are Bhatt Surendra B, Patel Jiten R, Panchasara Dinesh, Shah Hetal R, Deo Keshav and Kansal Vinod Kumar. Alembic Limited filed the patent application on Dec. 21, 2004. The patent application number is 1387/MUM/2004 A. The international classification number is A61K31/400. According to the Controller General of Patents, Designs & Trade Marks, "Process for the preparation of Modafinil which is a CNS stimulant and used for the treatment of narcolepsia. The process comprises reacting 2-[(diphenylmethyl)thio]acetic acid with alcohols, in presence of catalytic amount of inorganic acid or organic acid at reflux temperature of alcohol to obtain corresponding ester which is reacted with ammonia to give 2-[(diphenylmethyl)thio]acetamide, which is reacted with hydrogen peroxide to produce Modafinil." About the Company Alembic Limited (Public, BOM:506235) is engaged in manufacturing synthetic active pharmaceutical ingredients (APIs), consisting of independent manufacturing blocks for Macrolides, non-steroidal anti-inflammatory drugs (NSAIDs) and other drugs. The Company's veterinary products include antibiotics/anti-microbials injectables/orals, speciality injectables, endectocides, boli, feed supplements and poultry. The Company's therapeutic category includes anti-infectives, caphalosporins, anti-protozoal, musculo skeletal, erectile dtsfunction, anti-parkinsons, anti-depressants, anti-epileptics, CNS stimulant, anti anziety and cardiovascular. Its basket of formulation products contain 150 products in several forms belonging to diverse therapeutic segments, including anti-infective, cough and cold products to cardiovascular and oral anti-diabetics. The wholly owned subsidiary of the Company is Alembic Global Holding SA. LOAD-DATE: July 31, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Indian Patents News, distributed by Contify.com All Rights Reserved 33 of 998 DOCUMENTS Spicy IP July 30, 2011 Saturday 9:00 PM EST Does size matter: the case of an anti-narcoleptic drug, modafinil? BYLINE: Rajiv Kr. Choudhry LENGTH: 1245 words Long post follows: About a month ago, the UK Chancery division patents courts (England and Wales) rendered an opinion (http://www.bailii.org/ew/cases/EWHC/Patents/2011/1591.html) (Justice Floyd) regarding claim construction in defining size of particles of an anti-narcoleptic drug, modafinil, in pharmaceutical compositions. The patent court construed patent claims to determine whether there is an infringement, if any. Facts: The dispute involves three patents related to the drug modafinil, used to treat sleep disorders such as narcolepsy. Orchid Europe is the manufacturer of generic modafinil and Mylan intended to manufacture the drug in UK. Cephalon is the proprietor, an exclusive licensee in the UK and a sub-licensee of the patents involved (European Patents (https://data.epo.org/publication-server/?lg=en) (UK) Numbers 0 731 698 ("698"), 0 966 962 ("962") and 1 088 549 ("549")). These patents contain a very similar disclosure with differentiated claims, and they all claim a priority date of 6th October 1994. Mylan denied infringement and challenged the validity of all three Cephalon patents on the grounds of lack of inventive step and insufficiency. Background: Modafinil, the active substance, was discovered and developed by a French company, Lafon. Cephalon licensed modafinil in the USA in 1994 and conducted further tests on it to bring it to the market as an agent to treat sleep disorders. In the course of the tests in the US, modafinil caused more side effects than in Europe in corresponding trials involving equivalent doses. The cause was traced to smaller particle size of the input active pharmaceutical ingredient ("API") of the lots used in the US trials. In the first human trials performed on non-commercial samples of modafinil ("early lots"), the median particle size diameter was between 80 and 150 m. The studies in US involved "late lots", revealed unanticipated side effects at doses of 800 mg per day. These late lots employed a particle size of 30 to 50 m. This led the patentee to conclude that the late lots could be more readily absorbed than the early lots, and therefore leading to an increased plasma concentration (increased bioavailability) of modafinil. Claims: Each patent claimed different formulations of modafinil, with different particle sizes. The relevant portions of the first independent claims of each patent are reproduced below. '698 patent '962 patent '549 patent ....comprising .... .... ... wherein at least about modafinil particles, wherein comprising 95% of the cumulative total of at least about 95% of the modafinil said modafinil particles in cumulative total of particles said composition have a modafinil particles in said having a diameter of less than about 200 composition have a diameter median m and wherein the median of less than about 200 particle size particle size is about 10 to 60 micrometers (m). of about 2 to m. about 60 m... Issue: "Whether the claims were referring to the particle size within the composition (Cephalon's contention) or whether they were referring to the particle size in the active ingredient used to make the composition (Mylan's contention)." Additionally, during the tabletting process, the size of the particles in the final finished tablet differed from that in the API from which the tablets are made. Therefore, the sizes of the particles in the API did not correspond to the size of the particles in the finished tablets, and vice versa. Claim construction and analysis: In the claim construction, both sides pointed to claim language that supported their particular construction. For example, Cephalon pointed to the '698 patent, which claimed 'compositions comprising' modafinil particles and hence referring to the size of the particles in the final tablets. Mylan pointed to the claims in the '962 patent for use of ' modafinil particles ...at least about 95% of the cumulative total of said particles have a diameter of less than about 200 micrometers for the manufacture of a pharmaceutical composition " and hence points to the particle size in the input API, as it is used in the manufacturing process.Several industry practices were listed to aid in the interpretation of claims, one of which was, "[A] general practice in the pharmaceutical industry was not to measure particle size in a solid formulation, but to make measurements on the input API." Conclusion: Based on the common knowledge, the Judge concluded that the patentee must have meant particle size to be measured on the bulk API. "Particle size is never measured in the dosage form, and the skilled person would not know how to do so." Although it routine industry practice to measure the particle size of API, the particle size in finished tablets could not have been measured at the priority date of the patents (1994). Additionally, particle size of the API has a direct correlation with bioavailability in the final tablet. Therefore contentions of Mylan were accepted. Infringement: Both parties agreed that if Mylan's construction of the claims was the correct one, there was no infringement. Obviousness: Mylan contended that the patents were invalid in view of prior publications, 'Drugs of the future, and Nguyen, a PCT application applied for by Lafon. On the basis of 'common general knowledge' and the knowledge of the relationship between lower particle size and improved plasma concentration or bioavailability, it was held that it would be routine to investigate the particle size to improve the bioavailability of a compound, with the expectation that this investigation would be fruitful. Hence Cephalon patents were obvious in view of the first publication. As regards the Nguyen publication, no dosage for modafinil specified but it did provide a formulation with a particle size of 2-5 m. J. Floyd rejected the contention that it would require significant experimentation/investment to the results of Nguyen to reach an appropriate dosage for modafinil. "The skilled person is entitled to implement a disclosure in a technically obvious way, even if doing so might not appear commercially attractive. Had I not come to the conclusions I had already reached in relation to obviousness, I would have required the claims to be limited so as to avoid the attack."Significance to Indian scenario:Shamnad, in a previous post (http://spicyipindia.blogspot.com/2007/09/section-3d-and-efficacy-more-cases_09. html), referred to a need for having broad guidelines for defining 'efficacy.' In that post, the question was whether increased bioavailability would constitute as a significant enhancement in efficacy. If this case was decided under the Indian law, increased bioavailability and (therefore efficacy) would have been the argument to counter a 3(d) opposition and it would have overcome the challenge. This case therefore highlights when the patent office should undertake the 3(d) analysis: Only when the basic issues (inventive and non-obvious) should the Controller decide the issue of patentability under section 3(d). This case also highlights whether it makes sense to equate bioavailability to efficacy. The exclusionary test (http://spicyipindia.blogspot.com/2010/08/exclusionary-definition-for-term.html) may perhaps make more sense in such a scenario for formulation applications like the one described here. LOAD-DATE: October 17, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Web Publication Copyright 2011 Spicy IP, distributed by Contify.com All Rights Reserved 34 of 998 DOCUMENTS Indian Patents News July 19, 2011 Tuesday 6:30 AM EST Cephalon Inc Files Patent Application for Pharmaceutical Formulations of Modafinil LENGTH: 286 words New Delhi, July 19 -- USA based Cephalon Inc filed patent application for pharmaceutical formulations of modafinil. The inventors are Craig Heacock, Alpa Parikh and Piyush Patel. Cephalon Inc filed the patent application on April 13, 2005. The patent application number is 00632/KOLNP/2005 A. The international classification numbers are A61K 31/165 and A61P 25/00. According to the Controller General of Patents, Designs & Trade Marks, "Compositions of modafinil and methods of treating neurologically related conditions with the administration of modafinil. Also compositions that include modafinil and one or more excipients such as diluents, disintegrants, binders and lubricants." About the Company Cephalon, Inc. (Public, NASDAQ:CEPH) is an international biopharmaceutical company engaged in the discovery, development and commercialization of products in four core therapeutic areas: central nervous system (CNS), pain, oncology and inflammatory disease. In addition to conducting an active research and development program, it markets seven products in the United States and numerous products in various countries throughout Europe and the world. Its principal product are its wakefulness products, PROVIGIL (modafinil) Tablets [C-IV] and NUVIGIL (armodafinil) Tablets [C-IV], which comprised 51% of its total consolidated net sales during the year ended December 31, 2009. During 2009, Cephalon, Inc. acquired an exclusive, worldwide license to the ImmuPharma investigational compound, LUPUZOR, which is in Phase IIb development for the treatment of systemic lupus erythematosus. In August 2009, Cephalon, Inc. acquired Arana Therapeutics Limited. In April 2010, the Company acquired Mepha, a pharmaceutical company. LOAD-DATE: July 19, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Indian Patents News, distributed by Contify.com All Rights Reserved 35 of 998 DOCUMENTS Washington Drug Letter July 11, 2011 Monday Barr Must Produce Settlement Docs in Provigil Pay-for-Delay Case SECTION: Vol. 43 No. 27 LENGTH: 153 words A federal court is ordering Teva subsidiary Barr Pharmaceuticals to disclose a number of previously withheld documents in a long-running Provigil antitrust case. The 18 documents "relate to the settlement between Barr and Provigil maker Cephalon and how, financially, the settlement terms would affect Chemagis," Barr's active pharmaceutical ingredient supplier and partner in developing generic Provigil (modafinil). Barr must produce the documents by July 12, according to the Tuesday filing in the U.S. District court for the Eastern District of Pennsylvania. The case, King Drug Company of Florence, Inc. et al. v. Cephalon, Inc. et al., concerns settlements made between Cephalon and several generic-drug makers to delay generic versions of sleepiness drug Provigil (modafinil). The suit was initially filed in 2006. Teva did not return a request for comment by press time. -- Kevin O'Rourke Release date: July 11, 2011 LOAD-DATE: July 9, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2011 Washington Business Information, Inc. All Rights Reserved 36 of 998 DOCUMENTS Drug Industry Daily July 7, 2011 Thursday Court Orders Barr to Produce Settlement Documents in Provigil Pay-for-Delay Case SECTION: Vol. 10 No. 132 LENGTH: 391 words A federal court is ordering Teva subsidiary Barr Pharmaceuticals to disclose a number of previously withheld documents in a long-running Provigil antitrust case. The 18 documents "relate to the settlement between Barr and Cephalon and how, financially, the settlement terms would affect Chemagis," Barr's active pharmaceutical ingredient supplier and partner in developing generic Provigil ( modafinil). Barr must produce the documents by July 12. The case, King Drug Company of Florence, Inc. et al. v. Cephalon, Inc. et al., concerns settlements made between Cephalon and several generic-drug makers to delay generic versions of Cephalon's sleepiness drug Provigil (modafinil). The suit was initially filed in 2006. A collection of distributors and pharmacies, including CVS, allege the settlements "constitute an unlawful restraint of trade" and have sued Cephalon, Barr and three other generic companies for antitrust violations, according to Tuesday's filing in the U.S. District court for the Eastern District of Pennsylvania. The plaintiffs are seeking access to communications between Barr and Chemagis between December 2005 and January 2006 -- prior to Barr's February 2006 agreement with Cephalon regarding generic Provigil. The plaintiffs also argued that Barr waived attorney-client privilege on other communications from the settlement with Cephalon, and must allow discovery of the documents, but presiding judge Mitchell Goldberg denied that motion. Since the case began, Teva has acquired a number of the companies involved, including Barr. In a twist that shocked many analysts, Teva outbid Valeant in May to buy Cephalon for $6.8 billion (DID, May 3). The Provigil agreement has been the subject of government scrutiny for several years. In 2006, the FTC asked Cephalon for information about settlements it made with generic companies (DID, March 17, 2006). The European Commission also recently announced that it had launched an investigation into the agreement between Cephalon and Teva to delay generic Provigil (DID, May 2). An FTC report released in May found deals struck between brand and generic pharmaceutical companies are on the rise, despite efforts to restrict agreements that delay market entry of cheaper drugs (DID, May 5). Teva did not return a request for comment by press time. -- Kevin O'Rourke Release date: July 7, 2011 LOAD-DATE: July 7, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2011 Washington Business Information, Inc. All Rights Reserved 37 of 998 DOCUMENTS Indian Patents News July 1, 2011 Friday 6:30 AM EST Cephalon Inc. Files Patent Application for Novel Pharmaceutical Formulations of Modafinil LENGTH: 282 words New Delhi, July 1 -- USA based Cephalon Inc. filed patent application for novel pharmaceutical formulations of modafinil. The inventors are Corvari Vincent, Grandolfi George and Parikh Alpa. Cephalon Inc. filed the patent application on Dec. 12, 2003. The patent application number is 01616/KOLNP/2003 A. The international classification numbers are A61K31/165, 9/20 and 9/16. According to the Controller General of Patents, Designs & Trade Marks, "The present invention is related to compositions of modafinil, including compositions of modafinil and one or more diluents, disintegrants, binders and lubricants, and the processes for the preparation thereof." About the Company Cephalon, Inc. (Public, NASDAQ:CEPH) is an international biopharmaceutical company engaged in the discovery, development and commercialization of products in four core therapeutic areas: central nervous system (CNS), pain, oncology and inflammatory disease. In addition to conducting an active research and development program, it markets seven products in the United States and numerous products in various countries throughout Europe and the world. Its principal product are its wakefulness products, PROVIGIL (modafinil) Tablets [C-IV] and NUVIGIL (armodafinil) Tablets [C-IV], which comprised 51% of its total consolidated net sales during the year ended December 31, 2009. During 2009, Cephalon, Inc. acquired an exclusive, worldwide license to the ImmuPharma investigational compound, LUPUZOR, which is in Phase IIb development for the treatment of systemic lupus erythematosus. In August 2009, Cephalon, Inc. acquired Arana Therapeutics Limited. In April 2010, the Company acquired Mepha, a pharmaceutical company. LOAD-DATE: July 1, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Indian Patents News, distributed by Contify.com All Rights Reserved 38 of 998 DOCUMENTS Indian Patents News June 30, 2011 Thursday 6:30 AM EST Cephalon Inc Files Patent Application for Novel Pharmaceutical Formulations of Modafinil LENGTH: 283 words New Delhi, June 30 -- USA based Cephalon Inc filed patent application for novel pharmaceutical formulations of modafinil. The inventors are Vincent Corvari, George Grandolfi and Alpa Parikh. Cephalon Inc filed the patent application on April 13, 2005. The patent application number is 00633/KOLNP/2005A. The international classification numbers are A61K 31/165 9/16,9/20 and 9/48. According to the Controller General of Patents, Designs & Trade Marks, "The present invention is related to compositions of modafinil, including compositions of modafinil and one or more diluents, disintegrants, binders and lubricants, and the processes for their preparation thereof." About the Company Cephalon, Inc. (Public, NASDAQ:CEPH) is an international biopharmaceutical company engaged in the discovery, development and commercialization of products in four core therapeutic areas: central nervous system (CNS), pain, oncology and inflammatory disease. In addition to conducting an active research and development program, it markets seven products in the United States and numerous products in various countries throughout Europe and the world. Its principal product are its wakefulness products, PROVIGIL (modafinil) Tablets [C-IV] and NUVIGIL (armodafinil) Tablets [C-IV], which comprised 51% of its total consolidated net sales during the year ended December 31, 2009. During 2009, Cephalon, Inc. acquired an exclusive, worldwide license to the ImmuPharma investigational compound, LUPUZOR, which is in Phase IIb development for the treatment of systemic lupus erythematosus. In August 2009, Cephalon, Inc. acquired Arana Therapeutics Limited. In April 2010, the Company acquired Mepha, a pharmaceutical company. LOAD-DATE: June 30, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Indian Patents News, distributed by Contify.com All Rights Reserved 39 of 998 DOCUMENTS The Irish Times May 17, 2011 Tuesday Student abuse of wakefulness drug leads to restrictions BYLINE: DR MUIRIS HOUSTON SECTION: HEALTH; Health News; Pg. 2 LENGTH: 417 words DOCTORS HAVE been warned to severely restrict their use of a wakefulness promoting drug with a history of abuse by students seeking to boost exam performance because of new concerns about its safety. In its latest Drug Safety newsletter, the Irish Medicines Board has advised prescribers that the drug Modafinil must no longer be used to treat excessive sleepiness associated with sleep apnoea (a condition where breathing stops during sleep), chronic shift work sleep disorder and other causes of hypersomnia. Modafinil, which is marketed under the trade name Provigil, may now only be prescribed for adults with excessive drowsiness due to narcolepsy. Although never sanctioned by global drugs regulators for short-term use by students preparing for exams or facing imminent project deadlines, there is some evidence that Modafinil has been used in this way. A 2009 survey of Cambridge University students found 10 per cent of students had said they used performance-enhancing drugs to help them study. In the US, it has been reported that up to 25 per cent of students at some US universities have been purchasing drugs such as Ritalin and Provigil in an effort to boost memory and concentration. A recent systematic review by German doctors found Modafinil improved attention for well-rested individuals, while maintaining wakefulness, memory and executive functions to a significantly higher degree in sleep-deprived individuals than did a placebo (dummy pill). However, repeated doses of Modafinil appeared to induce overconfidence in a person s own cognitive performance and the drug lost its potency as sleep deprivation increased. But the European Medicines Agency has carried out a safety review of the wakefulness drug and concluded that the risk-benefit balance was positive only for patients with the sleep disorder narcolepsy. It has also expressly forbidden the use of Modafinil in people up to the age of 18 and in patients with uncontrolled high blood pressure. It wants doctors to carry out an electrocardiogram of the heart before starting the drug and it wants those prescribed Modafinil to have their blood pressure and heart rate monitored regularly. The IMB advises that the drug must be used with caution in patients with a history of psychosis, depression or mania. It also wants doctors to review the treatment of patients taking Modafinil at their next routine appointment. Modafinil should be withdrawn in patients who experience skin reactions or psychiatric symptoms, the regulator says. LOAD-DATE: May 16, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2011 The Irish Times All Rights Reserved 40 of 998 DOCUMENTS The Irish Times May 17, 2011 Tuesday Waking up to the use and abuse of 'study drugs' in Irish colleges BYLINE: LOUISE HOLDEN SECTION: HEALTH; Your Health; Pg. 5 LENGTH: 833 words Will Irish students follow their US counterparts by using neuro-enhancing drugs in the run-up to exams? STUDY DRUGS are an established feature of American campus life and there is increasing evidence to suggest that pressured employees are using neuro-enhancing drugs to improve performance in the workplace. These drugs, which are prescribed to treat disorders such as ADHD and narcolepsy, have also been found to increase concentration and energy for specific tasks. American children who grew up on drug treatments for disorders such as ADHD are finding that when they reach third level, and beyond, their prescribed bottle of Ritalin or Adderall is a prized commodity. These drugs, as well as the narcolepsy treatment Modafinil, are now widely used off-label in the US, especially by students hoping to boost their study performance and employees seeking a competitive edge. All through college I took Ritalin in the weeks coming up to my exams. I would take a pill, stay up for 14 hours studying, then take another and sit the exam. Then I d sleep. It was common practice on campus, a recent graduate of the University of Mississippi told The Irish Times. This graduate would buy from other students who got prescribed Ritalin to treat symptoms of ADHD and sold them on for about $5 a pill. Is there any evidence that these drugs are being used in Irish universities or workplaces? Dr Ciara Kelly, a GP in Co Wicklow, believes that while there is likely to be some abuse of neuro-enhancing drugs in Ireland, it is on a very small scale. She cautions against patients experimenting with these drugs. In some users, Ritalin has been linked with anxiety, raised blood pressure and palpitations. There are probably users who boost their concentration and energy levels without any negative side effects, but for other users the effect could be disastrous, she says. Modafinil (often sold under the name Provigil) is another prescription drug that has found favour among students looking for an academic edge. Usually prescribed for people suffering from sleep apnoea or narcolepsy, the drug is reported to help the user stay awake, and on task, for long periods an obvious attraction for a hassled student counting down to exams. The perception among some students is that these drugs are harmless, but this week the Irish Medicines Board has issued a warning to GPs to severely restrict the prescription of Modafinil/Provigil to adult sufferers of narcolepsy. The IMB has warned that doctors should not prescribe the drug for excessive sleepiness, due to concerns about its safety. Both Modafinil and Ritalin/Adderall have been linked to increased blood pressure. Doctors have this week been warned to carry out electrocardiograms on patients prior to prescribing Modafinil. Another cause of concern is the potential interaction between these drugs and prescribed medications in users. Any substance that interferes with the binding of other drugs to proteins in the blood could make prescribed drugs, such as the contraceptive pill, less effective, says Orla Hardiman, consultant neurologist at the Beaumont Hospital in Dublin. However, she says that she has not come across incidents of off-label Ritalin or Modafinil use in Ireland. These drugs can cause seizures in students prone to epilepsy. If they were in wide use here, I would expect to be treating seizures as result. I am not. Dr Hardiman is not concerned about the issue in Ireland for the moment because, she says, these drugs are not widely available here. These are controlled substances and they are not easy to get, she says. However, given the routine use of these drugs in the US, and growing concerns about their impact in the UK, do we need to be watchful here? Gary Redmond of the Union of Students in Ireland does not believe there is widespread use of study drugs in Ireland, and has come across only a small number of incidents here. However, he is concerned about the level of stress that students are under, now that the jobs market is so small. He worries that the new economic reality might feed an appetite for drugs that are perceived to enhance academic performance. A couple of years ago final year students already had jobs lined up before graduating, says Redmond. Now they know they will be competing for a small pool of jobs, and with many planning to emigrate, they will be competing with the top students from international universities. Students are under unprecedented pressure to get top grades. Gary believes the best way to protect students against the creep of drug-enhanced study is to reform assessment practices at both second and third level. Final terminal exams that account for a large proportion of the overall grade are too stressful for students. This is an even bigger problem at Leaving Cert level, where students are also at risk from these types of drugs. We need to take a step back and look at new ways of assessing students that would make the abuse of study drugs less attractive. LOAD-DATE: May 16, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2011 The Irish Times All Rights Reserved 41 of 998 DOCUMENTS Drug Industry Daily May 2, 2011 Monday EC Launches Pay-For-Delay Investigation into Cephalon, Teva Over Provigil SECTION: Vol. 10 No. 86 LENGTH: 243 words The European Commission (EC) has launched an informal investigation into a potential pay-for-delay agreement between Cephalon and Teva Pharmaceutical regarding the narcolepsy treatment Provigil. The EC's ex officio investigation will examine a December 2005 patent dispute settlement and additional side deals between the companies to see if it hindered the entry of generic Provigil (modafinil) in Europe, which would breach an EU regulation on restrictive business practices. Under the settlement, Teva agreed to not sell generic modafinil before October 2012. There has been no finding that Cephalon's actions were improper and the EC is simply investigating, Natalie de Vane, a Cephalon spokeswoman, told DID. Cephalon is also under investigation from the FTC for an alleged pay-for-delay deal with Watson over Provigil (DID, Jan. 25). But Cephalon views the settlement with Teva and its conduct as entirely proper and intends to fully cooperate with the EC, de Vane said. She also pointed out the EC is examining the impact of patent settlements on competition. The EC has requested copies of patent-settlement agreements from some pharmaceutical companies to ensure generic medicines are not delayed from the market (DID, Jan. 18). The EC has become more forceful with pharmaceutical companies, such as raiding them for pay-for-delay agreement information, instead of requesting copies of such documents (DID, Dec. 6, 2010). -- Molly Cohen Release date: May 2, 2011 LOAD-DATE: May 2, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2011 Washington Business Information, Inc. All Rights Reserved 42 of 998 DOCUMENTS Europolitics (daily in English) May 2, 2011 Monday ANTI-TRUST POLICY : EU LAUNCHES PROBE INTO MODAFINIL DEAL BYLINE: Eric van Puyvelde SECTION: No. 4192 LENGTH: 289 words An agreement between the American pharmaceutical company Cephalon and Teva, an Israeli manufacturer of generic medicines, could prevent the arrival of the generic product Modafinil on the European Economic Area (EEA) market. On April 28, the European Commission opened an inquiry into this agreement, based on EU rules relating to restrictive commercial practises (Article 101). Modafinil is a medication used in the treatment of sleep problems. In December 2005, Cephalon and Teva resolved litigation relating to patents in the United Kingdom and the United States concerning Modafinil (commercial brand name Provigil®) via a friendly agreement, which saw Teva agreeing not to sell its product Modafinil on the EEA market before October 2012. A series of accessory agreements was included in the friendly accord, which is also the subject of a litigation procedure by the United States' anti-trust authority, the FTC, for abuse of a leading position on the market. In the last few years, the European Commission has been leading a drive against pharmaceutical laboratories suspected of impeding the arrival on the EU market of generic and less expensive versions of their star' medicines. In 2008 and 2009, the Commission carried out a huge inquiry into the sector, which resulted in the launch of legal proceedings against several companies: in July 2009, against the French company Servier, and a series of manufacturers of generic medicines, including Teva, suspected of working together to delay the commercialisation of certain generic medicines, and in January 2010 against the Danish group Lundbeck. In December 2010, the Commission carried out further inquiries into the sector, notably into the British company AstraZeneca. LOAD-DATE: April 29, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: EURE Copyright 2011 Europolitique All Rights Reserved 43 of 998 DOCUMENTS PharmaGossip April 29, 2011 Friday 11:05 AM EST Antitrust: Commission opens investigation against pharmaceutical companies Cephalon and Teva BYLINE: insider LENGTH: 744 words Apr. 29, 2011 (PharmaGossip delivered by Newstex) -- IP/11/511 Brussels, 28 April 2011 Antitrust: Commission opens investigation against pharmaceutical companies Cephalon and Teva The European Commission has opened a formal antitrust investigation to assess whether an agreement between US-based pharmaceutical company Cephalon and Israel-based generic drugs firm Teva may have had the object or effect of hindering the entry of generic Modafinil in the European Economic Area. Modafinil is a medicine used for the treatment of certain types of sleeping disorders. The opening of proceedings does not mean that the Commission has conclusive proof of an infringement, only that it will investigate the case as a matter of priority. The Commission has started an ex officio investigation to assess an agreement between Cephalon, Inc. (NASDAQ:CEPH) and Teva Pharmaceutical Industries Ltd. (NASDAQ:TEVA) that may have the object or effect of hindering the entry of generic Modafinil products in the markets of the European Economic Area. In particular it is assessed whether the agreement is in breach of the EU Treaty's rules on restrictive business practices (Article 101). In December 2005 Cephalon and Teva settled patent infringement disputes in the United Kingdom and the United States concerning Modafinil (brand name Provigil®). As part of the settlement agreement Teva undertook not to sell its generic Modafinil products in the EEA markets before October 2012. A series of side deals were included into the settlement agreement, which is also subject to antitrust litigation in the United States initiated by the US antitrust authority FTC. The opening of proceedings does not mean that the Commission has a definitive finding of an infringement, but indicates that it will investigate the case as a matter of priority. There is no legal deadline to complete inquiries into anticompetitive conduct. Their duration depends on a number of factors, including the complexity of each case, the extent to which the undertakings concerned co-operate with the Commission and the exercise of the rights of defence. Background to antitrust investigations Article 101 of the Treaty on the Functioning of the EU prohibits agreements and concerted practices which may affect trade and prevent or restrict competition. The implementation of this provision is defined in the Antitrust Regulation (Council Regulation No 1/2003) which can be applied by the Commission and by the national competition authorities of EU Member States. Article 11(6) of the Antitrust Regulation provides that the initiation of proceedings by the Commission relieves the competition authorities of the Member States of their competence to also apply Articles 101 and 102 (ban on abuse of a dominant market position) to the practices concerned. Article 16(1) provides that national courts must avoid giving decisions which would conflict with a decision contemplated by the Commission in proceedings that it has initiated. The Commission has informed the parties and the competition authorities of the Member States, that it has opened proceedings in this case. Background on investigation of the pharma sector In 2008 and 2009 the Commission carried out a broad inquiry of the pharmaceutical sector. Among others, the inquiry pointed to significant risks for European consumers stemming from certain types of patent settlements between originator and generic companies aimed at delaying the arrival into the market of cheaper generic medicines (sometimes also referred to as "pay-for-delay" settlements). The Commission regularly monitors potentially problematic patent settlements. The second such monitoring exercise was launched in January and the results are expected before the summer break (see IP/10/887 and IP/11/40). The Commission has a number of ongoing individual investigations into suspected anti-competitive practice. In July 2010, the Commission took warmth from the confirmation, by the General Court, of the Commission's decision in the AstraZeneca case, which was its first abuse decision in the pharmaceutical sector. The company had misused the regulatory framework to prevent or, in the very least, delay the market entry of competing generic products, something that has now clearly been ruled as illegal. AstraZeneca (NYSE:AZN) has appealed the decision of the General Court. via europa.eu Posted via email from Jack's posterous Newstex ID: PHAG-0001-103327812 LOAD-DATE: April 29, 2011 LANGUAGE: ENGLISH NOTES: The views expressed on blogs distributed by Newstex and its re-distributors ("Blogs on Demand®") are solely the author's and not necessarily the views of Newstex or its re-distributors. Posts from such authors are provided "AS IS", with no warranties, and confer no rights. The material and information provided in Blogs on Demand® are for general information only and should not, in any respect, be relied on as professional advice. No content on such Blogs on Demand® is "read and approved" before it is posted. Accordingly, neither Newstex nor its re-distributors make any claims, promises or guarantees about the accuracy, completeness, or adequacy of the information contained therein or linked to from such blogs, nor take responsibility for any aspect of such blog content. All content on Blogs on Demand® shall be construed as author-based content and commentary. Accordingly, no warranties or other guarantees will be offered as to the quality of the opinions, commentary or anything else offered on such Blogs on Demand®. Reader's comments reflect their individual opinion and their publication within Blogs on Demand® shall not infer or connote an endorsement by Newstex or its re-distributors of such reader's comments or views. Newstex and its re-distributors expressly reserve the right to delete posts and comments at its and their sole discretion. PUBLICATION-TYPE: Web Blog Copyright 2011 Newstex LLC All Rights Reserved Newstex Web Blogs Copyright 2011 PharmaGossip 44 of 998 DOCUMENTS Agence France Presse -- English April 28, 2011 Thursday 3:38 PM GMT EU opens anti-trust probe into stay-awake drug deal LENGTH: 346 words DATELINE: BRUSSELS, April 28 2011 European antitrust authorities announced Thursday the opening of a formal antitrust probe into US drugs company Cephalon and Israel-based generic drugs firm Teva over stay-awake drug Modafinil. The controversial anti-tiredness drug, marketed under the brand-name Provigil, can keep people awake for days and is normally used to treat the rare sleeping disorder narcolepsy. But it became popular among night-workers such as truckers and was even tested in its early days for military use. The probe concerns a deal struck between the two that "may have had the object or effect of hindering the entry of generic Modafinil" into the European Economic Area. The European Commission "has started an ex officio investigation to assess an agreement between Cephalon, Inc. and Teva Pharmaceutical Industries Ltd.," a statement said. A probe does not indicate "a definitive finding of an infringement," it stressed, but means it will be investigated as "a matter of priority," although there is no set deadline for an outcome. The case arises from a December 2005 deal to settle patent infringement disputes in Britain and the United States, which saw Teva undertake not to sell its generic Modafinil products in the European single market before October 2012. Side deals are also under investigation by US antitrust authorities. The EU has been probing the sector repeatedly since a report showed that the number of new drugs reaching the market annually had dropped by over a third since 2000 and that people were being deprived of innovative, affordable and safe medicine. Generic drugs are far cheaper -- the report said they cost on average 40 percent less two years after they enter the market -- and save patients and insurance firms money without compromising on effectiveness. Among initial tactics often used to hold up generic entry, drug developers were found to file multiple patent applications for the same medicine, leaving little scope for generics to be developed. In the worst example uncovered, 1,300 separate filings were made for a single medicine across the 27-nation EU. LOAD-DATE: April 29, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Agence France Presse All Rights Reserved 45 of 998 DOCUMENTS Kuwait News Agency (KUNA) April 28, 2011 Thursday EU probes US, Israeli firms for preventing entry of cheap generic drugs to LENGTH: 212 words The European Commission opened Thursday a formal investigation to assess whether an agreement between US-based pharmaceutical company Cephalon and Israel-based generic drugs firm Teva may have had the object or effect of hindering the entry of generic Modafinil in the European market. Modafinil is a medicine used for the treatment of certain types of sleeping disorders. In particular the probe will assess whether the agreement is in breach of the EU competition rules, said the EU's executive body in a statement. In December 2005, Cephalon and Teva settled patent infringement disputes in the United Kingdom and the United States concerning Modafinil (brand name Provigil). As part of the settlement agreement Teva undertook not to sell its generic Modafinil products in the European markets before October 2012. EU rules prohibit agreements and practices which may affect trade and prevent or restrict competition. In 2008 and 2009, the European Commission carried out a broad inquiry of the pharmaceutical sector. Among others, the inquiry pointed to significant risks for European consumers stemming from certain types of patent settlements between originator and generic companies aimed at delaying the arrival into the market of cheaper generic medicines. LOAD-DATE: May 1, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire JOURNAL-CODE: 365 Copyright 2011 KUNA. All Rights Reserved Syndigate.info, Al Bawaba.com 46 of 998 DOCUMENTS M2 PressWIRE April 28, 2011 Thursday Antitrust: Commission opens investigation against pharmaceutical companies Cephalon and Teva LENGTH: 696 words April 28, 2011 Brussels --The European Commission has opened a formal antitrust investigation to assess whether an agreement between US-based pharmaceutical company Cephalon and Israel-based generic drugs firm Teva may have had the object or effect of hindering the entry of generic Modafinil in the European Economic Area. Modafinil is a medicine used for the treatment of certain types of sleeping disorders. The opening of proceedings does not mean that the Commission has conclusive proof of an infringement, only that it will investigate the case as a matter of priority. The Commission has started an ex officio investigation to assess an agreement between Cephalon, Inc. and Teva Pharmaceutical Industries Ltd. that may have the object or effect of hindering the entry of generic Modafinil products in the markets of the European Economic Area. In particular it is assessed whether the agreement is in breach of the EU Treaty's rules on restrictive business practices (Article 101). In December 2005 Cephalon and Teva settled patent infringement disputes in the United Kingdom and the United States concerning Modafinil (brand name Provigil®). As part of the settlement agreement Teva undertook not to sell its generic Modafinil products in the EEA markets before October 2012. A series of side deals were included into the settlement agreement, which is also subject to antitrust litigation in the United States initiated by the US antitrust authority FTC. The opening of proceedings does not mean that the Commission has a definitive finding of an infringement, but indicates that it will investigate the case as a matter of priority. There is no legal deadline to complete inquiries into anticompetitive conduct. Their duration depends on a number of factors, including the complexity of each case, the extent to which the undertakings concerned co-operate with the Commission and the exercise of the rights of defence. Background to antitrust investigations Article 101 of the Treaty on the Functioning of the EU prohibits agreements and concerted practices which may affect trade and prevent or restrict competition. The implementation of this provision is defined in the Antitrust Regulation (Council Regulation No 1/2003) which can be applied by the Commission and by the national competition authorities of EU Member States. Article 11(6) of the Antitrust Regulation provides that the initiation of proceedings by the Commission relieves the competition authorities of the Member States of their competence to also apply Articles 101 and 102 (ban on abuse of a dominant market position) to the practices concerned. Article 16(1) provides that national courts must avoid giving decisions which would conflict with a decision contemplated by the Commission in proceedings that it has initiated. The Commission has informed the parties and the competition authorities of the Member States, that it has opened proceedings in this case. Background on investigation of the pharma sector In 2008 and 2009 the Commission carried out a broad inquiry of the pharmaceutical sector. Among others, the inquiry pointed to significant risks for European consumers stemming from certain types of patent settlements between originator and generic companies aimed at delaying the arrival into the market of cheaper generic medicines (sometimes also referred to as "pay-for-delay" settlements). The Commission regularly monitors potentially problematic patent settlements. The second such monitoring exercise was launched in January and the results are expected before the summer break (see IP/10/887 and IP/11/40). The Commission has a number of ongoing individual investigations into suspected anti-competitive practice. In July 2010, the Commission took warmth from the confirmation, by the General Court, of the Commission's decision in the AstraZeneca case, which was its first abuse decision in the pharmaceutical sector. The company had misused the regulatory framework to prevent or, in the very least, delay the market entry of competing generic products, something that has now clearly been ruled as illegal. AstraZeneca has appealed the decision of the General Court. LOAD-DATE: April 28, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire JOURNAL-CODE: M2PW Copyright 2011 Normans Media Limited All Rights Reserved 47 of 998 DOCUMENTS States News Service April 28, 2011 Thursday ANTITRUST: COMMISSION OPENS INVESTIGATION AGAINST PHARMACEUTICAL COMPANIES CEPHALON AND TEVA BYLINE: States News Service LENGTH: 699 words DATELINE: BRUSSELS The following information was released by the European Union: The European Commission has opened a formal antitrust investigation to assess whether an agreement between US-based pharmaceutical company Cephalon and Israel-based generic drugs firm Teva may have had the object or effect of hindering the entry of generic Modafinil in the European Economic Area. Modafinil is a medicine used for the treatment of certain types of sleeping disorders. The opening of proceedings does not mean that the Commission has conclusive proof of an infringement, only that it will investigate the case as a matter of priority. The Commission has started an ex officio investigation to assess an agreement between Cephalon, Inc. and Teva Pharmaceutical Industries Ltd. that may have the object or effect of hindering the entry of generic Modafinil products in the markets of the European Economic Area. In particular it is assessed whether the agreement is in breach of the EU Treaty's rules on restrictive business practices (Article 101). In December 2005 Cephalon and Teva settled patent infringement disputes in the United Kingdom and the United States concerning Modafinil (brand name Provigil). As part of the settlement agreement Teva undertook not to sell its generic Modafinil products in the EEA markets before October 2012. A series of side deals were included into the settlement agreement, which is also subject to antitrust litigation in the United States initiated by the US antitrust authority FTC. The opening of proceedings does not mean that the Commission has a definitive finding of an infringement, but indicates that it will investigate the case as a matter of priority. There is no legal deadline to complete inquiries into anticompetitive conduct. Their duration depends on a number of factors, including the complexity of each case, the extent to which the undertakings concerned co-operate with the Commission and the exercise of the rights of defence. Background to antitrust investigations Article 101 of the Treaty on the Functioning of the EU prohibits agreements and concerted practices which may affect trade and prevent or restrict competition. The implementation of this provision is defined in the Antitrust Regulation (Council Regulation No 1/2003) which can be applied by the Commission and by the national competition authorities of EU Member States. Article 11(6) of the Antitrust Regulation provides that the initiation of proceedings by the Commission relieves the competition authorities of the Member States of their competence to also apply Articles 101 and 102 (ban on abuse of a dominant market position) to the practices concerned. Article 16(1) provides that national courts must avoid giving decisions which would conflict with a decision contemplated by the Commission in proceedings that it has initiated. The Commission has informed the parties and the competition authorities of the Member States, that it has opened proceedings in this case. Background on investigation of the pharma sector In 2008 and 2009 the Commission carried out a broad inquiry of the pharmaceutical sector. Among others, the inquiry pointed to significant risks for European consumers stemming from certain types of patent settlements between originator and generic companies aimed at delaying the arrival into the market of cheaper generic medicines (sometimes also referred to as "pay-for-delay" settlements). The Commission regularly monitors potentially problematic patent settlements. The second such monitoring exercise was launched in January and the results are expected before the summer break (see IP/10/887 and IP/11/40). The Commission has a number of ongoing individual investigations into suspected anti-competitive practice. In July 2010, the Commission took warmth from the confirmation, by the General Court, of the Commission's decision in the AstraZeneca case, which was its first abuse decision in the pharmaceutical sector. The company had misused the regulatory framework to prevent or, in the very least, delay the market entry of competing generic products, something that has now clearly been ruled as illegal. AstraZeneca has appealed the decision of the General Court. LOAD-DATE: April 28, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 States News Service 48 of 998 DOCUMENTS Xinhua General News Service April 28, 2011 Thursday 4:27 PM EST EU launches antitrust probe into Cephalon, Teva SECTION: WORLD NEWS; Political LENGTH: 162 words DATELINE: BRUSSELS April 28 The European Union (EU) antitrust regulator said on Thursday it had launched a probe into pharmaceutical companies Cephalon and Teva for possible collusion to keep a generic drug out of the EU market. The U.S.-based Cephalon and Israel-based Teva, the two leading generic drugs makers in the world, in December 2005 settled patent infringement disputes in Britain and the United States concerning Modafinil, a sleep-disorder drug with brand name Provigil. As part of the settlement agreement Teva undertook not to sell its generic Modafinil products in European markets before October 2012. The investigation is to assess whether the agreement "may have had the object or effect of hindering the entry of generic Modafinil," the European Commission said. The commission said the opening of proceedings does not mean that it has a definitive finding of an infringement, but indicates that it will investigate the case as a matter of priority. LOAD-DATE: April 29, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Xinhua News Agency 49 of 998 DOCUMENTS Xinhua General News Service April 28, 2011 Thursday 1:20 AM EST EU launches antitrust probe into Cephalon, Teva SECTION: WORLD NEWS; Political LENGTH: 162 words DATELINE: BRUSSELS April 28 The European Union (EU) antitrust regulator said on Thursday it had launched a probe into pharmaceutical companies Cephalon and Teva for possible collusion to keep a generic drug out of the EU market. The U.S.-based Cephalon and Israel-based Teva, the two leading generic drugs makers in the world, in December 2005 settled patent infringement disputes in Britain and the United States concerning Modafinil, a sleep-disorder drug with brand name Provigil. As part of the settlement agreement Teva undertook not to sell its generic Modafinil products in European markets before October 2012. The investigation is to assess whether the agreement "may have had the object or effect of hindering the entry of generic Modafinil," the European Commission said. The commission said the opening of proceedings does not mean that it has a definitive finding of an infringement, but indicates that it will investigate the case as a matter of priority. LOAD-DATE: April 30, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Xinhua News Agency 50 of 998 DOCUMENTS The Pharmaceutical Journal February 23, 2011 Wednesday Modafinil's indications restricted LENGTH: 256 words Modafinil (Provigil) has had its licensed indications restricted and can now only be used to treat excessive sleepiness in adult patients with narcolepsy. The drug is no longer licensed for treatment of excessive sleepiness associated with obstructive sleep apnoea/hypopnoea syndrome and moderate to severe chronic shift work sleep disorder. The move follows an assessment by the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP), which has concluded that the benefit/risk profile for modafinil is no longer favourable for these conditions. Cephalon (UK) Ltd, the company that markets Provigil, has written to healthcare professionals in the UK advising them of the change. In its letter the company explains that safety concerns, including psychiatric and serious skin reactions and the potential for cardiovascular adverse effects are now considered to outweigh the limited benefits of modafinil in obstructive sleep apnoea and chronic shift work sleep disorder. As well as restricting modafinil's indications, the CHMP has concluded that it should not be used by children, pregnant or lactating women or by patients with uncontrolled hypertension or cardiac arrhythmias. It also recommends that the starting daily dose is 200mg and that the drug is used with caution in patients with a history of psychosis, depression or mania, or substance abuse. Cephalon says there is no need for patients to stop treatment immediately but that they should have their treatment reviewed at their next routine appointment. LOAD-DATE: February 23, 2011 Wednesday LANGUAGE: ENGLISH PUBLICATION-TYPE: Journal Copyright 2011 PJ Online All Rights Reserved 51 of 998 DOCUMENTS The Associated Press February 18, 2011 Friday 01:58 PM GMT Turkish team to sue lab for Taurasi doping report BYLINE: By SUZAN FRASER, Associated Press SECTION: SPORTS NEWS LENGTH: 462 words DATELINE: ANKARA, Turkey Diana Taurasi's Turkish club demanded an apology Friday and the resignation of the directors of the doping lab that issued an apparent "false positive" report on the American basketball player. Fenerbahce also said it would take legal action. Sekip Mosturoglu, a member of Fenerbahce's executive board, accused the Ankara-based lab of "inadequacies" and said its report declaring Taurasi's "A" and "B" samples positive for the banned stimulant modafinil had sullied both the reputation of both the WNBA star and Fenerbahce. "This is the greatest scandal in world sports," Mosturoglu said. "They cannot get away with simple apologies." Fenerbahce terminated Taurasi's contract after she tested positive following a Nov. 13 league game. The Turkish Basketball Federation subsequently suspended her from play but lifted the suspension Wednesday. Mosturoglu said Taurasi's absence had put Fenerbahce's chances to win the Euroleague at "risk." He also faulted some Turkish Basketball Federation officials for refusing to allow Taurasi's "B" sample to be tested at another lab and demanded their resignations, too. "Our club will take every kind of legal action to the compensation of our losses," Mosturoglu said. Taurasi insisted all along that she never used performance-enhancing drugs. The 28-year-old American will be able to compete at the 2012 Olympics now that she has been cleared of the doping charges. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. Mosturoglu said Fenerbahce would work hard to convince Taurasi and teammate Penny Taylor to return. Taylor left Fenerbahce in a show of solidarity with Taurasi. But Taurasi, who plans to return to the WNBA when the season begins in June, told The Associated Press on Wednesday that her return to the Turkish league was "pretty unlikely." Nevertheless, thousands of Turkish fans urged the star to come back, posting messages on the specially-created comebackdiana.com website. The World Anti-Doping Agency, which can suspend or revoke the accreditation for doping labs, said it has asked the lab to explain why it declared Taurasi positive for modafinil. WADA, which has 35 accredited labs worldwide, previously suspended the Ankara facility for three months in 2009 for failing to meet international standards. Mosturoglu said the lab had accepted its mistake only after an international drug-testing expert looking into the Taurasi case pointed out the lab's error. The federation this week also lifted the provisional suspension for American player Monique Coker, who plays for Ceyhan Belediyesi and had tested positive for modafinil in tests carried out at the same lab. Associated Press Writer Selcan Hacaoglu contributed to this report. LOAD-DATE: February 19, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 52 of 998 DOCUMENTS Associated Press Worldstream February 18, 2011 Friday 1:51 PM GMT Fenerbahce to sue lab for Taurasi doping report BYLINE: By SUZAN FRASER, Associated Press SECTION: SPORTS NEWS LENGTH: 469 words DATELINE: ANKARA Turkey Diana Taurasi's Turkish club demanded an apology Friday and the resignation of the directors of the local doping lab that issued an apparent "false positive" report on the American basketball player. Fenerbahce also said it would take legal action against those responsible. Sekip Mosturoglu, a member of Fenerbahce's executive board, accused the Ankara-based lab of "inadequacies" and said its report declaring Taurasi's "A" and "B" samples positive for the banned stimulant modafinil had sullied both the reputation of both the WNBA star and Fenerbahce. "This is the greatest scandal in world sports," Mosturoglu said. "They cannot get away with simple apologies." Fenerbahce terminated Taurasi's contract after she tested positive following a Nov. 13 league game. The Turkish Basketball Federation subsequently suspended her from play but lifted the suspension Wednesday. Mosturoglu said Taurasi's absence had put Fenerbahce's chances to win the Euroleague at "risk." He also faulted some Turkish Basketball Federation officials for refusing to allow Taurasi's "B" sample to be tested at another lab and demanded their resignations, too. "Our club will take every kind of legal action to the compensation of our losses," Mosturoglu said. Taurasi insisted all along that she never used performance-enhancing drugs. The 28-year-old American will be able to compete at the 2012 Olympics now that she has been cleared of the doping charges. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. Mosturoglu said Fenerbahce would work hard to convince Taurasi and teammate Penny Taylor to return. Taylor left Fenerbahce in a show of solidarity with Taurasi. But Taurasi, who plans to return to the WNBA when the season begins in June, told The Associated Press on Wednesday that her return to the Turkish league was "pretty unlikely." Nevertheless, thousands of Turkish fans urged the star to come back, posting messages on the specially-created comebackdiana.com website. The World Anti-Doping Agency, which can suspend or revoke the accreditation for doping labs, said it has asked the Ankara lab to explain why it declared Taurasi positive for modafinil. WADA, which has 35 accredited labs worldwide, previously suspended the Ankara facility for three months in 2009 for failing to meet international standards. Mosturoglu said the lab had accepted its mistake only after an international drug-testing expert looking into the Taurasi case pointed out the lab's error. The federation this week also lifted the provisional suspension for American player Monique Coker, who plays for Ceyhan Belediyesi and had tested positive for modafinil in tests carried out at the same lab. Associated Press writer Selcan Hacaoglu contributed to this report. LOAD-DATE: February 19, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 53 of 998 DOCUMENTS Associated Press Online February 18, 2011 Friday 1:58 PM GMT Turkish team to sue lab for Taurasi doping report BYLINE: By SUZAN FRASER, Associated Press SECTION: SPORTS NEWS LENGTH: 462 words DATELINE: ANKARA Turkey Diana Taurasi's Turkish club demanded an apology Friday and the resignation of the directors of the doping lab that issued an apparent "false positive" report on the American basketball player. Fenerbahce also said it would take legal action. Sekip Mosturoglu, a member of Fenerbahce's executive board, accused the Ankara-based lab of "inadequacies" and said its report declaring Taurasi's "A" and "B" samples positive for the banned stimulant modafinil had sullied both the reputation of both the WNBA star and Fenerbahce. "This is the greatest scandal in world sports," Mosturoglu said. "They cannot get away with simple apologies." Fenerbahce terminated Taurasi's contract after she tested positive following a Nov. 13 league game. The Turkish Basketball Federation subsequently suspended her from play but lifted the suspension Wednesday. Mosturoglu said Taurasi's absence had put Fenerbahce's chances to win the Euroleague at "risk." He also faulted some Turkish Basketball Federation officials for refusing to allow Taurasi's "B" sample to be tested at another lab and demanded their resignations, too. "Our club will take every kind of legal action to the compensation of our losses," Mosturoglu said. Taurasi insisted all along that she never used performance-enhancing drugs. The 28-year-old American will be able to compete at the 2012 Olympics now that she has been cleared of the doping charges. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. Mosturoglu said Fenerbahce would work hard to convince Taurasi and teammate Penny Taylor to return. Taylor left Fenerbahce in a show of solidarity with Taurasi. But Taurasi, who plans to return to the WNBA when the season begins in June, told The Associated Press on Wednesday that her return to the Turkish league was "pretty unlikely." Nevertheless, thousands of Turkish fans urged the star to come back, posting messages on the specially-created comebackdiana.com website. The World Anti-Doping Agency, which can suspend or revoke the accreditation for doping labs, said it has asked the lab to explain why it declared Taurasi positive for modafinil. WADA, which has 35 accredited labs worldwide, previously suspended the Ankara facility for three months in 2009 for failing to meet international standards. Mosturoglu said the lab had accepted its mistake only after an international drug-testing expert looking into the Taurasi case pointed out the lab's error. The federation this week also lifted the provisional suspension for American player Monique Coker, who plays for Ceyhan Belediyesi and had tested positive for modafinil in tests carried out at the same lab. Associated Press Writer Selcan Hacaoglu contributed to this report. LOAD-DATE: February 19, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 54 of 998 DOCUMENTS The Associated Press State & Local Wire February 18, 2011 Friday 1:58 PM GMT Turkish team to sue lab for Taurasi doping report BYLINE: By SUZAN FRASER, Associated Press SECTION: SPORTS NEWS LENGTH: 462 words DATELINE: ANKARA Turkey Diana Taurasi's Turkish club demanded an apology Friday and the resignation of the directors of the doping lab that issued an apparent "false positive" report on the American basketball player. Fenerbahce also said it would take legal action. Sekip Mosturoglu, a member of Fenerbahce's executive board, accused the Ankara-based lab of "inadequacies" and said its report declaring Taurasi's "A" and "B" samples positive for the banned stimulant modafinil had sullied both the reputation of both the WNBA star and Fenerbahce. "This is the greatest scandal in world sports," Mosturoglu said. "They cannot get away with simple apologies." Fenerbahce terminated Taurasi's contract after she tested positive following a Nov. 13 league game. The Turkish Basketball Federation subsequently suspended her from play but lifted the suspension Wednesday. Mosturoglu said Taurasi's absence had put Fenerbahce's chances to win the Euroleague at "risk." He also faulted some Turkish Basketball Federation officials for refusing to allow Taurasi's "B" sample to be tested at another lab and demanded their resignations, too. "Our club will take every kind of legal action to the compensation of our losses," Mosturoglu said. Taurasi insisted all along that she never used performance-enhancing drugs. The 28-year-old American will be able to compete at the 2012 Olympics now that she has been cleared of the doping charges. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. Mosturoglu said Fenerbahce would work hard to convince Taurasi and teammate Penny Taylor to return. Taylor left Fenerbahce in a show of solidarity with Taurasi. But Taurasi, who plans to return to the WNBA when the season begins in June, told The Associated Press on Wednesday that her return to the Turkish league was "pretty unlikely." Nevertheless, thousands of Turkish fans urged the star to come back, posting messages on the specially-created comebackdiana.com website. The World Anti-Doping Agency, which can suspend or revoke the accreditation for doping labs, said it has asked the lab to explain why it declared Taurasi positive for modafinil. WADA, which has 35 accredited labs worldwide, previously suspended the Ankara facility for three months in 2009 for failing to meet international standards. Mosturoglu said the lab had accepted its mistake only after an international drug-testing expert looking into the Taurasi case pointed out the lab's error. The federation this week also lifted the provisional suspension for American player Monique Coker, who plays for Ceyhan Belediyesi and had tested positive for modafinil in tests carried out at the same lab. Associated Press Writer Selcan Hacaoglu contributed to this report. LOAD-DATE: February 19, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 55 of 998 DOCUMENTS The Associated Press State & Local Wire February 18, 2011 Friday 1:58 PM GMT LENGTH: 507 words BC-BKL--Doping-Taurasi, 1st Ld-Writethru,0657 Turkish team to sue lab for Taurasi doping report 2030 Eds: Updates with details; adds byline. AP Photo NY150, NY161 sptd/rrosenblatt elfd/lon/clehourites fasst4922 fasst4921 By SUZAN FRASER Associated Press ANKARA, Turkey (AP) Diana Taurasi's Turkish club demanded an apology Friday and the resignation of the directors of the doping lab that issued an apparent "false positive" report on the American basketball player. Fenerbahce also said it would take legal action. Sekip Mosturoglu, a member of Fenerbahce's executive board, accused the Ankara-based lab of "inadequacies" and said its report declaring Taurasi's "A" and "B" samples positive for the banned stimulant modafinil had sullied both the reputation of both the WNBA star and Fenerbahce. "This is the greatest scandal in world sports," Mosturoglu said. "They cannot get away with simple apologies." Fenerbahce terminated Taurasi's contract after she tested positive following a Nov. 13 league game. The Turkish Basketball Federation subsequently suspended her from play but lifted the suspension Wednesday. Mosturoglu said Taurasi's absence had put Fenerbahce's chances to win the Euroleague at "risk." He also faulted some Turkish Basketball Federation officials for refusing to allow Taurasi's "B" sample to be tested at another lab and demanded their resignations, too. "Our club will take every kind of legal action to the compensation of our losses," Mosturoglu said. Taurasi insisted all along that she never used performance-enhancing drugs. The 28-year-old American will be able to compete at the 2012 Olympics now that she has been cleared of the doping charges. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. Mosturoglu said Fenerbahce would work hard to convince Taurasi and teammate Penny Taylor to return. Taylor left Fenerbahce in a show of solidarity with Taurasi. But Taurasi, who plans to return to the WNBA when the season begins in June, told The Associated Press on Wednesday that her return to the Turkish league was "pretty unlikely." Nevertheless, thousands of Turkish fans urged the star to come back, posting messages on the specially-created comebackdiana.com website. The World Anti-Doping Agency, which can suspend or revoke the accreditation for doping labs, said it has asked the lab to explain why it declared Taurasi positive for modafinil. WADA, which has 35 accredited labs worldwide, previously suspended the Ankara facility for three months in 2009 for failing to meet international standards. Mosturoglu said the lab had accepted its mistake only after an international drug-testing expert looking into the Taurasi case pointed out the lab's error. The federation this week also lifted the provisional suspension for American player Monique Coker, who plays for Ceyhan Belediyesi and had tested positive for modafinil in tests carried out at the same lab. Associated Press Writer Selcan Hacaoglu contributed to this report. LOAD-DATE: February 19, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 56 of 998 DOCUMENTS The Associated Press February 17, 2011 Thursday 05:48 PM GMT WADA could suspend Turkish lab in Taurasi case BYLINE: By STEPHEN WILSON, AP Sports Writer SECTION: SPORTS NEWS LENGTH: 732 words DATELINE: LONDON The World Anti-Doping Agency could suspend the Turkish drug-testing laboratory that reported an apparent "false positive" for American basketball star Diana Taurasi. WADA director general David Howman told The Associated Press on Thursday the agency has asked the Ankara lab to explain why it declared Taurasi's samples positive for the banned stimulant modafinil, a decision which led to her contract being terminated by her Turkish club. "We are still awaiting all the information from the laboratory," Howman said. "It appears that it was a false positive. In any of those cases we need to review all the data to determine whether any steps need to be taken, including any steps against the laboratory." WADA can suspend and revoke the accreditation of doping labs. WADA, which has 35 accredited labs worldwide, previously suspended the Ankara center for three months in 2009 for failing to meet international standards. "Anything which goes wrong has to be a worry," Howman said. "That's why we have to investigate it pretty thoroughly. The reputation of the athlete who's been aggrieved is pretty important, too, and that has to be acknowledged." The Turkish lab reported that Taurasi's "A" and "B" samples both tested positive for modafinil following a Turkish league game on Nov. 13. Her club, Fenerbahce, terminated her contract last month and she was suspended by the Turkish Basketball Federation. The federation lifted the suspension Wednesday, saying the lab retracted its positive finding after it "evaluated" Taurasi's statements in her defense. The federation also lifted the provisional suspension for American player Monique Coker, who plays for Ceyhan Belediyesi and had tested positive for modafinil in tests carried out by the same lab. False positives are rare in international drug testing. "We have more of an issue with false negatives," Howman said. The WADA-accredited lab in Malaysia was suspended for false positives last year. The lab is appealing the decision to the Court of Arbitration for Sport. "There is a process that has to be followed, including the gathering of all the data," Howman said in a telephone interview from Montreal. "If it's sufficiently bad, then the lab should go to a disciplinary panel and have a hearing. They've got a right to put every excuse and reasoning before the panel." Taurasi insisted all along that she never used performance-enhancing drugs. "It's really good that the facts came out and the truth came out," Taurasi told the AP on Wednesday. "Life can throw you curveballs at any given time. I can be mad and angry, but I will move forward." The 28-year-old Taurasi intends to return to the WNBA when the season begins in June. The Mercury guard has led the U.S. league in scoring the last four seasons. She is also now eligible to compete for the U.S. at the 2012 London Olympics. The Turkish Doping Control Center at the Hacettepe University declined to comment on the case Thursday. But the HaberTurk newspaper quoted Ugur Erdener, dean of the university, as admitting the lab made a mistake. "There are two evaluations to analyze the test results and the average of them is taken. The (lab) officials' evaluation was based on one data. However, the average should have been taken as the base," Erdener was quoted as saying. Fenerbahce President Aziz Yildirim met Turkey's Prime Minister Recep Tayyip Erdogan to discuss the case Thursday. No statement was made after the meeting but Ali Koc, a club official, denied reports that Fenerbahce asked authorities to shut down the doping lab. Turgay Demirel, president of the Turkish Basketball Federation, said two soccer players were also cleared of doping after the lab retracted its reports about them. "It is very sad for our country that an institution accredited to WADA committed such a huge mistake," he said. "Both Turkey, Turkish sports and Turkish basketball could pay a fairly high price for this. Sportsmen and federations or clubs in their countries and even us could file compensation suits against this institution." Demirel said about 3,500 doping tests have been carried out annually in Turkey, with most analyzed by the Ankara lab. "From now on, I don't think the certificate of Hacettepe University can remain valid," Demirel said. "But we will have to use centers in Lisbon, Cologne or maybe Athens." Associated Press writer Selcan Hacaoglu in Ankara contributed to this report. LOAD-DATE: February 18, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 57 of 998 DOCUMENTS The Houston Chronicle February 17, 2011 Thursday 3 STAR EDITION Taurasi cleared of doping charge WNBA star will be eligible for 2012 Games BYLINE: CHRONICLE NEWS SERVICES SECTION: SPORTS; Pg. 2 LENGTH: 330 words Diana Taurasi was always confident she would be cleared of doping allegations. It finally happened on Wednesday. Taurasi had her provisional suspension lifted by the Turkish Basketball Federation, which said the lab that returned a positive test retracted its report after it "evaluated" Taurasi's statements in her defense. The federation did not say whether the lab made a mistake. "I got the news this morning at 5 a.m. and was in shock," Taurasi told the Associated Press by phone from her Phoenix home. "It was kind of like the first time when I heard the test result had come back positive. It's really good that the facts came out and the truth came out." Taurasi had insisted that she never used performance-enhancing drugs, even though she had her contract terminated by Turkish club Fenerbahce last month. The lab that tested her sample said the results came back positive for the stimulant modafinil. "Life can throw you curveballs at any given time," said Taurasi, who will also be able to compete in the 2012 Olympics. "I can be mad and angry, but I will move forward ." With the lifting of the suspension, Taurasi is free to continue playing in the Turkish basketball league, although she doesn't plan on going back there. "That's pretty unlikely," the 28-year-old WNBA star said. "I'm here in Phoenix working out and am more focused on getting myself in the best shape of my life and going from there." She intends to return to the WNBA when the season begins in June. The Mercury guard has led the league in scoring the last four seasons and signed a multiyear extension last August. Fenerbahce had terminated Taurasi's contract after the lab within Hacettepe University confirmed that her "A" and "B" samples tested positive for modafinil following a Turkish league game Nov. 13. Taurasi had been suspended by Fenerbahce ever since. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. LOAD-DATE: February 17, 2011 LANGUAGE: ENGLISH GRAPHIC: ROSS D. FRANKLIN: AP REVERSAL: After months of uncertainty, Diana Taurasi received good news from the Turkish Basketball Federation. PUBLICATION-TYPE: Newspaper Copyright 2011 The Houston Chronicle Publishing Company All Rights Reserved 58 of 998 DOCUMENTS Associated Press Worldstream February 17, 2011 Thursday 5:25 PM GMT WADA could suspend Turkish lab in Taurasi case BYLINE: By STEPHEN WILSON, AP Sports Writer SECTION: SPORTS NEWS LENGTH: 733 words DATELINE: LONDON The World Anti-Doping Agency could suspend the Turkish drug-testing laboratory that reported an apparent "false positive" for American basketball star Diana Taurasi. WADA director general David Howman told The Associated Press on Thursday the agency has asked the Ankara lab to explain why it declared Taurasi's samples positive for the banned stimulant modafinil, a decision which led to her contract being terminated by her Turkish club. "We are still awaiting all the information from the laboratory," Howman said. "It appears that it was a false positive. In any of those cases we need to review all the data to determine whether any steps need to be taken, including any steps against the laboratory." WADA can suspend and revoke the accreditation of doping labs. WADA, which has 35 accredited labs worldwide, previously suspended the Ankara center for three months in 2009 for failing to meet international standards. "Anything which goes wrong has to be a worry," Howman said. "That's why we have to investigate it pretty thoroughly. The reputation of the athlete who's been aggrieved is pretty important, too, and that has to be acknowledged." The Turkish lab reported that Taurasi's "A" and "B" samples both tested positive for modafinil following a Turkish league game on Nov. 13. Her club, Fenerbahce, terminated her contract last month and she was suspended by the Turkish Basketball Federation. The federation lifted the suspension Wednesday, saying the lab retracted its positive finding after it "evaluated" Taurasi's statements in her defense. The federation also lifted the provisional suspension for American player Monique Coker, who plays for Ceyhan Belediyesi and had tested positive for modafinil in tests carried out by the same lab. False positives are rare in international drug testing. "We have more of an issue with false negatives," Howman said. The WADA-accredited lab in Malaysia was suspended for false positives last year. The lab is appealing the decision to the Court of Arbitration for Sport. "There is a process that has to be followed, including the gathering of all the data," Howman said in a telephone interview from Montreal. "If it's sufficiently bad, then the lab should go to a disciplinary panel and have a hearing. They've got a right to put every excuse and reasoning before the panel." Taurasi insisted all along that she never used performance-enhancing drugs. "It's really good that the facts came out and the truth came out," Taurasi told the AP on Wednesday. "Life can throw you curveballs at any given time. I can be made and angry, but I will move forward." The 28-year-old Taurasi intends to return to the WNBA when the season begins in June. The Mercury guard has led the U.S. league in scoring the last four seasons. She is also now eligible to compete for the U.S. at the 2012 London Olympics. The Turkish Doping Control Center at the Hacettepe University declined to comment on the case Thursday. But the HaberTurk newspaper quoted Ugur Erdener, dean of the university, as admitting the lab made a mistake. "There are two evaluations to analyze the test results and the average of them is taken. The (lab) officials' evaluation was based on one data. However, the average should have been taken as the base," Erdener was quoted as saying. Fenerbahce President Aziz Yildirim met Turkey's Prime Minister Recep Tayyip Erdogan to discuss the case Thursday. No statement was made after the meeting but Ali Koc, a club official, denied reports that Fenerbahce asked authorities to shut down the doping lab. Turgay Demirel, president of the Turkish Basketball Federation, said two football players were also cleared of doping after the lab retracted its reports about them. "It is very sad for our country that an institution accredited to WADA committed such a huge mistake," he said. "Both Turkey, Turkish sports and Turkish basketball could pay a fairly high price for this. Sportsmen and federations or clubs in their countries and even us could file compensation suits against this institution." Demirel said about 3,500 doping tests have been carried out annually in Turkey, with most analyzed by the Ankara lab. "From now on, I don't think the certificate of Hacettepe University can remain valid," Demirel said. "But we will have to use centers in Lisbon, Cologne or maybe Athens." Associated Press writer Selcan Hacaoglu in Ankara contributed to this report. LOAD-DATE: February 18, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 59 of 998 DOCUMENTS Associated Press Online February 17, 2011 Thursday 5:48 PM GMT WADA could suspend Turkish lab in Taurasi case BYLINE: By STEPHEN WILSON, AP Sports Writer SECTION: SPORTS NEWS LENGTH: 732 words DATELINE: LONDON The World Anti-Doping Agency could suspend the Turkish drug-testing laboratory that reported an apparent "false positive" for American basketball star Diana Taurasi. WADA director general David Howman told The Associated Press on Thursday the agency has asked the Ankara lab to explain why it declared Taurasi's samples positive for the banned stimulant modafinil, a decision which led to her contract being terminated by her Turkish club. "We are still awaiting all the information from the laboratory," Howman said. "It appears that it was a false positive. In any of those cases we need to review all the data to determine whether any steps need to be taken, including any steps against the laboratory." WADA can suspend and revoke the accreditation of doping labs. WADA, which has 35 accredited labs worldwide, previously suspended the Ankara center for three months in 2009 for failing to meet international standards. "Anything which goes wrong has to be a worry," Howman said. "That's why we have to investigate it pretty thoroughly. The reputation of the athlete who's been aggrieved is pretty important, too, and that has to be acknowledged." The Turkish lab reported that Taurasi's "A" and "B" samples both tested positive for modafinil following a Turkish league game on Nov. 13. Her club, Fenerbahce, terminated her contract last month and she was suspended by the Turkish Basketball Federation. The federation lifted the suspension Wednesday, saying the lab retracted its positive finding after it "evaluated" Taurasi's statements in her defense. The federation also lifted the provisional suspension for American player Monique Coker, who plays for Ceyhan Belediyesi and had tested positive for modafinil in tests carried out by the same lab. False positives are rare in international drug testing. "We have more of an issue with false negatives," Howman said. The WADA-accredited lab in Malaysia was suspended for false positives last year. The lab is appealing the decision to the Court of Arbitration for Sport. "There is a process that has to be followed, including the gathering of all the data," Howman said in a telephone interview from Montreal. "If it's sufficiently bad, then the lab should go to a disciplinary panel and have a hearing. They've got a right to put every excuse and reasoning before the panel." Taurasi insisted all along that she never used performance-enhancing drugs. "It's really good that the facts came out and the truth came out," Taurasi told the AP on Wednesday. "Life can throw you curveballs at any given time. I can be mad and angry, but I will move forward." The 28-year-old Taurasi intends to return to the WNBA when the season begins in June. The Mercury guard has led the U.S. league in scoring the last four seasons. She is also now eligible to compete for the U.S. at the 2012 London Olympics. The Turkish Doping Control Center at the Hacettepe University declined to comment on the case Thursday. But the HaberTurk newspaper quoted Ugur Erdener, dean of the university, as admitting the lab made a mistake. "There are two evaluations to analyze the test results and the average of them is taken. The (lab) officials' evaluation was based on one data. However, the average should have been taken as the base," Erdener was quoted as saying. Fenerbahce President Aziz Yildirim met Turkey's Prime Minister Recep Tayyip Erdogan to discuss the case Thursday. No statement was made after the meeting but Ali Koc, a club official, denied reports that Fenerbahce asked authorities to shut down the doping lab. Turgay Demirel, president of the Turkish Basketball Federation, said two soccer players were also cleared of doping after the lab retracted its reports about them. "It is very sad for our country that an institution accredited to WADA committed such a huge mistake," he said. "Both Turkey, Turkish sports and Turkish basketball could pay a fairly high price for this. Sportsmen and federations or clubs in their countries and even us could file compensation suits against this institution." Demirel said about 3,500 doping tests have been carried out annually in Turkey, with most analyzed by the Ankara lab. "From now on, I don't think the certificate of Hacettepe University can remain valid," Demirel said. "But we will have to use centers in Lisbon, Cologne or maybe Athens." Associated Press writer Selcan Hacaoglu in Ankara contributed to this report. LOAD-DATE: February 18, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 60 of 998 DOCUMENTS The Associated Press State & Local Wire February 17, 2011 Thursday 5:48 PM GMT WADA could suspend Turkish lab in Taurasi case BYLINE: By STEPHEN WILSON, AP Sports Writer SECTION: SPORTS NEWS LENGTH: 732 words DATELINE: LONDON The World Anti-Doping Agency could suspend the Turkish drug-testing laboratory that reported an apparent "false positive" for American basketball star Diana Taurasi. WADA director general David Howman told The Associated Press on Thursday the agency has asked the Ankara lab to explain why it declared Taurasi's samples positive for the banned stimulant modafinil, a decision which led to her contract being terminated by her Turkish club. "We are still awaiting all the information from the laboratory," Howman said. "It appears that it was a false positive. In any of those cases we need to review all the data to determine whether any steps need to be taken, including any steps against the laboratory." WADA can suspend and revoke the accreditation of doping labs. WADA, which has 35 accredited labs worldwide, previously suspended the Ankara center for three months in 2009 for failing to meet international standards. "Anything which goes wrong has to be a worry," Howman said. "That's why we have to investigate it pretty thoroughly. The reputation of the athlete who's been aggrieved is pretty important, too, and that has to be acknowledged." The Turkish lab reported that Taurasi's "A" and "B" samples both tested positive for modafinil following a Turkish league game on Nov. 13. Her club, Fenerbahce, terminated her contract last month and she was suspended by the Turkish Basketball Federation. The federation lifted the suspension Wednesday, saying the lab retracted its positive finding after it "evaluated" Taurasi's statements in her defense. The federation also lifted the provisional suspension for American player Monique Coker, who plays for Ceyhan Belediyesi and had tested positive for modafinil in tests carried out by the same lab. False positives are rare in international drug testing. "We have more of an issue with false negatives," Howman said. The WADA-accredited lab in Malaysia was suspended for false positives last year. The lab is appealing the decision to the Court of Arbitration for Sport. "There is a process that has to be followed, including the gathering of all the data," Howman said in a telephone interview from Montreal. "If it's sufficiently bad, then the lab should go to a disciplinary panel and have a hearing. They've got a right to put every excuse and reasoning before the panel." Taurasi insisted all along that she never used performance-enhancing drugs. "It's really good that the facts came out and the truth came out," Taurasi told the AP on Wednesday. "Life can throw you curveballs at any given time. I can be mad and angry, but I will move forward." The 28-year-old Taurasi intends to return to the WNBA when the season begins in June. The Mercury guard has led the U.S. league in scoring the last four seasons. She is also now eligible to compete for the U.S. at the 2012 London Olympics. The Turkish Doping Control Center at the Hacettepe University declined to comment on the case Thursday. But the HaberTurk newspaper quoted Ugur Erdener, dean of the university, as admitting the lab made a mistake. "There are two evaluations to analyze the test results and the average of them is taken. The (lab) officials' evaluation was based on one data. However, the average should have been taken as the base," Erdener was quoted as saying. Fenerbahce President Aziz Yildirim met Turkey's Prime Minister Recep Tayyip Erdogan to discuss the case Thursday. No statement was made after the meeting but Ali Koc, a club official, denied reports that Fenerbahce asked authorities to shut down the doping lab. Turgay Demirel, president of the Turkish Basketball Federation, said two soccer players were also cleared of doping after the lab retracted its reports about them. "It is very sad for our country that an institution accredited to WADA committed such a huge mistake," he said. "Both Turkey, Turkish sports and Turkish basketball could pay a fairly high price for this. Sportsmen and federations or clubs in their countries and even us could file compensation suits against this institution." Demirel said about 3,500 doping tests have been carried out annually in Turkey, with most analyzed by the Ankara lab. "From now on, I don't think the certificate of Hacettepe University can remain valid," Demirel said. "But we will have to use centers in Lisbon, Cologne or maybe Athens." Associated Press writer Selcan Hacaoglu in Ankara contributed to this report. LOAD-DATE: February 18, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 61 of 998 DOCUMENTS The Associated Press State & Local Wire February 17, 2011 Thursday 5:48 PM GMT LENGTH: 775 words BC-BKL--WADA-Doping-Taurasi, 1st Ld-Writethru,0936 WADA could suspend Turkish lab in Taurasi case 2030 Eds: Updates with detail, quotes. AP Photo NY161, NY150 sptd/rrosenblatt elfd/lon/clehourites fasst4922 fasst4921 By STEPHEN WILSON AP Sports Writer LONDON (AP) The World Anti-Doping Agency could suspend the Turkish drug-testing laboratory that reported an apparent "false positive" for American basketball star Diana Taurasi. WADA director general David Howman told The Associated Press on Thursday the agency has asked the Ankara lab to explain why it declared Taurasi's samples positive for the banned stimulant modafinil, a decision which led to her contract being terminated by her Turkish club. "We are still awaiting all the information from the laboratory," Howman said. "It appears that it was a false positive. In any of those cases we need to review all the data to determine whether any steps need to be taken, including any steps against the laboratory." WADA can suspend and revoke the accreditation of doping labs. WADA, which has 35 accredited labs worldwide, previously suspended the Ankara center for three months in 2009 for failing to meet international standards. "Anything which goes wrong has to be a worry," Howman said. "That's why we have to investigate it pretty thoroughly. The reputation of the athlete who's been aggrieved is pretty important, too, and that has to be acknowledged." The Turkish lab reported that Taurasi's "A" and "B" samples both tested positive for modafinil following a Turkish league game on Nov. 13. Her club, Fenerbahce, terminated her contract last month and she was suspended by the Turkish Basketball Federation. The federation lifted the suspension Wednesday, saying the lab retracted its positive finding after it "evaluated" Taurasi's statements in her defense. The federation also lifted the provisional suspension for American player Monique Coker, who plays for Ceyhan Belediyesi and had tested positive for modafinil in tests carried out by the same lab. False positives are rare in international drug testing. "We have more of an issue with false negatives," Howman said. The WADA-accredited lab in Malaysia was suspended for false positives last year. The lab is appealing the decision to the Court of Arbitration for Sport. "There is a process that has to be followed, including the gathering of all the data," Howman said in a telephone interview from Montreal. "If it's sufficiently bad, then the lab should go to a disciplinary panel and have a hearing. They've got a right to put every excuse and reasoning before the panel." Taurasi insisted all along that she never used performance-enhancing drugs. "It's really good that the facts came out and the truth came out," Taurasi told the AP on Wednesday. "Life can throw you curveballs at any given time. I can be mad and angry, but I will move forward." The 28-year-old Taurasi intends to return to the WNBA when the season begins in June. The Mercury guard has led the U.S. league in scoring the last four seasons. She is also now eligible to compete for the U.S. at the 2012 London Olympics. The Turkish Doping Control Center at the Hacettepe University declined to comment on the case Thursday. But the HaberTurk newspaper quoted Ugur Erdener, dean of the university, as admitting the lab made a mistake. "There are two evaluations to analyze the test results and the average of them is taken. The (lab) officials' evaluation was based on one data. However, the average should have been taken as the base," Erdener was quoted as saying. Fenerbahce President Aziz Yildirim met Turkey's Prime Minister Recep Tayyip Erdogan to discuss the case Thursday. No statement was made after the meeting but Ali Koc, a club official, denied reports that Fenerbahce asked authorities to shut down the doping lab. Turgay Demirel, president of the Turkish Basketball Federation, said two soccer players were also cleared of doping after the lab retracted its reports about them. "It is very sad for our country that an institution accredited to WADA committed such a huge mistake," he said. "Both Turkey, Turkish sports and Turkish basketball could pay a fairly high price for this. Sportsmen and federations or clubs in their countries and even us could file compensation suits against this institution." Demirel said about 3,500 doping tests have been carried out annually in Turkey, with most analyzed by the Ankara lab. "From now on, I don't think the certificate of Hacettepe University can remain valid," Demirel said. "But we will have to use centers in Lisbon, Cologne or maybe Athens." Associated Press writer Selcan Hacaoglu in Ankara contributed to this report. LOAD-DATE: February 18, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 62 of 998 DOCUMENTS The Associated Press February 16, 2011 Wednesday 08:56 PM GMT Taurasi cleared of doping charges BYLINE: By DOUG FEINBERG, AP Basketball Writer SECTION: SPORTS NEWS LENGTH: 702 words Diana Taurasi was always confident she would be cleared of doping allegations. It finally happened on Wednesday. Taurasi had her provisional suspension lifted by the Turkish Basketball Federation, which said the lab that returned a positive test retracted its report after it "evaluated" Taurasi's statements in her defense. The federation did not say whether the lab made a mistake. "I got the news this morning at 5 a.m. and was in shock," Taurasi told The Associated Press by phone from her Phoenix home. "It was kind of like the first time when I heard the test result had come back positive. It's really good that the facts came out and the truth came out." Taurasi had insisted that she never used performance-enhancing drugs, even though she had her contract terminated by Turkish club Fenerbahce last month. The lab that tested her sample had said the results came back positive for the stimulant modafinil. "Life can throw you curveballs at any given time," said Taurasi, who will also be able to compete in the 2012 Olympics. "I can be mad and angry, but I will move forward. Not everyone has the same financial resources I did. Hopefully this will let people know every process has holes and to wait for the facts to come out before making decisions." With the lifting of the suspension, Taurasi is also free to continue playing in the Turkish basketball league, although she doesn't plan on going back there anytime soon. "That's pretty unlikely," the 28-year-old WNBA star said. "I'm here in Phoenix working out and am more focused on getting myself in the best shape of my life and going from there." She intends to return to the WNBA when the season begins in June. The Mercury guard has led the league in scoring the last four seasons and signed a multiyear extension last August. The last two months haven't been easy for the former UConn star. Yet she kept her faith that she would be cleared. "I tried to handle it as best as possible," Taurasi said. "There might have been times in my own private moments when I was angry or questioned why me, but I am glad the truth came out. It's scary that our careers can be taken away from us." Taurasi was the first prominent WNBA player to test positive for a banned substance. Had she not been cleared, Taurasi could have missed the London Games, because the International Olympic Committee bars any athlete given a doping penalty of six months or more from competing. Fenerbahce had terminated Taurasi's contract after the Ankara-based lab within Hacettepe University confirmed that her "A" and "B" samples tested positive for modafinil following a Turkish league game Nov. 13. Taurasi had been suspended by Fenerbahce ever since. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. "It's always great when the right result happens," Taurasi's lawyer Howard Jacobs said. "When it happens reasonably quickly it's even better." The federation also lifted the provisional doping suspension for American player Monique Coker, who plays for Ceyhan Belediyesi and had tested positive for modafinil in doping tests carried out by the same lab. "I was thrilled to read today's report that the precautionary ban on Diana had been lifted by the Turkish Federation," UConn and U.S. basketball coach Geno Auriemma said in a statement. "Throughout this entire ordeal, Dee maintained her innocence and for her to be exonerated makes me incredibly happy for her," Auriemma said. "I hope she can put this behind her and focus all her efforts on continuing to be the best player in the world." Taurasi helped the Americans win gold medals at the past two Olympics and was the leading scorer when the U.S. won the women's world championship this past October. "We're delighted that Diana has been cleared and can now put this behind her and continue her remarkable basketball career," USA Basketball executive director Jim Tooley said in a statement. "She has been an exemplary member of numerous USA Basketball teams since 2000, and we look forward to her continued involvement with USA Basketball." Associated Press writers Selcan Hacaoglu and Suzan Fraser in Ankara contributed to this report. LOAD-DATE: February 17, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 63 of 998 DOCUMENTS Associated Press Worldstream February 16, 2011 Wednesday 1:55 PM GMT Turkey lifts provisional doping ban on Taurasi BYLINE: By SELCAN HACAOGLU, Associated Press SECTION: SPORTS NEWS LENGTH: 463 words DATELINE: ANKARA Turkey Turkey's basketball federation lifted American star Diana Taurasi's provisional doping suspension Wednesday after a lab retracted its finding that she tested positive. The Turkish Basketball Federation said the lab retracted its report after it "evaluated" Taurasi's statements in her defense. The federation did not say outright if the lab had made a mistake. The federation said Taurasi was free to continue playing in the Turkish basketball league, a decision which is also likely to revive her chances of playing for the United States at the 2012 London Olympics. "The federation has decided to lift the precautionary ban imposed on player Diana Lorena Taurasi to prevent the club and the player from being aggrieved further," the Turkish body said in a statement. Taurasi, who has insisted that she never used performance-enhancing drugs, had her contract terminated by Turkish club Fenerbahce last month after the lab said she tested positive for modafinil in December. It was not clear if Taurasi would return to Turkey. Taurasi said in an interview with The Associated Press last month that "there's no way I've ever taken anything. ... Only thing that I'm guilty of is taking too many jump shots." Taurasi intends to return to the WNBA when the season begins in June. The Phoenix guard has led the U.S. league in scoring the last four seasons and signed a multiyear extension last August. Fenerbahce President Aziz Yildirim said Wednesday he was furious that Taurasi had been banned even though she was apparently innocent. "Our player was right. We will pursue this. We have documents," the club's website quoted Yildirim as saying. "This is a disgrace ... it probably cost us the European Championship." Fenerbahce had terminated Taurasi's contract after the Ankara-based lab within Hacettepe University confirmed that her both "A" and "B" samples tested positive for the banned stimulant modafinil following a Turkish league game on Nov. 13. Taurasi had been suspended by Fenerbahce ever since. The federation also lifted the provisional doping suspension for American player Monique Coker, who plays for Ceyhan Belediyesi and had tested positive for modafinil in doping tests carried out by the same lab. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. Wednesday's decision is expected to clear the way for Taurasi to play in the Olympics. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next games. Taurasi helped the Americans win gold medals at the past two Olympics and was the leading scorer when the U.S. won the women's world championships. Associated Press Writer Suzan Fraser contributed to this report. LOAD-DATE: February 17, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 64 of 998 DOCUMENTS Associated Press Online February 16, 2011 Wednesday 4:48 PM GMT Turkey lifts provisional doping ban on Taurasi BYLINE: By SELCAN HACAOGLU, Associated Press SECTION: SPORTS NEWS LENGTH: 543 words DATELINE: ANKARA Turkey Turkey's basketball federation lifted American star Diana Taurasi's provisional doping suspension Wednesday after a lab retracted its finding that she tested positive for a performance-enhancing substance. The Turkish Basketball Federation said the lab retracted its report after it "evaluated" Taurasi's statements in her defense. The federation did not say whether the lab made a mistake. Taurasi not only is free to continue playing in the Turkish basketball league, she also is cleared to participate for the United States at the 2012 London Olympics. "The Federation has decided to lift the precautionary ban imposed on player Diana Lorena Taurasi to prevent the club and the player from being aggrieved further," the Turkish body said in a statement Wednesday. Taurasi, who has insisted that she never used performance-enhancing drugs, had her contract terminated by Turkish club Fenerbahce last month after the lab said she tested positive for modafinil in December. It was not clear whether Taurasi would return to Turkey. Taurasi said in an interview with The Associated Press last month that "there's no way I've ever taken anything. ... Only thing that I'm guilty of is taking too many jump shots." Taurasi intends to return to the WNBA when the season begins in June. The Phoenix guard has led the league in scoring the last four seasons and signed a multiyear extension last August. Fenerbahce President Aziz Yildirim said Wednesday he was furious that Taurasi had been banned even though she was apparently innocent. "Our player was right. We will pursue this. We have documents," Yildirim said on the club's website. "This is a disgrace. ... It probably cost us the European Championship." Fenerbahce had terminated Taurasi's contract after the Ankara-based lab within Hacettepe University confirmed that her "A" and "B" samples tested positive for the stimulant modafinil following a Turkish league game Nov. 13. Taurasi had been suspended by Fenerbahce ever since. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. The federation also lifted the provisional doping suspension for American player Monique Coker, who plays for Ceyhan Belediyesi and had tested positive for modafinil in doping tests carried out by the same lab. The decision Wednesday is expected to clear the way for Taurasi to play in the Olympics. The International Olympic Committee bars any athlete who receives a doping penalty of six months or more from competing in the next games. "I was thrilled to read today's report that the precautionary ban on Diana had been lifted by the Turkish Federation," UConn and U.S. basketball coach Geno Auriemma said in a statement. "Throughout this entire ordeal, Dee maintained her innocence and for her to be exonerated makes me incredibly happy for her," Auriemma said. "I hope she can put this behind her and focus all her efforts on continuing to be the best player in the world." Taurasi helped the Americans win gold medals at the past two Olympics and was the leading scorer when the U.S. won the women's world championships. Associated Press Writer Suzan Fraser in Ankara and AP Basketball Writer Doug Feinberg in New York contributed to this report. LOAD-DATE: February 17, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 65 of 998 DOCUMENTS Associated Press Online February 16, 2011 Wednesday 8:57 PM GMT Taurasi cleared of doping charges BYLINE: By DOUG FEINBERG, AP Basketball Writer SECTION: SPORTS NEWS LENGTH: 702 words Diana Taurasi was always confident she would be cleared of doping allegations. It finally happened on Wednesday. Taurasi had her provisional suspension lifted by the Turkish Basketball Federation, which said the lab that returned a positive test retracted its report after it "evaluated" Taurasi's statements in her defense. The federation did not say whether the lab made a mistake. "I got the news this morning at 5 a.m. and was in shock," Taurasi told The Associated Press by phone from her Phoenix home. "It was kind of like the first time when I heard the test result had come back positive. It's really good that the facts came out and the truth came out." Taurasi had insisted that she never used performance-enhancing drugs, even though she had her contract terminated by Turkish club Fenerbahce last month. The lab that tested her sample had said the results came back positive for the stimulant modafinil. "Life can throw you curveballs at any given time," said Taurasi, who will also be able to compete in the 2012 Olympics. "I can be mad and angry, but I will move forward. Not everyone has the same financial resources I did. Hopefully this will let people know every process has holes and to wait for the facts to come out before making decisions." With the lifting of the suspension, Taurasi is also free to continue playing in the Turkish basketball league, although she doesn't plan on going back there anytime soon. "That's pretty unlikely," the 28-year-old WNBA star said. "I'm here in Phoenix working out and am more focused on getting myself in the best shape of my life and going from there." She intends to return to the WNBA when the season begins in June. The Mercury guard has led the league in scoring the last four seasons and signed a multiyear extension last August. The last two months haven't been easy for the former UConn star. Yet she kept her faith that she would be cleared. "I tried to handle it as best as possible," Taurasi said. "There might have been times in my own private moments when I was angry or questioned why me, but I am glad the truth came out. It's scary that our careers can be taken away from us." Taurasi was the first prominent WNBA player to test positive for a banned substance. Had she not been cleared, Taurasi could have missed the London Games, because the International Olympic Committee bars any athlete given a doping penalty of six months or more from competing. Fenerbahce had terminated Taurasi's contract after the Ankara-based lab within Hacettepe University confirmed that her "A" and "B" samples tested positive for modafinil following a Turkish league game Nov. 13. Taurasi had been suspended by Fenerbahce ever since. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. "It's always great when the right result happens," Taurasi's lawyer Howard Jacobs said. "When it happens reasonably quickly it's even better." The federation also lifted the provisional doping suspension for American player Monique Coker, who plays for Ceyhan Belediyesi and had tested positive for modafinil in doping tests carried out by the same lab. "I was thrilled to read today's report that the precautionary ban on Diana had been lifted by the Turkish Federation," UConn and U.S. basketball coach Geno Auriemma said in a statement. "Throughout this entire ordeal, Dee maintained her innocence and for her to be exonerated makes me incredibly happy for her," Auriemma said. "I hope she can put this behind her and focus all her efforts on continuing to be the best player in the world." Taurasi helped the Americans win gold medals at the past two Olympics and was the leading scorer when the U.S. won the women's world championship this past October. "We're delighted that Diana has been cleared and can now put this behind her and continue her remarkable basketball career," USA Basketball executive director Jim Tooley said in a statement. "She has been an exemplary member of numerous USA Basketball teams since 2000, and we look forward to her continued involvement with USA Basketball." Associated Press writers Selcan Hacaoglu and Suzan Fraser in Ankara contributed to this report. LOAD-DATE: February 17, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 66 of 998 DOCUMENTS The Associated Press State & Local Wire February 16, 2011 Wednesday 5:09 PM GMT Turkey lifts provisional doping ban on Taurasi BYLINE: By SELCAN HACAOGLU, Associated Press SECTION: SPORTS NEWS LENGTH: 550 words DATELINE: ANKARA Turkey Turkey's basketball federation lifted American star Diana Taurasi's provisional doping suspension Wednesday after a lab retracted its finding that she tested positive for a performance-enhancing substance. The Turkish Basketball Federation said the lab retracted its report after it "evaluated" Taurasi's statements in her defense. The federation did not say whether the lab made a mistake. Taurasi not only is free to continue playing in the Turkish basketball league, she also is cleared to participate for the United States at the 2012 London Olympics. "The Federation has decided to lift the precautionary ban imposed on player Diana Lorena Taurasi to prevent the club and the player from being aggrieved further," the Turkish body said in a statement Wednesday. The former Connecticut women's basketball star, who has insisted that she never used performance-enhancing drugs, had her contract terminated by Turkish club Fenerbahce last month after the lab said she tested positive for modafinil in December. It was not clear whether Taurasi would return to Turkey. Taurasi said in an interview with The Associated Press last month that "there's no way I've ever taken anything. ... Only thing that I'm guilty of is taking too many jump shots." Taurasi intends to return to the WNBA when the season begins in June. The Phoenix guard has led the league in scoring the last four seasons and signed a multiyear extension last August. Fenerbahce President Aziz Yildirim said Wednesday he was furious that Taurasi had been banned even though she was apparently innocent. "Our player was right. We will pursue this. We have documents," Yildirim said on the club's website. "This is a disgrace. ... It probably cost us the European Championship." Fenerbahce had terminated Taurasi's contract after the Ankara-based lab within Hacettepe University confirmed that her "A" and "B" samples tested positive for the stimulant modafinil following a Turkish league game Nov. 13. Taurasi had been suspended by Fenerbahce ever since. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. The federation also lifted the provisional doping suspension for American player Monique Coker, who plays for Ceyhan Belediyesi and had tested positive for modafinil in doping tests carried out by the same lab. The decision Wednesday is expected to clear the way for Taurasi to play in the Olympics. The International Olympic Committee bars any athlete who receives a doping penalty of six months or more from competing in the next games. "I was thrilled to read today's report that the precautionary ban on Diana had been lifted by the Turkish Federation," UConn and U.S. basketball coach Geno Auriemma said in a statement. "Throughout this entire ordeal, Dee maintained her innocence and for her to be exonerated makes me incredibly happy for her," Auriemma said. "I hope she can put this behind her and focus all her efforts on continuing to be the best player in the world." Taurasi helped the Americans win gold medals at the past two Olympics and was the leading scorer when the U.S. won the women's world championships. Associated Press Writer Suzan Fraser in Ankara and AP Basketball Writer Doug Feinberg in New York contributed to this report. LOAD-DATE: February 17, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 67 of 998 DOCUMENTS The Associated Press State & Local Wire February 16, 2011 Wednesday 5:09 PM GMT LENGTH: 595 words BC-BKL--Doping-Taurasi, 3rd Ld-Writethru,0548 Turkey lifts provisional doping ban on Taurasi Eds: Adds comment from Geno Auriemma. usae/swingfield sptd/dskretta elfd/lon/srwilson elfd/lon/clehourites fasst4922 fasst4921 By SELCAN HACAOGLU Associated Press ANKARA, Turkey (AP) Turkey's basketball federation lifted American star Diana Taurasi's provisional doping suspension Wednesday after a lab retracted its finding that she tested positive for a performance-enhancing substance. The Turkish Basketball Federation said the lab retracted its report after it "evaluated" Taurasi's statements in her defense. The federation did not say whether the lab made a mistake. Taurasi not only is free to continue playing in the Turkish basketball league, she also is cleared to participate for the United States at the 2012 London Olympics. "The Federation has decided to lift the precautionary ban imposed on player Diana Lorena Taurasi to prevent the club and the player from being aggrieved further," the Turkish body said in a statement Wednesday. The former Connecticut women's basketball star, who has insisted that she never used performance-enhancing drugs, had her contract terminated by Turkish club Fenerbahce last month after the lab said she tested positive for modafinil in December. It was not clear whether Taurasi would return to Turkey. Taurasi said in an interview with The Associated Press last month that "there's no way I've ever taken anything. ... Only thing that I'm guilty of is taking too many jump shots." Taurasi intends to return to the WNBA when the season begins in June. The Phoenix guard has led the league in scoring the last four seasons and signed a multiyear extension last August. Fenerbahce President Aziz Yildirim said Wednesday he was furious that Taurasi had been banned even though she was apparently innocent. "Our player was right. We will pursue this. We have documents," Yildirim said on the club's website. "This is a disgrace. ... It probably cost us the European Championship." Fenerbahce had terminated Taurasi's contract after the Ankara-based lab within Hacettepe University confirmed that her "A" and "B" samples tested positive for the stimulant modafinil following a Turkish league game Nov. 13. Taurasi had been suspended by Fenerbahce ever since. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. The federation also lifted the provisional doping suspension for American player Monique Coker, who plays for Ceyhan Belediyesi and had tested positive for modafinil in doping tests carried out by the same lab. The decision Wednesday is expected to clear the way for Taurasi to play in the Olympics. The International Olympic Committee bars any athlete who receives a doping penalty of six months or more from competing in the next games. "I was thrilled to read today's report that the precautionary ban on Diana had been lifted by the Turkish Federation," UConn and U.S. basketball coach Geno Auriemma said in a statement. "Throughout this entire ordeal, Dee maintained her innocence and for her to be exonerated makes me incredibly happy for her," Auriemma said. "I hope she can put this behind her and focus all her efforts on continuing to be the best player in the world." Taurasi helped the Americans win gold medals at the past two Olympics and was the leading scorer when the U.S. won the women's world championships. Associated Press Writer Suzan Fraser in Ankara and AP Basketball Writer Doug Feinberg in New York contributed to this report. LOAD-DATE: February 17, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 68 of 998 DOCUMENTS Cancer Drug News February 10, 2011 Lundbeck granted commercial rights to Cephalon products in Canada and/or Latin America SECTION: NEWS LENGTH: 447 words Lundbeck has been granted commercial rights to several Cephalon products in Canada and Latin America. As part of the agreement, Lundbeck will register and commercialise several key products that are currently available in the US and/or Europe on behalf of Cephalon. Key products in the agreement include Fentora (fentanyl buccal tablet) [C-II], Provigil (modafinil), Treanda (bendamustine), Trisenox (arsenic trioxide) injection, Myocet (liposomal doxorubicin) and Nuvigil (armodafinil). According to Lundbeck, the Cephalon brands will significantly strengthen its position in these markets while leveraging on existing sales and marketing capabilities, adding significant sales in Canada and Latin America from 2012. The Cephalon products for improving wakefulness, Provigil and Nuvigil, as well as the pain product, Fentora, are considered to have a strong fit to Lundbeck's already strong central nervous system franchise. Lundbeck is currently successfully promoting modafinil in Mexico. Nuvigil is expected to be approved in Canada and Latin America in the 2012-2014 time period, and Lundbeck expects to promote these products with the existing sales and marketing organisation. Also included in the deal is the Cephalon oncology product, Treanda, which is to be commercialised by Lundbeck in Canada. The new oncology franchise in Canada will be complemented by Trisenox and the pain product, Fentora. Treanda has proven clinical activity in the treatment of haematological malignancies, including those refractory to conventional anticancer agents. Treanda is expected to be filed during 2011 in Canada, and Lundbeck will establish a dedicated oncology sales organisation in Latin America and Canada in order to achieve the full potential of the oncology portfolio. The financial terms were not disclosed, but Lundbeck is to pay double-digit royalties on sales, which will be the main overall revenue stream for Cephalon from these products in these territories. Product Indication Territory Provigil, Improve wakefulness in adults who Canada (Nuvigil only) Nuvigil experience excessive sleepiness and Latin America due to treated obstructive sleep apnoea, shift work disorder, or narcolepsy Treanda Treatment of indolent B-cell Canada non-Hodgkin's lymphoma and chronic lymphocytic leukaemia Fentora Compound for breakthrough pain in Canada and Latin America opioid-tolerant patients with cancer Trisenox Cytotoxin for acute promyelocytic Canada leukaemia Myocet1 Cytotoxin for metastatic breast Latin America cancer 1Myocet will be included in the agreement at a later stage. Cephalon holds exclusive rights to market and develop Treanda, which is licensed from Astellas Deutschland (Astellas Pharma LOAD-DATE: February 10, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter JOURNAL-CODE: Cancer Drug News Copyright 2011 Espicom Business Intelligence All Rights Reserved 69 of 998 DOCUMENTS Drug Delivery Insight February 9, 2011 Lundbeck expands commercial opportunities in Canada/Latin America with help from Cephalon SECTION: NEWS LENGTH: 404 words Lundbeck has been granted commercial rights to a number of Cephalon products in Canada and Latin America. As part of the agreement, Lundbeck will register and commercialise several key products that are currently available in the US and/or Europe, on behalf of Cephalon. Key products in the agreement include Fentora (fentanyl buccal tablet) [C-II], Provigil (modafinil tablet), Treanda (bendamustine hydrochloride injection), Trisenox (arsenic trioxide injection), Myocet (liposomal- doxorubicin) and Nuvigil (armodafinil tablet). The Cephalon products for improving wakefulness, Provigil and Nuvigil, as well as the pain product, Fentora, have a strong fit to Lundbeck's CNS franchise and will contribute to the continued growth in both Canada and Latin America. Lundbeck is currently successfully promoting modafinil in Mexico. Provigil and Nuvigil address a market with a substantial under-diagnosed and under-treated patient group. Nuvigil is expected to be approved in Canada and Latin America in the 2012 to 2014 time period. In 2009, Cephalon realised revenue of US $73 million in the US on Nuvigil and in the first nine months of 2010, revenues were US $127 million. Lundbeck expects to promote these products with the existing sales and marketing organisation. Also included in the deal is the leading Cephalon oncology product Treanda, which is to be commercialised by Lundbeck in Canada. Treanda will add significantly to revenue and earnings in Lundbeck's Canadian business. The new oncology franchise in Canada will be complemented by Trisenox and Fentora. Treanda has proven clinical activity in the treatment of haematological malignancies, including those refractory to conventional anti-cancer agents. In 2008, the American Society of Clinical Oncology recognised Treanda as one of the major advances in cancer treatment. In 2009, Cephalon realised total revenue of US $222 million on the product and in the first nine months of 2010, revenue reached US $285 million in the US. Treanda is expected to be filed during 2011 in Canada and Lundbeck will establish a dedicated oncology sales organisation in Latin America and Canada in order to achieve the full potential of the oncology portfolio. The financial terms of the agreement have not been disclosed, but Lundbeck is to pay double-digit royalties on sales which will be the main overall revenue stream for Cephalon from these products in these territories. LOAD-DATE: February 9, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter JOURNAL-CODE: Drug Delivery Insight Copyright 2011 Espicom Business Intelligence All Rights Reserved 70 of 998 DOCUMENTS US Fed News February 9, 2011 Wednesday 10:00 AM EST US Patent Issued to NeuroHealing Pharmaceuticals on Feb. 8 for "Modafinil-Based Treatment for Premature Ejaculation" (Massachusetts Inventor) LENGTH: 142 words DATELINE: ALEXANDRIA, Va. ALEXANDRIA, Va., Feb. 9 -- United States Patent no. 7,884,135, issued on Feb. 8, was assigned to NeuroHealing Pharmaceuticals Inc. (Newton, Mass.). "Modafinil-Based Treatment for Premature Ejaculation" was invented by Daniel E. Katzman (Newton, Mass.). According to the abstract released by the U.S. Patent & Trademark Office: "Methods and compositions comprising modafinil are described for treating premature ejaculation in a male individual." The patent was filed on Aug. 13, 2007, under Application No. 12/310,175. For further information please visit: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetah tml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=7884135&OS=7884135&R S=7884135 For any query with respect to this article or any other content requirement, please contact Editor at htsyndication@hindustantimes.com LOAD-DATE: February 11, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 HT Media Ltd. All Rights Reserved 71 of 998 DOCUMENTS Global Insight February 8, 2011 Lundbeck Obtains Commercial Rights to Several Cephalon Products in Canada, Latin America BYLINE: Anne-Charlotte Honore SECTION: In Brief LENGTH: 324 words Danish firm Lundbeck has been granted commercial rights to several Cephalon products in Canada and/or Latin America. Under the terms of agreement, Lundbeck will register and commercialise Provigil (modafinil) and Nuvigil (armodafinil) in Canada (Nuvigil only) and Latin America; Treanda (bendamustine HCI) in Canada; Fentora (fentanyl buccal tablet) in Canada and Latin America; Trisenox (arsenic trioxide) in Canada and at a later stage Myocet (liposomal doxorubicin) in Latin America. Lundbeck will pay double-digit royalties on sales to Cephalon. Financial terms were not disclosed. Significance:All products in-licensed from Cephalon are already approved in the United States, meaning that the clinical and regulatory risk is minimal for Lundbeck which takes here the opportunity to expand its presence in Latin America and Canada while strengthening its CNS and oncology franchises. Cephalon's drugs Treanda (bendamustine HCI), Provigil (modafinil) and Nuvigil (armodafinil) are expected to boost Lundbeck's sales performance in Canada and Latin America from 2012 onwards. Nuvigil is expected to be approved in the period 2012-14 in Canada and Latin America while Treanda is set to be filed during 2011 in Canada. Lundbeck said it will set a "dedicated oncology sales organisation in Latin America and Canada in order to achieve the full potential of the oncology portfolio". Its new oncology franchise in Canada will be composed of Treanda (bendamustine HCI) for the treatment of indolent B-cell non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukaemia (CLL), Fentora (fentanyl buccal tablet) for breakthrough pain in opioid-tolerant patients with cancer and of Trisenox (arsenic trioxide) for acute promyelocytic leukaemia (APL). Fentora (fentanyl buccal tablet) will be the only oncology-related Cephalon product commercialised by Lundbeck in Latin America until Myocet (liposomal doxorubicin) is included in the deal at a later stage. LOAD-DATE: April 30, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Web Publication Copyright 2011 World Markets Research Limited All Rights Reserved 72 of 998 DOCUMENTS Cynic Central February 5, 2011 Saturday 10:09 PM EST Losers and plastic dolls, women's basketball remains boring and Serbia gets in on a Week O' Riots BYLINE: andy LENGTH: 2072 words Feb. 5, 2011 (Cynic Central delivered by Newstex) -- - If I actually cared about womens basketball (or anyone else did), then this would be a fascinating story. One of the most accomplished players in the history of a sport embroiled in a scandal over whether or not she used performance-enhancing drugs, with the added intrigue of an international component to the saga. But alas, it is womens basketball and so Diana Taurasi testing positive in Turkey for the banned stimulant Modafinil and subsequently passing a polygraph test last month in which she insisted she never took the drug isnt a big deal. Taurasi used the polygraph results as part of a written defense that Taurasi sent to the Turkish Basketball Federation last week in which she seeks dismissal of the case against her. The test was conducted by former Chicago police officer John Fritz, who said he asked Taurasi two "relevant" questions Jan. 18: Did you at any time take the drug Modafinil or any similar generic brand name drug? And did you lie to club management when you denied ever using the drug Modafinil or any similar generic brand name drug? Fritz's report states that her score showed "that Subject was truthful when she answered 'no' to the above relevant questions." So whats at stake here? For the average sports fan, nothing. That average sports fan doesnt pay attention to the WNBA, so he or she surely pays even less attention to international womens hoops. For Taurasi, there is much more to lose. She was fired by her Turkish club, Fenerbahce, in December and faces a ban of up to two years that endangers her chance to play for the United States at the 2012 London Olympics. Also, if she is ultimately found guilty and officially suspended, Taurasi would also be subject to a World Anti-Doping Agency (WADA) rule that would erase any time she served if she went to play for the WNBA. The rule is intended to prevent banned athletes from merely going to play in leagues not regulated by WADA to sidestep a ban. Taurasi's Los Angeles defense attorney, Howard Jacobs, is arguing for dismissal of her case and has criticized several irregularities in the way her case was handled by Turkish authorities. Chief among those criticisms is the handling of her urine samples prior to testing, including a seven-day period, he says, during which there was no documentation indicating where they were kept during transportation from Istanbul to Ankara. That could be a problem because WADA maintains specific criteria for identifying Modafinil in labs and Jacobs insists Taurasi's results fell outside the agency's allowable margin of error. Questioning this particular lab in Ankara is a wise move because the lab had its drug-testing credentials suspended by WADA for three months in 2009 due to problems with its methods. As for Modafinil, it is a stimulant prescribed to treat narcolepsy patients who suffer (OOTC:WLVTQ) from excessive sleepiness and need help staying up - the very sort of thing that would help anyone trying to watch womens professional basketball. The next step in the process for Taurasi is to wait for the Turkish Basketball Federation to rule. After that, the first appeal would be to the Turkish Sports and Youth Arbitration Association, and if necessary, the international Court for Arbitration in Sport, which is the Supreme Court for doping cases. The legal battle could take a few months, but odds are it won't be any more boring than your typical WNBA game......... - Attention, Massachusetts residents: Rep. Cleon Turner or a member of his staff will soon be coming to your driveway or parking lot to clean the snow and ice off your car before you get out on the road......wait, you mean thats not going to happen? Then Turners idea for a law that would fine drivers for not cleaning winter debris off their car before pulling onto the road is just asinine. Sure, having snow and chunks of ice come flying off the car in front of you can be tough, but a little bit of safe driving on your part can alleviate much of the danger. The incident that took place Friday morning on I-93 in Andover, when ice flew off of a tractor trailer in front of a Honda Civic and landed so hard that it cracked the windshield is scary, to be certain, but the driver of that car was unharmed and the incident was nothing more than a blip on the radar. Its certainly no reason to overreact, but overreact someone must in every situation and in this case, its Rep. Cleon Turner. oeIm more concerned about having legislation there or a statute there eventually that will give police the tools they need to stop a vehicle and say, [#x2dc]Look. You need to clean the snow off your vehicle because its dangerous, said Rep. Turner. Great, an alarmist lawmaker looking to make a name for himself. And by making a name for himself, I mean this kook wants to fine people $500 for not brushing the snow and ice off their ride. Left unsaid is exactly what the standard will be. After all, if you brush off 95 percent of the snow on the roof of your SUV but miss one chunk that flies off and a cop sees it, then what? Or how about someone elses debris flies off their car, lands on your roof and then flies off your roof, but the cop only sees it come from your vehicle? Its a ginormous can of worms youre opening here, Rep. Cleon Turner, quite a can of worms.......... - My bad In writing about Fridays riots in Sri Lanka, I made it seem like they were the capper on a week of uprisings stretching from north Africa to the Middle East to Asia, but that was a mistake. To imply that would be to overlook the great riot effort turned in by tens of thousands of Serbian opposition supporters who have rallied against their government, calling for early elections and economic reforms. This group of outraged Serbs was led in their uprising by the Serbian Progressive Party. SPP leader Tomislav Nikolic addressed the crowd in front of the parliament building in the capital, Belgrade. While the gathering may not have produced the sort of furor and awe-inspiring violence that the clashes in Egypt have produced this week, the numbers were impressive. Serbian police estimate at least 55,000 people gathered for the rally, but objective observers put the number closer to 70,000. In his remarks, Nikolic did a solid job of inflaming the crowd by calling for higher wages and an end to government corruption. Claiming that the other side is corrupt and dishonest is always a solid play and so is referencing the recent protests in Tunisia and Egypt and saying that governments around the world are learning they need to listen to the people. Even if your situation has nothing to do with theirs and nothing in common with what they are going through, try to tie it to a higher cause. I like it.....check that, I love it. Even though parliamentary elections are scheduled for 2012 in Serbia, the opposition wants them held sooner. Much like President Hosni Mubarak is dragging his feet and trying to prolong his reign of terror in Egypt by promising not to seek re-election but refusing to resign early, the current regime in Serbia seems content to take the same course even as rising prices, unemployment and poverty have led to discontent with the pro-European Union government. Unfortunately, protests have remained mostly peaceful thus far and only a handful of dissidents have been arrested. The time has come to change that if those demanding change actually want to see it happen............ - How do you know your life is waaaaaay out of control? When youre texting multiple porn stars from rehab to inform them that your partying days are finished, thats when. Im looking right at you, Charlie Sheen (not that I needed to specify) because youre the one breaking out the BlackBerry from Promises or whatever rehab facility youve checked in to this time and firing off texts to Bambi, Ginger, Destiny and the girls to let them know that no longer will you be renting $1,000-a-night hotel room with hot tubs and balconies and using those rooms to have massive porn-star-and-coke orgies until you pass out and are rushed to the hospital. On some level, I suppose you could give the "Two and a Half Men" star credit for attempting to get clean and return to the show by the end of February, but thats the sort of vow were heard from Sheen before and it always ends the same way - with him face down in a pile of the Bolivian marching powder, surrounded by women who take some on film from strangers for money. But hey, maybe this is that moment of clarity for Sheen, the one where everything comes into focus. Lets check out his texts to his porn star pals: "Please lose the number, we are closed ... please drive through ... thank you," he wrote to one. "Right now we are on lockdown," he texted another. Hang on.....right now? So youre on lockdown for the time being, but maybe not for long? And no, I dont care that sheen urged these women not to contact him when his treatment ends. There are too many porn stars out there and too much Colombian nose candy to be snorted for Sheen to stay down for too long. Yes, an alleged 36-hour cocaine and drinking bender with several porn actresses led to his hospitalization Jan. 28, but coke addicts are not renowned for their commitment to anything but blow and a relapse would surprise no one. On account of not wanting to see anyone snort themselves into an early grave, I hope Im wrong, but I doubt it............ - One of my biggest pet peeves in life: people who pretend that a) dogs are human members of their family or b) anyone who acts as if fictional characters are real. This story involves the latter half of that beef and it centers on Mattel, the world's largest toy company, which has launched a digital marketing campaign in hopes of reuniting none other than Barbie and Ken. If you remember, Mattel oebroke up the two plastic dolls on Valentine's Day in 2004. Since then, they have led separate, but successful lives. However, Mattel has pretended that Ken is something other than an overpriced piece of plastic crap made by sweatshop workers in Indonesia and had him revamping his mind, body and soul to win Barbie back since 2006. That quest has now kicked into high gear, as Ken hopes to win back his plastic woman in time for Valentine's Day, with a little help from the social networking universe. Thats right, Mattel is asking Facebook, Twitter, Foursquare and YouTube losers who have far, far too much time on their hands and have wasted a sufficient amount of time on Facebook oeYes/No quizzes and oeLike my status and Ill post on your wall ploys to vote on whether Barbie should "take Ken back" or not. From those platforms, losers are directed to barbieandken.com, where users can vote and check out a Love-O-Meter, gauging voters' feelings on the topic. The campaign marks Ken's 50th anniversary and comes just in time for the release of a new "Sweet Talking Ken" doll that Mattel describes as "the ultimate boyfriend for every occasion," because he "says whatever you want him to say!" Oh Mattel, how I love your feeble attempts and relationship humor. The extent of the online world Mattel has crafted for Ken is truly disturbing. On Facebook, Twitter and Foursquare, fans can follow Ken's adventures to win back the love of his plastic, inanimate life, follow along with tweets promoting his romantic efforts and even get involved in a text campaign, where users can text THUMBS UP or THUMBS DOWN to 51684 to vote on whether the two dolls should get together again. According to the tiny plastic dolls Twitter page, Ken is also busy following his favorite sports team, the Lakers, and reading Men's Health and Esquire. Hes oevisited the Metropolitan Museum of Art in an attempt to infuse culture into his fake life. Sadly, there are kooks out there who are actually interacting with Ken as if they would a real person. Oh, and Ken is an Apple fan, using a MacBook Prop and enjoying his Internet time by browsing on Google (NASDAQ:GOOG) Chrome. Mattel has really embarrassed itself on this whole project, going back to last year's Fashion's Night Out event in New York City where it staged a "Catch Me If You Ken" promotion. Perhaps the most absurd part of the show has been Ken appearing on Canadian entertainment show ETalk and buying a spot in Us Weekly to confess his love. Now please excuse me while I go find something to vomit into............ Newstex ID: CYNC-0001-100440633 LOAD-DATE: February 6, 2011 LANGUAGE: ENGLISH NOTES: The views expressed on blogs distributed by Newstex and its re-distributors ("Blogs on Demand®") are solely the author's and not necessarily the views of Newstex or its re-distributors. Posts from such authors are provided "AS IS", with no warranties, and confer no rights. The material and information provided in Blogs on Demand® are for general information only and should not, in any respect, be relied on as professional advice. No content on such Blogs on Demand® is "read and approved" before it is posted. Accordingly, neither Newstex nor its re-distributors make any claims, promises or guarantees about the accuracy, completeness, or adequacy of the information contained therein or linked to from such blogs, nor take responsibility for any aspect of such blog content. All content on Blogs on Demand® shall be construed as author-based content and commentary. Accordingly, no warranties or other guarantees will be offered as to the quality of the opinions, commentary or anything else offered on such Blogs on Demand®. Reader's comments reflect their individual opinion and their publication within Blogs on Demand® shall not infer or connote an endorsement by Newstex or its re-distributors of such reader's comments or views. Newstex and its re-distributors expressly reserve the right to delete posts and comments at its and their sole discretion. PUBLICATION-TYPE: Web Blog Copyright 2011 Newstex LLC All Rights Reserved Newstex Web Blogs Copyright 2011 Cynic Central 73 of 998 DOCUMENTS Star-News (Wilmington, NC) February 1, 2011 Tuesday 1ST Edition SECTION: Pg. 2C LENGTH: 430 words Taurasi denies taking modafinil Former UConn women's basketball star Diana Taurasi is adamant: No matter what the test results showed, she never used performance-enhancing drugs. "There's no way I've ever taken anything," she told the Associated Press by telephone Sunday night from her parents' home in Chino, Calif. In her first interview since testing positive in December for the stimulant modafinil, Taurasi and her lawyer blamed the Turkish lab where the sample was analyzed. Taurasi is regarded by many as one of the best women's players in the world. She said she intends to return to the WNBA when the season begins in June. Tennis rankings truly global LONDON | For the first time, the top 10 players in the women's tennis rankings represent 10 different countries. Eleven different nations are represented among the top 11 spots and 30 different countries among the top 60 in Monday's rankings. "Having 10 different players represent the top 10 rankings shows how truly global tennis has become," WTA Chair and CEO Stacey Allaster said. Denmark's Caroline Wozniacki remained No. 1, followed by Australian Open champion Kim Clijsters of Belgium, Russia's Vera Zvonareva, Italy's Francesca Schiavone and Australia's Sam Stosur. The next five: Venus Williams of the United States, China's Li Na, Jelena Jankovic of Serbia, Victoria Azarenka of Belarus and Poland's Agnieszka Radwanska. Israel's Shahar Peer moved to a career high of No. 11. King's son: Mets' talk premature NEW YORK | Martin Luther King Jr.'s oldest son says any discussion of his potential interest in becoming a minority owner of the New York Mets is premature. Martin Luther King III said he was contacted Saturday by television executive Larry Meli, who is interested in putting together a group that would include former Mets first baseman Ed Kranepool and Donn Clendenon Jr., whose father was MVP of the Mets' 1969 World Series victory. King said he encouraged Meli because it would increase diversity. But King also said he was not actively putting together a group. in other baseball news | Pitcher R.A. Dickey has agreed to a $7.8 million, two-year contract with the New York Mets and outfielder Angel Pagan has agreed to a $3.5 million, one-year deal. Dickey, a 36-year-old knuckleballer who revived his career last season, gets a $1 million signing bonus. ... Right-hander Edinson Volquez and the Cincinnati Reds have agreed to a one-year contract worth $1,625,000. The deal, which avoided salary arbitration, includes $50,000 in performance bonuses: $25,000 each for 24 and 28 starts. - From wire service reports LOAD-DATE: February 4, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2011 Star-News, Inc. All Rights Reserved 74 of 998 DOCUMENTS The Associated Press January 31, 2011 Monday 04:00 AM GMT AP Interview: Taurasi denies taking modafinil BYLINE: By DOUG FEINBERG, AP Basketball Writer SECTION: SPORTS NEWS LENGTH: 777 words Former UConn women's basketball star Diana Taurasi is adamant: No matter what the test results showed, she never used performance-enhancing drugs. "There's no way I've ever taken anything," she told The Associated Press by telephone Sunday night from her parents' home in Chino, Calif. In her first interview since testing positive in December for the stimulant modafinil, Taurasi and her lawyer blamed the Turkish lab where the sample was analyzed. Taurasi is regarded by many as one of the best women's players in the world. She was the first prominent WNBA player to test positive for a banned substance. Taurasi said she intends to return to the WNBA when the season begins in June. The Phoenix guard has led the league in scoring the last four seasons and signed a multiyear extension with the Mercury last August. The 28-year-old also plans to play for the U.S. team and coach Geno Auriemma in the 2012 Olympics. She's already helped the Americans win the last two gold medals. Taurasi has talked to Auriemma, who coached her in college, at length since she tested positive. He said he'll stand by her. "My goal has been to play basketball," she said. "Things have come up in my life, but that's life for you. ... This one was an unexpected one. I've been doing the right thing for my career. I'll take this and move forward." "I went from being really angry to wondering, 'Why me?' I won't let it bring me down," she said. Taurasi's contract was terminated by the Turkish club Fenerbahce earlier this month after both her and A and B samples tested positive. The Turkish federation still hasn't announced a punishment the organization was awaiting a response from Taurasi, and her lawyer, Howard Jacobs, said it would be delivered by Monday. Taurasi faces a ban of up to two years and said she will appeal any suspension. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next games. "This will be resolved well in advance of 2012," Jacobs said. "My understanding is that we have the right of appeal to the sport of arbitration body in Turkey. That could take a couple of months. All the appeals should be done by the end of this year." Taurasi said she was at her home in Turkey, on her couch, when the Fenerbahce general manager handed her the paper stating that she had tested positive for modafinil. Taurasi said the news shocked her. "I had never heard of it and couldn't pronounce it," she said. "I had to Google it to find out the side effects. I never have come in contact with it." The drug has been involved in several major doping cases, including that of American sprinter Kelli White, and is on the World Anti-Doping Agency's list of banned substances. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. Jacobs said he's handled about 75 athlete drug cases, including those of Floyd Landis and Marion Jones. He's questioning the lab's handling of Taurasi's sample and pointed out that it had been suspended by WADA. Efforts to reach WADA officials by telephone for comment were not immediately successful. After Taurasi's positive test, two of her Turkish teammates refused to have their samples examined by that same lab. "I have the most respect for the testing process. When it's not done the right way, when protocol isn't followed, I do have some problems with it," Taurasi said. "I've never needing anything to help me. Only thing that I'm guilty of is taking too many jump shots. Taurasi is one of many WNBA stars who play overseas in the winter because of higher salaries. The best players can make up to 10 times their WNBA salaries, which top out at about $100,000. This isn't the first trouble Taurasi has run into trouble in her career. She served one day in jail and was suspended by the Mercury for two games in 2009 after pleading guilty to a DUI charge. "The DUI was a mistake I made and I owned up to and I did my time," she said. "That really did help me in the long run growing up as a person. This is different, waking up one morning and having something pinned on you that you had no clue about. It's been a difficult month coming to terms with everything. I know I've never taken it." Taurasi, who said she's been tested at least three times a year since joining the WNBA, knows that it may be tough to get rid of the stigma that she's doping even if she's vindicated. "I trust that the truth will come out. At the end of the day you can try and convince the whole world but if you know it's true and you've never taken performance-enhancing drugs that's what you have to live by." LOAD-DATE: January 31, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 75 of 998 DOCUMENTS The Associated Press January 31, 2011 Monday 06:52 PM GMT AP Interview: Taurasi denies taking stimulant BYLINE: By DOUG FEINBERG, AP Basketball Writer SECTION: SPORTS NEWS LENGTH: 892 words Diana Taurasi insists she did nothing wrong. The former Connecticut women's basketball star says she hadn't even heard of the banned stimulant modafinil until she found out she had tested positive for it. And no matter what those results showed, Taurasi is adamant that she never used performance-enhancing drugs. "I've never needed anything to help me. Only thing that I'm guilty of is taking too many jump shots," she told The Associated Press by telephone Sunday night from her parents' home in Chino, Calif. In her first interview since testing positive in December for modafinil, Taurasi and her lawyer blamed the Turkish lab where the sample was analyzed. "There's no way I've ever taken anything," she said. Taurasi is regarded by many as one of the best women's players in the world. She was the first prominent WNBA player to test positive for a banned substance. Taurasi said she intends to return to the WNBA when the season begins in June. The Phoenix guard has led the league in scoring the last four seasons and signed a multiyear extension with the Mercury last August. The 28-year-old also plans to play for the U.S. team and coach Geno Auriemma in the 2012 Olympics. She's already helped the Americans win the last two gold medals. Taurasi has talked to Auriemma, who coached her in college, at length since she tested positive. He said he'll stand by her. "My goal has been to play basketball," she said. "Things have come up in my life, but that's life for you. ... This one was an unexpected one. I've been doing the right thing for my career. I'll take this and move forward. "I went from being really angry to wondering, 'Why me?' I won't let it bring me down," she said. Taurasi's contract was terminated by the Turkish club Fenerbahce this month after both her A and B samples tested positive. The Turkish federation still hasn't announced a punishment the organization was awaiting a response from Taurasi. Her lawyer, Howard Jacobs, said it was delivered Monday. Despite reports of Taurasi's positive test surfacing last month, Jacobs only received the official report from the federation on Wednesday. Taurasi faces a ban of up to two years and said she will appeal any suspension. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next games. "This will be resolved well in advance of 2012," Jacobs said. "My understanding is that we have the right of appeal to the sport of arbitration body in Turkey. That could take a couple of months. All the appeals should be done by the end of this year." Taurasi said she was at her home in Turkey, on her couch, when the Fenerbahce general manager handed her the paper stating that she had tested positive for modafinil. Taurasi said the news shocked her. "I had never heard of it and couldn't pronounce it," she said. "I had to Google it to find out the side effects. I never have come in contact with it." The drug has been involved in several major doping cases, including that of American sprinter Kelli White, and is on the World Anti-Doping Agency's list of banned substances. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. Jacobs said he's handled about 75 athlete drug cases, including those of Floyd Landis and Marion Jones. He's questioning the lab's handling of Taurasi's sample and pointed out that it had been suspended by WADA. WADA spokesman Catherine Coley wrote in an e-mail to the AP that the organization won't comment until the case is resolved "in order to protect the integrity of the proceedings." For Taurasi's part, her lawyers noted she passed a polygraph test and that the Turkish lab was suspended by WADA for three months in 2009. The player's legal team also contends that the lab has failed to properly identify modafinil and that there are questions about the chain of custody for Taurasi's test. After Taurasi tested positive, two of her teammates in Turkey refused to have their samples examined by that same lab. "I have the most respect for the testing process. When it's not done the right way, when protocol isn't followed, I do have some problems with it," Taurasi said. Taurasi is one of many WNBA stars who play overseas in the winter because of higher salaries. The best players can make up to 10 times their WNBA salaries, which top out at about $100,000. This isn't the first time Taurasi has run into trouble during her career. She served one day in jail and was suspended by the Mercury for two games in 2009 after pleading guilty to a DUI charge. "The DUI was a mistake I made and I owned up to and I did my time," she said. "That really did help me in the long run growing up as a person. This is different, waking up one morning and having something pinned on you that you had no clue about. It's been a difficult month coming to terms with everything. I know I've never taken it." Taurasi, who said she's been tested at least three times a year since joining the WNBA, knows that it might be tough to get rid of the stigma that she's doping even if she's vindicated. "I trust that the truth will come out," she said. "At the end of the day you can try and convince the whole world, but if you know it's true and you've never taken performance-enhancing drugs, that's what you have to live by." LOAD-DATE: February 1, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 76 of 998 DOCUMENTS The Bismarck Tribune January 31, 2011 Monday SECTION: SPORTS LENGTH: 764 words Taurasi denies taking modafinil Former UConn women's basketball star Diana Taurasi is adamant: No matter what the test results showed, she never used performance-enhancing drugs. "There's no way I've ever taken anything," she said Sunday. In her first interview since testing positive in December for the stimulant modafinil, Taurasi and her lawyer blamed the Turkish lab where the sample was analyzed. Taurasi is regarded by many as one of the best women's players in the world. She was the first prominent WNBA player to test positive for a banned substance. Taurasi intends to return to the WNBA when the season begins in June. The Phoenix guard has led the league in scoring the last four seasons and signed a multiyear extension with the Mercury. The 28-year-old also plans to play for the U.S. team and Geno Auriemma in the 2012 Olympics. She's already helped the Americans win the last two gold medals. Taurasi has talked to Auriemma, who coached her in college, at length since she tested positive. He said he'll stand by her. "My goal has been to play basketball," she said. "Things have come up in my life, but that's life for you. ... This one was an unexpected one. I've been doing the right thing for my career. I'll take this and move forward." "I went from being really angry to wondering, 'Why me?' I won't let it bring me down," she said. Taurasi's contract was terminated by the Turkish club Fenerbahce earlier this month after both her and A and B samples tested positive. The Turkish federation still hasn't announced a punishment - the organization was awaiting a response from Taurasi, and her lawyer, Howard Jacobs, said it would be delivered by Monday. Taurasi faces a ban of up to two years and said she will appeal any suspension. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next games. "This will be resolved well in advance of 2012," Jacobs said. "My understanding is that we have the right of appeal to the sport of arbitration body in Turkey. That could take a couple of months. All the appeals should be done by the end of this year." Taurasi said she was at her home in Turkey, on her couch, when the Fenerbahce general manager handed her the paper stating that she had tested positive for modafinil. Taurasi said the news shocked her. "I had never heard of it and couldn't pronounce it," she said. "I had to Google it to find out the side effects. I never have come in contact with it." The drug has been involved in several major doping cases, including that of American sprinter Kelli White, and is on the World Anti-Doping Agency's list of banned substances. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. Jacobs said he's handled about 75 athlete drug cases, including those of Floyd Landis and Marion Jones. He's questioning the lab's handling of Taurasi's sample and pointed out that it had been suspended by WADA. Efforts to reach WADA officials by telephone for comment were not immediately successful. After Taurasi's positive test, two of her Turkish teammates refused to have their samples examined by that same lab. "I have the most respect for the testing process. When it's not done the right way, when protocol isn't followed, I do have some problems with it," Taurasi said. "I've never needing anything to help me. Only thing that I'm guilty of is taking too many jump shots. Taurasi is one of many WNBA stars who play overseas in the winter because of higher salaries. The best players can make up to 10 times their WNBA salaries, which top out at about $100,000. This isn't the first trouble Taurasi has run into trouble in her career. She served one day in jail and was suspended by the Mercury for two games in 2009 after pleading guilty to a DUI charge. "The DUI was a mistake I made and I owned up to and I did my time," she said. "That really did help me in the long run growing up as a person. This is different, waking up one morning and having something pinned on you that you had no clue about. It's been a difficult month coming to terms with everything. I know I've never taken it." Taurasi, who said she's been tested at least three times a year since joining the WNBA, knows that it may be tough to get rid of the stigma that she's doping even if she's vindicated. "I trust that the truth will come out. At the end of the day you can try and convince the whole world but if you know it's true and you've never taken performance-enhancing drugs that's what you have to live by." LOAD-DATE: January 31, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2011 The Bismarck Tribune, a division of Lee Enterprises All Rights Reserved 77 of 998 DOCUMENTS Jezebel January 31, 2011 Monday 2:21 PM EST Could Diana Taurasi Be Exonerated For Doping? [Sports] LENGTH: 515 words Jan. 31, 2011 (Gawker Media delivered by Newstex) -- Basketball star Diana Taurasi tested positive for a banned drug, and her shot at the 2012 Olympics could be in jeopardy. But she swears she didn't take anything " we asked an expert if she could be telling the truth. The former UConn star dropped from her Turkish team earlier this month when a second sample of her urine tested positive for the banned stimulant modafinil. The Turkish league hasn't formally suspended her, but if they do, she could be barred from competing in the 2012 Olympics " any suspension of six months or longer would make her ineligible. Yesterday, she told the AP she hadn't taken the drug: "I've never needed anything to help me. Only thing that I'm guilty of is taking too many jump shots." And her lawyer Howard Jacobs is projecting confidence, saying, "This will be resolved well in advance of 2012." So could Taurasi really be innocent? Daniel M. Rosen, author of Dope: A History of Performance Enhancement in Sports from the Nineteenth Century to Today told me Taurasi could be telling the truth. He explains, Lab testing is a curious thing. One of the things we need to know about it is that no test is perfect. Just because the A and the B samples actually give the same result doesn't necessarily mean that the result is correct. There are these funny things called false positives. [...] The fact that the lab got the same result both times only means that the test was consistent, but the way the anti-doping system works is that there's really no taking into account the idea of false positives, [...] so if the lab says you're positive, you're basically screwed. And even if modafinil did show up in Taurasi's bloodstream, she might not have intentionally put it there. Rosen gave me numerous examples of athletes who tested positive for banned substances after accidentally consuming them in supplements, over-the-counter medications, and even contaminated meat. If Taurasi can show that she inadvertently ingested the modafinil, she might be able to get a reduced punishment. Her best shot at full exoneration, though, is to show sloppy handling of her sample or some "break in the chain of custody" that might have led to contamination. Jacobs notes that the lab in question has been suspended in the past by the World Anti-Doping Agency " Rosen says such suspensions can occur for a variety of reasons, including simply not performing enough tests, but questions about the lab's bona fides could help Taurasi's defense. When it comes to an Olympic bid, though, time is not on her side. Says Rosen, "some of these appeals take forever, and it all depends on how fast the various arbitration panels move, and how fast the arbitrators come up with their decisions." Even if Taurasi's appeal makes it all the way to the highest authority, Court of Arbitration for Sport, their decision could take six months. So despite Jacobs's optimism, Rosen says, "I'm afraid that she's probably not going to be able to compete." AP Interview: Taurasi Denies Taking Stimulant [AP] Newstex ID: GAWK-0016-100296348 LOAD-DATE: January 31, 2011 LANGUAGE: ENGLISH NOTES: The views expressed on blogs distributed by Newstex and its re-distributors ("Blogs on Demand®") are solely the author's and not necessarily the views of Newstex or its re-distributors. Posts from such authors are provided "AS IS", with no warranties, and confer no rights. The material and information provided in Blogs on Demand® are for general information only and should not, in any respect, be relied on as professional advice. No content on such Blogs on Demand® is "read and approved" before it is posted. Accordingly, neither Newstex nor its re-distributors make any claims, promises or guarantees about the accuracy, completeness, or adequacy of the information contained therein or linked to from such blogs, nor take responsibility for any aspect of such blog content. 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PUBLICATION-TYPE: Web Blog Copyright 2011 Newstex LLC All Rights Reserved Newstex Web Blogs Copyright 2011 Jezebel 78 of 998 DOCUMENTS Associated Press Worldstream January 31, 2011 Monday 4:02 AM GMT AP Interview: Taurasi denies taking modafinil BYLINE: By DOUG FEINBERG, AP Basketball Writer SECTION: SPORTS NEWS LENGTH: 773 words Women's basketball star Diana Taurasi is adamant: No matter what the test results showed, she never used performance-enhancing drugs. "There's no way I've ever taken anything," she told The Associated Press by telephone Sunday from her parents' home in California. In her first interview since testing positive in December for the stimulant modafinil, Taurasi and her lawyer blamed the Turkish lab where the sample was analyzed. Taurasi is regarded by many as one of the best women's players in the world. She was the first prominent WNBA player to test positive for a banned substance. Taurasi said she intends to return to the WNBA when the season begins in June. The Phoenix guard has led the league in scoring the last four seasons and signed a multiyear extension with the Mercury last August. The 28-year-old also plans to play for the U.S. team and coach Geno Auriemma in the 2012 Olympics. She's already helped the Americans win the last two gold medals. Taurasi has talked to Auriemma, who coached her in college, at length since she tested positive. He said he'll stand by her. "My goal has been to play basketball," she said. "Things have come up in my life, but that's life for you. ... This one was an unexpected one. I've been doing the right thing for my career. I'll take this and move forward." "I went from being really angry to wondering, 'Why me?' I won't let it bring me down," she said. Taurasi's contract was terminated by the Turkish club Fenerbahce earlier this month after both her and A and B samples tested positive. The Turkish federation still hasn't announced a punishment the organization was awaiting a response from Taurasi, and her lawyer, Howard Jacobs, said it would be delivered by Monday. Taurasi faces a ban of up to two years and said she will appeal any suspension. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next games. "This will be resolved well in advance of 2012," Jacobs said. "My understanding is that we have the right of appeal to the sport of arbitration body in Turkey. That could take a couple of months. All the appeals should be done by the end of this year." Taurasi said she was at her home in Turkey, on her couch, when the Fenerbahce general manager handed her the paper stating that she had tested positive for modafinil. Taurasi said the news shocked her. "I had never heard of it and couldn't pronounce it," she said. "I had to Google it to find out the side effects. I never have come in contact with it." The drug has been involved in several major doping cases, including that of American sprinter Kelli White, and is on the World Anti-Doping Agency's list of banned substances. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. Jacobs said he's handled about 75 athlete drug cases, including those of Floyd Landis and Marion Jones. He's questioning the lab's handling of Taurasi's sample and pointed out that it had been suspended by WADA. Efforts to reach WADA officials by telephone for comment were not immediately successful. After Taurasi's positive test, two of her Turkish teammates refused to have their samples examined by that same lab. "I have the most respect for the testing process. When it's not done the right way, when protocol isn't followed, I do have some problems with it," Taurasi said. "I've never needing anything to help me. Only thing that I'm guilty of is taking too many jump shots. Taurasi is one of many WNBA stars who play overseas in the winter because of higher salaries. The best players can make up to 10 times their WNBA salaries, which top out at about $100,000. This isn't the first trouble Taurasi has run into trouble in her career. She served one day in jail and was suspended by the Mercury for two games in 2009 after pleading guilty to a DUI charge. "The DUI was a mistake I made and I owned up to and I did my time," she said. "That really did help me in the long run growing up as a person. This is different, waking up one morning and having something pinned on you that you had no clue about. It's been a difficult month coming to terms with everything. I know I've never taken it." Taurasi, who said she's been tested at least three times a year since joining the WNBA, knows that it may be tough to get rid of the stigma that she's doping even if she's vindicated. "I trust that the truth will come out. At the end of the day you can try and convince the whole world but if you know it's true and you've never taken performance-enhancing drugs that's what you have to live by." LOAD-DATE: January 31, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 79 of 998 DOCUMENTS Associated Press Online January 31, 2011 Monday 6:53 PM GMT AP Interview: Taurasi denies taking stimulant BYLINE: By DOUG FEINBERG, AP Basketball Writer SECTION: SPORTS NEWS LENGTH: 892 words Diana Taurasi insists she did nothing wrong. The former Connecticut women's basketball star says she hadn't even heard of the banned stimulant modafinil until she found out she had tested positive for it. And no matter what those results showed, Taurasi is adamant that she never used performance-enhancing drugs. "I've never needed anything to help me. Only thing that I'm guilty of is taking too many jump shots," she told The Associated Press by telephone Sunday night from her parents' home in Chino, Calif. In her first interview since testing positive in December for modafinil, Taurasi and her lawyer blamed the Turkish lab where the sample was analyzed. "There's no way I've ever taken anything," she said. Taurasi is regarded by many as one of the best women's players in the world. She was the first prominent WNBA player to test positive for a banned substance. Taurasi said she intends to return to the WNBA when the season begins in June. The Phoenix guard has led the league in scoring the last four seasons and signed a multiyear extension with the Mercury last August. The 28-year-old also plans to play for the U.S. team and coach Geno Auriemma in the 2012 Olympics. She's already helped the Americans win the last two gold medals. Taurasi has talked to Auriemma, who coached her in college, at length since she tested positive. He said he'll stand by her. "My goal has been to play basketball," she said. "Things have come up in my life, but that's life for you. ... This one was an unexpected one. I've been doing the right thing for my career. I'll take this and move forward. "I went from being really angry to wondering, 'Why me?' I won't let it bring me down," she said. Taurasi's contract was terminated by the Turkish club Fenerbahce this month after both her A and B samples tested positive. The Turkish federation still hasn't announced a punishment the organization was awaiting a response from Taurasi. Her lawyer, Howard Jacobs, said it was delivered Monday. Despite reports of Taurasi's positive test surfacing last month, Jacobs only received the official report from the federation on Wednesday. Taurasi faces a ban of up to two years and said she will appeal any suspension. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next games. "This will be resolved well in advance of 2012," Jacobs said. "My understanding is that we have the right of appeal to the sport of arbitration body in Turkey. That could take a couple of months. All the appeals should be done by the end of this year." Taurasi said she was at her home in Turkey, on her couch, when the Fenerbahce general manager handed her the paper stating that she had tested positive for modafinil. Taurasi said the news shocked her. "I had never heard of it and couldn't pronounce it," she said. "I had to Google it to find out the side effects. I never have come in contact with it." The drug has been involved in several major doping cases, including that of American sprinter Kelli White, and is on the World Anti-Doping Agency's list of banned substances. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. Jacobs said he's handled about 75 athlete drug cases, including those of Floyd Landis and Marion Jones. He's questioning the lab's handling of Taurasi's sample and pointed out that it had been suspended by WADA. WADA spokesman Catherine Coley wrote in an e-mail to the AP that the organization won't comment until the case is resolved "in order to protect the integrity of the proceedings." For Taurasi's part, her lawyers noted she passed a polygraph test and that the Turkish lab was suspended by WADA for three months in 2009. The player's legal team also contends that the lab has failed to properly identify modafinil and that there are questions about the chain of custody for Taurasi's test. After Taurasi tested positive, two of her teammates in Turkey refused to have their samples examined by that same lab. "I have the most respect for the testing process. When it's not done the right way, when protocol isn't followed, I do have some problems with it," Taurasi said. Taurasi is one of many WNBA stars who play overseas in the winter because of higher salaries. The best players can make up to 10 times their WNBA salaries, which top out at about $100,000. This isn't the first time Taurasi has run into trouble during her career. She served one day in jail and was suspended by the Mercury for two games in 2009 after pleading guilty to a DUI charge. "The DUI was a mistake I made and I owned up to and I did my time," she said. "That really did help me in the long run growing up as a person. This is different, waking up one morning and having something pinned on you that you had no clue about. It's been a difficult month coming to terms with everything. I know I've never taken it." Taurasi, who said she's been tested at least three times a year since joining the WNBA, knows that it might be tough to get rid of the stigma that she's doping even if she's vindicated. "I trust that the truth will come out," she said. "At the end of the day you can try and convince the whole world, but if you know it's true and you've never taken performance-enhancing drugs, that's what you have to live by." LOAD-DATE: February 1, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 80 of 998 DOCUMENTS Associated Press Online January 31, 2011 Monday 9:20 AM GMT AP Interview: Taurasi denies taking modafinil BYLINE: By DOUG FEINBERG, AP Basketball Writer SECTION: SPORTS NEWS LENGTH: 777 words Former UConn women's basketball star Diana Taurasi is adamant: No matter what the test results showed, she never used performance-enhancing drugs. "There's no way I've ever taken anything," she told The Associated Press by telephone Sunday night from her parents' home in Chino, Calif. In her first interview since testing positive in December for the stimulant modafinil, Taurasi and her lawyer blamed the Turkish lab where the sample was analyzed. Taurasi is regarded by many as one of the best women's players in the world. She was the first prominent WNBA player to test positive for a banned substance. Taurasi said she intends to return to the WNBA when the season begins in June. The Phoenix guard has led the league in scoring the last four seasons and signed a multiyear extension with the Mercury last August. The 28-year-old also plans to play for the U.S. team and coach Geno Auriemma in the 2012 Olympics. She's already helped the Americans win the last two gold medals. Taurasi has talked to Auriemma, who coached her in college, at length since she tested positive. He said he'll stand by her. "My goal has been to play basketball," she said. "Things have come up in my life, but that's life for you. ... This one was an unexpected one. I've been doing the right thing for my career. I'll take this and move forward." "I went from being really angry to wondering, 'Why me?' I won't let it bring me down," she said. Taurasi's contract was terminated by the Turkish club Fenerbahce earlier this month after both her and A and B samples tested positive. The Turkish federation still hasn't announced a punishment the organization was awaiting a response from Taurasi, and her lawyer, Howard Jacobs, said it would be delivered by Monday. Taurasi faces a ban of up to two years and said she will appeal any suspension. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next games. "This will be resolved well in advance of 2012," Jacobs said. "My understanding is that we have the right of appeal to the sport of arbitration body in Turkey. That could take a couple of months. All the appeals should be done by the end of this year." Taurasi said she was at her home in Turkey, on her couch, when the Fenerbahce general manager handed her the paper stating that she had tested positive for modafinil. Taurasi said the news shocked her. "I had never heard of it and couldn't pronounce it," she said. "I had to Google it to find out the side effects. I never have come in contact with it." The drug has been involved in several major doping cases, including that of American sprinter Kelli White, and is on the World Anti-Doping Agency's list of banned substances. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. Jacobs said he's handled about 75 athlete drug cases, including those of Floyd Landis and Marion Jones. He's questioning the lab's handling of Taurasi's sample and pointed out that it had been suspended by WADA. Efforts to reach WADA officials by telephone for comment were not immediately successful. After Taurasi's positive test, two of her Turkish teammates refused to have their samples examined by that same lab. "I have the most respect for the testing process. When it's not done the right way, when protocol isn't followed, I do have some problems with it," Taurasi said. "I've never needing anything to help me. Only thing that I'm guilty of is taking too many jump shots. Taurasi is one of many WNBA stars who play overseas in the winter because of higher salaries. The best players can make up to 10 times their WNBA salaries, which top out at about $100,000. This isn't the first trouble Taurasi has run into trouble in her career. She served one day in jail and was suspended by the Mercury for two games in 2009 after pleading guilty to a DUI charge. "The DUI was a mistake I made and I owned up to and I did my time," she said. "That really did help me in the long run growing up as a person. This is different, waking up one morning and having something pinned on you that you had no clue about. It's been a difficult month coming to terms with everything. I know I've never taken it." Taurasi, who said she's been tested at least three times a year since joining the WNBA, knows that it may be tough to get rid of the stigma that she's doping even if she's vindicated. "I trust that the truth will come out. At the end of the day you can try and convince the whole world but if you know it's true and you've never taken performance-enhancing drugs that's what you have to live by." LOAD-DATE: February 1, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 81 of 998 DOCUMENTS The Associated Press State & Local Wire January 31, 2011 Monday 4:00 AM GMT AP Interview: Taurasi denies taking modafinil BYLINE: By DOUG FEINBERG, AP Basketball Writer SECTION: SPORTS NEWS LENGTH: 777 words Former UConn women's basketball star Diana Taurasi is adamant: No matter what the test results showed, she never used performance-enhancing drugs. "There's no way I've ever taken anything," she told The Associated Press by telephone Sunday night from her parents' home in Chino, Calif. In her first interview since testing positive in December for the stimulant modafinil, Taurasi and her lawyer blamed the Turkish lab where the sample was analyzed. Taurasi is regarded by many as one of the best women's players in the world. She was the first prominent WNBA player to test positive for a banned substance. Taurasi said she intends to return to the WNBA when the season begins in June. The Phoenix guard has led the league in scoring the last four seasons and signed a multiyear extension with the Mercury last August. The 28-year-old also plans to play for the U.S. team and coach Geno Auriemma in the 2012 Olympics. She's already helped the Americans win the last two gold medals. Taurasi has talked to Auriemma, who coached her in college, at length since she tested positive. He said he'll stand by her. "My goal has been to play basketball," she said. "Things have come up in my life, but that's life for you. ... This one was an unexpected one. I've been doing the right thing for my career. I'll take this and move forward." "I went from being really angry to wondering, 'Why me?' I won't let it bring me down," she said. Taurasi's contract was terminated by the Turkish club Fenerbahce earlier this month after both her and A and B samples tested positive. The Turkish federation still hasn't announced a punishment the organization was awaiting a response from Taurasi, and her lawyer, Howard Jacobs, said it would be delivered by Monday. Taurasi faces a ban of up to two years and said she will appeal any suspension. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next games. "This will be resolved well in advance of 2012," Jacobs said. "My understanding is that we have the right of appeal to the sport of arbitration body in Turkey. That could take a couple of months. All the appeals should be done by the end of this year." Taurasi said she was at her home in Turkey, on her couch, when the Fenerbahce general manager handed her the paper stating that she had tested positive for modafinil. Taurasi said the news shocked her. "I had never heard of it and couldn't pronounce it," she said. "I had to Google it to find out the side effects. I never have come in contact with it." The drug has been involved in several major doping cases, including that of American sprinter Kelli White, and is on the World Anti-Doping Agency's list of banned substances. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. Jacobs said he's handled about 75 athlete drug cases, including those of Floyd Landis and Marion Jones. He's questioning the lab's handling of Taurasi's sample and pointed out that it had been suspended by WADA. Efforts to reach WADA officials by telephone for comment were not immediately successful. After Taurasi's positive test, two of her Turkish teammates refused to have their samples examined by that same lab. "I have the most respect for the testing process. When it's not done the right way, when protocol isn't followed, I do have some problems with it," Taurasi said. "I've never needing anything to help me. Only thing that I'm guilty of is taking too many jump shots. Taurasi is one of many WNBA stars who play overseas in the winter because of higher salaries. The best players can make up to 10 times their WNBA salaries, which top out at about $100,000. This isn't the first trouble Taurasi has run into trouble in her career. She served one day in jail and was suspended by the Mercury for two games in 2009 after pleading guilty to a DUI charge. "The DUI was a mistake I made and I owned up to and I did my time," she said. "That really did help me in the long run growing up as a person. This is different, waking up one morning and having something pinned on you that you had no clue about. It's been a difficult month coming to terms with everything. I know I've never taken it." Taurasi, who said she's been tested at least three times a year since joining the WNBA, knows that it may be tough to get rid of the stigma that she's doping even if she's vindicated. "I trust that the truth will come out. At the end of the day you can try and convince the whole world but if you know it's true and you've never taken performance-enhancing drugs that's what you have to live by." LOAD-DATE: January 31, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 82 of 998 DOCUMENTS The Associated Press State & Local Wire January 31, 2011 Monday 4:00 AM GMT LENGTH: 810 words BC-BKL--Taurasi Speaks, 1st Ld-Writethru,0958 AP Interview: Taurasi denies taking modafinil 2030 Eds: Updates with details, quotes. AP Photo NY157 sptd/rrusso fasst4921 By DOUG FEINBERG AP Basketball Writer Former UConn women's basketball star Diana Taurasi is adamant: No matter what the test results showed, she never used performance-enhancing drugs. "There's no way I've ever taken anything," she told The Associated Press by telephone Sunday night from her parents' home in Chino, Calif. In her first interview since testing positive in December for the stimulant modafinil, Taurasi and her lawyer blamed the Turkish lab where the sample was analyzed. Taurasi is regarded by many as one of the best women's players in the world. She was the first prominent WNBA player to test positive for a banned substance. Taurasi said she intends to return to the WNBA when the season begins in June. The Phoenix guard has led the league in scoring the last four seasons and signed a multiyear extension with the Mercury last August. The 28-year-old also plans to play for the U.S. team and coach Geno Auriemma in the 2012 Olympics. She's already helped the Americans win the last two gold medals. Taurasi has talked to Auriemma, who coached her in college, at length since she tested positive. He said he'll stand by her. "My goal has been to play basketball," she said. "Things have come up in my life, but that's life for you. ... This one was an unexpected one. I've been doing the right thing for my career. I'll take this and move forward." "I went from being really angry to wondering, 'Why me?' I won't let it bring me down," she said. Taurasi's contract was terminated by the Turkish club Fenerbahce earlier this month after both her and A and B samples tested positive. The Turkish federation still hasn't announced a punishment the organization was awaiting a response from Taurasi, and her lawyer, Howard Jacobs, said it would be delivered by Monday. Taurasi faces a ban of up to two years and said she will appeal any suspension. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next games. "This will be resolved well in advance of 2012," Jacobs said. "My understanding is that we have the right of appeal to the sport of arbitration body in Turkey. That could take a couple of months. All the appeals should be done by the end of this year." Taurasi said she was at her home in Turkey, on her couch, when the Fenerbahce general manager handed her the paper stating that she had tested positive for modafinil. Taurasi said the news shocked her. "I had never heard of it and couldn't pronounce it," she said. "I had to Google it to find out the side effects. I never have come in contact with it." The drug has been involved in several major doping cases, including that of American sprinter Kelli White, and is on the World Anti-Doping Agency's list of banned substances. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. Jacobs said he's handled about 75 athlete drug cases, including those of Floyd Landis and Marion Jones. He's questioning the lab's handling of Taurasi's sample and pointed out that it had been suspended by WADA. Efforts to reach WADA officials by telephone for comment were not immediately successful. After Taurasi's positive test, two of her Turkish teammates refused to have their samples examined by that same lab. "I have the most respect for the testing process. When it's not done the right way, when protocol isn't followed, I do have some problems with it," Taurasi said. "I've never needing anything to help me. Only thing that I'm guilty of is taking too many jump shots. Taurasi is one of many WNBA stars who play overseas in the winter because of higher salaries. The best players can make up to 10 times their WNBA salaries, which top out at about $100,000. This isn't the first trouble Taurasi has run into trouble in her career. She served one day in jail and was suspended by the Mercury for two games in 2009 after pleading guilty to a DUI charge. "The DUI was a mistake I made and I owned up to and I did my time," she said. "That really did help me in the long run growing up as a person. This is different, waking up one morning and having something pinned on you that you had no clue about. It's been a difficult month coming to terms with everything. I know I've never taken it." Taurasi, who said she's been tested at least three times a year since joining the WNBA, knows that it may be tough to get rid of the stigma that she's doping even if she's vindicated. "I trust that the truth will come out. At the end of the day you can try and convince the whole world but if you know it's true and you've never taken performance-enhancing drugs that's what you have to live by." LOAD-DATE: January 31, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 83 of 998 DOCUMENTS The Associated Press State & Local Wire January 31, 2011 Monday 6:53 PM GMT AP Interview: Taurasi denies taking stimulant BYLINE: By DOUG FEINBERG, AP Basketball Writer SECTION: SPORTS NEWS LENGTH: 892 words Diana Taurasi insists she did nothing wrong. The former Connecticut women's basketball star says she hadn't even heard of the banned stimulant modafinil until she found out she had tested positive for it. And no matter what those results showed, Taurasi is adamant that she never used performance-enhancing drugs. "I've never needed anything to help me. Only thing that I'm guilty of is taking too many jump shots," she told The Associated Press by telephone Sunday night from her parents' home in Chino, Calif. In her first interview since testing positive in December for modafinil, Taurasi and her lawyer blamed the Turkish lab where the sample was analyzed. "There's no way I've ever taken anything," she said. Taurasi is regarded by many as one of the best women's players in the world. She was the first prominent WNBA player to test positive for a banned substance. Taurasi said she intends to return to the WNBA when the season begins in June. The Phoenix guard has led the league in scoring the last four seasons and signed a multiyear extension with the Mercury last August. The 28-year-old also plans to play for the U.S. team and coach Geno Auriemma in the 2012 Olympics. She's already helped the Americans win the last two gold medals. Taurasi has talked to Auriemma, who coached her in college, at length since she tested positive. He said he'll stand by her. "My goal has been to play basketball," she said. "Things have come up in my life, but that's life for you. ... This one was an unexpected one. I've been doing the right thing for my career. I'll take this and move forward. "I went from being really angry to wondering, 'Why me?' I won't let it bring me down," she said. Taurasi's contract was terminated by the Turkish club Fenerbahce this month after both her A and B samples tested positive. The Turkish federation still hasn't announced a punishment the organization was awaiting a response from Taurasi. Her lawyer, Howard Jacobs, said it was delivered Monday. Despite reports of Taurasi's positive test surfacing last month, Jacobs only received the official report from the federation on Wednesday. Taurasi faces a ban of up to two years and said she will appeal any suspension. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next games. "This will be resolved well in advance of 2012," Jacobs said. "My understanding is that we have the right of appeal to the sport of arbitration body in Turkey. That could take a couple of months. All the appeals should be done by the end of this year." Taurasi said she was at her home in Turkey, on her couch, when the Fenerbahce general manager handed her the paper stating that she had tested positive for modafinil. Taurasi said the news shocked her. "I had never heard of it and couldn't pronounce it," she said. "I had to Google it to find out the side effects. I never have come in contact with it." The drug has been involved in several major doping cases, including that of American sprinter Kelli White, and is on the World Anti-Doping Agency's list of banned substances. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. Jacobs said he's handled about 75 athlete drug cases, including those of Floyd Landis and Marion Jones. He's questioning the lab's handling of Taurasi's sample and pointed out that it had been suspended by WADA. WADA spokesman Catherine Coley wrote in an e-mail to the AP that the organization won't comment until the case is resolved "in order to protect the integrity of the proceedings." For Taurasi's part, her lawyers noted she passed a polygraph test and that the Turkish lab was suspended by WADA for three months in 2009. The player's legal team also contends that the lab has failed to properly identify modafinil and that there are questions about the chain of custody for Taurasi's test. After Taurasi tested positive, two of her teammates in Turkey refused to have their samples examined by that same lab. "I have the most respect for the testing process. When it's not done the right way, when protocol isn't followed, I do have some problems with it," Taurasi said. Taurasi is one of many WNBA stars who play overseas in the winter because of higher salaries. The best players can make up to 10 times their WNBA salaries, which top out at about $100,000. This isn't the first time Taurasi has run into trouble during her career. She served one day in jail and was suspended by the Mercury for two games in 2009 after pleading guilty to a DUI charge. "The DUI was a mistake I made and I owned up to and I did my time," she said. "That really did help me in the long run growing up as a person. This is different, waking up one morning and having something pinned on you that you had no clue about. It's been a difficult month coming to terms with everything. I know I've never taken it." Taurasi, who said she's been tested at least three times a year since joining the WNBA, knows that it might be tough to get rid of the stigma that she's doping even if she's vindicated. "I trust that the truth will come out," she said. "At the end of the day you can try and convince the whole world, but if you know it's true and you've never taken performance-enhancing drugs, that's what you have to live by." LOAD-DATE: February 1, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 84 of 998 DOCUMENTS The Associated Press State & Local Wire January 31, 2011 Monday 6:53 PM GMT LENGTH: 935 words BC-BKL--Taurasi Speaks, 1st Ld-Writethru,1172 AP Interview: Taurasi denies taking stimulant 2030 Eds: Updates with WADA comment and details of Taurasi's defense. AP Photo NY157 sptd/jaffleck sptd/mfitzpatrick sptd/rrusso fasst4921 By DOUG FEINBERG AP Basketball Writer Diana Taurasi insists she did nothing wrong. The former Connecticut women's basketball star says she hadn't even heard of the banned stimulant modafinil until she found out she had tested positive for it. And no matter what those results showed, Taurasi is adamant that she never used performance-enhancing drugs. "I've never needed anything to help me. Only thing that I'm guilty of is taking too many jump shots," she told The Associated Press by telephone Sunday night from her parents' home in Chino, Calif. In her first interview since testing positive in December for modafinil, Taurasi and her lawyer blamed the Turkish lab where the sample was analyzed. "There's no way I've ever taken anything," she said. Taurasi is regarded by many as one of the best women's players in the world. She was the first prominent WNBA player to test positive for a banned substance. Taurasi said she intends to return to the WNBA when the season begins in June. The Phoenix guard has led the league in scoring the last four seasons and signed a multiyear extension with the Mercury last August. The 28-year-old also plans to play for the U.S. team and coach Geno Auriemma in the 2012 Olympics. She's already helped the Americans win the last two gold medals. Taurasi has talked to Auriemma, who coached her in college, at length since she tested positive. He said he'll stand by her. "My goal has been to play basketball," she said. "Things have come up in my life, but that's life for you. ... This one was an unexpected one. I've been doing the right thing for my career. I'll take this and move forward. "I went from being really angry to wondering, 'Why me?' I won't let it bring me down," she said. Taurasi's contract was terminated by the Turkish club Fenerbahce this month after both her A and B samples tested positive. The Turkish federation still hasn't announced a punishment the organization was awaiting a response from Taurasi. Her lawyer, Howard Jacobs, said it was delivered Monday. Despite reports of Taurasi's positive test surfacing last month, Jacobs only received the official report from the federation on Wednesday. Taurasi faces a ban of up to two years and said she will appeal any suspension. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next games. "This will be resolved well in advance of 2012," Jacobs said. "My understanding is that we have the right of appeal to the sport of arbitration body in Turkey. That could take a couple of months. All the appeals should be done by the end of this year." Taurasi said she was at her home in Turkey, on her couch, when the Fenerbahce general manager handed her the paper stating that she had tested positive for modafinil. Taurasi said the news shocked her. "I had never heard of it and couldn't pronounce it," she said. "I had to Google it to find out the side effects. I never have come in contact with it." The drug has been involved in several major doping cases, including that of American sprinter Kelli White, and is on the World Anti-Doping Agency's list of banned substances. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. Jacobs said he's handled about 75 athlete drug cases, including those of Floyd Landis and Marion Jones. He's questioning the lab's handling of Taurasi's sample and pointed out that it had been suspended by WADA. WADA spokesman Catherine Coley wrote in an e-mail to the AP that the organization won't comment until the case is resolved "in order to protect the integrity of the proceedings." For Taurasi's part, her lawyers noted she passed a polygraph test and that the Turkish lab was suspended by WADA for three months in 2009. The player's legal team also contends that the lab has failed to properly identify modafinil and that there are questions about the chain of custody for Taurasi's test. After Taurasi tested positive, two of her teammates in Turkey refused to have their samples examined by that same lab. "I have the most respect for the testing process. When it's not done the right way, when protocol isn't followed, I do have some problems with it," Taurasi said. Taurasi is one of many WNBA stars who play overseas in the winter because of higher salaries. The best players can make up to 10 times their WNBA salaries, which top out at about $100,000. This isn't the first time Taurasi has run into trouble during her career. She served one day in jail and was suspended by the Mercury for two games in 2009 after pleading guilty to a DUI charge. "The DUI was a mistake I made and I owned up to and I did my time," she said. "That really did help me in the long run growing up as a person. This is different, waking up one morning and having something pinned on you that you had no clue about. It's been a difficult month coming to terms with everything. I know I've never taken it." Taurasi, who said she's been tested at least three times a year since joining the WNBA, knows that it might be tough to get rid of the stigma that she's doping even if she's vindicated. "I trust that the truth will come out," she said. "At the end of the day you can try and convince the whole world, but if you know it's true and you've never taken performance-enhancing drugs, that's what you have to live by." LOAD-DATE: February 1, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 85 of 998 DOCUMENTS Indian Patents News January 25, 2011 Tuesday 6:30 AM EST Cephalon Inc. Files Patent Application for Methods for the Separation of Modafinil LENGTH: 258 words New Delhi, Jan. 25 -- USA based Cephalon Inc. filed patent application for methods for the separation of modafinil. The inventors are Wilhelm Hauck, Oliver Ludemann-Hombourger, Yvan Ruland, Nelson Landmesser and John Mallamo. Cephalon Inc. filed the patent application on Feb. 7, 2007. The patent application number is 465/KOLNP/2007 A. The international classification numbers are C07B57/00 and C07C317/24. According to the Controller General of Patents, Designs & Trade Marks, "The present invention is directed to a process for the isolation of the enantiomeric forms of modafinil with high enantiomeric purity and high overall yields by means of a continuous chromatographic process." Cephalon, Inc. is an international biopharmaceutical company engaged in the discovery, development and commercialization of products in four core therapeutic areas: central nervous system (CNS), pain, oncology and inflammatory disease. In addition to conducting an active research and development program, it markets seven products in the United States and numerous products in various countries throughout Europe and the world. Its principal product are its wakefulness products, PROVIGIL (modafinil) Tablets [C-IV] and NUVIGIL (armodafinil) Tablets [C-IV], which comprised 51% of its total consolidated net sales during the year ended December 31, 2009. During 2009, Cephalon, Inc. acquired an exclusive, worldwide license to the ImmuPharma investigational compound, LUPUZOR, which is in Phase IIb development for the treatment of systemic lupus erythematosus. LOAD-DATE: January 25, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Indian Patents News, distributed by Contify.com All Rights Reserved 86 of 998 DOCUMENTS Chicago Daily Herald January 8, 2011 Saturday L2 Edition Taurasi's breach damages WNBA SECTION: SPORTS; Pg. 2 LENGTH: 587 words What a dope Diana Taurasi appears to be. On Thursday, Taurasi, arguably the best female basketball player in the world, had her contract with the Turkish team she plays for during the WNBA's off-season voided. For doping. She has reportedly denied the charges in conversations with her former college coach, Geno Auriemma of Connecticut. It will be interesting to see what her next move is. For now, this certainly is a surreal development, to say the least. In the world of professional sports, women's basketball is the closest thing to squeaky clean. For more than a decade, the WNBA has being trying to emulate its professional sports brethren by developing a quality and high-level sports entertainment option. Just without the drugs. It's no secret that just about every men's professional sports league has had bouts with drug problems over the course of their histories. From Major League Baseball to the NFL to the NBA, we've seen athletes ruin their careers with steroids, hard-core street drugs and even the misuse of prescription medications. Fifteen years into its existence, the WNBA hasn't really had to face those demons. "I'd say that only 2 to 5 percent of the players in the WNBA even risk violating the substance policy," said Chicago Sky strength and conditioning coach Ann Crosby. "When I say that, people are always like, 'Really?' But it's true. The WNBA really doesn't have the problems that a lot of sports leagues have with drugs." Yes, but when it rains on the WNBA, it apparently pours. This isn't a benchwarmer in trouble. This is the face of the league. Not good news for the WNBA. Taurasi, who has been an A-list superstar ever since she was drafted by the Phoenix Mercury in 2004, has tested positive for the banned stimulant modafinil. On Thursday, her second sample, or "B" sample, confirmed what her original sample read in November. Taurasi's team in Turkey made its decision to terminate her contract after the "B" sample also came back positive. Modafinil is used to counter excessive sleepiness due to narcolepsy, sleep apnea and other sleep disorders. It is on the World Anti-Doping Agency's list and is the substance that got American sprinter Kelli White into trouble in 2004. She won gold medals in the 100 and 200 meters at the 2003 World Championships. But those results were stricken from the records in the wake of news that White tested positive for modafinil as well as the steroid THG. White received a two-year ban from competition. Taurasi also faces tough repercussions. She could be banned for up to two years from the Turkish league. And that would comprise her standing with the U.S. women's national basketball team for the 2012 Olympics in London. Already a two-time gold medalist, Taurasi would not be allowed to participate in any Olympic event if she is saddled with a ban of two years or more by any other athletic agency. On top of all that, Taurasi would likely be faced with a punishment from the WNBA for the 2011 season. "She could be hit with a triple whammy, and that's such a bummer for the league because she is such a draw. People come out to see her play," said Crosby, who confirmed that the Sky has never had a substance violation in its six years of existence. Crosby helps to ensure every Sky player is in compliance. "I'm not sure how the WNBA will deal with it, but I would think she would get some kind of suspension, whether it be for two or three games or more," Crosby said. "Things like this are really dealt with on a case-by-case basis." pbabcock@dailyherald.com LOAD-DATE: January 10, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2011 Paddock Publications, Inc. 87 of 998 DOCUMENTS The New York Times January 7, 2011 Friday Late Edition - Final Taurasi's Deal Terminated As Test Confirms Violation BYLINE: By JERE LONGMAN SECTION: Section B; Column 0; Sports Desk; Pg. 11 LENGTH: 373 words Diana Taurasi's Olympic and professional basketball career grew more uncertain Thursday when the Turkish basketball federation said it had confirmed her doping violation and that her club team in Istanbul had terminated her contract. Taurasi, 28, considered by many the world's top women's basketball player, had been suspended from her Istanbul team since the ''A'' sample of a two-part urinalysis tested positive last month for the banned stimulant modafinil. The ''B'' sample also tested positive, the Turkish basketball federation said Thursday on its Web site. The federation also posted a notice saying that Taurasi's team, Fenerbahce, had dropped her. No sanctions were announced, but Taurasi now faces a suspension from international competition of up to two years, according to the rules of the World Anti-Doping Agency. Through her lawyer, she has denied knowingly taking any prohibited substances. A suspension longer than six months would leave Taurasi ineligible to compete for the United States at the 2012 London Games, according to a rule implemented by the International Olympic Committee. Any proposed suspension by the Turkish federation was not likely to be for less than six months, said Taurasi's lawyer, Howard L. Jacobs. She could appeal any suspension. Jacobs said he could not take his next step until he received official notification of a doping violation. ''At some point, they're going to have to tell me and provide me with lab documents,'' Jacobs said. ''So far that has not happened.'' Earlier this week, Geno Auriemma, who coached Taurasi at Connecticut and will be the 2012 United States Olympic coach, said that Taurasi told him she never took modafinil, an alertness drug designed to treat sleep disorders. Taurasi plays for the Phoenix Mercury of the W.N.B.A. during the summer and for Fenerbahce during the league's off-season. It remained unclear whether Taurasi's W.N.B.A. eligibility would be affected. The Turkish lab that performed Taurasi's urinalysis has previously been suspended for a brief period by WADA, Jacobs noted. Two of Taurasi's teammates at Fenerbahce recently agreed to provide urine samples only if they would be tested in Germany. ''The whole thing is unbelievably stressful,'' Jacobs said. URL: http://www.nytimes.com LOAD-DATE: January 7, 2011 LANGUAGE: ENGLISH GRAPHIC: PHOTO: Diana Taurasi, playing in a W.N.B.A. playoff game for the Phoenix Mercury in 2010, tested positive for the stimulant modafinil. (PHOTOGRAPH BY ERIC GAY/ASSOCIATED PRESS) PUBLICATION-TYPE: Newspaper Copyright 2011 The New York Times Company 88 of 998 DOCUMENTS The Associated Press January 6, 2011 Thursday 04:21 PM GMT Taurasi has Turkish contract voided for doping BYLINE: By SELCAN HACAOGLU, Associated Press SECTION: SPORTS NEWS LENGTH: 447 words DATELINE: ANKARA, Turkey American basketball star Diana Taurasi had her contract terminated by Turkish club Fenerbahce on Thursday after her "B" sample tested positive for doping. The Istanbul-based club made its decision after the Turkish Basketball Federation announced the results of the doping test on its website. Taurasi faces a ban of up to two years, putting in jeopardy her chances of playing for the United States at the 2012 London Olympics. The federation has not announced a decision on Taurasi's punishment. Taurasi's "A" sample tested positive last month for the banned stimulant modafinil following a Turkish league game on Nov. 13. Taurasi had been suspended by Fenerbahce ever since. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next games. Taurasi helped the Americans win gold medals at the past two Olympics and was the leading scorer when the U.S. won the women's world championships. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. On Tuesday, Geno Auriemma, the United States coach for the 2012 Olympics, said the former University of Connecticut star told him that she did not take modafinil. He also said he didn't know if Taurasi had any problems with sleeplessness. One of the most decorated women's players in history, Taurasi led the WNBA in scoring for a league-record fourth straight year, averaging 22.6 points last season. The five-time All-Star and two-time WNBA champion signed a multiyear contract extension with Phoenix in August. The Mercury have not commented publicly on the doping case. Taurasi is one of many American stars who play overseas in the winter because salaries are significantly higher than in the WNBA. She played in Russia for four years for Spartak before joining the Turkish league this season. Taurasi was leading the league in scoring with 24.6 points per game. Two of Taurasi's teammates at Fenerbahce have resisted doping tests in Turkey because they do not trust the lab that tests the samples. Australian player Penny Taylor and Czech teammate Hana Horakova provided samples only after the Turkish federation agreed to send them to Germany for testing at a lab in Cologne. The two players were tested after Fenerbahce's Turkish league game on Sunday. Modafinil has been involved in several major doping cases, including that of American sprinter Kelli White, and is on the World Anti-Doping Agency's list of banned substances. White won the 100- and 200-meter races at the 2003 world championships in Paris, but both her medals were stripped after she tested positive for the stimulant. LOAD-DATE: January 7, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 89 of 998 DOCUMENTS Indian Patents News January 6, 2011 Thursday 6:30 AM EST Organisation De Synthese Mondiale Orsymonde Files Patent Application for Modafinil Synthesis Process LENGTH: 140 words New Delhi, Jan. 6 -- France based Organisation De Synthese Mondiale Orsymonde filed patent application for modafinil synthesis process. The inventor is Rose Sebastien. Organisation De Synthese Mondiale Orsymonde filed the patent application on Nov. 16, 2006. The patent application number is 3018/CHENP/2005 A. The international classification number is C07C 315/00. According to the Controller General of Patents, Designs & Trade Marks, "The invention relates to a process for preparing modafinil having a defined granulometry which comprises the steps of: a) preparing a solution of DMSAM ; b) contacting the solution obtained with NH3 at a predetermined temperature and a predetermined stirring; and c) isolating the modafinil formed, wherein said temperature and said stirring are predetermined in order to obtain said defined granulometry." LOAD-DATE: January 6, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Indian Patents News, distributed by Contify.com All Rights Reserved 90 of 998 DOCUMENTS Associated Press Worldstream January 6, 2011 Thursday 4:03 PM GMT Taurasi's 'B' sample positive for banned stimulant BYLINE: By SELCAN HACAOGLU, Associated Press SECTION: SPORTS NEWS LENGTH: 435 words DATELINE: ANKARA Turkey American basketball star Diana Taurasi's "B" sample tested positive for doping, a result which threatens her chances of playing for the United States at the 2012 London Olympics. Taurasi's "A" sample tested positive last month for the banned stimulant modafinil following a Turkish league game on Nov. 13. The Fenerbahce player, who faces a two-year doping ban, had her contract with the club terminated Thursday following the announcement of the positive result on the website of the Turkish Basketball Federation. The federation, however, has yet to make a decision on Tauarsi's punishment. If Taurasi is suspended for more than six months it would put her 2012 Olympic status in jeopardy. She helped the team win gold medals at the past two Olympics and was the leading scorer at the women's world championships, which the Americans won in early October. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next games. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. On Tuesday, Geno Auriemma, the United States coach for the 2012 Olympics, said the former University of Connecticut star told him that she did not take modafinil. He also said he didn't know if Taurasi had any problems with sleeplessness. Taurasi led the WNBA in scoring for a league-record fourth straight year, averaging 22.6 points. The five-time All-Star and two-time WNBA champion signed a multiyear contract extension with Phoenix in August. Taurasi is one of many American stars who play overseas in the winter because salaries are significantly higher than in the WNBA. She played in Russia for four years for Spartak before joining the Turkish league this season. Taurasi was leading the league in scoring with 24.6 points per game. Two of Taurasi's teammates at Fenerbahce have resisted doping tests in Turkey because they do not trust the lab that tested her samples. Australian player Penny Taylor and Czech teammate Hana Horakova provided samples only after the Turkish federation agreed to send them to Germany for testing at a lab in Cologne. The two players were tested after Fenerbahce's Turkish league game against Besiktas on Sunday. Modafinil has been involved in several major doping cases, including that of American sprinter Kelli White, and is on the World Anti-Doping Agency's list of banned substances. White won the 100- and 200-meter races at the 2003 world championships in Paris, but both her medals were stripped after she tested positive for the stimulant. LOAD-DATE: January 7, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 91 of 998 DOCUMENTS Associated Press Online January 6, 2011 Thursday 3:45 PM GMT Taurasi's 'B' sample positive for banned stimulant BYLINE: By SELCAN HACAOGLU, Associated Press SECTION: SPORTS NEWS LENGTH: 440 words DATELINE: ANKARA Turkey Diana Taurasi's "B" sample tested positive for doping, putting in jeopardy her chances of playing for the United States at the 2012 London Olympics. Taurasi's "A" sample tested positive last month for the banned stimulant modafinil following a Turkish league game on Nov. 13. The Fenerbahce player, who has been provisionally suspended by the team, could now be banned for two years. The Turkish Basketball Federation, which announced the positive "B" sample result Thursday on its website, said there was no immediate decision on Tauarsi's punishment. Fenerbahce said the club would make a final decision on her case at a later date. If Taurasi is suspended for more than six months it could keep her from playing in the 2012 Olympics. She helped the team win gold medals at the past two Olympics and was the leading scorer at the women's world championships, which the Americans won in early October. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next games. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. On Tuesday, Geno Auriemma, the U.S. coach for the 2012 Olympics, said the former University of Connecticut star told him that she did not take modafinil. He also said he didn't know if Taurasi had any problems with sleeplessness. Taurasi led the WNBA in scoring for a league-record fourth straight year, averaging 22.6 points last season. The five-time All-Star and two-time WNBA champion signed a multiyear contract extension with Phoenix in August. Taurasi is one of many American stars who play overseas in the winter because salaries are significantly higher than in the WNBA. She played in Russia for four years for Spartak before joining the Turkish league this season. Taurasi was leading the league in scoring with 24.6 points per game. Two of Taurasi's teammates at Fenerbahce have resisted doping tests in Turkey because they do not trust the lab that tested her samples. Australian player Penny Taylor and Czech teammate Hana Horakova provided samples only after the Turkish federation agreed to send them to Germany for testing at a lab in Cologne. The two players were tested after Fenerbahce's Turkish league game on Sunday. Modafinil has been involved in several major doping cases, including that of American sprinter Kelli White, and is on the World Anti-Doping Agency's list of banned substances. White won the 100- and 200-meter races at the 2003 world championships in Paris, but both of her medals were stripped after she tested positive for the stimulant. LOAD-DATE: January 7, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 92 of 998 DOCUMENTS Associated Press Online January 6, 2011 Thursday 3:59 PM GMT Taurasi has Turkish contract voided for doping BYLINE: By SELCAN HACAOGLU, Associated Press SECTION: SPORTS NEWS LENGTH: 583 words DATELINE: ANKARA Turkey American basketball star Diana Taurasi has had her contract terminated by Turkish club Fenerbahce after her "B" sample tested positive for doping. The Istanbul club says the decision was made Thursday following the results announcement by the Turkish Basketball Federation. Taurasi faces a ban of up to two years, putting in jeopardy her chances of playing for the United States at the 2012 London Olympics. Taurasi's "A" sample tested positive last month for the banned stimulant modafinil following a Turkish league game on Nov. 13. Taurasi had been suspended by Fenerbahce ever since. The Turkish federation, which announced the positive "B" sample result on its website, says there has been no immediate decision on Taurasi's punishment. THIS IS A BREAKING NEWS UPDATE. Check back soon for further information. AP's earlier story is below. ANKARA, Turkey (AP) Diana Taurasi's "B" sample tested positive for doping, putting in jeopardy her chances of playing for the United States at the 2012 London Olympics. Taurasi's "A" sample tested positive last month for the banned stimulant modafinil following a Turkish league game on Nov. 13. The Fenerbahce player, who has been provisionally suspended by the team, could now be banned for two years. The Turkish Basketball Federation, which announced the positive "B" sample result Thursday on its website, said there was no immediate decision on Tauarsi's punishment. Fenerbahce said the club would make a final decision on her case at a later date. If Taurasi is suspended for more than six months it could keep her from playing in the 2012 Olympics. She helped the team win gold medals at the past two Olympics and was the leading scorer at the women's world championships, which the Americans won in early October. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next games. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. On Tuesday, Geno Auriemma, the U.S. coach for the 2012 Olympics, said the former University of Connecticut star told him that she did not take modafinil. He also said he didn't know if Taurasi had any problems with sleeplessness. Taurasi led the WNBA in scoring for a league-record fourth straight year, averaging 22.6 points last season. The five-time All-Star and two-time WNBA champion signed a multiyear contract extension with Phoenix in August. Taurasi is one of many American stars who play overseas in the winter because salaries are significantly higher than in the WNBA. She played in Russia for four years for Spartak before joining the Turkish league this season. Taurasi was leading the league in scoring with 24.6 points per game. Two of Taurasi's teammates at Fenerbahce have resisted doping tests in Turkey because they do not trust the lab that tested her samples. Australian player Penny Taylor and Czech teammate Hana Horakova provided samples only after the Turkish federation agreed to send them to Germany for testing at a lab in Cologne. The two players were tested after Fenerbahce's Turkish league game on Sunday. Modafinil has been involved in several major doping cases, including that of American sprinter Kelli White, and is on the World Anti-Doping Agency's list of banned substances. White won the 100- and 200-meter races at the 2003 world championships in Paris, but both of her medals were stripped after she tested positive for the stimulant. LOAD-DATE: January 7, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 93 of 998 DOCUMENTS The Associated Press State & Local Wire January 6, 2011 Thursday 3:07 PM GMT Taurasi's 'B' sample positive for banned stimulant SECTION: SPORTS NEWS LENGTH: 136 words DATELINE: ANKARA Turkey The Turkish Basketball Federation says American star Diana Taurasi's "B" sample tested positive for doping. Taurasi's "A" sample tested positive last month for the banned stimulant modafinil, following a Turkish league game on Nov. 13. The Fenerbahce player, who has been provisionally suspended by the team, could be banned for two years. If Taurasi is suspended for more than six months it would put her 2012 Olympics status with the U.S. national basketball team in jeopardy. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. Taurasi led the WNBA in scoring for a league-record fourth straight year this past season, averaging 22.6 points. The five-time All-Star signed a multiyear contract extension with Phoenix in August. LOAD-DATE: January 7, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 94 of 998 DOCUMENTS The Associated Press State & Local Wire January 6, 2011 Thursday 3:07 PM GMT LENGTH: 167 words BC-BKL--Doping-Taurasi,0289 Taurasi's 'B' sample positive for banned stimulant 2030 Eds: APNewsNow. AP Photo TXEG107 sptd/dskretta elfd/lon/clehourites fasst4922 fasst4921 ANKARA, Turkey (AP) The Turkish Basketball Federation says American star Diana Taurasi's "B" sample tested positive for doping. Taurasi's "A" sample tested positive last month for the banned stimulant modafinil, following a Turkish league game on Nov. 13. The Fenerbahce player, who has been provisionally suspended by the team, could be banned for two years. If Taurasi is suspended for more than six months it would put her 2012 Olympics status with the U.S. national basketball team in jeopardy. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. Taurasi led the WNBA in scoring for a league-record fourth straight year this past season, averaging 22.6 points. The five-time All-Star signed a multiyear contract extension with Phoenix in August. LOAD-DATE: January 7, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 95 of 998 DOCUMENTS Indian Patents News January 5, 2011 Wednesday 6:30 AM EST Mallinckrodt Inc. Files Patent Application for Improved Process for Preparing Benzhydrylthioacetamide LENGTH: 252 words New Delhi, Jan. 5 -- USA based Mallinckrodt Inc. filed patent application for improved process for preparing benzhydrylthioacetamide. The inventor is Liang Sidney. Mallinckrodt Inc. filed the patent application on April 21, 2006. The patent application number is 1383/CHENP/2006 A. The international classification number is C07C317/44. According to the Controller General of Patents, Designs & Trade Marks, "The present invention is directed to an improved process for preparing modafinil wherein benzhydrylthioacetate is prepared in high yield and purity by the reaction of a haloacetate with the reaction product of thiourea and benzhydrol. The reaction employing the haloacetate is conducted in a solvent comprising an organic solvent such as methanol having dissolved therein an organic base or an inorganic basic salt such as sodium bicarbonate. The resulting benzhydrylthioacetate can be amidated and then oxidized to provide the pharmaceutical grade modafinil in high yield and purity." Mallinckrodt, Inc. designs, manufactures, and distributes respiratory care, imaging products, and prescription pharmaceuticals. It offers contrast media and delivery systems, radiopharmaceuticals, and urology imaging systems for the diagnosis and treatment of diseases in various imaging procedures. The company also provides peptide products, including amino acid derivatives and resins, as well as solid liquid phase peptides, and hybrid fragment synthesis; and active pharmaceutical ingredients and specialty generics. LOAD-DATE: January 5, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Indian Patents News, distributed by Contify.com All Rights Reserved 96 of 998 DOCUMENTS Associated Press Worldstream January 3, 2011 Monday 6:16 PM GMT Report: Diana Taurasi's B sample also positive BYLINE: By SUZAN FRASER, Associated Press SECTION: SPORTS NEWS LENGTH: 494 words DATELINE: ANKARA Turkey Diana Taurasi's backup doping sample also came back positive for a banned substance and the American basketball star faces a possible two-year ban, Turkish news reports said Monday. The Turkish basketball federation did not immediately confirm the reports by the Dogan News agency and private NTV news channel, and neither news outlet cited a source for their reports. An official at Taurasi's Turkish club, Fenerbahce, also would not confirm the report and said the team had not yet been notified of the result. WNBA standout and former University of Connecticut star Taurasi tested positive for the stimulant modafinil while playing in Turkey's professional women's league. She was tested following a league game on Nov. 13 and the positive result was confirmed last month. Taurasi had been provisionally suspended by Fenerbahce pending the result of her "B" sample test, which was analyzed at the doping lab at Hacettepe University in Ankara. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to drug manufacturers. The stimulant has been involved in several major doping cases, including that of U.S. sprinter Kelli White, and is on the World Anti-Doping Agency's list of banned substances. White won the 100- and 200-meter races at the 2003 world championships in Paris, but both her medals were stripped after she tested positive for the stimulant. If the positive "B" sample finding is confirmed by Turkey's basketball federation, it could lead to a ban of up to two years for Taurasi. It could also put Taurasi's 2012 Olympics standing with the U.S. national basketball team in jeopardy. She has helped the team win gold medals at the past two Olympics and was the leading scorer at the women's world championships, which the Americans won in early October. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next games. Meanwhile, two of Taurasi's teammates at Fenerbahce resisted doping tests in Turkey because they do not trust the lab that tested her samples, Turkey's Haberturk newspaper said. Australian forward Penny Taylor and Hana Horakova of the Czech Republic provided samples only after the Turkish federation agreed to send them to Germany for testing at a lab in Cologne. The two players were tested after Fenerbahce's Turkish league game against Besiktas late Sunday. A Fenerbahce official confirmed the report. Taurasi led the WNBA in scoring for a league-record fourth straight year, averaging 22.6 points per game. The five-time All-Star and two-time WNBA champion signed a multiyear contract extension with the Phoenix Mercury in August. She played in Russia for four years for powerhouse Spartak before joining the Turkish League this season. Taurasi was leading the league in scoring this season with 24.6 points a game. Taurasi is one of many WNBA stars who play overseas in the winter because of higher salaries. LOAD-DATE: January 4, 2011 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2011 Associated Press All Rights Reserved 97 of 998 DOCUMENTS Indian Patents News December 28, 2010 Tuesday 6:30 AM EST Cephalon Inc Files Patent Application for Modafinil Compositions LENGTH: 199 words New Delhi, Dec. 28 -- USA based Cephalon Inc filed patent application for modafinil compositions. The inventors are Magali Bourghol Hickey, Matthew Peterson, Orn Almarsson and Mark Oliveria. Cephalon Inc filed the patent application on Feb. 20, 2006. The patent application number is 00371/KOLNP/2006 A. The international classification number is A61K. According to the Controller General of Patents, Designs & Trade Marks, "Co-crystals and solvates of racemic, enantiomerically pure and enantiomerically mixed modafinil are formed and several important physical properties are modulated. The solubility, dissolution, bioavailability, dose response, and stability of modafinil can be modulated to improve efficacy in pharmaceutical compositions." Cephalon, Inc. (NASDAQ: CEPH) is a U.S. biopharmaceutical company co-founded in 1987 by Dr. Frank Baldino, Jr., a pharmacologist and former scientist with the DuPont Company, who served as the company's chairman and chief executive officer until his death in December 2010. The company's name comes from the adjective "cephalic" meaning "related to the head or brain," and it was established primarily to pursue treatments for neurodegenerative diseases. LOAD-DATE: December 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 Indian Patents News, distributed by Contify.com All Rights Reserved 98 of 998 DOCUMENTS Indian Patents News December 27, 2010 Monday 6:30 AM EST Cephalon Inc Files Patent Application for Modafinil Compositions LENGTH: 283 words New Delhi, Dec. 27 -- UAE based Cephalon Inc filed patent application for modafinil compositions. The inventors are Magali Bourghol Hickey, Matthew Peterson, Orn Almarssonh and Mark Oliveira. Cephalon Inc filed the patent application on Sept. 4, 2006. The patent application number is 2534/KOLNP/2006 A. The international classification number is C07C 317/10. According to the Controller General of Patents, Designs & Trade Marks, "Polymorphs and solvates of racemic, enantiomerieally pure, and enantiomeriealiy mixed modafinil and formed and discussed, In addition, said forms are described as useful for the treatment of many conditions including, but not limited to, narcolepsy." Cephalon, Inc. (Public, NASDAQ:CEPH) is an international biopharmaceutical company engaged in the discovery, development and commercialization of products in four core therapeutic areas: central nervous system (CNS), pain, oncology and inflammatory disease. In addition to conducting an active research and development program, it markets seven products in the United States and numerous products in various countries throughout Europe and the world. Its principal product are its wakefulness products, PROVIGIL (modafinil) Tablets [C-IV] and NUVIGIL (armodafinil) Tablets [C-IV], which comprised 51% of its total consolidated net sales during the year ended December 31, 2009. During 2009, Cephalon, Inc. acquired an exclusive, worldwide license to the ImmuPharma investigational compound, LUPUZOR, which is in Phase IIb development for the treatment of systemic lupus erythematosus. In August 2009, Cephalon, Inc. acquired Arana Therapeutics Limited. In April 2010, the Company acquired Mepha, a pharmaceutical company. LOAD-DATE: December 27, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 Indian Patents News, distributed by Contify.com All Rights Reserved 99 of 998 DOCUMENTS PR Newswire December 27, 2010 Monday 8:30 AM EST Cephalon Receives Complete Response Letter for NUVIGIL for the Treatment of Excessive Sleepiness Associated With Jet Lag Disorder LENGTH: 822 words DATELINE: FRAZER, Pa., Dec. 27, 2010 FRAZER, Pa., Dec. 27, 2010 /PRNewswire/ -- Cephalon, Inc. (Nasdaq: CEPH) today announced that the company received a second Complete Response Letter from the U.S. Food and Drug Administration (FDA) for the supplemental new drug application (sNDA) for NUVIGIL(R) (armodafinil) Tablets [C-IV] for the treatment of patients with excessive sleepiness associated with jet lag disorder resulting from eastbound travel. In its letter to the company, the FDA reiterated its previously stated concerns regarding the NUVIGIL sNDA. "Cephalon believes we met the agreed upon safety and efficacy endpoints in the NUVIGIL sNDA clinical study conducted under a Special Protocol Assessment. However, following several conversations with the agency, and given this second complete response letter, the company believes that further communications with the FDA will not result in an approval of this application," said Dr. Lesley Russell, Chief Medical Officer at Cephalon. "As a result, the company is no longer pursuing this indication." About NUVIGIL NUVIGIL is indicated to improve wakefulness in patients with excessive sleepiness associated with treated obstructive sleep apnea (OSA), shift work disorder (SWD), or narcolepsy. In patients with OSA, NUVIGIL is used along with airway treatments for this condition. The NUVIGIL (armodafinil) label includes a bolded warning for serious or life-threatening rash, including Stevens-Johnson Syndrome, requiring hospitalization and discontinuation of treatment, that has been reported in adults in association with the use of modafinil and armodafinil and in children in association with the use of modafinil, a racemic mixture of S and R modafinil (the latter is armodafinil, the active ingredient in NUVIGIL). NUVIGIL is not approved for use in pediatric patients for any indication. The most common adverse events in controlled clinical trials (five percent or greater) in labeled indications were headache, nausea, dizziness, and insomnia. Full prescribing information for NUVIGIL is available at www.nuvigil.com. About Cephalon, Inc. Cephalon is a global biopharmaceutical company dedicated to discovering, developing and bringing to market medications to improve the quality of life of individuals around the world. Since its inception in 1987, Cephalon has brought first-in-class and best-in-class medicines to patients in several therapeutic areas. Cephalon has the distinction of being one of the world's fastest-growing biopharmaceutical companies, now among the Fortune 1000 and a member of the S&P 500 Index, employing approximately 4,000 people worldwide. The company sells numerous branded and generic products around the world. In total, Cephalon sells more than 150 products in nearly 100 countries. More information on Cephalon and its products is available at www.cephalon.com. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide the Cephalon current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs; development of potential pharmaceutical products; interpretation of clinical results; prospects for regulatory approval; manufacturing development and capabilities; market prospects for its products; and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. Contacts: Media: Candace Steele Flippin 610-727-6231 (office) csteele@cephalon.com Investor Relations: Chip Merritt 610-738-6376 (office) cmerritt@cephalon.com Joseph Marczely 610-883-5894 (office) jmarczely@cephalon.com SOURCE Cephalon, Inc. CONTACT:Media: Candace Steele Flippin, +1-610-727-6231 (office), csteele@cephalon.com, or Investor Relations: Chip Merritt, +1-610-738-6376 (office), cmerritt@cephalon.com, or Joseph Marczely, +1-610-883-5894 (office), jmarczely@cephalon.com URL: http://www.prnewswire.com LOAD-DATE: December 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 PR Newswire Association LLC All Rights Reserved 100 of 998 DOCUMENTS The Sunday Times (Australia) December 26, 2010 Sunday 6 - Early Edition SHORTPASSES SECTION: Pg. 105 LENGTH: 397 words Murphy, Kelly back V8 SUPERCARS: Holden legend Greg Murphy's career is set to continue with former teammate Rick Kelly throwing the Kiwi icon a V8 lifeline. The former Bathurst winner is set to sign with Kelly Brothers Racing in a move that evokes memories of the famous K-Mart racing team. Murphy and Kelly won back-to-back Bathurst titles together in 2003-04. The duo will return to the golden days next year, with the talented veteran joining his former partner in a Pepsi-backed car. Maradona: I'm clean SOCCER: Diego Maradona says he is taking the president of the Argentine Football Association to court, accusing Julio Grondona of spreading false information about his problems with drugs and alcohol. Maradona says he has not had drugs or alcohol for six years. Grondona implied in a television interview this week that Maradona was using again. ``There are reasons for what happens (with Maradona) and everybody knows them,'' Grondona said. Taurasi drug shock BASKETBALL: American star Diana Taurasi tested positive for Modafinil while playing in a professional women's league in Turkey, the country's federation said. Neither her lawyer nor her team, Fenerbahce, would confirm Taurasi tested positive for the stimulant, which has been involved in several major doping cases, including that of US sprinter Kelli White. Modafinil is used to counter excessive sleepiness due to narcolepsy or sleep apnea. Smith all-a-Twitter CRICKET: South African captain Graeme Smith appealed for help on Twitter after discovering his much-loved Test cap had been stolen ahead of the Second Test against India. Smith said his green Proteas cap, which he was given for his first Test in 2002, had gone missing while travelling from Cape Town to Durban for the match beginning today. ``Realise this is a long shot, but had my test cap that I've used since my 1st test for proteas stolen on travel up to durbs,'' Smith tweeted. Leonardo's big leap SOCCER: Leonardo has crossed the great San Siro divide, with the former AC Milan coach being named as the successor to Rafael Benitez as boss of Inter Milan. The appointment makes him the first person to have coached both Milan giants. Long on personality, short on managerial experience, Leonardo Nascimento de Araujo was appointed AC Milan manager in May 2009, succeeding Chelsea-bound Carlo Ancelotti when still lacking the required managerial badges. LOAD-DATE: December 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: SDT Copyright 2010 Nationwide News Pty Limited All Rights Reserved 101 of 998 DOCUMENTS Buffalo News (New York) December 25, 2010 Saturday FINAL EDITION Around & About / News and notes SECTION: SPORTS; Pg. C3 LENGTH: 535 words Heat, Lakers ready to play Kobe Bryant and Lakers coach Phil Jackson haven't really checked out the Miami Heat much this season. They've caught late-night highlights and maybe logged a few minutes with a game from the opposite coast, but not a whole lot more. It's finally time for the two-time champions to get an up-close look at their most intriguing challengers. When LeBron James, Chris Bosh and -- maybe -- Dwyane Wade take on the Lakers in the NBA's Christmas showcase today (5 p.m., Chs. 7, 11), most players in both uniforms hesitate to pile any extra significance onto a television-manufactured event. Most minimize every aspect of it, saying it's no more than a holiday amusement for fans seeking a break from present-opening and eggnog-drinking. "I don't think it's a measuring stick for us," James said. "It's just another game." Yet competitiveness usually trumps Christmas for elite NBA players. Just ask Bryant -- or don't, since he tellingly hasn't spoken to the media since getting ejected from the Lakers' last game. "The personalities that are going to be matching up in this game, I don't know if it can get any bigger," said Derek Fisher, the Lakers point guard. The contest is one of five on the NBA schedule for today; all will be televised. ----- Taurasi fails test Diana Taurasi is facing one of the most difficult challenges to her stellar basketball career. The WNBA standout and former UConn star tested positive for a mild stimulant while playing in a pro league in Turkey, her lawyer told The Associated Press on Thursday night. Howard Jacobs said Taurasi's "A" sample came back positive from a lab in Turkey last week. He said the substance "was not a steroid or recreational drug," and that Taurasi has asked that her "B" sample be tested. The Turkish basketball federation said Friday that the substance in Taurasi's positive test was modafinil. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift work sleep disorder or sleep apnea, according to the website for prescription drug Provigil, which contains the substance. Neither Jacobs nor Taurasi's team, Fenerbahce, would confirm it was modafinil, which has been involved in several major doping cases. ----- Fay will step down David Fay is retiring from the U.S. Golf Association, his two decades as executive director marked by a steady push for golf's return to the Olympics and for the U.S. Open to be held on golf courses that anyone could play at a reasonable price. Fay's announcement Friday was somewhat of a surprise, although he turned 60 two months ago and said it was an important milestone for cancer survivors. He joined the USGA in 1978 and became its sixth executive director in 1989, serving under 12 presidents. Mike Butz, the deputy executive director since 1995, will take over Jan. 1 until a national search to find Fay's replacement. "Things are in good order," Fay said in a statement. "Our senior staff leaders, each of whom I have put into place, are highly talented and motivated. And looking ahead, there are a number of multiyear projects on the drawing board ... which makes this, for me, a good time to move on. Leave on a high note, as Seinfeld would say." From News and wire service reports. LOAD-DATE: December 27, 2010 LANGUAGE: ENGLISH DOCUMENT-TYPE: Briefs PUBLICATION-TYPE: Newspaper Copyright 2010 The Buffalo News All Rights Reserved 102 of 998 DOCUMENTS The Houston Chronicle December 25, 2010 Saturday 3 STAR EDITION Taurasi's woes compound Positive test could jeopardize Olympic status BYLINE: CHRONICLE NEWS SERVICES SECTION: SPORTS; Pg. 2 LENGTH: 436 words NEW YORK - WNBA standout and former Con- necticut star Diana Taurasi tested positive for modafinil while playing in a professional women's league in Turkey, the country's basketball federation said Friday. Neither her lawyer nor Fenerbahce, her team, would confirm that Taurasi tested positive for the stimulant, which has been involved in several major doping cases, including that of U.S. sprinter Kelli White. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to the website for the prescription drug Provigil, which contains the substance. The Turkish Basketball Federation statement cited a report from the lab at Hacettepe University and said: "... the urine sample taken from Diana Taurasi as a part of the regular process, after a game between Istanbul University and Fenerbahce ... tested positive for modafinil, one of the illegal substances on WADA's banned stimulants list, according to preliminary test results." WADA is the World Anti-Doping Agency. "We're not going to confirm what the drug is," Howard Jacobs, Taurasi's lawyer, told the Associated Press. "We'll revisit it after the 'B' sample returns. They shouldn't be speaking about it at all." Jacobs said Taurasi's "A" sample came back positive last week and that the substance "was not a steroid or recreational drug." Taurasi, 28, has been provisionally suspended pending the testing of her "B" sample, early next month. If the "B' sample comes back positive, it could put her 2012 Olympics status with the U.S. national basketball team in jeopardy. She has helped the team win gold medals at the past two Olympics and was the leading scorer at the women's world championships, which the Americans won in early October. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next Games. She has missed three games with Fenerbahce. The team's website said she and another player were asked to submit to a test Nov. 13, after the game against Istanbul. It said they were selected as a result of a draw. The other player tested negative. Taurasi's test came to light two days after the top-ranked Huskies won their 89th straight game, surpassing the UCLA men's winning streak from 1971-74. Taurasi helped lead UConn to three straight national titles as well as 70 consecutive victories from 2001-03. She was the AP Player of the Year in 2003. Taurasi is one of many WNBA stars who play overseas in the winter because of higher salaries. The best players can make up to 10 times their WNBA salaries, which top out at about $100,000. LOAD-DATE: December 27, 2010 LANGUAGE: ENGLISH GRAPHIC: TAURASI PUBLICATION-TYPE: Newspaper Copyright 2010 The Houston Chronicle Publishing Company All Rights Reserved 103 of 998 DOCUMENTS Lewiston Morning Tribune (Idaho) December 25, 2010 Saturday Officials say substance in Taurasi case is modafinil :Turkish officials claim U.S. star tested positive for stimulant typically used to treat sleep disorders BYLINE: DOUG FEINBERG LENGTH: 735 words NEW YORK - WNBA standout and former UConn star Diana Taurasi tested positive for modafinil while playing in a professional women's league in Turkey, the country's basketball federation said Friday. Neither her lawyer nor her team, Fenerbahce, would confirm that Taurasi tested positive for the stimulant, which has been involved in several major doping cases, including that of U.S. sprinter Kelli White. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to the website for the prescription drug Provigil, which contains the substance. The Turkish Basketball Federation statement cited a report from the lab at Hacettepe University and said: "... the urine sample taken from Diana Taurasi as a part of the regular process, after a game between Istanbul University and Fenerbahce ... tested positive for modafinil, one of the illegal substances on WADA's banned stimulants list, according to preliminary test results." WADA is the World Anti-Doping Agency. "We're not going to confirm what the drug is," Taurasi's lawyer, Howard Jacobs, told The Associated Press Friday. "We'll revisit it after the "B" sample returns. They shouldn't be speaking about it at all." White won the 100- and 200-meter races at the 2003 world championships in Paris, but both her medals were stripped after she tested positive for the stimulant. Jacobs said Taurasi's "A" sample came back positive last week and that the substance "was not a steroid or recreational drug." Taurasi has been provisionally suspended pending the testing of her "B" sample, sometime early next month. She has already missed three games with Fenerbahce. The team's website said she and another player were asked to submit to a test on Nov. 13, following the game against Istanbul. It said they were selected as a result of a draw. The other player tested negative. Fenerbahce said Taurasi was upset that the doping claims broke before the testing process was finalized. "She is extremely disturbed that her right to confidentiality has been breached and doping claims have been made even before the results of her test are out," the team's website said. If the "B' sample comes back positive, it could put her 2012 Olympics status with the U.S. national basketball team in jeopardy. She has helped the team win gold medals at the past two Olympics and was the leading scorer at the women's world championships, which the Americans won in early October. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next games. "At this point we're aware of the situation and we're monitoring things and letting the process take its course," USA Basketball spokesman Craig Miller said. "Until that happens we can't comment." Taurasi's test came to light two days after the top-ranked Huskies won their 89th straight game, surpassing the UCLA men's winning streak from 1971-74. Taurasi helped lead UConn to three straight national championships as well as 70 consecutive victories from 2001-03. She was the AP Player of the Year in 2003. UConn's Geno Auriemma, who coached Taurasi and will lead the 2012 Olympic team, couldn't be reached for comment by telephone Friday. At the WNBA All-Star game last summer, Taurasi said the grind of playing basketball continuously for seven straight years was beginning to wear on her. At the time, she indicated fatigue could eventually force her to skip either the WNBA or European seasons. Taurasi is one of many WNBA stars who play overseas in the winter because of higher salaries. The best players can make up to 10 times their WNBA salaries, which top out at about $100,000. She led the WNBA in scoring for a league-record fourth straight year, averaging 22.6 points per game. The five-time All-Star and two-time WNBA champion signed a multiyear contract extension with the Phoenix Mercury in August. Taurasi served one day in jail and was suspended by the team for two games in 2009 after pleading guilty to a DUI charge. She played in Russia for four years for powerhouse Spartak before joining the Turkish League this season. That league also features WNBA stars Sylvia Fowles, Penny Taylor and Seimone Augustus. Taurasi is leading the league in scoring this season with 24.6 points a game. --- Associated Press Writers Suzan Fraser in Ankara, Turkey, and Erol Israfil in Istanbul contributed to the report. LOAD-DATE: December 25, 2010 LANGUAGE: ENGLISH GRAPHIC: No Caption: Diana Taurasi drives on Laura Summerton during an exhibition game this year between the U.S. and Australia. PUBLICATION-TYPE: Newspaper Copyright 2010 Tribune Publishing Co. All Rights Reserved 104 of 998 DOCUMENTS Monterey County Herald (California) December 25, 2010 Saturday Taurasi tests positive for stimulant in Turkey BYLINE: The Monterey County Herald SECTION: SPORTS LENGTH: 736 words NEW YORK (AP) WNBA standout and former UConn star Diana Taurasi tested positive for modafinil while playing in a professional women's league in Turkey, the country's basketball federation said Friday. Neither her lawyer nor her team, Fenerbahce, would confirm that Taurasi tested positive for the stimulant, which has been involved in several major doping cases, including that of U.S. sprinter Kelli White. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to the website for the prescription drug Provigil, which contains the substance. The Turkish Basketball Federation statement cited a report from the lab at Hacettepe University and said: "... the urine sample taken from Diana Taurasi as a part of the regular process, after a game between Istanbul University and Fenerbahce ... tested positive for modafinil, one of the illegal substances on WADA's banned stimulants list, according to preliminary test results." WADA is the World Anti-Doping Agency. "We're not going to confirm what the drug is," Taurasi's lawyer, Howard Jacobs, told The Associated Press Friday. "We'll revisit it after the "B" sample returns. They shouldn't be speaking about it at all." White won the 100- and 200-meter races at the 2003 world championships in Paris, but both her medals were stripped after she tested positive for the stimulant. Jacobs said Taurasi's "A" sample came back positive last week and that the substance "was not a steroid or recreational drug." Taurasi has been provisionally suspended pending the testing of her "B" sample, sometime early next month. She has already missed three games with Fenerbahce. The team's website said she and another player were asked to submit to a test on Nov. 13, following the game against Istanbul. It said they were selected as a result of a draw. The other player tested negative. Fenerbahce said Taurasi was upset that the doping claims broke before the testing process was finalized. "She is extremely disturbed that her right to confidentiality has been breached and doping claims have been made even before the results of her test are out," the team's website said. If the "B' sample comes back positive, it could put her 2012 Olympics status with the U.S. national basketball team in jeopardy. She has helped the team win gold medals at the past two Olympics and was the leading scorer at the women's world championships, which the Americans won in early October. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next games. "At this point we're aware of the situation and we're monitoring things and letting the process take its course," USA Basketball spokesman Craig Miller said. "Until that happens we can't comment." Taurasi's test came to light two days after the top-ranked Huskies won their 89th straight game, surpassing the UCLA men's winning streak from 1971-74. Taurasi helped lead UConn to three straight national championships as well as 70 consecutive victories from 2001-03. She was the AP Player of the Year in 2003. UConn's Geno Auriemma, who coached Taurasi and will lead the 2012 Olympic team, couldn't be reached for comment by telephone Friday. At the WNBA All-Star game last summer, Taurasi said the grind of playing basketball continuously for seven straight years was beginning to wear on her. At the time, she indicated fatigue could eventually force her to skip either the WNBA or European seasons. Taurasi is one of many WNBA stars who play overseas in the winter because of higher salaries. The best players can make up to 10 times their WNBA salaries, which top out at about $100,000. She led the WNBA in scoring for a league-record fourth straight year, averaging 22.6 points per game. The five-time All-Star and two-time WNBA champion signed a multiyear contract extension with the Phoenix Mercury in August. Taurasi served one day in jail and was suspended by the team for two games in 2009 after pleading guilty to a DUI charge. She played in Russia for four years for powerhouse Spartak before joining the Turkish League this season. That league also features WNBA stars Sylvia Fowles, Penny Taylor and Seimone Augustus. Taurasi is leading the league in scoring this season with 24.6 points a game. Associated Press Writers Suzan Fraser in Ankara, Turkey, and Erol Israfil in Istanbul contributed to the report. LOAD-DATE: December 25, 2010 LANGUAGE: ENGLISH GRAPHIC: PUBLICATION-TYPE: Newspaper Copyright 2010 The Monterey County Herald All Rights Reserved 105 of 998 DOCUMENTS The New York Times December 25, 2010 Saturday Late Edition - Final Positive Test Could Mean Olympic Ban For Taurasi BYLINE: By JERE LONGMAN SECTION: Section B; Column 0; Sports Desk; Pg. 7 LENGTH: 958 words The Turkish basketball federation said Friday that the star player Diana Taurasi had tested positive for a stimulant that was identified as modafinil, a drug that enhances wakefulness and vigilance and is designed to treat narcolepsy, sleep apnea and sleep disorders related to shift work. Modafinil is also used off-label to combat jet lag and attention deficit disorder and recreationally to enhance alertness. The stimulant does not cause the anxiety and jitteriness associated with amphetamines. Athletes who use modafinil as a banned performance-enhancing substance, however, face suspension from competition for up to two years, according to the rules of the World Anti-Doping Agency. That could keep Taurasi from playing in the 2012 Olympics. Taurasi's case could still be declared a false positive and dismissed. But even if it were determined that Taurasi had taken the stimulant inadvertently, and a two-year ban were reduced, she could still face the loss of her Olympic eligibility. The International Olympic Committee instituted a controversial rule in 2008 that prohibits athletes from competing in the next Winter or Summer Games if they have served a doping suspension of six months or longer. Taurasi has been provisionally suspended by her Turkish club team, Fenerbahce of Istanbul, until the drug testing is completed, Howard L. Jacobs, Taurasi's California-based lawyer, said Friday. So far, she has missed two or three games, Jacobs said. Her doping case was first reported by The Associated Press. ''She doesn't believe that she's ever taken anything that's banned; the most logical explanation at this point is that the test is simply wrong,'' Jacobs said in a telephone interview. Taurasi, 28, a six-foot guard and forward, starred at the University of Connecticut and has won two league titles with the Phoenix Mercury of the W.N.B.A. She was named the league's most valuable player in 2009 and has led the league in scoring four times. She and Australia's Lauren Jackson are regarded by many as the two best women's players in the world. Taurasi played on the United States teams that won gold at the 2004 and 2008 Olympics, and in October, she helped lead the Americans to a gold medal at the world championships. She is considered vital to the Americans' chances of winning another gold at the 2012 London Olympics, where the favored Americans will be coached by Geno Auriemma, Taurasi's college coach. The news about Taurasi emerged only days after UConn set the major-college basketball record with its 89th consecutive victory. And although her doping case is unresolved, it was the second recent public embarrassment for Taurasi, who spent a day in jail in 2009 and was briefly suspended by the Mercury after pleading guilty to a charge of driving under the influence. A routine drug test was administered to Taurasi after a Fenerbahce game in early November, Jacobs said. Each urine sample is divided into two parts, an A sample and B sample. The A sample has tested positive, but the B sample has yet to be tested, Jacobs said. If an athlete's B sample comes back negative, the A sample is considered to have been a false positive, and the case is dismissed. Jacobs said that he hoped the B sample would be tested ''as soon as possible,'' perhaps the first week in January, but that the holidays ''were complicating things.'' Taurasi was upset that news about her test leaked before the testing was completed, Jacobs said. And because the entire case would be thrown out with a negative B sample, he said it was premature to talk about any possible sanctions like Olympic ineligibility. ''That's jumping three or four steps down the road,'' Jacobs said. ''Right now, we're focusing on getting the B sample tested. If it's negative, all this goes away.'' If the B sample does test positive, Jacobs will probably argue that Taurasi took the stimulant without her knowledge, perhaps in a mislabeled product like a supplement. ''When you're in a foreign country where you don't speak the language, it opens up possibilities,'' Jacobs said. It is unclear what sanctions would be applied by the Turkish basketball federation if the B sample returned positive, Jacobs said. Under the rules of the World Anti-Doping Agency, modafinil belongs to a class of drugs that calls for a two-year suspension from competition. It is also uncertain how Taurasi's W.N.B.A. eligibility would be affected. There are relatively few cases of known use of modafinil by athletes, especially not in association with other substances. Perhaps the most notorious case involved the American sprinter Kelli White, who tested positive for the stimulant while winning the 100 and 200 meters at the 2003 world track and field championships in Paris. White was later stripped of her medals upon admitting that modafinil was used with a cocktail of other prohibited substances as part of the Bay Area Laboratory Co-operative scandal. Other sports stars like Barry Bonds and Marion Jones were eventually linked to Balco. Dr. Gary Wadler of New York, chairman of the antidoping agency's prohibited list committee, said the illicit use by athletes of modafinil to gain an edge was ''another example of the advances of modern medicine being bastardized for non-legitimate purposes.'' ''It has stimulant effects akin to amphetamines,'' Wadler said. If Taurasi's B sample does test positive, and any suspension is reduced to six months to two years, her Olympic eligibility could still remain unsettled until shortly before the London Olympics. As of now, the International Olympic Committee does not permit a waiver request until an athlete is named to the team, Jacobs said. ''Somebody before London is going to challenge that rule,'' Jacobs said. ''It's a virtual certainty.'' URL: http://www.nytimes.com LOAD-DATE: December 25, 2010 LANGUAGE: ENGLISH GRAPHIC: PHOTO: The former UConn star Diana Taurasi, right, helped lead the United States to a gold medal at the world championships in October. (PHOTOGRAPH BY JAROSLAV OZANA/CTK, VIA ASSOCIATED PRESS) PUBLICATION-TYPE: Newspaper Copyright 2010 The New York Times Company 106 of 998 DOCUMENTS St. Louis Post-Dispatch (Missouri) December 25, 2010 Saturday THIRD EDITION Sports Digest SECTION: SPORTS; Pg. B2 LENGTH: 510 words DATELINE: 0 Taurasi's Olympic status in limbo after drug test Basketball player Diana Taurasi's positive test for a banned stimulant while playing professionally in Turkey could threaten her eligibility to play for the United States in the 2012 London Olympics. The Turkish basketball federation said Friday that she tested positive for a stimulant that was identified as modafinil, a drug that enhances wakefulness and vigilance and is designed to treat narcolepsy, sleep apnea and sleep disorders related to shift work. It also is used off-label to combat jet lag and attention deficit disorder, and it is used recreationally to enhance alertness. Athletes who use modafinil as a banned performance-enhancing substance, however, face suspension from competition for up to 2 years, according to the rules of the World Anti-Doping Agency. Taurasi's case still could be declared a false positive and dismissed. But even if it were determined that Taurasi took the stimulant inadvertently, and a 2-year ban was reduced, she still could face the loss of Olympic eligibility. She has been provisionally suspended by her Turkish club team, Fenerbahce of Istanbul, until the drug-testing procedure is completed. "She doesn't believe that she's ever taken anything that's banned; the most logical explanation at this point is that the test is simply wrong," said Howard L. Jacobs, Taurasi's lawyer. Taurasi, 28, a 6-foot guard, starred at the University of Connecticut and has won 2 WNBA titles while with Phoenix. She was named the WNBA's most valuable player in 2009 and has led the league in scoring 4 times. Taurasi played on the U.S. teams that won gold at the 2004 and 2008 Olympics. (New York Times) Fay to leave USGA - David Fay, 60, has decided to retire from the U.S. Golf Association after 21 years as the executive director, leaving a legacy that includes his successful push to stage the U.S. Open on public golf courses. Mike Butz, the deputy executive director, will replace Fay on an interim basis. Fay was behind bringing the U.S. Open to Bethpage Black in New York in 2002. It was such a big success that it returned in 2009, along with going to another public course at Torrey Pines in 2008. In coming years the U.S. Open will go to Chambers Bay outside Seattle and Erin Hills in Wisconsin, also public courses. (AP) Elsewhere - Diego Maradona says he is taking the president of Argentina's soccer federation to court, accusing Julio Grondona of spreading false information about his problems with drugs and alcohol. Maradona said he has not had drugs or alcohol for 6 years. Grondona implied in a TV interview this week that Maradona was using again. Maradona has been involved in a spat with Grondona since July, when Maradona's contract as national coach was not renewed. ... Former Clemson baseball coach Bill Wilhelm, who led the Tigers to more than 1,100 wins and 6 College World Series berths, died in Columbia, S.C., at age 81. A cause of death was not given. He coached the Tigers from 1958-1993 and never had a losing year. He had a record of 1,161-536-10. (AP) LOAD-DATE: December 27, 2010 LANGUAGE: ENGLISH DOCUMENT-TYPE: BRIEF PUBLICATION-TYPE: Newspaper Copyright 2010 St. Louis Post-Dispatch, Inc. All Rights Reserved 107 of 998 DOCUMENTS Tulsa World (Oklahoma) December 25, 2010 Saturday Final Edition Sports FYI BYLINE: Staff and Wire Reports SECTION: Sports; Pg. B2 LENGTH: 477 words Basketball Taurasi tests positive for modafinil: WNBA standout and former UConn star Diana Taurasi tested positive for modafinil while playing in a professional women's league in Turkey, the country's basketball federation said Friday. Neither her lawyer nor her team, Fenerbahce, would confirm that Taurasi tested positive for the stimulant. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to the website for the prescription drug Provigil, which contains the substance. The Turkish Basketball Federation statement cited a report from the lab at Hacettepe University and said: "... the urine sample taken from Diana Taurasi as a part of the regular process, after a game between Istanbul University and Fenerbahce ... tested positive for modafinil, one of the illegal substances on WADA's banned stimulants list, according to preliminary test results." WADA is the World Anti-Doping Agency. "We're not going to confirm what the drug is," Taurasi's lawyer, Howard Jacobs said. "We'll revisit it after the "B" sample returns. They shouldn't be speaking about it at all." The team's website said: "(Taurasi) is extremely disturbed that her right to confidentiality has been breached and doping claims have been made even before the results of her test are out." If the "B' sample comes back positive, it could put her 2012 Olympics status in jeopardy. Players suspended for fighting in stands: The two Mississippi State players caught on camera fighting in the stands of the Diamond Head Classic have been suspended indefinitely and sent home from Hawaii. Renardo Sidney and Elgin Bailey, who are roommates, were involved in a fistfight after the Bulldogs' game Thursday night. The altercation lasted for several minutes before being broken up by teammates and coaches. MSU athletic director Scott Stricklin sent out a tweet on Friday saying "The actions that took place in Hawaii were embarrassing to all of us who love Mississippi State. This behavior will not be tolerated." Coach Rick Stansbury expressed his disappointment in a press release: "In my 13 years as a head coach, we've never had anything like this happen before," he said. It's the latest in a string of issues for Sidney. The NCAA ruled last March he had to repay $11,800 in improper benefits and sit out the remainder of the 2010 season and nine more games this season. Baseball Padres sign Hawpe: The San Diego Padres have agreed to terms of a one-year contract with Brad Hawpe to play first base, two people with knowledge said on Friday. Hawpe will replace three-time All-Star Adrian Gonzalez, who was traded to the Boston Red Sox earlier this month. Hawpe has mostly been an outfielder in seven big league seasons, with a handful of starts at first base. He was released by Colorado in August and signed by Tampa Bay. LOAD-DATE: December 26, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2010 The Tulsa World 108 of 998 DOCUMENTS The Washington Post December 25, 2010 Saturday Suburban Edition Taurasi tested positive for modafinil SECTION: SPORTS; Pg. D02 LENGTH: 757 words WNBA standout and former Connecticut star Diana Taurasi tested positive for modafinil while playing in a professional women's league in Turkey, the country's basketball federation said Friday. Neither her lawyer nor her team, Fenerbahce, would confirm that Taurasi tested positive for the stimulant, which has been involved in several major doping cases, including that of U.S. sprinter Kelli White. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to the Web site for the prescription drug Provigil, which contains the substance. The Turkish Basketball Federation statement cited a report from the lab at Hacettepe University and said: "the urine sample taken from Diana Taurasi as a part of the regular process, after a game between Istanbul University and Fenerbahce . . . tested positive for modafinil, one of the illegal substances on WADA's banned stimulants list, according to preliminary test results." WADA is the World Anti-Doping Agency. "We're not going to confirm what the drug is," Taurasi's attorney, Howard Jacobs, told the Associated Press. "We'll revisit it after the 'B' sample returns. They shouldn't be speaking about it at all." Right-handed pitcher Ricky Nolasco has signed a three-year, $26.5 million contract with the Florida Marlins. Nolasco is expected to earn $6 million in 2011, $9 million in 2012 and $11.5 in 2013. He made $3.8 million last season, when he went 14-9 with a 4.51 ERA. The 28-year-old missed the final month after undergoing arthroscopic right knee surgery. . . . The San Diego Padres have agreed to terms of a one-year contract with Brad Hawpe to play first base, two people with knowledge of the deal told the Associated Press. They spoke on condition of anonymity because the deal is pending Hawpe passing a physical exam. Hawpe will replace three-time all-star Adrian Gonzalez, who was traded to the Boston Red Sox earlier this month. . . . The Pittsburgh Pirates claimed minor league left-hander Aaron Thompson off waivers and designated left-hander Wil Ledezma for assignment. Thompson was left unprotected by the Washington Nationals, who acquired him from Florida for first baseman Nick Johnson in 2009. Thompson, who made 26 starts at Class AA Harrisburg last season, was a first-round pick in 2005. Buffalo Sabres leading scorer Derek Roy will miss the rest of the season after tearing his left quadriceps tendon. General Manager Darcy Regier announced the center is expected to miss between four to six months, and will have surgery to repair the injury in the next couple of days. Roy was hurt Thursday in the first period of a 4-3 loss to Florida when he was driven into the boards by Dmitry Kulikov. . . . David Fay is retiring from the U.S. Golf Association, his two decades as executive director marked by a steady push for golf's return to the Olympics and for the U.S. Open to be held on golf courses that anyone could play. Fay's announcement was somewhat of a surprise, although he turned 60 two months ago and said it was an important milestone for cancer survivors. He joined the USGA in 1978 and became its sixth executive director in 1989. Mike Butz, the deputy executive director since 1995, will take over Jan. 1 until a national search to find Fay's replacement. . . . The two Mississippi State players caught on camera fighting in the stands of the Diamond Head Classic in Honolulu have been suspended indefinitely and sent home from Hawaii. Renardo Sidney and Elgin Bailey, who are roommates, were involved in a fistfight after the Bulldogs' game Thursday night. The altercation lasted for several minutes before being broken up by teammates and coaches. "I'm very sorry for this incident," Sidney said in a statement released by the university. "I had no intention of this ever happening. I apologize for embarrassing my family, all the Mississippi State fans, my teammates and coaches. I will learn from this and move on." MSU Athletic Director Scott Stricklin sent out a tweet, saying "The actions that took place in Hawaii were embarrassing to all of us who love Mississippi State. This behavior will not be tolerated." In a release from the university, Coach Rick Stansbury expressed his disappointment. "In my 13 years as a head coach, we've never had anything like this happen before," he said. "I am very disappointed in the actions of Elgin Bailey and Renardo Sidney and in no way does it reflect the overall picture of our program. It is not how we want our men's basketball team to be viewed nationally." LOAD-DATE: December 25, 2010 LANGUAGE: ENGLISH DISTRIBUTION: Every Zone PUBLICATION-TYPE: Newspaper Copyright 2010 The Washington Post All Rights Reserved 109 of 998 DOCUMENTS The Associated Press December 24, 2010 Friday 10:18 PM GMT Federation: Taurasi tests positive for modafinil BYLINE: By DOUG FEINBERG, AP Basketball Writer SECTION: SPORTS NEWS LENGTH: 733 words DATELINE: NEW YORK WNBA standout and former UConn star Diana Taurasi tested positive for modafinil while playing in a professional women's league in Turkey, the country's basketball federation said Friday. Neither her lawyer nor her team, Fenerbahce, would confirm that Taurasi tested positive for the stimulant, which has been involved in several major doping cases, including that of U.S. sprinter Kelli White. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to the website for the prescription drug Provigil, which contains the substance. The Turkish Basketball Federation statement cited a report from the lab at Hacettepe University and said: "... the urine sample taken from Diana Taurasi as a part of the regular process, after a game between Istanbul University and Fenerbahce ... tested positive for modafinil, one of the illegal substances on WADA's banned stimulants list, according to preliminary test results." WADA is the World Anti-Doping Agency. "We're not going to confirm what the drug is," Taurasi's lawyer, Howard Jacobs, told The Associated Press Friday. "We'll revisit it after the "B" sample returns. They shouldn't be speaking about it at all." White won the 100- and 200-meter races at the 2003 world championships in Paris, but both her medals were stripped after she tested positive for the stimulant. Jacobs said Taurasi's "A" sample came back positive last week and that the substance "was not a steroid or recreational drug." Taurasi has been provisionally suspended pending the testing of her "B" sample, sometime early next month. She has already missed three games with Fenerbahce. The team's website said she and another player were asked to submit to a test on Nov. 13, following the game against Istanbul. It said they were selected as a result of a draw. The other player tested negative. Fenerbahce said Taurasi was upset that the doping claims broke before the testing process was finalized. "She is extremely disturbed that her right to confidentiality has been breached and doping claims have been made even before the results of her test are out," the team's website said. If the "B' sample comes back positive, it could put her 2012 Olympics status with the U.S. national basketball team in jeopardy. She has helped the team win gold medals at the past two Olympics and was the leading scorer at the women's world championships, which the Americans won in early October. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next games. "At this point we're aware of the situation and we're monitoring things and letting the process take its course," USA Basketball spokesman Craig Miller said. "Until that happens we can't comment." Taurasi's test came to light two days after the top-ranked Huskies won their 89th straight game, surpassing the UCLA men's winning streak from 1971-74. Taurasi helped lead UConn to three straight national championships as well as 70 consecutive victories from 2001-03. She was the AP Player of the Year in 2003. UConn's Geno Auriemma, who coached Taurasi and will lead the 2012 Olympic team, couldn't be reached for comment by telephone Friday. At the WNBA All-Star game last summer, Taurasi said the grind of playing basketball continuously for seven straight years was beginning to wear on her. At the time, she indicated fatigue could eventually force her to skip either the WNBA or European seasons. Taurasi is one of many WNBA stars who play overseas in the winter because of higher salaries. The best players can make up to 10 times their WNBA salaries, which top out at about $100,000. She led the WNBA in scoring for a league-record fourth straight year, averaging 22.6 points per game. The five-time All-Star and two-time WNBA champion signed a multiyear contract extension with the Phoenix Mercury in August. Taurasi served one day in jail and was suspended by the team for two games in 2009 after pleading guilty to a DUI charge. She played in Russia for four years for powerhouse Spartak before joining the Turkish League this season. That league also features WNBA stars Sylvia Fowles, Penny Taylor and Seimone Augustus. Taurasi is leading the league in scoring this season with 24.6 points a game. Associated Press Writers Suzan Fraser in Ankara, Turkey, and Erol Israfil in Istanbul contributed to the report. LOAD-DATE: December 25, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 Associated Press All Rights Reserved 110 of 998 DOCUMENTS Breaking News from globeandmail.com December 24, 2010 Friday 2:37 PM GMT WNBA's Taurasi tests positive for banned substance; Women s league All-Star fails drug test while playing in Turkish pro league BYLINE: DOUG FEINBERG New York AP SECTION: GLOBESPORTS LENGTH: 736 words ABSTRACT Women s league All-Star fails drug test while playing in Turkish pro league FULL TEXT Diana Taurasi is facing one of the most difficult challenges to her stellar basketball career. The WNBA standout and former UConn star tested positive for a mild stimulant while playing in a pro league in Turkey, her lawyer told The Associated Press on Thursday night. Howard Jacobs said Taurasi's "A" sample came back positive from a lab in Turkey last week. He said the substance "was not a steroid or recreational drug," and that Taurasi has asked that her "B" sample be tested. The Turkish basketball federation said Friday that the substance in Taurasi's positive test was modafinil. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift work sleep disorder or sleep apnea, according to the website for prescription drug Provigil, which contains the substance. Neither Jacobs nor Taurasi's team, Fenerbahce, would confirm it was modafinil, which has been involved in several major doping cases, including that of U.S. sprinter Kelli White. White won the 100- and 200-meter races at the 2003 world championships in Paris, but both her medals were stripped after she tested positive for the stimulant. Taurasi has been provisionally suspended pending the testing of her "B" sample in the first week of January. She has already missed three games with Fenerbahce. In a statement posted on its website, the team said Taurasi was upset that the doping claims broke before the testing process was finalized. "She is extremely disturbed that her right to confidentially has been breached and doping claims have been made even before the results of her test are out," the team said. Taurasi's positive test came to light two days after the top-ranked Huskies won their 89th straight game, surpassing the UCLA men's winning streak from 1971-74. Taurasi helped lead UConn to three straight national championships as well as 70 consecutive victories from 2001-03. She was the AP Player of the Year in 2003. "We're taking it one step at a time," Jacobs said. "I'd rather not say what it is at this stage, they've only tested the 'A' sample. Somehow it leaked over in Turkey. We're waiting for the 'B' sample to be tested. We've had some difficulty with getting a date so far, mostly because of the holidays. We're hoping to get it as soon as we can." UConn coach Geno Auriemma could not be reached for comment by telephone. "While she is fully cooperating with authorities, there are serious doubts about the accuracy of the test results," Jacobs said in a statement to the AP. "We are confident that Diana will be fully vindicated once all the evidence is reviewed. She regrets that someone has violated the confidentiality rules of this process, and will make no further statement at this time." WNBA spokesman Ron Howard said the league had no comment. "In the 10 years of competition at the collegiate, professional and Olympic level," said Jacobs. "Diana Taurasi has never taken, been suspected of using, or tested positive for any performance enhancing substance." Jacobs said he didn't know what the length of the suspension would be, nor was he familiar with the details of the Turkish league's anti-doping code. He also said it was too early to know how this might affect Taurasi's eligibility for the London 2012 Olympics. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next games. Taurasi, who has won two Olympic gold medals, helped guide the U.S. national team to the world championship in early October. She led the WNBA in scoring for a league-record fourth straight year, averaging 22.6 points per game. The five-time All-Star and two-time WNBA champion signed a multiyear contract extension with the Phoenix Mercury in August. Reached at the Miami Heat-Phoenix Suns game, Rick Weltz, president of the Suns and Mercury, said the team had no comment. Taurasi served one day in jail and was suspended by the team for two games in 2009 after pleading guilty to a DUI charge. She played in Russia for four years for powerhouse Spartak before joining the Turkish League this season. That league also features WNBA stars Sylvia Fowles, Penny Taylor and Seimone Augustus. Taurasi is leading the league this season with 24.6 points a game. Associated Press Writers Suzan Fraser in Ankara, Turkey, and Erol Israfil in Istanbul contributed to the report. LOAD-DATE: December 24, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Web Publication Copyright 2010 The Globe and Mail, a division of CTVglobemedia Publishing Inc. All Rights Reserved 111 of 998 DOCUMENTS St. Paul Pioneer Press (Minnesota) December 24, 2010 Friday Quick Hits / Taurasi may face Olympic ban BYLINE: From news services SECTION: SPORTS LENGTH: 510 words Diana Taurasi's positive test for a banned stimulant while playing professionally in Turkey could threaten her eligibility to play for the United States in the 2012 London Olympics. The Turkish basketball federation said Friday that Taurasi had tested positive for a stimulant identified as modafinil, a drug designed to treat narcolepsy, sleep apnea and sleep. It also is used off-label to combat jet lag and to enhance alertness. Athletes who use modafinil as a banned performance-enhancing substance face suspension from competition for up to two years, according to World Anti-Doping Agency rules. Even if it were determined that Taurasi took the stimulant inadvertently, and a two-year ban were reduced, she still could face the loss of Olympic eligibility.Colleges / NCAA weighs tougher penalties The NCAA has been busy this year investigating schools from Auburn to Georgia to North Carolina while trying to crack down on problems tied to sports agents. Most of the investigations are open cases with unknown consequences for the schools. But recommendations made by an NCAA panel two years ago for stricter punishments for schools tabbed as serious rules violators remain under consideration and could mark the first substantive revision to the NCAA's penalty system since 1985. "It's definitely not a dead issue," NCAA spokeswoman Stacey Osburn said. The panel's report is confidential. But interviews with the group's former chairman and others knowledgeable about its contents indicate the recommendations include: · A requirement that all schools found guilty of major violations lose scholarships. Current NCAA rules list that sanction as a "presumptive" penalty. · TV bans, a penalty not applied to Division I violators since 1996. · Clarified penalties for repeat offenders. The "death penalty" -- a program-crippling blow that keeps a team off the field while banning recruiting and scholarship awards -- has been on the books for 25 years but applied only once, to Southern Methodist for a pay-for-play football scandal in 1987. Repeat violators are defined as schools that run afoul of the NCAA more than once every five years. Miscellaneous / Marlins' Nolasco signs 3-year deal Right-handed pitcher Ricky Nolasco has signed a three-year, $26.5 million contract with the Florida Marlins. Nolasco, 28, made $3.8 million last season, when he went 14-9 with a 4.51 earned-run average. · The San Diego Padres agreed to terms of a one-year contract with Brad Hawpe to play first base, two people with knowledge of the deal told the Associated Press. Hawpe will replace three-time all-star Adrian Gonzalez, who was traded to the Boston Red Sox this month. · Former Clemson baseball coach Bill Wilhelm, who led the Tigers to more than 1,100 wins and six College World Series appearances, died in a Clemson, S.C., hospital. He was 81. · David Fay, 60, is retiring from the U.S. Golf Association, his two decades as executive director marked by a steady push for golf's return to the Olympics and for the U.S. Open to be held on golf courses that anyone could play at a reasonable price. LOAD-DATE: December 25, 2010 LANGUAGE: ENGLISH GRAPHIC: PUBLICATION-TYPE: Newspaper Copyright 2010 St. Paul Pioneer Press All Rights Reserved 112 of 998 DOCUMENTS Associated Press Worldstream December 24, 2010 Friday 2:31 PM GMT Federation: Taurasi tested positive for modafinil BYLINE: By SUZAN FRASER, Associated Press SECTION: SPORTS NEWS LENGTH: 608 words DATELINE: ANKARA Turkey Basketball great Diana Taurasi tested positive for the stimulant modafinil and was provisionally suspended pending the result of her "B" sample test in January, Turkey's basketball federation and team officials said Friday. Taurasi was tested last month, following a Turkish league game between her team Fenerbahce and Istanbul University. A lab in the capital Ankara detected the stimulant in her "A" sample, the federation said in a statement. "A final decision (on her situation) will be taken as soon as the process leading to the opening of the 'B' sample is complete," the federation said. Taurasi's lawyer, Howard Jacobs, told The Associated Press Thursday that the player, who has so far missed three games with Fenerbahce, has stayed away from performance enhancing substances throughout her 10 years of competition at college, professional and Olympic level. "Diana Taurasi has never taken, been suspected of using, or tested positive for any performance enhancing substance," he said. Fenerbahce said in a statement posted on its website that Taurasi was upset that the doping claims broke before the testing process was finalized. Taurasi and teammate Anna Vajda were routinely tested following the Nov. 13 league game, the club said. Vajda tested negative for any banned substances, it said. Taurasi requested the "B" sample test, with the result to be disclosed on Jan. 2 or Jan. 4 in the presence of lawyers, Fenerbahce said. "She is extremely disturbed that her right to confidentially has been breached and doping claims have been made even before the results of her test are out," Fenerbahce said. Neither Jacobs nor Fenerbahce confirmed that Taurasi tested positive for modafinil, a banned stimulant involved in several major doping cases, including that of Kelli White. White won the 100 and 200-meter races at the 2003 world championships in Paris, but both her medals were stripped after she tested positive for modafinil. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift work sleep disorder or sleep apnea, according to the website for prescription drug Provigil, which contains the substance. Jacobs told the AP in a statement that while the player was fully cooperating with authorities, "there are serious doubts about the accuracy of the test results." "We are confident that Diana will be fully vindicated once all the evidence is reviewed." Jacobs said it was too early to tell how this might affect Taurasi's eligibility for the 2012 Olympics in London. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the subsequent games. Taurasi helped lead the University of Connecticut to three straight national championships as well as 70 consecutive victories from 2001-03. She was the AP Player of the Year in 2003. Taurasi, who has won two Olympic gold medals, helped guide the U.S. national team to the world championship in early October. She led the WNBA in scoring for a league-record four straight years, averaging 22.6 points per game. The five-time All-Star and two-time WNBA champion signed a multiyear contract extension with the Phoenix Mercury in August. Taurasi served one day in jail and was suspended by the team for two games in 2009 after pleading guilty to a drunk-driving charge. She played in Russia for four years for powerhouse Spartak before joining the Turkish League this season. That league also features WNBA stars Sylvia Fowles, Penny Taylor and Seimone Augustus. Taurasi leads the league in scoring with 24.6 points a game. AP Basketball Writer Doug Feinberg in New York and Erol Israfil in Istanbul contributed to the report. LOAD-DATE: December 25, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 Associated Press All Rights Reserved 113 of 998 DOCUMENTS Associated Press Worldstream December 24, 2010 Friday 10:07 PM GMT Federation: Taurasi tests positive for modafinil BYLINE: By DOUG FEINBERG, AP Basketball Writer SECTION: SPORTS NEWS LENGTH: 728 words DATELINE: NEW YORK Basketball great Diana Taurasi tested positive for modafinil while playing in a professional women's league in Turkey, the country's federation said Friday. Neither her lawyer nor her team, Fenerbahce, would confirm that Taurasi tested positive for the stimulant, which has been involved in several major doping cases, including that of U.S. sprinter Kelli White. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to the website for the prescription drug Provigil, which contains the substance. The Turkish Basketball Federation statement cited a report from the lab at Hacettepe University and said: "... the urine sample taken from Diana Taurasi as a part of the regular process, after a game between Istanbul University and Fenerbahce ... tested positive for modafinil, one of the illegal substances on WADA's banned stimulants list, according to preliminary test results." WADA is the World Anti-Doping Agency. "We're not going to confirm what the drug is," Taurasi's lawyer, Howard Jacobs, told The Associated Press Friday. "We'll revisit it after the "B" sample returns. They shouldn't be speaking about it at all." White won the 100- and 200-meter races at the 2003 world championships in Paris, but both her medals were stripped after she tested positive for the stimulant. Jacobs said Taurasi's "A" sample came back positive last week and that the substance "was not a steroid or recreational drug." Taurasi has been provisionally suspended pending the testing of her "B" sample, sometime early next month. She has already missed three games with Fenerbahce. The team's website said she and another player were asked to submit to a test on Nov. 13, following the game against Istanbul. It said they were selected as a result of a draw. The other player tested negative. Fenerbahce said Taurasi was upset that the doping claims broke before the testing process was finalized. "She is extremely disturbed that her right to confidentiality has been breached and doping claims have been made even before the results of her test are out," the team's website said. If the "B' sample comes back positive, it could put her 2012 Olympics status with the U.S. national basketball team in jeopardy. She has helped the team win gold medals at the past two Olympics and was the leading scorer at the women's world championships, which the Americans won in early October. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next games. "At this point we're aware of the situation and we're monitoring things and letting the process take its course," USA Basketball spokesman Craig Miller said. "Until that happens we can't comment." Taurasi's test came to light two days after the top-ranked Huskies won their 89th straight game, surpassing the UCLA men's winning streak from 1971-74. Taurasi helped lead UConn to three straight national championships as well as 70 consecutive victories from 2001-03. She was the AP Player of the Year in 2003. UConn's Geno Auriemma, who coached Taurasi and will lead the 2012 Olympic team, couldn't be reached for comment by telephone Friday. At the WNBA All-Star game last summer, Taurasi said the grind of playing basketball continuously for seven straight years was beginning to wear on her. At the time, she indicated fatigue could eventually force her to skip either the WNBA or European seasons. Taurasi is one of many WNBA stars who play overseas in the winter because of higher salaries. The best players can make up to 10 times their WNBA salaries, which top out at about $100,000. She led the WNBA in scoring for a league-record fourth straight year, averaging 22.6 points per game. The five-time All-Star and two-time WNBA champion signed a multiyear contract extension with the Phoenix Mercury in August. Taurasi served one day in jail and was suspended by the team for two games in 2009 after pleading guilty to a DUI charge. She played in Russia for four years for powerhouse Spartak before joining the Turkish League this season. That league also features WNBA stars Sylvia Fowles, Penny Taylor and Seimone Augustus. Taurasi is leading the league in scoring this season with 24.6 points a game. Associated Press Writers Suzan Fraser in Ankara, Turkey, and Erol Israfil in Istanbul contributed to the report. LOAD-DATE: December 25, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 Associated Press All Rights Reserved 114 of 998 DOCUMENTS Associated Press Online December 24, 2010 Friday 6:24 PM GMT WNBA's Taurasi tests positive for banned substance BYLINE: By DOUG FEINBERG, AP Basketball Writer SECTION: SPORTS NEWS LENGTH: 721 words DATELINE: NEW YORK Diana Taurasi is facing one of the most difficult challenges to her stellar basketball career. The WNBA standout and former UConn star tested positive for a mild stimulant while playing in a pro league in Turkey, her lawyer told The Associated Press on Thursday night. Howard Jacobs said Taurasi's "A" sample came back positive from a lab in Turkey last week. He said the substance "was not a steroid or recreational drug," and that Taurasi has asked that her "B" sample be tested. The Turkish basketball federation said Friday that the substance in Taurasi's positive test was modafinil. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift work sleep disorder or sleep apnea, according to the website for prescription drug Provigil, which contains the substance. Neither Jacobs nor Taurasi's team, Fenerbahce, would confirm it was modafinil, which has been involved in several major doping cases, including that of U.S. sprinter Kelli White. White won the 100- and 200-meter races at the 2003 world championships in Paris, but both her medals were stripped after she tested positive for the stimulant. Taurasi has been provisionally suspended pending the testing of her "B" sample in the first week of January. She has already missed three games with Fenerbahce. In a statement posted on its website, the team said Taurasi was upset that the doping claims broke before the testing process was finalized. "She is extremely disturbed that her right to confidentially has been breached and doping claims have been made even before the results of her test are out," the team said. Taurasi's positive test came to light two days after the top-ranked Huskies won their 89th straight game, surpassing the UCLA men's winning streak from 1971-74. Taurasi helped lead UConn to three straight national championships as well as 70 consecutive victories from 2001-03. She was the AP Player of the Year in 2003. "We're taking it one step at a time," Jacobs said. "I'd rather not say what it is at this stage, they've only tested the 'A' sample. Somehow it leaked over in Turkey. We're waiting for the 'B' sample to be tested. We've had some difficulty with getting a date so far, mostly because of the holidays. We're hoping to get it as soon as we can." UConn coach Geno Auriemma could not be reached for comment by telephone. "While she is fully cooperating with authorities, there are serious doubts about the accuracy of the test results," Jacobs said in a statement to the AP. "We are confident that Diana will be fully vindicated once all the evidence is reviewed. She regrets that someone has violated the confidentiality rules of this process, and will make no further statement at this time." WNBA spokesman Ron Howard said the league had no comment. "In the 10 years of competition at the collegiate, professional and Olympic level," said Jacobs. "Diana Taurasi has never taken, been suspected of using, or tested positive for any performance enhancing substance." Jacobs said he didn't know what the length of the suspension would be, nor was he familiar with the details of the Turkish league's anti-doping code. He also said it was too early to know how this might affect Taurasi's eligibility for the London 2012 Olympics. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next games. Taurasi, who has won two Olympic gold medals, helped guide the U.S. national team to the world championship in early October. She led the WNBA in scoring for a league-record fourth straight year, averaging 22.6 points per game. The five-time All-Star and two-time WNBA champion signed a multiyear contract extension with the Phoenix Mercury in August. Reached at the Miami Heat-Phoenix Suns game, Rick Weltz, president of the Suns and Mercury, said the team had no comment. Taurasi served one day in jail and was suspended by the team for two games in 2009 after pleading guilty to a DUI charge. She played in Russia for four years for powerhouse Spartak before joining the Turkish League this season. That league also features WNBA stars Sylvia Fowles, Penny Taylor and Seimone Augustus. Taurasi is leading the league this season with 24.6 points a game. Associated Press Writers Suzan Fraser in Ankara, Turkey, and Erol Israfil in Istanbul contributed to the report. LOAD-DATE: December 25, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 Associated Press All Rights Reserved 115 of 998 DOCUMENTS Associated Press Online December 24, 2010 Friday 10:18 PM GMT Federation: Taurasi tests positive for modafinil BYLINE: By DOUG FEINBERG, AP Basketball Writer SECTION: SPORTS NEWS LENGTH: 740 words DATELINE: NEW YORK WNBA standout and former UConn star Diana Taurasi tested positive for modafinil while playing in a professional women's league in Turkey, the country's basketball federation said Friday. Neither her lawyer nor her team, Fenerbahce, would confirm that Taurasi tested positive for the stimulant, which has been involved in several major doping cases, including that of U.S. sprinter Kelli White. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to the website for the prescription drug Provigil, which contains the substance. The Turkish Basketball Federation statement cited a report from the lab at Hacettepe University and said: "... the urine sample taken from Diana Taurasi as a part of the regular process, after a game between Istanbul University and Fenerbahce ... tested positive for modafinil, one of the illegal substances on WADA's banned stimulants list, according to preliminary test results." WADA is the World Anti-Doping Agency. "We're not going to confirm what the drug is," Taurasi's lawyer, Howard Jacobs, told The Associated Press Friday. "We'll revisit it after the "B" sample returns. They shouldn't be speaking about it at all." White won the 100- and 200-meter races at the 2003 world championships in Paris, but both her medals were stripped after she tested positive for the stimulant. Jacobs said Taurasi's "A" sample came back positive last week and that the substance "was not a steroid or recreational drug." Taurasi has been provisionally suspended pending the testing of her "B" sample, sometime early next month. She has already missed three games with Fenerbahce. The team's website said she and another player were asked to submit to a test on Nov. 13, following the game against Istanbul. It said they were selected as a result of a draw. The other player tested negative. Fenerbahce said Taurasi was upset that the doping claims broke before the testing process was finalized. "She is extremely disturbed that her right to confidentiality has been breached and doping claims have been made even before the results of her test are out," the team's website said. If the "B' sample comes back positive, it could put her 2012 Olympics status with the U.S. national basketball team in jeopardy. She has helped the team win gold medals at the past two Olympics and was the leading scorer at the women's world championships, which the Americans won in early October. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next games. "At this point we're aware of the situation and we're monitoring things and letting the process take its course," USA Basketball spokesman Craig Miller said. "Until that happens we can't comment." Taurasi's test came to light two days after the top-ranked Huskies won their 89th straight game, surpassing the UCLA men's winning streak from 1971-74. Taurasi helped lead UConn to three straight national championships as well as 70 consecutive victories from 2001-03. She was the AP Player of the Year in 2003. UConn's Geno Auriemma, who coached Taurasi and will lead the 2012 Olympic team, couldn't be reached for comment by telephone Friday. At the WNBA All-Star game last summer, Taurasi said the grind of playing basketball continuously for seven straight years was beginning to wear on her. At the time, she indicated fatigue could eventually force her to skip either the WNBA or European seasons. Taurasi is one of many WNBA stars who play overseas in the winter because of higher salaries. The best players can make up to 10 times their WNBA salaries, which top out at about $100,000. She led the WNBA in scoring for a league-record fourth straight year, averaging 22.6 points per game. The five-time All-Star and two-time WNBA champion signed a multiyear contract extension with the Phoenix Mercury in August. Taurasi served one day in jail and was suspended by the team for two games in 2009 after pleading guilty to a DUI charge. She played in Russia for four years for powerhouse Spartak before joining the Turkish League this season. That league also features WNBA stars Sylvia Fowles, Penny Taylor and Seimone Augustus. Taurasi is leading the league in scoring this season with 24.6 points a game. Associated Press Writers Suzan Fraser in Ankara, Turkey, and Erol Israfil in Istanbul contributed to the report. (This version CORRECTS to "confidentiality") LOAD-DATE: December 25, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 Associated Press All Rights Reserved 116 of 998 DOCUMENTS The Associated Press State & Local Wire December 24, 2010 Friday 6:24 PM GMT WNBA's Taurasi tests positive for banned substance BYLINE: By DOUG FEINBERG, AP Basketball Writer SECTION: STATE AND REGIONAL LENGTH: 721 words DATELINE: NEW YORK Diana Taurasi is facing one of the most difficult challenges to her stellar basketball career. The WNBA standout and former UConn star tested positive for a mild stimulant while playing in a pro league in Turkey, her lawyer told The Associated Press on Thursday night. Howard Jacobs said Taurasi's "A" sample came back positive from a lab in Turkey last week. He said the substance "was not a steroid or recreational drug," and that Taurasi has asked that her "B" sample be tested. The Turkish basketball federation said Friday that the substance in Taurasi's positive test was modafinil. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift work sleep disorder or sleep apnea, according to the website for prescription drug Provigil, which contains the substance. Neither Jacobs nor Taurasi's team, Fenerbahce, would confirm it was modafinil, which has been involved in several major doping cases, including that of U.S. sprinter Kelli White. White won the 100- and 200-meter races at the 2003 world championships in Paris, but both her medals were stripped after she tested positive for the stimulant. Taurasi has been provisionally suspended pending the testing of her "B" sample in the first week of January. She has already missed three games with Fenerbahce. In a statement posted on its website, the team said Taurasi was upset that the doping claims broke before the testing process was finalized. "She is extremely disturbed that her right to confidentially has been breached and doping claims have been made even before the results of her test are out," the team said. Taurasi's positive test came to light two days after the top-ranked Huskies won their 89th straight game, surpassing the UCLA men's winning streak from 1971-74. Taurasi helped lead UConn to three straight national championships as well as 70 consecutive victories from 2001-03. She was the AP Player of the Year in 2003. "We're taking it one step at a time," Jacobs said. "I'd rather not say what it is at this stage, they've only tested the 'A' sample. Somehow it leaked over in Turkey. We're waiting for the 'B' sample to be tested. We've had some difficulty with getting a date so far, mostly because of the holidays. We're hoping to get it as soon as we can." UConn coach Geno Auriemma could not be reached for comment by telephone. "While she is fully cooperating with authorities, there are serious doubts about the accuracy of the test results," Jacobs said in a statement to the AP. "We are confident that Diana will be fully vindicated once all the evidence is reviewed. She regrets that someone has violated the confidentiality rules of this process, and will make no further statement at this time." WNBA spokesman Ron Howard said the league had no comment. "In the 10 years of competition at the collegiate, professional and Olympic level," said Jacobs. "Diana Taurasi has never taken, been suspected of using, or tested positive for any performance enhancing substance." Jacobs said he didn't know what the length of the suspension would be, nor was he familiar with the details of the Turkish league's anti-doping code. He also said it was too early to know how this might affect Taurasi's eligibility for the London 2012 Olympics. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next games. Taurasi, who has won two Olympic gold medals, helped guide the U.S. national team to the world championship in early October. She led the WNBA in scoring for a league-record fourth straight year, averaging 22.6 points per game. The five-time All-Star and two-time WNBA champion signed a multiyear contract extension with the Phoenix Mercury in August. Reached at the Miami Heat-Phoenix Suns game, Rick Weltz, president of the Suns and Mercury, said the team had no comment. Taurasi served one day in jail and was suspended by the team for two games in 2009 after pleading guilty to a DUI charge. She played in Russia for four years for powerhouse Spartak before joining the Turkish League this season. That league also features WNBA stars Sylvia Fowles, Penny Taylor and Seimone Augustus. Taurasi is leading the league this season with 24.6 points a game. Associated Press Writers Suzan Fraser in Ankara, Turkey, and Erol Israfil in Istanbul contributed to the report. LOAD-DATE: December 25, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 Associated Press All Rights Reserved 117 of 998 DOCUMENTS The Associated Press State & Local Wire December 24, 2010 Friday 10:18 PM GMT LENGTH: 791 words BC-BKL--Taurasi-Banned Substance, 7th Ld-Writethru,0982 Federation: Taurasi tests positive for modafinil 2030 Eds: Corrects to "confidentiality.". This story is part of AP's general news and sports services. AP Photo NY164, NY163, NY133 sptd/rrosenblatt sptd/sbuttar sptd/hrumberg sptd/jkosik fasst4921 By DOUG FEINBERG AP Basketball Writer NEW YORK (AP) WNBA standout and former UConn star Diana Taurasi tested positive for modafinil while playing in a professional women's league in Turkey, the country's basketball federation said Friday. Neither her lawyer nor her team, Fenerbahce, would confirm that Taurasi tested positive for the stimulant, which has been involved in several major doping cases, including that of U.S. sprinter Kelli White. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to the website for the prescription drug Provigil, which contains the substance. The Turkish Basketball Federation statement cited a report from the lab at Hacettepe University and said: "... the urine sample taken from Diana Taurasi as a part of the regular process, after a game between Istanbul University and Fenerbahce ... tested positive for modafinil, one of the illegal substances on WADA's banned stimulants list, according to preliminary test results." WADA is the World Anti-Doping Agency. "We're not going to confirm what the drug is," Taurasi's lawyer, Howard Jacobs, told The Associated Press Friday. "We'll revisit it after the "B" sample returns. They shouldn't be speaking about it at all." White won the 100- and 200-meter races at the 2003 world championships in Paris, but both her medals were stripped after she tested positive for the stimulant. Jacobs said Taurasi's "A" sample came back positive last week and that the substance "was not a steroid or recreational drug." Taurasi has been provisionally suspended pending the testing of her "B" sample, sometime early next month. She has already missed three games with Fenerbahce. The team's website said she and another player were asked to submit to a test on Nov. 13, following the game against Istanbul. It said they were selected as a result of a draw. The other player tested negative. Fenerbahce said Taurasi was upset that the doping claims broke before the testing process was finalized. "She is extremely disturbed that her right to confidentiality has been breached and doping claims have been made even before the results of her test are out," the team's website said. If the "B' sample comes back positive, it could put her 2012 Olympics status with the U.S. national basketball team in jeopardy. She has helped the team win gold medals at the past two Olympics and was the leading scorer at the women's world championships, which the Americans won in early October. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next games. "At this point we're aware of the situation and we're monitoring things and letting the process take its course," USA Basketball spokesman Craig Miller said. "Until that happens we can't comment." Taurasi's test came to light two days after the top-ranked Huskies won their 89th straight game, surpassing the UCLA men's winning streak from 1971-74. Taurasi helped lead UConn to three straight national championships as well as 70 consecutive victories from 2001-03. She was the AP Player of the Year in 2003. UConn's Geno Auriemma, who coached Taurasi and will lead the 2012 Olympic team, couldn't be reached for comment by telephone Friday. At the WNBA All-Star game last summer, Taurasi said the grind of playing basketball continuously for seven straight years was beginning to wear on her. At the time, she indicated fatigue could eventually force her to skip either the WNBA or European seasons. Taurasi is one of many WNBA stars who play overseas in the winter because of higher salaries. The best players can make up to 10 times their WNBA salaries, which top out at about $100,000. She led the WNBA in scoring for a league-record fourth straight year, averaging 22.6 points per game. The five-time All-Star and two-time WNBA champion signed a multiyear contract extension with the Phoenix Mercury in August. Taurasi served one day in jail and was suspended by the team for two games in 2009 after pleading guilty to a DUI charge. She played in Russia for four years for powerhouse Spartak before joining the Turkish League this season. That league also features WNBA stars Sylvia Fowles, Penny Taylor and Seimone Augustus. Taurasi is leading the league in scoring this season with 24.6 points a game. Associated Press Writers Suzan Fraser in Ankara, Turkey, and Erol Israfil in Istanbul contributed to the report. LOAD-DATE: December 25, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 Associated Press All Rights Reserved 118 of 998 DOCUMENTS The Associated Press State & Local Wire December 24, 2010 Friday 10:18 PM GMT Federation: Taurasi tests positive for modafinil BYLINE: By DOUG FEINBERG, AP Basketball Writer SECTION: STATE AND REGIONAL LENGTH: 733 words DATELINE: NEW YORK WNBA standout and former UConn star Diana Taurasi tested positive for modafinil while playing in a professional women's league in Turkey, the country's basketball federation said Friday. Neither her lawyer nor her team, Fenerbahce, would confirm that Taurasi tested positive for the stimulant, which has been involved in several major doping cases, including that of U.S. sprinter Kelli White. Modafinil is used to counter excessive sleepiness due to narcolepsy, shift-work sleep disorder or sleep apnea, according to the website for the prescription drug Provigil, which contains the substance. The Turkish Basketball Federation statement cited a report from the lab at Hacettepe University and said: "... the urine sample taken from Diana Taurasi as a part of the regular process, after a game between Istanbul University and Fenerbahce ... tested positive for modafinil, one of the illegal substances on WADA's banned stimulants list, according to preliminary test results." WADA is the World Anti-Doping Agency. "We're not going to confirm what the drug is," Taurasi's lawyer, Howard Jacobs, told The Associated Press Friday. "We'll revisit it after the "B" sample returns. They shouldn't be speaking about it at all." White won the 100- and 200-meter races at the 2003 world championships in Paris, but both her medals were stripped after she tested positive for the stimulant. Jacobs said Taurasi's "A" sample came back positive last week and that the substance "was not a steroid or recreational drug." Taurasi has been provisionally suspended pending the testing of her "B" sample, sometime early next month. She has already missed three games with Fenerbahce. The team's website said she and another player were asked to submit to a test on Nov. 13, following the game against Istanbul. It said they were selected as a result of a draw. The other player tested negative. Fenerbahce said Taurasi was upset that the doping claims broke before the testing process was finalized. "She is extremely disturbed that her right to confidentiality has been breached and doping claims have been made even before the results of her test are out," the team's website said. If the "B' sample comes back positive, it could put her 2012 Olympics status with the U.S. national basketball team in jeopardy. She has helped the team win gold medals at the past two Olympics and was the leading scorer at the women's world championships, which the Americans won in early October. The International Olympic Committee bars any athlete given a doping penalty of six months or more from competing in the next games. "At this point we're aware of the situation and we're monitoring things and letting the process take its course," USA Basketball spokesman Craig Miller said. "Until that happens we can't comment." Taurasi's test came to light two days after the top-ranked Huskies won their 89th straight game, surpassing the UCLA men's winning streak from 1971-74. Taurasi helped lead UConn to three straight national championships as well as 70 consecutive victories from 2001-03. She was the AP Player of the Year in 2003. UConn's Geno Auriemma, who coached Taurasi and will lead the 2012 Olympic team, couldn't be reached for comment by telephone Friday. At the WNBA All-Star game last summer, Taurasi said the grind of playing basketball continuously for seven straight years was beginning to wear on her. At the time, she indicated fatigue could eventually force her to skip either the WNBA or European seasons. Taurasi is one of many WNBA stars who play overseas in the winter because of higher salaries. The best players can make up to 10 times their WNBA salaries, which top out at about $100,000. She led the WNBA in scoring for a league-record fourth straight year, averaging 22.6 points per game. The five-time All-Star and two-time WNBA champion signed a multiyear contract extension with the Phoenix Mercury in August. Taurasi served one day in jail and was suspended by the team for two games in 2009 after pleading guilty to a DUI charge. She played in Russia for four years for powerhouse Spartak before joining the Turkish League this season. That league also features WNBA stars Sylvia Fowles, Penny Taylor and Seimone Augustus. Taurasi is leading the league in scoring this season with 24.6 points a game. Associated Press Writers Suzan Fraser in Ankara, Turkey, and Erol Israfil in Istanbul contributed to the report. LOAD-DATE: December 25, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 Associated Press All Rights Reserved 119 of 998 DOCUMENTS Canadian Medical Association. Journal December 14, 2010 Uplifting tales of life in the emergency department BYLINE: Deady, Brian SECTION: Pg. E870 Vol. 182 No. 18 ISSN: 0820-3946; CODEN: CMAJAX LENGTH: 688 words Books Uplifting tales of life in the emergency department The Night Shift: Real Life in the Heart of the E.R. Dr. Brian Goldman HarperCollins Publishers Ltd., 2010. Brian Goldman is one of those rare individuals who simultaneously pursues two careers. He has toiled for more than 20 years as an emergency physician at Mount Sinai Hospital in Toronto, Ontario while working as a medical journalist for the CBC, currently as host of CBC radio's White Coat, Black Art. Without claiming the same far-reaching influence of American media darlings, Oprah's Dr. Oz or CNN's Dr. Sanjay Gupta, he is as close as we get in this country to a medical celebrity. Goldman trades on his media personality with a book of his experiences in the emergency department and I am happy to report that it's a satisfying read. The storyline proceeds as if over one night shift, but the author concedes in the introduction that the book is a composite of his most interesting cases over the many years of his career. In addition to being a medical memoir, it's also a compilation of other physician's stories. The Night Shift rolls out along a timeline that begins at 9:15 pm one Friday evening as Goldman sets off to work. He arrives for a 10 pm start and is immediately thrust into the action. Cases are then laid out in chronological order, each one allowing the writer to riff onto other anecdotes. Along the way, the author weighs in on the many topics fundamental to emergency physicians including interactions with patients, police, consultants, residents and nurses, medical error and the schadenfreude that we sometimes feel (but shouldn't) when talking about a colleague's diagnostic blunder. Trauma care is central to the idea of what makes emergency medicine absorbing - at least in the public's mind - and Mount Sinai is not a trauma hospital, but this obstacle is neatly hurdled when our doctor-journalist draws on his radio interviews to bring the stories of other Canadian emergency physicians to the page. Reading like a who's who of Canadian emergency medicine, their narratives add considerable storytelling muscle to the book's physique. I was particularly struck by former Vancouver General emergency specialist, Bruce Campana, who is quoted throughout the volume. He should consider writing his own book. The pace is fast and the writing is engaging, but make no mistake, this is a book written for the nonmedical public. To that end, while the reader in me enjoyed the tour, my inner physician was sometimes nonplussed with the clinical explanations. For example, in describing the writhing discomfort of a 30-year-old woman, we learn that "It (the patient's abdomen) was rigid, which now suggested peritonitis, an inflammation of the membrane that lines part of the abdominal cavity, often caused by infection and treatable with antibiotics." While the patient, it quickly becomes apparent, is not suffering from this condition, the statement as presented is incomplete. Although I doubt it would detract from the flow of the paragraph for most readers, surely this gross simplification is likely to induce metaphorical scalpscratching among MDs. Goldman himself comes across as earnest, dedicated and diagnostically astute. And while he didn't have to do so, he bravely discusses his own perceived weaknesses as an emergency physician, medical miscalculations, sleep disorder and use of a prescription drug modafinil to stay alert during night shifts. Goldman admits to disliking criticism but these tablets serve as an example of the occasionally weak editing of the text. For example, at 9:15 pm on the way to his shift, "I popped a couple of modafinil pills." At 2:44 am, "I took a modafinil and headed to my next patient." At 5:18 am, "I resisted the urge to pop another modafinil. ... I do worry that one day I'll need three pills, then four, then five." Dear Brian, either that day has arrived or your editor needs a little pharmacologic assistance in the awake and alert department. But these comments seem like mere grousing. I finished the book surprisingly uplifted and proud to be part of the club which Goldman so ably describes. LOAD-DATE: December 20, 2010 LANGUAGE: ENGLISH ACC-NO: 2216346761 GRAPHIC: Photographs DOCUMENT-TYPE: Book Review-Favorable PUBLICATION-TYPE: Other (Periodical) JOURNAL-CODE: CMAJ Copyright 2010 Micromedia Limited All Rights Reserved Canadian Business and Current Affairs Copyright 2010 Canadian Medical Association 120 of 998 DOCUMENTS Indian Patents News December 14, 2010 Tuesday 6:30 AM EST Teva Pharmaceutical Industries Ltd Files Patent Application for Crystalline and Pure Modafinil and Process of Preparing the Same LENGTH: 348 words New Delhi, Dec. 14 -- Israel based Teva Pharmaceutical Industries Ltd filed patent application for crystalline and pure modafinil and process of preparing the same. The Inventors are Claude Singer, Neomi Gershon, Arina Ceausu, Anita Lieberman and Judith Aronhime. Teva Pharmaceutical Industries Ltd filed the patent application Oct. 26, 2006. The patent application number is 1259/MUMNP/2006 A. The International classification numbers are A61K31/165, C07C315/02 and C07C315/06. According to the Controller General of Patents, Designs & Trade Marks, "The present invention provides an improved process for preparing modafinil, whereby it may be isolated in high purity by a single crystallization. The process produces modafinil free of sulphone products of over-oxidation and other byproducts. The invention further provides new crystalline Forms II-VI of modafinil and processes for preparing them. Each of the new forms is differentiated by a unique powder X-ray diffraction pattern. The invention further provides pharmaceutical compositions containing novel modafinil Forms II-IV and VI." Teva Pharmaceutical Industries Limited (Teva) (Public, NASDAQ:TEVA) is a global pharmaceutical company that develops, produces and markets generic drugs covering all treatment categories. The Company has a pharmaceutical business, whose principal products are Copaxone for multiple sclerosis and Azilect for Parkinson's disease, respiratory products and women's health products. Teva's active pharmaceutical ingredient (API) business provides vertical integration to Teva's own pharmaceutical production. The Company's global operations are conducted in North America, Europe, Latin America, Asia and Israel. Teva has operations in more than 60 countries, including 38 finished dosage pharmaceutical manufacturing sites in 17 countries, 15 generic research and development (R&D) centers operating mostly within certain manufacturing sites and 21 API manufacturing sites around the world. On January 29, 2009, the Company sold its Israeli animal health product line to Phibro Animal Health Corporation. LOAD-DATE: December 14, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 Indian Patents News, distributed by Contify.com All Rights Reserved 121 of 998 DOCUMENTS The Times (London) December 7, 2010 Tuesday Edition 1; National Edition Pop go the pep pills; Jaded students, housewives, even doctors, have turned to smart drugs. Dr Margaret McCartney asks whether it is such a wise move BYLINE: Margaret McCartney SECTION: T2;FEATURES; Pg. 9 LENGTH: 1004 words It's the middle of the night and I'm e-mailing my anesthesiologist friend in the US. "I'm tired," I moan, although with the time-difference it is already evening for him. He, however, is organised and bright of eye. "You need modafinil," he replies, his e-mail pert and swift. "Seriously, it's the best thing." As a Scottish GP with too much to do, I harbour a suspicion of most drugs, prescribed or not. But as I cast my eyes around the room, piled with washing and ironing, and contemplate the week's taxi service requirements for my children, I realise that he is merely telling me what I'd rather not know: that lots of people, from students to housewives, have turned to "smart drugs". In 2000, it became apparent that the American Armed Forces were using such drugs, including Dexedrine and Restoril, to "prevent fatigue and maintain combat-ready performance" in pilots, according to a report. Only a few months ago, the British Medical Journal ran an editorial, "Pharmacological enhancement of performance in doctors", in which the authors, who were doctors and scientists, stated that the use of caffeine, Viagra, antidepressants and multivitamins was common and acceptable. Although the issues relating to the use of such medication might be complex, they wrote, "performance-enhancing drugs may have benefits for healthy, non-fatigued individuals". They concluded that "early indications are that members of society are more likely to agree with cognitive enhancement [of doctors] if motivations for using them are seen to be unselfish". But what's the reality behind the alluring prospect of better fighter pilots and more effective surgeons? Do "smart drugs" have the potential to make us smarter or do the side-effects do more harm than good? Amphetamines What are they: This group of drugs includes Dexedrine and treatments prescribed for attention deficit hyperactivity disorder (ADHD). Amphetamines are Class B drugs, also known as speed, which have long been favoured by clubbers keen to dance the night away. The drugs have been used in diet pills, for their effect on increasing metabolism, and are still sold illegally for this purpose. Useful for a boost? Even in cases of ADHD, they should be used only after other psychological and behavioural measures have been tried, according to NICE, the health service's treatment watchdog. Studies that suggest that there are benefits from taking amphetamines have involved only small numbers of patients - the studies that the BMJ report referred to involved 70 men and no women, and focused on lab tests, rather than real-life tasks. What are the side-effects: Addiction, cardiac problems, overdose, jitteriness and paranoia. There is a lack of research into the effects of amphetamines on routine tasks, including driving. Modafinil What is it: This drug, marketed as Provigil, can be prescribed to deal with "daytime sleepiness" caused by shift working or for narcolepsy (a condition where the person falls asleep without warning). However it is available on the internet, allowing buyers to use it for tiredness unrelated to shift work. Useful for a boost? A study published in the New England Journal of Medicine in 2005 compared 209 people with "shift-work disorder" who were given either modafinil or a placebo. Those taking modafinil reported less sleepiness during their night shift, but the real revelation was the proportion of people who reported an accident or a near accident on their commute home to bed. In the placebo group, it was 58 per cent and in the modafinil group, a third. So although fewer people in the group taking the drug were at risk of an accident, the proportion was still worryingly high. Another study claiming that emergency doctors worked smarter with modafinil was widely publicised, even though it had only 25 participants and the results were measured with paper-based tests rather than real-life outcomes. Modafinil was put on the list of banned drugs for athletes in 2004. What are the side-effects? Anxiety, high blood pressure, agitation and decreased libido as well as mania and suicidal thoughts. As many studies have been short, the longer-term effects, good or bad, aren't known. Some studies using MRI scans have suggested that the drug affects not just cognitive circuits but emotional ones. Is this a good thing? No one knows. Donepezil What is it: Known as Aricept, the drug for treating dementia, studies have recently suggested that it improves learning in people without dementia better than a placebo. It is not, at present, licensed for use to treat anything other than Alzheimer's. Useful for a boost? The study had just 12 people in it and has to be regarded as very preliminary. Other studies - notably from the US - have examined the use of Aricept in older adults and haven't found medium or longer-term boosts to learning or memory. Internet chatrooms are full of students who swear by it but, on the evidence at present, they'd be better off swotting instead. What are the side-effects? Heart irregularities but, in people who are prescribed it, it's usually tolerated. Pro-plus What is it: This is the older version of the modern smart pill, known to students everywhere. The makers say it "gives you a fast-acting caffeine boost that relieves fatigue and tiredness and helps you feel more awake". Two tablets contain 100mg of caffeine: in Starbucks, a small (short) coffee contains 160mg caffeine, with the biggest containing 400mg. Useful for a boost? Caffeine raises the heart rate and blood pressure, waking up tired minds. It's a quick fix that rapidly wears off so the dose has to be topped up. A Cochrane review - which examines all the evidence available - found some evidence that caffeine improved performance and memory in shift workers. What are the side-effects? Caffeine is legal, easy to obtain and delicious to drink. But we all know that getting to sleep after too much is difficult, and, of course, if sleep is what you really need, caffeine might end up being your enemy rather than your friend. LOAD-DATE: December 7, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: TIM Copyright 2010 Times Newspapers Limited All Rights Reserved 122 of 998 DOCUMENTS Indian Patents News November 19, 2010 Friday 6:30 AM EST Universitatsklinikum Freiburg Files Patent Application for the Gene PRV-1 and its Use LENGTH: 249 words New Delhi, Nov. 19 -- Germany based Universitatsklinikum Freiburg filed patent application for the gene PRV-1 and its use. The inventor is Heike Pahl. Universitatsklinikum Freiburg filed the patent application on March 27, 2002. The patent application number is IN/PCT/2002/00335/DEL A. The international classification number is A61K31/16. According to the Controller General of Patents, Designs & Trade Marks, "This invention relates to new uses of Modafinil and its D/L enantiomers, particularly the new uses in the pharmaceutical preparation field. This invention provides new uses of Modafinil and its D/L enantiomers in preparing the medicine for increasing and enhancing the quantity and quality of normal spermatozoa in male mammals, the medicine for enhancing the pregnant capacity in female mammals, the medicine for treating infertility, subfertility and sex dysfunction in male and female mammals, and the medicine for enhancing the sexual function in mammals." The University Medical Center Freiburg (Universitatsklinikum Freiburg) in Freiburg, Germany is the teaching hospital and part of the medical research unit of the University of Freiburg and home to its Faculty of Medicine. The medical center is one of the largest and most reputable in Europe, due to its extensive clinical capabilities and advances in research. Medical services at the University of Freiburg date back to the university's founding in 1457, as the Faculty of Medicine was one of the four founding faculties. LOAD-DATE: November 19, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 Indian Patents News, distributed by Contify.com All Rights Reserved 123 of 998 DOCUMENTS CNS Drug News October 25, 2010 FDA approves REMS for Nuvigil and Provigil SECTION: NEWS LENGTH: 252 words On 21st October, Risk Evaluation and Mitigation Strategies (REMS) for Cephalon's medications, Nuvigil (armodafinil) Tablets [C-IV] and Provigil (modafinil) Tablets [C-IV], were approved by the FDA. Nuvigil, the longer-lasting isomer of modafinil, is indicated to improve wakefulness in patients with excessive sleepiness associated with treated obstructive sleep apnoea (OSA), shift work disorder (SWD) or narcolepsy. Meanwhile, Provigil is indicated to improve wakefulness in patients with excessive sleepiness associated with treated OSA, shift work sleep disorder, also known as SWD, and narcolepsy. Both the Nuvigil and Provigil REMS consist of a medication guide to inform patients about the potential risks associated with the use of these medications, a communication plan and a timetable for submission of assessments of the REMS. The communication plan includes a "Dear Healthcare Professional" letter, a prescriber brochure, a pharmacist action letter and a dedicated REMS internet site. The goal of each REMS is to inform healthcare providers, patients and caregivers about the risks associated with these medications, including serious skin rash and hypersensitivity reactions. The current product labelling for both medications contains a bolded warning that includes these risks. Neither medication is approved for use in the paediatric population for any indication. In accordance with the approved REMS, the company is currently updating Nuvigil and Provigil labelling to include the medication guide. LOAD-DATE: October 25, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter JOURNAL-CODE: CNS Drug News Copyright 2010 Espicom Business Intelligence All Rights Reserved 124 of 998 DOCUMENTS PR Newswire October 22, 2010 Friday 4:38 PM EST Cephalon Announces FDA Approval of Risk Evaluation and Mitigation Strategies for NUVIGIL and PROVIGIL; REMS Addresses Potential Risks Currently Included In Labeling LENGTH: 1087 words DATELINE: FRAZER, Pa., Oct. 22 FRAZER, Pa., Oct. 22 /PRNewswire-FirstCall/ -- Cephalon, Inc. (Nasdaq: CEPH) today announced that Risk Evaluation and Mitigation Strategies (REMS) for its medications NUVIGIL® (armodafinil) Tablets [C-IV] and PROVIGIL® (modafinil) Tablets [C-IV] have been approved by the U.S. Food and Drug Administration (FDA). Both the NUVIGIL and PROVIGIL REMS consist of a Medication Guide to inform patients about the potential risks associated with the use of these medications, a communication plan and a timetable for submission of assessments of the REMS. The communication plan includes a Dear Healthcare Professional Letter, a Prescriber Brochure, a Pharmacist Action Letter and a dedicated REMS Internet Site. The introduction of the NUVIGIL and PROVIGIL REMS programs is consistent with the company's commitment to safe and appropriate use of its medications. The goal of each REMS is to inform healthcare providers, patients and caregivers about the risks associated with these medications, including serious skin rash and hypersensitivity reactions. The current product labeling for both medications contains a bolded warning that includes these risks. Neither medication is approved for use in the pediatric population for any indication. In accordance with the approved REMS, the company is currently updating NUVIGIL and PROVIGIL labeling to include the Medication Guide. The NUVIGIL and PROVIGIL Medication Guides will be available on each product website, www.nuvigil.com and www.provigil.com, and will be dispensed with every prescription. Information on both products is also available by calling 1-800-896-5855. More information on Cephalon and its products is available at www.cephalon.com. About NUVIGIL NUVIGIL is indicated to improve wakefulness in patients with excessive sleepiness associated with treated obstructive sleep apnea (OSA), shift work disorder (SWD), or narcolepsy. In patients with OSA, NUVIGIL is used along with other medical treatments for this condition. The NUVIGIL (armodafinil) label includes a bolded warning for serious or life-threatening rash, including Stevens-Johnson Syndrome, requiring hospitalization and discontinuation of treatment, that has been reported in adults in association with the use of modafinil and armodafinil and in children in association with the use of modafinil, a racemic mixture of S and R modafinil (the latter is armodafinil, the active ingredient in NUVIGIL). NUVIGIL is not approved for use in pediatric patients for any indication. The most common adverse events in controlled clinical trials (five percent or greater) were headache, nausea, dizziness, and insomnia. Full prescribing information for NUVIGIL is available at www.nuvigil.com. About PROVIGIL PROVIGIL is indicated to improve wakefulness in patients with excessive sleepiness associated with treated obstructive sleep apnea (OSA), shift work sleep disorder, also known as shift work disorder (SWD), and narcolepsy. In patients with OSA, PROVIGIL is used along with other medical treatments for this condition. The PROVIGIL label includes a bolded warning for serious or life-threatening rash, including Stevens-Johnson Syndrome, requiring hospitalization and discontinuation of treatment, that has been reported in adults and children taking modafinil. PROVIGIL is not approved for use in pediatric patients for any indication. The most common adverse events in controlled clinical trials (greater than five percent) were headache, nausea, nervousness, rhinitis, diarrhea, back pain, anxiety, insomnia, dizziness and dyspepsia. Full prescribing information for PROVIGIL is available at www.provigil.com. About Cephalon, Inc. Cephalon is a global biopharmaceutical company dedicated to discovering, developing and bringing to market medications to improve the quality of life of individuals around the world. Since its inception in 1987, Cephalon has brought first-in-class and best-in-class medicines to patients in several therapeutic areas. Cephalon has the distinction of being one of the world's fastest-growing biopharmaceutical companies, now among the Fortune 1000 and a member of the S&P 500 Index, employing approximately 4,000 people worldwide. The company sells numerous branded and generic products around the world. In total, Cephalon sells more than 150 products in nearly 100 countries. More information on Cephalon and its products is available at www.cephalon.com. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide the Cephalon current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs; development of potential pharmaceutical products; interpretation of clinical results; prospects for regulatory approval; manufacturing development and capabilities; market prospects for its products; and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. Contacts: Media: Candace Steele Flippin 610-727-6231 (office) csteele@cephalon.com Investor Relations: Chip Merritt 610-738-6376 (office) cmerritt@cephalon.com Joseph Marczely 610-883-5894 (office) jmarczely@cephalon.com SOURCE Cephalon, Inc. CONTACT:CONTACT: Media: Candace Steele Flippin, +1-610-727-6231, csteele@cephalon.com, or Investor Relations: Chip Merritt, +1-610-738-6376, cmerritt@cephalon.com, or Joseph Marczely, +1-610-883-5894, jmarczely@cephalon.com, all of Cephalon, Inc. URL: http://www.prnewswire.com LOAD-DATE: October 23, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 PR Newswire Association LLC All Rights Reserved 125 of 998 DOCUMENTS Indian Patents News October 15, 2010 Friday 6:30 AM EST Wockhardt Ltd Files Patent Application for Bilayer Tablet Composition of Modafinil LENGTH: 284 words New Delhi, Oct. 15 -- India based Wockhardt Ltd filed patent application for bilayer tablet composition of modafinil. The inventors are Jain Nitin Anand Kumar, Murali Narayanan and Jain Girish Kumar. Wockhardt Ltd filed the patent application on April 27, 2007. The patent application number is 811/MUM/2007 A. The International classification number is A61K9/20. According to the Controller General of Patents, Designs & Trade Marks, "The present invention provides a bilayer tablet comprising modafinil or pharmaceutical^ acceptable salts thereof wherein the tablet comprises micronized and unmicronized modafinil particles. Modafinil is a wakefulness-promoting agent indicated to improve wakefulness in patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome, and shift work sleep disorder. It has molecular weight of 273.36. The chemical name of modafinil is (2-[(diphenylmethyl) sulfinyl] acetamide. Its empirical formula is C15H15NO2S." Wockhardt Limited (WL) (Public, BOM:532300) is an India-based an integrated pharmaceutical, biotechnology and healthcare company. The Company is a subsidiary of Khorakwala Holdings and Investments Private Limited. The Company's cardiology division covers lifestyle diseases, which include diabetes and nephrology, supported by biotechnology products, such as Wosulin, Glaritus and Wepox. As of March 31, 2010, the Company had seven hospitals with 800 inpatient beds. The Company's subsidiaries includes Wockhardt Biopharm Limited, Vinton Healthcare Limited, Wockhardt Infrastructure Development Limited, Wockhardt UK Holdings Limited, CP Pharmaceuticals Limited, Wallis Group Limited and The Wallis Laboratory Limited. LOAD-DATE: October 15, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 Indian Patents News, distributed by Contify.com All Rights Reserved 126 of 998 DOCUMENTS Indian Patents News October 15, 2010 Friday 6:30 AM EST Wockhardt Ltd Files Patent Application for Pharmaceutical Composition of Modafinil or Salts Thereof LENGTH: 241 words New Delhi, Oct. 15 -- India based Wockhardt Ltd filed patent application for pharmaceutical composition of modafinil or salts thereof. The inventors are Huda Inderjeetsingh, Murali Narayanan and Jain Girish Kumar. Wockhardt Ltd filed the patent application on April 27, 2007. The patent application number is 810/MUM/2007 A. The International classification number is A61K9/16. According to the Controller General of Patents, Designs & Trade Marks, "The present invention provides a pharmaceutical composition of modafinil or pharmaceutical^ acceptable salts thereof comprising mixture of micronized and unmicronized modafinil particles, sodium starch glycolate in admixture with one or more pharmaceutically acceptable excipients." Wockhardt Limited (WL) (Public, BOM:532300) is an India-based an integrated pharmaceutical, biotechnology and healthcare company. The Company is a subsidiary of Khorakwala Holdings and Investments Private Limited. The Company's cardiology division covers lifestyle diseases, which include diabetes and nephrology, supported by biotechnology products, such as Wosulin, Glaritus and Wepox. As of March 31, 2010, the Company had seven hospitals with 800 inpatient beds. The Company's subsidiaries includes Wockhardt Biopharm Limited, Vinton Healthcare Limited, Wockhardt Infrastructure Development Limited, Wockhardt UK Holdings Limited, CP Pharmaceuticals Limited, Wallis Group Limited and The Wallis Laboratory Limited. LOAD-DATE: October 15, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 Indian Patents News, distributed by Contify.com All Rights Reserved 127 of 998 DOCUMENTS Mondaq September 22, 2010 Wednesday 12:00 AM EST "Grave Consequences" Defence may be Asserted Against a Generic in a Section 8 Action Under The PM(NOC) Regulations BYLINE: Mr Intellectual Property Group LENGTH: 869 words Sep. 22, 2010 (Mondaq delivered by Newstex) -- Apotex Inc. v. Shire Canada Inc., 2010 FC 828 In an action brought by Apotex Inc. (Apotex) to recover damages under section 8 of the Patented Medicines (Notice of Compliance) Regulations (SOR/93-133)(Regulations) in respect of the medicine modafinil, Shire Canada Inc. (Shire) brought this motion for leave to amend its statement of defence, alleging two new defences. Apotex opposed Shire's motion, arguing that the proposed amendments did not disclose a reasonable defence and ought not to be permitted. The prothonotary struck out the first proposed amendment, finding that a defence based on the outcome of a separate infringement action to which Shire was not a party would be speculative and hypothetical, but permitted the second proposed amendment which alleged a "grave consequences" defence. Background Apotex filed an abbreviated new drug submission (ANDS), seeking a notice of compliance (NOC) that would allow it to market its generic Apo-modafinil tablets, by comparing its tablets to Shire's modafinil product. Shire had listed Canadian patent no. 2,201,967 (the '967 patent) on the patent register in respect of its modafinil tablets. On March 16, 2006, Apotex served a notice of allegation (NOA) on Shire, alleging that the claims of its '967 patent were invalid, void and of no effect. In response, Shire commenced an application for an order prohibiting the issuance of a NOC to Apotex. This application was dismissed two years later, on April 25, 2008. Apotex obtained a NOC shortly after the judgment was released and now seeks damages under section 8 of the Regulations for the delay in issuance of the NOC resulting from Shire's unsuccessful application for a prohibition order. Defence based on a separate action by Cephalon Inc. (NASDAQ:CEPH) For its first proposed new defence, Shire proposed to rely on the outcome of a separate infringement action against Apotex commenced by the owner of the '967 patent, Cephalon Inc. (Cephalon). Shire argued that, should the '967 patent be found to be valid and infringed in that other action, Apotex should not be entitled to recover any damages in the present proceeding based on the loss of infringing sales. The prothonotary struck this proposed defence, finding that the outcome of the Cephalon action was an uncertain future event which was not susceptible of being determined or even influenced in the context of the present action. This was the essence of a speculative and hypothetical pleading that ought to be struck. Moreover, these issues could not be determined unless and until the proceedings by Cephalon in the other court file were resolved. This would unreasonably delay, embarrass and prejudice the trial of the present action by Apotex againt Shire. Defence based on the "Grave Consequences" Doctrine For its second proposed new defence, Shire sought to rely on the existence of Canadian patent no. 2,165,824 (the '824 patent), a second patent listed on the patent register against Shire's modafinil tablets. In particular, in a NOA served on Shire by Apotex, dated August 30, 2005, Apotex alleged that it would not infringe the '824 patent on the basis of its draft product monograph and gave an undertaking that it would not make, use or sell its tablets for the patented use of treatment of sleep apnea or ventilation problems of central origin. However, according to Shire, Apotex's product monograph does include the patented indication, and Apotex has sold its modafinil tablets for such use in breach of its undertaking. Shire therefore seeks to allege that Apotex breached this undertaking, giving rise to the possible finding of "grave consequences", alluded to by the Federal Court of Appeal, in the form of a denial of any remedy for delayed entry into the market pursuant to section 8 of the Regulations. Apotex argued that subsection 8(5) of the Regulations, which requires the court to take into account "all matters that it considers relevant to the assessment of the amount, including any conduct [of the parties] which contributed to delay the disposition of the application", should be interpreted as any valid defence arising exclusively in the context of the very prohibition proceeding that was dismissed or discontinued. The prothonotary, however, found that Apotex's argument raised a difficult question that should not be determined on a motion to strike. It was reasonably arguable that the Court could conclude that Apotex's breach of an undertaking, if established, could affect the assessment of damages. Apotex therefore did not meet the very heavy onus of showing that this proposed defence was plainly and obviously devoid of any merit and stood no chance of success whatsoever. The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances. Mr Intellectual Property Group Stikeman Elliott LLP Suite 5300 Commerce Court West 199 Bay Street Toronto M5L 1B9 CANADA Tel: 4168695500 Fax: 4169470866 E-mail: info@stikeman.com URL: www.stikeman.com Click Here for related articles(c) Mondaq Ltd, 2010 - Tel. +44 (0)20 8544 8300 - Newstex ID: MNDQ-5508-48970758 LOAD-DATE: September 22, 2010 LANGUAGE: ENGLISH NOTES: The views expressed on blogs distributed by Newstex and its re-distributors ("Blogs on Demand®") are solely the author's and not necessarily the views of Newstex or its re-distributors. Posts from such authors are provided "AS IS", with no warranties, and confer no rights. The material and information provided in Blogs on Demand® are for general information only and should not, in any respect, be relied on as professional advice. No content on such Blogs on Demand® is "read and approved" before it is posted. Accordingly, neither Newstex nor its re-distributors make any claims, promises or guarantees about the accuracy, completeness, or adequacy of the information contained therein or linked to from such blogs, nor take responsibility for any aspect of such blog content. All content on Blogs on Demand® shall be construed as author-based content and commentary. Accordingly, no warranties or other guarantees will be offered as to the quality of the opinions, commentary or anything else offered on such Blogs on Demand®. Reader's comments reflect their individual opinion and their publication within Blogs on Demand® shall not infer or connote an endorsement by Newstex or its re-distributors of such reader's comments or views. Newstex and its re-distributors expressly reserve the right to delete posts and comments at its and their sole discretion. PUBLICATION-TYPE: Web Blog Copyright 2010 Newstex LLC All Rights Reserved Newstex Web Blogs Copyright 2010 Mondaq 128 of 998 DOCUMENTS Mondaq Business Briefing September 22, 2010 Canada: "Grave Consequences" Defence may be Asserted Against a Generic in a Section 8 Action Under The PM(NOC) Regulations BYLINE: Intellectual Property Group LENGTH: 839 words Apotex Inc. v. Shire Canada Inc., 2010 FC 828 In an action brought by Apotex Inc. (Apotex) to recover damages under section 8 of the Patented Medicines (Notice of Compliance) Regulations (SOR/93-133) (Regulations) in respect of the medicine modafinil, Shire Canada Inc. (Shire) brought this motion for leave to amend its statement of defence, alleging two new defences. Apotex opposed Shire's motion, arguing that the proposed amendments did not disclose a reasonable defence and ought not to be permitted. The prothonotary struck out the first proposed amendment, finding that a defence based on the outcome of a separate infringement action to which Shire was not a party would be speculative and hypothetical, but permitted the second proposed amendment which alleged a "grave consequences" defence. Background Apotex filed an abbreviated new drug submission (ANDS), seeking a notice of compliance (NOC) that would allow it to market its generic Apo-modafinil tablets, by comparing its tablets to Shire's modafinil product. Shire had listed Canadian patent no. 2,201,967 (the '967 patent) on the patent register in respect of its modafinil tablets. On March 16, 2006, Apotex served a notice of allegation (NOA) on Shire, alleging that the claims of its '967 patent were invalid, void and of no effect. In response, Shire commenced an application for an order prohibiting the issuance of a NOC to Apotex. This application was dismissed two years later, on April 25, 2008. Apotex obtained a NOC shortly after the judgment was released and now seeks damages under section 8 of the Regulations for the delay in issuance of the NOC resulting from Shire's unsuccessful application for a prohibition order. Defence based on a separate action by Cephalon Inc. For its first proposed new defence, Shire proposed to rely on the outcome of a separate infringement action against Apotex commenced by the owner of the '967 patent, Cephalon Inc. (Cephalon). Shire argued that, should the '967 patent be found to be valid and infringed in that other action, Apotex should not be entitled to recover any damages in the present proceeding based on the loss of infringing sales. The prothonotary struck this proposed defence, finding that the outcome of the Cephalon action was an uncertain future event which was not susceptible of being determined or even influenced in the context of the present action. This was the essence of a speculative and hypothetical pleading that ought to be struck. Moreover, these issues could not be determined unless and until the proceedings by Cephalon in the other court file were resolved. This would unreasonably delay, embarrass and prejudice the trial of the present action by Apotex againt Shire. Defence based on the "Grave Consequences" Doctrine For its second proposed new defence, Shire sought to rely on the existence of Canadian patent no. 2,165,824 (the '824 patent), a second patent listed on the patent register against Shire's modafinil tablets. In particular, in a NOA served on Shire by Apotex, dated August 30, 2005, Apotex alleged that it would not infringe the '824 patent on the basis of its draft product monograph and gave an undertaking that it would not make, use or sell its tablets for the patented use of treatment of sleep apnea or ventilation problems of central origin. However, according to Shire, Apotex's product monograph does include the patented indication, and Apotex has sold its modafinil tablets for such use in breach of its undertaking. Shire therefore seeks to allege that Apotex breached this undertaking, giving rise to the possible finding of "grave consequences", alluded to by the Federal Court of Appeal, in the form of a denial of any remedy for delayed entry into the market pursuant to section 8 of the Regulations. Apotex argued that subsection 8(5) of the Regulations, which requires the court to take into account "all matters that it considers relevant to the assessment of the amount, including any conduct [of the parties] which contributed to delay the disposition of the application", should be interpreted as any valid defence arising exclusively in the context of the very prohibition proceeding that was dismissed or discontinued. The prothonotary, however, found that Apotex's argument raised a difficult question that should not be determined on a motion to strike. It was reasonably arguable that the Court could conclude that Apotex's breach of an undertaking, if established, could affect the assessment of damages. Apotex therefore did not meet the very heavy onus of showing that this proposed defence was plainly and obviously devoid of any merit and stood no chance of success whatsoever. The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances. Mr Intellectual Property Group Stikeman Elliott LLP Suite 5300 Commerce Court West 199 Bay Street Toronto M5L 1B9 CANADA Tel: 4168695500 Fax: 4169470866 E-mail: info@stikeman.com URL: www.stikeman.com LOAD-DATE: October 4, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 Mondaq Ltd. All Rights Reserved 129 of 998 DOCUMENTS Reuters Health Medical News September 15, 2010 Wednesday 9:00 PM EST Armodafinil does not improve cognitive deficits in schizophrenia SECTION: DRUG & DEVICE DEVELOPMENT LENGTH: 408 words DATELINE: NEW YORK Adjunctive armodafinil, the longer-lasting isomer of modafinil, doesn't improve cognitive deficits in patients with schizophrenia, researchers report in an August 24th online paper in the Journal of Clinical Psychiatry. Dr. John M. Kane, of The Zucker Hillside Hospital in Glen Oaks, New York, and colleagues randomized 60 patients (mean age 43 years) with stable schizophrenia to adjunctive treatment with once-daily placebo or armodafinil 50, 100, or 200 mg. Fifteen patients were assigned to each group; 49 (82%) completed the 4-week study. Changes in cognitive deficits from baseline to the final visit were similar following armodafinil or placebo, as measured by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) composite score. Mean changes ranged from 1.9 with 50 mg to 2.9 with 200 mg; scores in the placebo group fell in the middle. In two previous trials, modafinil-treated patients didn't differ from placebo-treated patients in the Scale for the Assessment of Negative Symptoms (SANS) scores. Similarly, in the current study, there were no clinically meaningful reductions in the SANS total score. Armodafinil was generally well tolerated. The most common adverse events were diarrhea and headache. Treatment did not cause psychosis to worsen. Patients who received armodafinil 200 mg did have greater improvement in the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) than those who received placebo, but the results were not statistically significant. The mechanism of action of armodafinil is not known. "A weak DAT (dopamine transporter) inhibitor such as armodafinil, which may preferentially influence the dopaminergic activity in the prefrontal cortex but not in the limbic system, could, hypothetically, reduce negative symptoms without worsening positive symptoms--the effect suggested in this study," Dr. Kane and colleagues write. They also say that "treating negative symptoms of schizophrenia is important because these symptoms are debilitating for patients and because antipsychotic therapies are often not adequate to treat them." Their conclusion is that more study is needed to determine the potential efficacy of modafinil on negative symptoms. The study was sponsored by Cephalon, the manufacturer of armodafinil, which either employs or has financial relationships with all the paper's seven authors. SOURCE: http://link.reuters.com/fek83p SOURCE: J Clin Psychiatry 2010. LOAD-DATE: September 16, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 Reuters Health All Rights Reserved 130 of 998 DOCUMENTS Generic Line August 4, 2010 Wednesday FTC Denies Improper Behavior in Watson Pay-for-Delay Case SECTION: Vol. 27 No. 15 LENGTH: 575 words The FTC says it did not engage in improper behavior as part of its pay-for-delay investigation into Watson Pharmaceuticals and has reaffirmed its request to subpoena CEO Paul Bisaro to see if the company brokered an illicit deal to keep Provigil generics off the market. The commission also rebuts an accusation from Bisaro that it attempted to broker a deal between Watson and Apotex to produce a generic version of Provigil ( modafinil), according to a detailed FTC filing to the U.S. District Court for the District of Columbia. The FTC is still waiting for Bisaro to explain whether a 2006 agreement Watson entered into with Cephalon, Provigil's manufacturer, included a stipulation that Watson delay launching generic modafinil in exchange for payments, it says. The commission was required to answer questions from Bisaro's lawyers as part of an order issued last month by Judge Alan Kay (Generic Line, July 21). "This Court finds that the facts before it present a strong possibility that the FTC did share confidential information with Watson's competitor, that it did attempt to broker a deal between Apotex and Watson that would require Watson to relinquish any statutory 'first filer' rights it had acquired, and that it did initiate this investigation to pressure Watson to relinquish these rights and to harass it when it refused," Kay wrote. During conversations with Watson counsel Steven Sunshine in March 2009, Markus Meier, assistant director in the FTC's Bureau of Competition, brought up an idea "through a series of hypothetical questions" that would involve Watson licensing, relinquishing or sharing its 180-day marketing exclusivity, the commission says. Sunshine then authorized Meier to contact Apotex regarding a possible deal between the two companies, the FTC adds. After informing Apotex of Watson's interests, the FTC says it didn't play any role in further discussions between the companies, nor did it divulge proprietary information as claimed by Bisaro. But Kay sided with Watson, saying that the commission pressured the company to enter into the deal. "The facts before us suggest that the FTC sought to place Watson between a rock and a hard place, where the only way Watson could clear its name and escape further FTC scrutiny was to give in to the pressure the FTC was placing on Watson to enter into the business deal with Apotex," Kay said. Heightened Suspicions The FTC's suspicions into Watson's actions were heightened in January 2009 when it learned that on the same day a second patent related to Provigil was listed in the FDA's Orange Book, Watson filed an ANDA challenging it. That would give Watson "first-filer" status. "FTC staff sought to understand practically how a generic company would be aware of a later-issued patent so that it would be in the position to file an ANDA amendment on precisely the same day that the brand company listed such later issued patent with the FDA," the commission says in its filing. "Put simply, FTC staff was trying to assess whether a generic company was likely to have such information independently or whether such information was likely available to the generic only as a result of collusion with the brand company to create an additional barrier to impede potential generic entry," it continues. Watson told Generic Line it would not respond to the FTC's filing in keeping with its policy of not commenting on ongoing litigation. -- Jonathan Block Release date: Aug. 4, 2010 LOAD-DATE: August 6, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2010 Washington Business Information, Inc. All Rights Reserved 131 of 998 DOCUMENTS Washington Drug Letter August 2, 2010 Monday FTC: Nothing Improper Done in Investigation of Watson SECTION: Vol. 42 No. 30 LENGTH: 306 words The FTC says it did not engage in improper behavior as part of its pay-for-delay investigation into Watson Pharmaceuticals and has reaffirmed its request to subpoena CEO Paul Bisaro to see if the company brokered an illicit deal to keep Provigil generics off the market. The commission also rebuts an accusation from Bisaro that it attempted to broker a deal between Watson and Apotex to produce a generic version of Provigil ( modafinil), according to a detailed FTC filing to the U.S. District Court for the District of Columbia. The FTC is still waiting for Bisaro to explain whether a 2006 agreement Watson entered into with Cephalon, Provigil's manufacturer, included a stipulation that Watson delay launching generic modafinil in exchange for payments, it says. The commission was required to answer questions from Bisaro's lawyers as part of an order issued earlier this month by Judge Alan Kay (WDL, July 19). The FTC's suspicions into Watson's actions were heightened in January 2009 when it learned that on the same day a second patent related to Provigil was listed in the FDA's Orange Book, Watson filed an ANDA challenging it. That would give Watson "first-filer" status. "FTC staff sought to understand practically how a generic company would be aware of a later-issued patent so that it would be in the position to file an ANDA amendment on precisely the same day that the brand company listed such later issued patent with the FDA," the commission says in its filing. "Put simply, FTC staff was trying to assess whether a generic company was likely to have such information independently or whether such information was likely available to the generic only as a result of collusion with the brand company to create an additional barrier to impede potential generic entry," it continues. -- Jonathan Block Release date: Aug. 2, 2010 LOAD-DATE: August 2, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2010 Washington Business Information, Inc. All Rights Reserved 132 of 998 DOCUMENTS Global Insight July 29, 2010 EMA Recommends Limiting Use of Modafinil to Narcolepsy Treatment BYLINE: Brendan Melck SECTION: In Brief LENGTH: 228 words The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has concluded a safety review of drugs including the active pharmaceutical ingredient modafinil, concluding with the recommendation that drugs including this API should only be used to treat narcolepsy. The drug should no longer be used in the treatment of idiopathic hypersomnia, shift-work sleep disorder, or excessive sleepiness associated with obstructive sleep apnoea, the committee concluded. The safety review was initiated due to concerns relating to potential skin and subcutaneous tissue reactions and psychiatric disorders resulting from the use of modafinil. The CHMP decided that only in the case of narcolepsy did modafinil's benefits outweigh its risks, and so all other indications should be removed from its marketing authorisation. Its recommendations have now been passed to the European Commission for final approval. Significance:The decision of the CHMP (assuming the Commission gives it binding approval) will certainly have some effect on producers of drugs containing modafinil, such as the drug's developer Cephalon (U.S.), with its Provigil product, Mitsubishi Tanabe of Japan, with its Modiodal, and generics producers. Such producers can expect to suffer some consequences in reduced revenues from these products if the recommendation is approved. LOAD-DATE: July 29, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Web Publication Copyright 2010 World Markets Research Limited All Rights Reserved 133 of 998 DOCUMENTS Drug Industry Daily July 26, 2010 Monday FTC Denies Improper Behavior in Watson Pay-for-Delay Investigation SECTION: Vol. 9 No. 143 LENGTH: 468 words The FTC says it did not engage in improper behavior as part of its pay-for-delay investigation into Watson Pharmaceuticals and has reaffirmed its request to subpoena CEO Paul Bisaro to see if the company brokered an illicit deal to keep Provigil generics off the market. The commission also rebutted an accusation from Bisaro that it attempted to broker a deal between Watson and Apotex to produce a generic version of Provigil (modafinil), according to a detailed filing to the U.S. District Court for the District of Columbia on Thursday. The FTC says it is still waiting for the executive to explain whether a 2006 agreement Watson entered into with Cephalon, Provigil's manufacturer, included a stipulation that Watson delay launching generic modafinil in exchange for payments. The commission was required to answer questions from Bisaro's lawyers as part of an order given earlier this month by Judge Alan Kay (DID, July 15). According to the FTC, during conversations with Watson counsel Steven Sunshine in March 2009, Markus Meier, assistant director in the agency's Bureau of Competition, brought up an idea "through a series of hypothetical questions" that would involve Watson licensing, relinquishing or sharing its 180-day marketing exclusivity. The commission says Sunshine then authorized Meier to contact Apotex regarding a possible deal between Apotex and Watson. The FTC further states that after informing Apotex of Watson's interests, it didn't play any role in further discussions between the two companies, nor did it ever divulge proprietary information as claimed by Bisaro. The FTC's suspicions into Watson were heightened in January 2009, after finding out that on the same day a second patent related to Provigil was listed in the FDA's Orange Book, Watson filed an ANDA challenging it. That would give Watson "first-filer" status. "FTC staff sought to understand practically how a generic company would be aware of a later-issued patent so that it would be in the position to file an ANDA amendment on precisely the same day that the brand company listed such later issued patent with the FDA," according to the commission's filing. "Put simply, FTC staff was trying to assess whether a generic company was likely to have such information independently or whether such information was likely available to the generic only as a result of collusion with the brand company to create an additional barrier to impede potential generic entry." Watson told DID it would not respond to the FTC's filing, as it has a policy of not commenting on ongoing litigation. Congress is attempting to scuttle pay-for-delay deals in the future. A provision in the supplemental war appropriations bill, currently before the Senate, would ban the practice (DID, July 6). -- Jonathan Block Release date: July 26, 2010 LOAD-DATE: July 26, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2010 Washington Business Information, Inc. All Rights Reserved 134 of 998 DOCUMENTS Global Insight July 26, 2010 New Zealand's Pharmac Seeks Feedback on Modavigil Application BYLINE: Aparna Krishnan SECTION: In Brief LENGTH: 202 words New Zealand's drug reimbursement agency, Pharmac, has proposed funding CSL Biotherapies' Modavigil (modafinil) under the restricted Special Authority criteria. The drug is intended for patients with narcolepsy, but the agency has sought to restrict its use to patients with narcolepsy who cannot tolerate methylphenidate or dexamphetamine or in whom both methylphenidate and dexamphetamine are contraindicated. Pharmac has sought feedback on the proposal in view of the proposed drug funding from 1 October 2010. Significance:If approved, modafinil 100-mg tablets would be listed in Section B of the Pharmaceutical Schedule at a price and subsidy of NZ$72.50 (US$52.8) per pack of 30 tablets. The scope of overall reimbursement revenues from the drug is expected to be affected due to the restrictions. It is significant to note that the Pharmacology and Therapeutics Advisory Committee reviewed CSL's application for modafinil in February 2007 and recommended restricted listing use to patients with diagnosed excessive daytime sleepiness associated with narcolepsy and who cannot tolerate methylphenidate and dexamphetamine or in whom methylphenidate and dexamphetamine were contraindicated, with a low priority. LOAD-DATE: July 27, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Web Publication Copyright 2010 World Markets Research Limited All Rights Reserved 135 of 998 DOCUMENTS The Pharmaceutical Journal July 26, 2010 Modafinil use should be restricted to narcolepsy, says European Medicines Agency LENGTH: 246 words Modafinil should be used for the treatment of narcolepsy only, the European Medicines Agency has advised. Currently, modafinil is licensed for the treatment of daytime sleepiness associated with narcolepsy, obstructive sleep apnoea syndrome and chronic shift work. However, a review by the agency's Committee for Medicinal Products for Human Use concluded that the benefits of modafinil only outweigh the risks when used for the treatment of narcolepsy - and that all other indications should be withdrawn from the medicine's marketing authorisation. The review was initiated because of safety concerns about psychiatric disorders and serious skin and subcutaneous tissue reactions associated with modafinil. The CHMP found the risk of developing skin and hypersensitivity reactions to be higher in children than in adults and also recommend that modafinil should not be prescribed for people under 18 years of age. The CHMP also identified a number of cardiovascular risks associated with the drug and advised that it should be contraindicated in patients with uncontrolled moderate-to-severe hypertension and in patients with cardiac arrhythmias. The CHMP's recommendations have been forwarded to the European Commission for the adoption of a binding decision valid throughout the EU. The decision-making phase usually takes two to three months and the European Commission follows the CHMP's scientific opinion in almost all cases, a spokeswoman for the EMA told PJ Online.   LOAD-DATE: July 30, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Journal Copyright 2010 PJ Online All Rights Reserved 136 of 998 DOCUMENTS CNS Drug News July 23, 2010 EMA recommends restricting use of modafinil SECTION: NEWS LENGTH: 361 words The European Medicines Agency (EMA) has recommended restricting the use of modafinil-containing medicines. The medicine should only be used to treat sleepiness associated with narcolepsy. Doctors and patients should no longer use the medicine for the treatment of idiopathic hypersomnia, excessive sleepiness associated with obstructive sleep apnoea and chronic shift work sleep disorder. Modafinil is a wakefulness-promoting agent, currently licensed in 21 countries in Europe. It is available as Modasomil, Modiodal, Provigil and Vigil (from Cephalon), and as generic medicines. The review by the Agency's CHMP was initiated because of a number of safety concerns, relating to psychiatric disorders, skin and subcutaneous tissue reactions, as well as significant off-label use and potential for abuse. On the basis of the available data, the Committee concluded that the benefits of these medicines only outweighed their risks in the therapeutic indication of narcolepsy. For all other indications, the Committee found that the risk for development of skin or hypersensitivity reactions and neuropsychiatric disorders outweighed the evidence for clinically-important efficacy. Therefore, the Committee concluded that all other indications should be withdrawn from the marketing authorisations of these medicines. The risk of development of serious skin and hypersensitivity adverse reactions appears to be higher in children than in adults. The Committee concluded that the product information should carry a recommendation saying that modafinil should not be prescribed to children. The CHMP also identified particular cardiovascular risks with modafinil and recommended that the use of the medicine be contraindicated in patients with uncontrolled moderate-to-severe hypertension and in patients with cardiac arrhythmias. There are some reports that modafinil is being used recreationally for "performance enhancement". However, the data seen by the Committee did not allow it to make firm recommendations regarding this risk. The CHMP has requested that the marketing authorisation holders continue to provide further information to monitor the potential for abuse. LOAD-DATE: July 23, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter JOURNAL-CODE: CNS Drug News Copyright 2010 Espicom Business Intelligence All Rights Reserved 137 of 998 DOCUMENTS Elsevier Global Medical News July 22, 2010 Thursday 08:06 PM GMT EMA Announces Review Findings, Decisions on Modafinil, Rotarix, and More BYLINE: By Jennie Smith, Elsevier Global Medical News LENGTH: 774 words A number of drugs ranging from treat sleep apnea medications to vaccines have been under review by the European Medicines Agency, and these review findings, as well as other decisions made by the agency were announced July 22. In a written statement, the agency reported that it would restrict the prescribing of medicines containing modafinil to people with narcolepsy only - preferably laboratory-confirmed narcolepsy - and requested that manufacturers change their product labeling accordingly. Concluding a 3-year review of the medications, the EMA cited concerns about abuse of the wakefulness-promoting drug, along with reports of psychiatric reactions including psychosis, adverse cardiovascular reactions, and serious allergic skin reactions, in its decision. The drug should no longer be used to treat obstructive sleep apnea, shift-work sleep disorder, or idiopathic hypersomnia, the agency said, all indications for which it is licensed in the European Union. The new, restricted indication must be approved by the European Commission before it becomes binding. According to the EMA's new prescribing information, modafinil should be used "only in patients who have had a complete evaluation of their excessive sleepiness, and in whom a diagnosis of narcolepsy has been made in accordance with ICSD [International Classification of Sleep Disorders] diagnostic criteria. Such an evaluation usually consists, in addition to the patient's history, of sleep measurements testing in a laboratory setting." The agency said it also was asking manufacturers to collect data on why modafinil was being prescribed off label and investigating reports of its abuse among university students. Also on July 22, the EMA said it had concluded a review of topical medicines containing the nonsteroidal anti-inflammatory drug ketoprofen. The drug has been licensed since 1978 in all European countries but the Netherlands, but recently has been plagued by reports of increased skin photosensitivity, photoallergy even in dim light, and cosensitization with octocrylene, a chemical used in sunscreens. In December 2009, France suspended the marketing authorization of medicines containing ketoprofen and asked the EMA to consider a similar ban in the EU. Though the EMA did not follow suit, concluding that the risk of reaction was very low, it did advise that topical ketoprofen be used only when prescribed and that manufacturers strengthen product warnings on sun exposure and octocrylene. These recommendations, too, await European Commission approval before they are binding. The EMA found that the porcine circovirus type 1 (PCV1) particles present in the Rotarix vaccine posed no health risk to the public. Rotarix is an oral vaccine used in infants, particularly in developing countries, to protect against gastroenteritis-causing rotavirus infections. The agency began its review of the vaccine after the surprise discovery of PCV1 in batches of the vaccine in March (J. Virol. 2010;84:6033-40). Data from tests carried out by the manufacturer, GlaxoSmithKline, "showed that the vaccine contained only very small amounts of live PCV1. The viral particles may have always been present in the vaccine, and have been found in the raw material used to make the vaccine. Their presence was detected only now because of the emergence of new technology," the agency said. Nonetheless, the EMA noted, the manufacturer has since pledged to eliminate PCV1 from future batches of vaccine. Earlier in the month, July 9, the EMA announced that it was reviewing medicines containing rosiglitazone, a second-line diabetes treatment used alone (Avandia) or in combination with metformin (Avandamet) or glimepiride (Avaglim). Since rosiglitazone's initial EU marketing authorization 10 years ago, rosiglitazone-containing regimens been associated with increased cardiovascular risks that product information and warnings have been altered to reflect. The EMA said on July 22 that it was continuing to evaluate newly published findings on rosiglitazone and cardiovascular events, including myocardial infarction, heart failure, and stroke (JAMA 2010;304 [doi:10.1001/jama.2010.920] and Arch. Intern Med. 2010;170 [doi:10.1001/archinternmed.2010.207]). The rosiglitazone review, the EMA said, would not be finished until September 2010. Until then, it cautioned clinicians to adhere closely to existing warnings and not prescribe rosiglitazone for patients with current or previous heart failure, acute coronary syndrome, ischemic heart disease, or peripheral arterial disease. Rosiglitazone and insulin can be used together only in exceptional cases and under close supervision. LOAD-DATE: July 22, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: NewsWire Copyright 2010 Elsevier Inc., International Medical News Group All Rights Reserved 138 of 998 DOCUMENTS Generic Line July 21, 2010 Wednesday Judge Orders FTC to Answer for Tactics in Provigil Case SECTION: Vol. 27 No. 14 LENGTH: 506 words A federal judge has ordered the FTC to answer questions about allegations it released proprietary information as it tried to thwart a reverse-payment settlement between Watson Pharmaceuticals and Cephalon over Cephalon's drug Provigil. Judge Alan Kay of the U.S. District Court of the District of Columbia this month issued an order instructing the FTC to answer questions posed in a motion by Watson CEO Paul Bisaro, who claims the commission shared proprietary company information with Apotex. The FTC challenged Watson's licensing agreement -- a "pay-for-delay" deal -- for the excessive sleepiness drug Provigil (modafinil) and tried to broker an agreement between Watson and Apotex instead, hoping the result would be cheaper modafinil generics. "This Court finds that the facts before it present a strong possibility that the FTC did share confidential information with Watson's competitor, that it did attempt to broker a deal between Apotex and Watson that would require Watson to relinquish any statutory 'first filer' rights it had acquired, and that it did initiate this investigation to pressure Watson to relinquish these rights and to harass it when it refused," Kay wrote. Bisaro has claimed that the FTC's efforts to subpoena him as part of a pay-for-delay investigation was tantamount to harassment, prompting his lawyers to file a request that the commission answer questions related to its alleged information sharing (Generic Line, June 9). The FTC must provide the court, by July 23, descriptions of communications it had with the FDA and third parties regarding potential marketing exclusivity for generic modafinil and whether any confidential information was disclosed. 'Rock and a Hard Place' "The facts before us suggest that the FTC sought to place Watson between a rock and a hard place, where the only way Watson could clear its name and escape further FTC scrutiny was to give in to the pressure the FTC was placing on Watson to enter into the business deal with Apotex," Kay added. Glenn Lammi, an attorney with the Washington Legal Foundation, told Generic Line Kay's ruling was "extraordinary, considering how infrequently judges allow discoveries in these cases." Kay, however, rejected a request from Bisaro's lawyers to depose Markus Meier, assistant director of the FTC's Bureau of Competition Health Care Division. Last month, two senators pressed FTC Chairman Jon Leibowitz on the agency's alleged action in the Watson matter, with Leibowitz claiming Meier did not breach the company's confidentiality (Generic Line, June 23). FTC Bureau of Competition Director Richard Feinstein disagreed with Kay's ruling, adding the agency has done nothing improper. The FTC "is simply trying to complete a law enforcement investigation into whether there is an agreement to keep generic drugs off the market and out of the hands of consumers," Feinstein said. "We are disappointed that our investigation has been sidetracked by the unfounded implications of opposing counsel." -- Jonathan Block Release date: July 21, 2010 LOAD-DATE: July 21, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2010 Washington Business Information, Inc. All Rights Reserved 139 of 998 DOCUMENTS Global Insight July 21, 2010 U.S. Court Reprimands FTC over Provigil Decision BYLINE: Aparna Krishnan SECTION: In Brief LENGTH: 265 words The U.S. Federal Trade Commission (FTC) has been reprimanded by a U.S. court, which indicated a "strong possibility" of engaging improperly in litigation relating to the sleep drug Provigil (modafinil). According to a written order by the judge at the U.S. District Court for the District of Columbia, the improper conduct refers to the FTC's sharing of confidential information about Provigil marketer, Watson Pharma, with its competitor, the generics firm Apotex (Canada), in an attempt to broker a deal between the two. The judge noted, "the FTC sought to place Watson between a rock and a hard place, where the only way Watson could clear its name and escape further FTC scrutiny was to give in to the pressure the FTC was placing on Watson to enter into the business deal with Apotex". The full order can be accessedhere. However, in an email statement to Reuters, the FTC Competition Bureau Director, Richard Feinstein, has strongly denied wrongdoing. Significance:The public reproach of the FTC's actions reflects on the federal agency's attempts to intervene in such generic drug deals. The FTC has been a strong and vocal advocator of prohibiting the "pay-for-delay" generic deals and has suggested that such agreements between innovators and generic drug makers keep lower cost generic drugs off the market. On the Provigil case, Watson Pharma entered into an agreement with Cephalon (U.S.) along with other generic drug makers to sell modafinil. The innovator, Cephalon, recently lost its bid to dismiss the pay-for-delay lawsuit in Pennsylvania (seeUnited States: 31 March 2010:). LOAD-DATE: July 21, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Web Publication Copyright 2010 World Markets Research Limited All Rights Reserved 140 of 998 DOCUMENTS Washington Drug Letter July 19, 2010 Monday Judge Orders FTC to Answer Watson CEO's Allegations SECTION: Vol. 42 No. 28 LENGTH: 496 words A federal judge has ordered the FTC to answer questions about allegations it released proprietary information as it tried to thwart a reverse-payment settlement between Watson Pharmaceuticals and Cephalon over Cephalon's drug Provigil. Judge Alan Kay of the U.S. District Court of the District of Columbia Tuesday issued an order instructing the FTC to answer questions posed in a motion by Watson CEO Paul Bisaro, who claims the commission shared proprietary company information with Apotex. The FTC challenged Watson's licensing agreement -- a "pay-for-delay" deal -- for the excessive sleepiness drug Provigil (modafinil) and tried to broker an agreement between Watson and Apotex instead, hoping the result would be cheaper modafinil generics. "This Court finds that the facts before it present a strong possibility that the FTC did share confidential information with Watson's competitor, that it did attempt to broker a deal between Apotex and Watson that would require Watson to relinquish any statutory 'first filer' rights it had acquired, and that it did initiate this investigation to pressure Watson to relinquish these rights and to harass it when it refused," Kay wrote. Bisaro has claimed the FTC's efforts to subpoena him as part of a pay-for-delay investigation was tantamount to harassment, prompting his lawyers to file a request that the commission answer questions related to its alleged information sharing (WDL, June 7). The FTC must provide the court, by July 23, descriptions of communications it had with the FDA and third parties regarding potential marketing exclusivity for generic modafinil and whether any confidential information was disclosed. "The facts before us suggest that the FTC sought to place Watson between a rock and a hard place, where the only way Watson could clear its name and escape further FTC scrutiny was to give in to the pressure the FTC was placing on Watson to enter into the business deal with Apotex," Kay added. Glenn Lammi, an attorney with the Washington Legal Foundation, told WDL Kay's ruling was "extraordinary, considering how infrequently judges allow discoveries in these cases." Kay, however, rejected a request from Bisaro's lawyers to depose Markus Meier, assistant director of the FTC's Bureau of Competition Health Care Division. Last month, two senators pressed FTC Chairman Jon Leibowitz on the agency's alleged action in the Watson matter, with Leibowitz claiming Meier did not breach the company's confidentiality (WDL, June 14). FTC Bureau of Competition Director Richard Feinstein disagreed with Kay's ruling, adding the agency has done nothing improper. The FTC "is simply trying to complete a law enforcement investigation into whether there is an agreement to keep generic drugs off the market and out of the hands of consumers," Feinstein said. "We are disappointed that our investigation has been sidetracked by the unfounded implications of opposing counsel." -- Jonathan Block Release date: July 19, 2010 LOAD-DATE: July 19, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2010 Washington Business Information, Inc. All Rights Reserved 141 of 998 DOCUMENTS Drug Industry Daily July 15, 2010 Thursday Judge Orders FTC to Answer Watson CEO's Allegations SECTION: Vol. 9 No. 136 LENGTH: 497 words A federal judge has ordered the FTC to answer questions about allegations it released proprietary information as it tried to thwart a reverse-payment settlement between Watson Pharmaceuticals and Cephalon over Cephalon's drug Provigil. Judge Alan Kay of the U.S. District Court of the District of Columbia Tuesday issued an order instructing the FTC to answer questions posed in a motion by Watson CEO Paul Bisaro, who claims the commission shared proprietary company information with Apotex. The FTC challenged Watson's licensing agreement -- a "pay-for-delay" deal -- for the excessive sleepiness drug Provigil (modafinil) and tried to broker an agreement between Watson and Apotex instead, hoping the result would be cheaper modafinil generics. "This Court finds that the facts before it present a strong possibility that the FTC did share confidential information with Watson's competitor, that it did attempt to broker a deal between Apotex and Watson that would require Watson to relinquish any statutory 'first filer' rights it had acquired, and that it did initiate this investigation to pressure Watson to relinquish these rights and to harass it when it refused," Kay wrote. Bisaro has claimed that the FTC's efforts to subpoena him as part of a pay-for-delay investigation was tantamount to harassment, prompting his lawyers to file a request that the commission answer questions related to its alleged information sharing (DID, June 1). The FTC must provide the court, by July 23, descriptions of communications it had with the FDA and third parties regarding potential marketing exclusivity for generic modafinil and whether any confidential information was disclosed. "The facts before us suggest that the FTC sought to place Watson between a rock and a hard place, where the only way Watson could clear its name and escape further FTC scrutiny was to give in to the pressure the FTC was placing on Watson to enter into the business deal with Apotex," Kay added. Glenn Lammi, an attorney with the Washington Legal Foundation, told DID Kay's ruling was "extraordinary, considering how infrequently judges allow discoveries in these cases." Kay, however, rejected a request from Bisaro's lawyers to depose Markus Meier, assistant director of the FTC's Bureau of Competition Health Care Division. Last month, two senators pressed FTC Chairman Jon Leibowitz on the agency's alleged action in the Watson matter, with Leibowitz claiming Meier did not breach the company's confidentiality (DID, June 11). FTC Bureau of Competition Director Richard Feinstein disagreed with Kay's ruling, adding the agency has done nothing improper. The FTC "is simply trying to complete a law enforcement investigation into whether there is an agreement to keep generic drugs off the market and out of the hands of consumers," Feinstein said. "We are disappointed that our investigation has been sidetracked by the unfounded implications of opposing counsel." -- Jonathan Block Release date: July 15, 2010 LOAD-DATE: July 15, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2010 Washington Business Information, Inc. All Rights Reserved 142 of 998 DOCUMENTS Indian Patents News July 12, 2010 Monday 6:30 AM EST French Inventors Develop 'Combination of Modafinil and an Antagonist or Inverse Agonist of the H3 Receptor' LENGTH: 107 words New Delhi, July 12 -- Schwartz Jean-Charles and Lecomte Jeanne-Marie of Bioprojet, Paris, France have developed 'combination of modafinil and an antagonist or inverse agonist of the H3 receptor'.Bioprojet filed the patent application on Feb. 18, 2009. The patent application number is 380/MUMNP/2009 A.According to the Controller General of Patents, Designs & Trade Marks, "The invention relates to the combination of modafinil and at least one antagonist or inverse agonist of the histamine H3 receptor, which is particularly useful for the treatment of narcolepsy-cataplexy and more generally for sleeping, vigilance or attention disorders." LOAD-DATE: July 12, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 Indian Patents News, distributed by Contify.com All Rights Reserved 143 of 998 DOCUMENTS The Express July 7, 2010 Wednesday Edition 1; National Edition 'Smart drugs' help students pass exams BYLINE: Sarah OGrady SECTION: NEWS; Pg. 7 LENGTH: 246 words MORE students than ever are using "smart drugs" to boost their exam performance, senior drug advisers warn. A growing number of undergraduates - and their professors - are buying prescription drugs such as Modafinil and Ritalin over the internet from suppliers as far away as India. Barbara Sahakian, professor of clinical neuropsychology at the University of Cambridge, said: "I've seen students tear open the envelope from Mumbai in excitement. "But when you are accessing drugs over the internet it's completely unsupervised. "You might be on other drugs or have some preexisting condition that means you shouldn't be taking it." Studies show Modafinil increases motivation and ability to concentrate, but it can be dangerous for people with high blood pressure. Side effects of Ritalin can include mood swings, increased heart rate, dizziness and insomnia. Prof Sahakian was asked to research the problem by the Advisory Council for the Misuse of Drugs. She has called for a Government policy review on smart drugs. A recent survey of 1,000 Cambridge undergraduates showed that one in 10 had used cognitive-enhancing drugs - also known as "professor's little helpers". Another third said they would use them if they had access to them. One in five academics also admitted taking the drugs. But fears are growing that students who order the drugs online could be exposing themselves to health risks or buying counterfeit drugs. They can also get hooked and can't wean themselves off them. LOAD-DATE: July 7, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: DXP Copyright 2010 Express Newspapers All Rights Reserved 144 of 998 DOCUMENTS Indian Patents News June 24, 2010 Thursday 6:30 AM EST Irish Inventors Develop Nanoparticulate Formulations of Modafinil LENGTH: 173 words New Delhi, June 24 -- Jenkins Scott, Liversidge Gary and Manser David of Elan Corporation, PLC, Dublin, Ireland have developed nanoparticulate formulations of modafinil.Elan Corporation, PLC filed the patent application on Jan. 16, 2009. The patent application number is 210/KOLNP/2009 A.According to the Controller General of Patents, Designs & Trade Marks, "The present invention is directed to compositions comprising a nanoparticulate modafinil compositions, or a salt(s), or an enantiomer(s), or a prodrug(s), or a polymorph(s) or derivative thereof, having improved bioavailability. The nanoparticulate modafinil composition formulation particles of the composition have an effective average particle size of less than about 2000 nm and are useful in the treatment of dyssomnias, including but not limited to, narcolepsy, chronic fatigue, eating disorders, compulsive behaviors, ADIID, addictions, substance abuse, sleepiness, nervous system diseases, conditions, syndromes, and symptoms and related diseases, conditions, and symptoms." LOAD-DATE: June 24, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 Indian Patents News, distributed by Contify.com All Rights Reserved 145 of 998 DOCUMENTS Generic Line June 9, 2010 Wednesday Watson CEO Alleges FTC Harassment in Provigil Pay-for-Delay Case SECTION: Vol. 27 No. 12 LENGTH: 339 words Watson Pharmaceuticals CEO Paul Bisaro is accusing the FTC of harassment in its effort to get him to testify in an ongoing case regarding a pay-for-delay settlement with Cephalon. "The FTC's pursuit of the subpoena demonstrates that its conduct is nothing short of harassment," Bisaro's lawyers claim in a document submitted recently to the U.S. District Court for the District of Columbia. Enforcing the subpoena would be tantamount to abuse of the court's process, they add. The FTC challenged Watson's licensing agreement for Cephalon's excessive sleepiness drug Provigil (modafinil) and tried to broker an agreement between Watson and Apotex instead, hoping to provide cheaper modafinil generics, according to court documents. Cephalon reached the settlement with Watson in 2006, allowing Watson partner Carlsbad Technology to manufacture the modafinil generic prior to patent expiry. Four other generic-drug makers also made deals with Cephalon on Provigil generics (Generic Line, May 12). The deals have been the subject of several lawsuits against the companies involved, the latest of which came May 27 when the supermarket and pharmacy chain Giant Eagle challenged the settlements in a suit filed in the U.S. District Court for the Northern District of Ohio. Cephalon's settlements with the various generic makers delay competition and amount to an effort to monopolize the market for Provigil, the suit says. In his action, Bisaro claims he should not be subpoenaed in Federal Trade Commission v. Paul M. Bisaro since he was not employed by Watson when the agreement with Cephalon was signed. The FTC is pursuing the subpoena either to pressure Watson into reaching an agreement with Apotex or to retaliate against the company, Bisaro's lawyers say. They also accuse the FTC of sharing with Apotex some of Watson's privileged information, submitted to the FDA, as evidenced by an internal email Apotex forwarded to Watson. The FTC has said ending pay-for-delay settlements is a top priority. -- Jonathan Block Release date: June 9, 2010 LOAD-DATE: June 9, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2010 Washington Business Information, Inc. All Rights Reserved 146 of 998 DOCUMENTS Washington Drug Letter June 7, 2010 Monday Watson CEO Claims FTC Subpoena Is Harassment or Retaliation SECTION: Vol. 42 No. 23 LENGTH: 341 words Watson Pharmaceuticals CEO Paul Bisaro is accusing the FTC of harassment in its effort to get him to testify in an ongoing case regarding a pay-for-delay settlement with Cephalon. "The FTC's pursuit of the subpoena demonstrates that its conduct is nothing short of harassment," Bisaro's lawyers claim in a document submitted recently to the U.S. District Court for the District of Columbia. Enforcing the subpoena would be tantamount to abuse of the court's process, they add. The FTC challenged Watson's licensing agreement for Cephalon's excessive sleepiness drug Provigil (modafinil) and tried to broker an agreement between Watson and Apotex instead, hoping to provide cheaper modafinil generics, according to court documents. Cephalon reached the settlement with Watson in 2006, allowing Watson partner Carlsbad Technology to manufacture the modafinil generic prior to patent expiry. Four other generic-drug makers also made deals with Cephalon on Provigil generics (WDL, May 3). Settlements Challenged The deals have been the subject of several lawsuits against the companies involved, the latest of which came May 27 when the supermarket and pharmacy chain Giant Eagle challenged the settlements in a suit filed in the U.S. District Court for the Northern District of Ohio. Cephalon's settlements with the various generic makers delay competition and amount to an effort to monopolize the market for Provigil, the suit says. In his action, Bisaro claims he should not be subpoenaed in Federal Trade Commission v. Paul M. Bisaro since he was not employed by Watson when the agreement with Cephalon was signed. The FTC is pursuing the subpoena either to pressure Watson into reaching an agreement with Apotex or to retaliate against the company, Bisaro's lawyers say. They also accuse the FTC of sharing some of Watson's privileged information, submitted to the FDA, with Apotex, as evidenced by an internal email Apotex forwarded to Watson. The FTC has said ending pay-for-delay settlements is a top priority. -- Jonathan Block Release date: June 7, 2010 LOAD-DATE: June 7, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2010 Washington Business Information, Inc. All Rights Reserved 147 of 998 DOCUMENTS PR Newswire June 2, 2010 Wednesday 4:30 PM EST Cephalon Provides Clinical Update on Phase II Study of NUVIGIL as an Adjunctive Therapy in Adults with Schizophrenia LENGTH: 947 words DATELINE: FRAZER, Pa., June 2 FRAZER, Pa., June 2 /PRNewswire-FirstCall/ -- Cephalon, Inc. (Nasdaq: CEPH) today announced that the primary endpoint was not met in a Phase II clinical trial that examined NUVIGIL® (armodafinil) Tablets [C-IV] as an adjunctive therapy for the treatment of the negative symptoms of schizophrenia, which include problems with motivation and emotional withdrawal. The analysis of the data showed that treatment with armodafinil did not lessen the severity of the negative symptoms of schizophrenia compared to placebo in the 24-week study. As a result of the outcome of this trial, Cephalon has decided not to move forward with this clinical program. The trial was designed to evaluate whether armodafinil treatment (150, 200, or 250 mg/day) was more effective than placebo treatment as an adjunctive therapy to antipsychotic medication in alleviating the negative symptoms of schizophrenia, as assessed by the primary outcome measure of the Positive and Negative Syndrome Scale. Although an interim analysis showed a trend towards a positive dose dependent treatment effect, it was not statistically significant and not maintained in the final analysis of all patients. Armodafinil was generally well tolerated in the study and the side effects were consistent with the known safety profile. Results of this study will be presented at a future medical meeting. "While we are disappointed that the results of this study did not demonstrate a benefit for this patient population, Cephalon remains committed to the NUVIGIL clinical development plan," said Dr. Lesley Russell, Chief Medical Officer at Cephalon. "We are continuing our discussions with the agency on our application for excessive sleepiness associated with jet lag disorder and Phase III trials are on track evaluating armodafinil in bipolar depression and excessive sleepiness resulting from traumatic brain injury." About NUVIGIL NUVIGIL is the longer-lasting isomer of modafinil. It is indicated to improve wakefulness in patients with excessive sleepiness associated with treated obstructive sleep apnea (OSA), shift work disorder (SWD), or narcolepsy. NUVIGIL is not approved as a treatment for jet lag disorder, bipolar depression, traumatic brain injury, or their associated symptoms. The NUVIGIL (armodafinil) label includes a bolded warning for serious or life-threatening rash, including Stevens-Johnson Syndrome, that has been reported in adults in association with the use of armodafinil and in adults and children in association with the use of modafinil, a racemic mixture of S and R modafinil (the latter is armodafinil, the active ingredient in NUVIGIL). NUVIGIL is not approved for use in pediatric patients for any indication. The most common adverse events in controlled clinical trials (five percent or greater) were headache, nausea, dizziness, and insomnia. Full prescribing information for NUVIGIL is available at http://www.nuvigil.com/. About Cephalon, Inc. Cephalon is a global biopharmaceutical company dedicated to discovering, developing and bringing to market medications to improve the quality of life of individuals around the world. Since its inception in 1987, Cephalon has brought first-in-class and best-in-class medicines to patients in several therapeutic areas. Cephalon has the distinction of being one of the world's fastest-growing biopharmaceutical companies, now among the Fortune 1000 and a member of the S&P 500 Index, employing approximately 4,000 people worldwide. The company sells numerous branded and generic products around the world. In total, Cephalon sells more than 150 products in nearly 100 countries. More information on Cephalon and its products is available at http://www.cephalon.com/. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs; development of potential pharmaceutical products; interpretation of clinical results; prospects for regulatory approval; manufacturing development and capabilities; market prospects for its products; and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. Contacts: Media: Investor Relations: Candace Steele Flippin Chip Merritt 610-727-6231 (office) 610-738-6376 (office) csteele@cephalon.com cmerritt@cephalon.com SOURCE Cephalon, Inc. CONTACT:Media: Candace Steele Flippin, +1-610-727-6231 (office), csteele@cephalon.com, Investor Relations: Chip Merritt, +1-610-738-6376 (office), cmerritt@cephalon.com URL: http://www.prnewswire.com LOAD-DATE: June 3, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 PR Newswire Association LLC All Rights Reserved 148 of 998 DOCUMENTS Drug Industry Daily June 1, 2010 Tuesday Watson CEO Accuses FTC of Harassment in Pay-for-Delay Case SECTION: Vol. 9 No. 105 LENGTH: 337 words Watson Pharmaceuticals CEO Paul Bisaro is accusing the FTC of harassment in its effort to get him to testify in an ongoing case regarding a pay-for-delay settlement with Cephalon. "The FTC's pursuit of the subpoena demonstrates that its conduct is nothing short of harassment," Bisaro's lawyers claim in a document submitted recently to the U.S. District Court for the District of Columbia. Enforcing the subpoena would be tantamount to abuse of the court's process, they add. The FTC challenged Watson's licensing agreement for Cephalon's excessive sleepiness drug Provigil (modafinil) and tried to broker an agreement between Watson and Apotex instead, hoping to provide cheaper modafinil generics, according to court documents. Cephalon reached the settlement with Watson in 2006, allowing Watson partner Carlsbad Technology to manufacture the modafinil generic prior to patent expiry. Four other generic-drug makers also made deals with Cephalon on Provigil generics (DID, April 27). The deals have been the subject of several lawsuits against the companies involved, the latest of which came Thursday when the supermarket and pharmacy chain Giant Eagle challenged the settlements in a suit filed in the U.S. District Court for the Northern District of Ohio. Cephalon's settlements with the various generic makers delay competition and amount to an effort to monopolize the market for Provigil, the suit says. In his action, Bisaro claims he should not be subpoenaed in Federal Trade Commission v. Paul M. Bisaro since he was not employed by Watson when the agreement with Cephalon was signed. The FTC is pursuing the subpoena either to pressure Watson into reaching an agreement with Apotex or to retaliate against the company, Bisaro's lawyers say. They also accuse the FTC of sharing some of Watson's privileged information, submitted to the FDA, with Apotex, citing an internal email Apotex forwarded to Watson. The FTC has said ending pay-for-delay settlements is a top priority. -- Jonathan Block Release date: June 1, 2010 LOAD-DATE: June 1, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2010 Washington Business Information, Inc. All Rights Reserved 149 of 998 DOCUMENTS Fleet Owner June 1, 2010 Help in a pill or a cup SECTION: Pg. 35 LENGTH: 498 words Songwriters may love to romanticize outlaw truckers who take amphetamines to keep driving for days, but the reality is drivers (who are routinely tested for illegal drug use) favor the same stimulant everyone else uses in our Starbucks culture - caffeine. When it comes to staying alert behind the driver's wheel, "caffeine is a very useful tool," according to Todd Dawson of Circadian. "It does what it's supposed to - it boosts reaction times, but it's overused in our society. Taken in high amounts, caffeine can not only create health problems, but you build up a tolerance." Instead of drinking coffee throughout the day, perhaps consuming as much as eight cups, truck drivers should drink a cup or two at the start of their workday and then another one or two cups only when they begin to feel drowsy later in the day. "The [caffeine] benefit is much higher when it's used carefully," Dawson says. Gerald Krueger, who is putting together a report on stimulants, hypnotics and nutritional supplements for the Transportation Research Board, agrees that caffeine used properly is a practical tool to help retain alertness. What concerns him are the "energy boost" products and other supplements marketed at truckstops. While caffeine is often a major component in these products, "there's not been much good, solid medical research published to be able to assess whether they're good or bad," says Krueger. Prescription stimulant drugs have much stronger effects than caffeine, but most of the well-known ones such as amphetamines have serious side effects. However, lately there's been a good deal of attention focused on a new stimulant compound known as Modafinil, which is available in the U.S. as the prescription drug Provigil. Krueger says that while Modafinil does boost alertness much like caffeine, an attractive feature is that "while under the influence of Modafinil, one can apparently still decide to go to sleep, for example, something no other stimulant would permit you to do." Krueger also said that the U.S. military administers prescription stimulants, including Modafinil, in some very select operational circumstances, but only after evaluating how individuals perform when taking the drugs in controlled settings and then monitoring them closely if they do take them in the field. "Currently, there doesn't seem to be any practical application in trucking for stimulants other than using caffeine because there's no way to control their use with a large population like truck drivers," says Krueger. "But we shouldn't hide our head in the sand. We should be doing good quality medical research on these compounds to see if there are practical applications for newer compounds as they are developed." For now, though, Krueger believes the best solution for drivers is "the natural way." Combining proper sleep habits with an understanding of circadian rhythms, "they can use the strengths of knowing more about their own body's physiology to help manage fatigue," he says. LOAD-DATE: June 10, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Magazine Copyright 2010 Penton Business Media, Inc. All Rights Reserved 150 of 998 DOCUMENTS Indian Patents News May 31, 2010 Monday 6:30 AM EST American Inventors Develop Pharmaceutical Formulations of Modafinil LENGTH: 136 words New Delhi, May 31 -- Craig Heacock, Alpa Parikh and Piyush Patel of Cephalon, Inc, West Chester, USA have developed pharmaceutical formulations of modafinil .Cephalon, Inc filed the patent application on Aug. 10, 2007. The patent application number is 2937/KOLNP/2007 A.According to the Controller General of Patents, Designs & Trade Marks, "Use of a composition consisting essentially of about 250 to about 450 mg of solid modafinil and one or more diluents, each independently chosen from a starch, a lactose monohydrate or a microcrystalline cellulose; one or more disintegrates, each independently chosen from a pre gelatinized starch or a cross-linked sodium carboxymethly cellulose; a binder; and a lubricant for preparation of a medicament for treating attention deficit hyperactivity disorder in a human subject." LOAD-DATE: June 21, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 Indian Patents News, distributed by Contify.com All Rights Reserved 151 of 998 DOCUMENTS Prospect May 27, 2010 Going mental BYLINE: Barbara J Sahakian and Ahmed D Mohamed LENGTH: 748 words Who could object to drugs that help people affected by mental disorders such as schizophrenia? Such treatments, known as pharmacological cognitive enhancers (PCEs) can improve memory, attention and motivation. Methylphenidate (Ritalin), for example, helps children with attention deficit hyperactivity disorder (ADHD) focus better in school, often making an important difference to their lives. Modafinil (Provigil) helps people stay awake and is licensed for the treatment of narcolepsy, a condition that causes sufferers to fall asleep involuntarily. So far, so good. But the past few years have seen an unprecedented rise in the use of PCEs by healthy people. For many students, the temptation to pop a few pills to aid concentration-especially at exam time-is hard to resist. Most of them see it as harmless and ethically acceptable. Others see it as cheating and, as yet, few universities have formal policies on the issue. According to a 2004 report in the Journal of the American Medical Association, around 90 per cent of modafinil is used by healthy, non-sleep-deprived individuals. In March 2009, an informal survey of 1,000 students by the Cambridge University student newspaper Varsity showed that one in ten were taking prescription drugs for cognitive enhancement. The year before, Nature conducted a poll of 1,400 scientists from 60 different countries. One in five respondents used drugs for cognitive enhancement, of which 62 per cent reported taking methylphenidate and 44 per cent modafinil, mainly to improve concentration. Fifteen per cent said they took beta-blockers for anxiety, when such drugs are normally prescribed to reduce blood pressure or irregular heart rhythms. One American professor said he obtained his drugs through his primary care doctor by claiming to have jet lag, while one British professor got his through the internet to "enhance productivity" and "for important intellectual challenges." More worrying, a 2009 survey by the US National Institute on Drug Abuse (Nida) found that 1.8 per cent of 13 to 14 year olds, 3.6 per cent of 15 to 16 year olds and 2.1 per cent of 17 to 18 year olds abused methylphenidate. The widespread use of cognition- enhancing drugs is perhaps not surprising given that the Academy of Medical Sciences's 2008 report on brain science, addiction and drugs suggested that a 10 per cent improvement in memory score could lead to a higher A-level grade or degree classification. Small improvements in intellectual performance can lead to significant improvements in outcomes. But what are the advantages and disadvantages of healthy people using PCEs? On the plus side, since PCEs may help those with low cognitive performance, it might be possible to mitigate the effects of poverty on the brain through their use. This could have positive effects on society and the economy as a whole: it has been estimated that a 3 per cent population-wide increase in IQ could reduce poverty rates by up to 25 per cent and increase GDP by up to 1.5 per cent. Of course, even healthy adults who normally function well do not necessarily do their best all the time, because of sleep deprivation, jet lag or other stressors. And PCEs might also enable us to perform better in pleasurable and competitive situations. For instance, Anjan Chatterjee, a neurologist at the University of Pennsylvania, reported that musicians often use beta-blockers to dampen physical tremors, improving their performance. Psychostimulants have also been used to boost soldiers in combat, shift workers and pilots. But not enough is known about the long-term side effects of PCEs, especially in the developing brain. A 2009 report by Nida found that modafinil stimulated areas in the brain known to trigger drug seeking behaviour and addiction. We must also consider why these drugs are being used. Is the pressure to do well in exams, clinch a business deal, or keep up with our "24/7 society" pushing people to use them, instead of traditional means of boosting cognition, such as exercise? Clearly, neuroscientists need to work together with social scientists, philosophers, ethicists, policymakers and other experts to establish clear, safe and ethical rules for PCE use in healthy people. This is the only way that the major advances now being made in brain science can be put to maximum benefit-and minimal harm. Barbara J Sahakian is a professor of clinical neuropsychology at Cambridge University. Ahmed D Mohamed is a PhD student at Clare Hall, Cambridge ? LOAD-DATE: May 21, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Magazine Copyright 2010 Prospect Magazine All Rights Reserved 152 of 998 DOCUMENTS Generic Line May 12, 2010 Wednesday FTC Labels Pay-for-Delay Fight an Agency Top Priority in 2010 SECTION: Vol. 27 No. 10 LENGTH: 502 words The FTC is making its fight against pay-for-delay settlements between brand- and generic-drug makers a top priority this year. The patent settlements, in which brand companies reward generic-drug makers to delay the introduction of less expensive versions of their medicines, keep generic drugs off the market for an average of 17 months longer than agreements without payments and will cost consumers and taxpayers $35 billion over the next 10 years, the commission says in its annual report. The FTC also is pursuing actions against drugmakers in federal court cases. In one case, the agency lodged a complaint against Cephalon in 2008, alleging the drugmaker paid four companies to refrain from selling generic versions of its sleep drug Provigil (modafinil) until 2012 (Generic Line, Feb. 20, 2008). The company entered into seemingly separate transactions worth a total of more than $200 million, the FTC said in 2008 (Generic Line, May 28, 2008). For example, Teva Pharmaceuticals agreed not to launch generic Provigil until April 2012 in exchange for a license agreement relating to its modafinil patents and patent applications worth up to $125 million in Provigil royalties. Cephalon also agreed to buy modafinil active pharmaceutical ingredient from Teva at prices higher than what it had been paying, the commission alleged at the time. The case is still pending in the U.S. District Court for the Eastern District of Pennsylvania, the FTC says. In a separate case, the commission obtained $2.1 million from Bristol-Myers Squibb (BMS) for failing to inform the FTC of agreements reached with Canadian drugmaker Apotex regarding potential generic competition for blockbuster drug Plavix, according to the report. The commission charged that, as part of a patent settlement with Apotex, BMS promised it would not compete with Apotex during the first 180 days that Apotex marketed its generic version of the drug. The FTC suffered a defeat, however, in a case in which it claimed reverse payment, or pay-for-delay, settlements Solvay Pharmaceuticals made with Watson Pharmaceuticals, Par Pharmaceutical and Paddock Laboratories for the marketing of generic AndroGel (testosterone) violated federal antitrust laws. The U.S. District Court for the Northern District of Georgia dismissed the case in February, saying patent litigation is too complex and the results too uncertain to assert such a claim (Generic Line, March 3). The agency also had hoped that a ban on the agreements would be included in healthcare overhaul legislation signed into law earlier this year, but the provision was not included in the final bill. Sen. Herb Kohl (D-Wis.) has indicated he will fight for his pay-for-delay bill, Preserve Access to Affordable Generics Act, S. 369, to be considered as an individual piece of legislation by the full Senate or piggyback on another bill (Generic Line, March 31). The FTC annual report is available at www.ftc.gov/os/2010/04/2010ChairmansReport_screen.pdf. -- David Belian Release date: May 12, 2010 LOAD-DATE: May 12, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2010 Washington Business Information, Inc. All Rights Reserved 153 of 998 DOCUMENTS Penton Insight May 11, 2010 Helping drivers stay alert BYLINE: By Jim Mele, editor-in-chief LENGTH: 561 words When it comes to staying alert behind the driver's wheel,"caffeine is a very useful tool," according to ToddDawson, vp of the fatigue management company Circadian. "It does what it'ssupposed to - it boosts reaction times, but it'soverused in our society. Taken in high amounts, caffeine can notonly create health problems, but you build up atolerance." The stimulant effect of the caffeine in two cups of coffee lastsfive to seven hours, he said. Instead of drinking coffee throughoutthe day, perhaps consuming as much as eight cups, truck driversshould drink a cup or two at the start of their work day and thenanother one or two cups only when they begin to feel drowsy laterin the day. "The benefit [from caffeine] is much higher whenit's used carefully," Dawson said Gerald Krueger, a well-known researcher who is currentlyputting together a report on stimulants, hypnotics and nutritionalsupplements for the Transportation Research Board, agrees thatcaffeine used properly is a practical tool to help truck driversretain alertness during those naturally occurring times when aperson becomes drowsy. What concerns him are the "energy boost" productsand other nutritional supplements commonly marketed to drivers attruckstops.  While caffeine is often a major component inthese products, "there's not been much good solidmedical research published to be able to assess whetherthey're good or bad, or whether they produce interactionswith other substances like allergy medicines," Kruegersaid. Prescription stimulant drugs have much stronger effects thancaffeine, but most of the well-known ones such as amphetamines haveserious side effects that after long-term use might includeinsomnia and addiction.  However lately there's been agood deal of attention focused on a new stimulant compound known asmodafinil which is available in the U.S. as the prescription drugProVigil.  Krueger said that while modafinil does boostalertness much like caffeine, an  attractive feature is that"while under the influence of modafinil, one can apparentlystill decide to go to sleep, to take a nap for example, somethingno other stimulant would permit you to do." Krueger also said that the U.S. military administersprescription stimulants, including modafinil, in some very selectoperational circumstances, but only after evaluating howindividuals perform when taking the drugs in controlled settingsand then monitoring them closely if they do take them in thefield. "Currently there doesn't seem to be any practicalapplication in trucking for stimulants other than using caffeinebecause there's no way to control their use with alarge population like truck drivers," said Krueger. "But we shouldn't hide our head in the sand,"said Krueger. "We should be doing good quality medicalresearch on these compounds to see if there are practicalapplications for some newer compounds as they aredeveloped."  For example, he pointed out that the U.S.military explored and now safely issues caffeinated chewing gum totired troops, and this would seem to be an appropriate applicationfor commercial drivers as well. For now, though, Krueger believes the best solution for driversis "the natural way." Combining proper sleep habitswith an understanding for their circadian rhythms, "they canuse the strengths of knowing more about their own body'sphysiology to help manage fatigue," Krueger noted. LOAD-DATE: May 12, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Web Publication Copyright 2010 Penton Business Media, Inc. All Rights Reserved 154 of 998 DOCUMENTS Washington Drug Letter May 3, 2010 Monday FTC Fight Against Pay-for-Delay Becomes a Top Priority in 2010 SECTION: Vol. 42 No. 18 LENGTH: 496 words The FTC is making its fight against pay-for-delay settlements between brand- and generic-drug makers a top priority this year. The patent settlements, in which brand companies reward generic-drug makers to delay the introduction of less expensive versions of their medicines, keep generic drugs off the market for an average of 17 months longer than agreements without payments and will cost consumers and taxpayers $35 billion over the next 10 years, the commission says in its annual report. The FTC also is pursuing actions against drugmakers in federal court cases. In one case, the agency lodged a complaint against Cephalon in 2008, alleging the drugmaker paid four companies to refrain from selling generic versions of its sleep drug Provigil (modafinil) until 2012 (WDL, Feb. 18, 2008). The company entered into seemingly separate transactions worth a total of more than $200 million, the FTC said in 2008 (WDL, May 26, 2008). For example, Teva Pharmaceuticals agreed not to launch generic Provigil until April 2012 in exchange for a license agreement relating to its modafinil patents and patent applications worth up to $125 million in Provigil royalties. Cephalon also agreed to buy modafinil active pharmaceutical ingredient from Teva at prices higher than what it had been paying, the commission alleged at the time. The case is still pending in the U.S. District Court for the Eastern District of Pennsylvania, the FTC says. In a separate case, the commission obtained $2.1 million from Bristol-Myers Squibb (BMS) for failing to inform the FTC of agreements reached with Canadian drugmaker Apotex regarding potential generic competition for blockbuster drug Plavix, according to the report. The commission charged that, as part of a patent settlement with Apotex, BMS promised it would not compete with Apotex during the first 180 days that Apotex marketed its generic version of the drug. The FTC suffered a defeat, however, in a case in which it claimed reverse payment, or pay-for-delay, settlements Solvay Pharmaceuticals made with Watson Pharmaceuticals, Par Pharmaceutical and Paddock Laboratories for the marketing of generic AndroGel (testosterone) violated federal antitrust laws. The U.S. District Court for the Northern District of Georgia dismissed the case in February, saying patent litigation is too complex and the results too uncertain to assert such a claim (WDL, March 1). The agency also had hoped that a ban on the agreements would be included in healthcare overhaul legislation signed into law earlier this year, but the provision was not included in the final bill. Sen. Herb Kohl (D-Wis.) has indicated he will fight for his pay-for-delay bill, Preserve Access to Affordable Generics Act, S. 369, to be considered as an individual piece of legislation by the full Senate or piggyback on another bill (WDL, March 22). The FTC annual report is available at www.ftc.gov/os/2010/04/2010ChairmansReport_screen.pdf. -- David Belian Release date: May 3, 2010 LOAD-DATE: May 3, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2010 Washington Business Information, Inc. All Rights Reserved 155 of 998 DOCUMENTS Drug Industry Daily April 27, 2010 Tuesday FTC: Ending Pay-for-Delay Settlements is Top Priority SECTION: Vol. 9 No. 81 LENGTH: 503 words The FTC is making its fight against pay-for-delay settlements between brand- and generic-drug makers a top priority this year. The patent settlements, in which brand companies reward generic-drug makers to delay the introduction of less expensive versions of their medicines, keep generic drugs off the market for an average of 17 months longer than agreements without payments and will cost consumers and taxpayers $35 billion over the next 10 years, the commission says in its annual report. The FTC also is pursuing actions against drugmakers in federal court cases. In one case, the agency lodged a complaint against Cephalon in 2008, alleging the drugmaker paid four companies to refrain from selling generic versions of its sleep drug Provigil (modafinil) until 2012 (DID, Feb. 15, 2008). The company entered into seemingly separate transactions worth a total of more than $200 million, the FTC said in 2008 (DID, May 23, 2008). For example, Teva Pharmaceuticals agreed not to launch generic Provigil until April 2012 in exchange for a license agreement relating to its modafinil patents and patent applications worth up to $125 million in Provigil royalties. Cephalon also agreed to buy modafinil active pharmaceutical ingredient from Teva at prices higher than what it had been paying, the commission alleged at the time. The case is still pending in the U.S. District Court for the Eastern District of Pennsylvania, the FTC says. In a separate case, the commission obtained $2.1 million from Bristol-Myers Squibb (BMS) for failing to inform the FTC of agreements reached with Canadian drugmaker Apotex regarding potential generic competition for blockbuster drug Plavix, the commission says in the report. The commission charged that, as part of a patent settlement with Apotex, BMS promised that it would not compete with Apotex during the first 180 days that Apotex marketed its generic version of the drug. The agency suffered a defeat, however, in a case in which it claimed reverse payment, or pay-for-delay, settlements Solvay Pharmaceuticals made with Watson Pharmaceuticals, Par Pharmaceutical and Paddock Laboratories for the marketing of generic AndroGel (testosterone) violated federal antitrust laws. The U.S. District Court for the Northern District of Georgia dismissed the case in February, saying patent litigation is too complex and the results too uncertain to assert such a claim (DID, Feb. 25). The agency had also hoped that a ban on the agreements would be included in healthcare overhaul legislation signed into law earlier this year, but the provision failed to be included in the final bill. Sen. Herb Kohl (D-Wis.), however, has indicated that he will fight for his pay-for-delay bill Preserve Access to Affordable Generics Act, S. 369, to be considered as an individual piece of legislation by the full Senate or piggyback on another bill (DID, March 23). The FTC annual report can be found at www.ftc.gov/os/2010/04/2010ChairmansReport_screen.pdf. -- David Belian Release date: April 27, 2010 LOAD-DATE: April 27, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2010 Washington Business Information, Inc. All Rights Reserved 156 of 998 DOCUMENTS The Guardian (London) - Final Edition April 6, 2010 Tuesday Education: Smart work: Students are increasingly taking neuroenhancing drugs to fight fatigue and help them concentrate. But how safe are they - and is it cheating? BYLINE: Catherine Nixey SECTION: GUARDIAN EDUCATION PAGES; Pg. 1 LENGTH: 1362 words It is an all too common story: a diligent student works hard and finally achieves a coveted place at Cambridge University. Once there, the pressure becomes too great and they turn to drugs. These days, however, the old narrative has changed. Instead of the spliffs that apparently so delighted generations of our politicians, the latest fad is for educational, not recreational, drugs. "It was the summer term of my second year," explains Raj Perera, in his final year of a natural sciences degree at Cambridge University. "I'm an international student, which means my parents are paying £20,000 for every year I am here. That sort of money puts a huge pressure on you. But last summer, I had two weeks to go before my exams, and I had done pretty much no revision. It was a make-or-break moment. So I bought modafinil." Modafinil is one of the new neuroenhancing "smart drugs" now being taken by growing numbers of students. It was originally developed for the treatment of narcolepsy, but is now used by students to combat fatigue. Another popular choice is Ritalin, originally designed as a treatment for attention deficit hyperactivity disorder (ADHD). Both increase levels of dopamine levels in the brain - and the alertness and wakefulness of those taking them. So popular have these drugs become that last month Barbara Sahakian, professor of clinical neuropsychology at Cambridge University's psychiatry department, warned that their use has "enormous implications" and that universities must act on them - even mentioning dope testing as one possibility. But this is not happening. "What universities are doing about (them) is nothing," she says. Last year, Sahakian was co-opted on to a committee, set up by the Medical Advisory Council on the Misuse of Drugs, to look at the use of cognitive enhancing drugs by healthy people. One American study, cited in the journal Nature, estimated that up to 25% of students at some campuses had taken neuroenhancing drugs in the past year. Many hear of these drugs through friends, others independently. "I read an article in the student press on them," says Lawrence Price, a third-year arts student at Sheffield Hallam University. "It was criticising them, but I thought they sounded great." Perera, similarly, found out about smart drugs through the media. "I read an article in Nature on them," he says. "They seemed a pretty good idea." Students believe the drugs enable them to do more work. "I take them when I need to get through lectures and I have a terrible hangover," says Price. At the other extreme, Lucy Makepeace, a postgraduate student at Cambridge, uses them less from a lack of diligence than an excess of it. Extremely hard working, she takes modafinil once or twice a week. "With study, work and sport I have a very full timetable," she says. "I want to do everything, but I don't want to do any of it at a mediocre level. Taking modafinil helps me to do it all." Perera similarly turned to modafinil from time pressures - which were, in his case, extreme. "Due to difficulty getting my visa last year, I couldn't return at the start of the summer term," he says. "When I eventually got my visa, I arrived back with just a fortnight before my exams, and no revision behind me." All the students are clear on the drug's effects. "Modafinil increases my enthusiasm for studying," says Perera. "It makes me feel that lazing around is the last thing I want to do." Price agrees: "Modafinil gives me the motivation I would otherwise lack." Makepeace, who clearly doesn't lack motivation, instead takes modafinil to stay alert. "Once I've taken a pill I can stay up all night without stopping. It just works so well," she says. "I need it." The way the students obtain the drugs varies. Some get them from friends, but many purchase them from online chemists. "I just Googled them," says Perera. "The cost, including shipping, came to about £2 each." "I bought them from an online pharmacy," says Price. "You just sign a disclaimer saying you won't sue them for selling you prescription drugs without a prescription, then they send you them." Unknown quantity Such a convenient process might please the consumer, but it is not one that impresses Sahakian. "When you get a drug off the internet, you don't know what it is, or whether you have some pre-existing condition that means you shouldn't be taking it," she says. "If you get a drug from your GP, they would check that." Even if the drugs are what they purport to be, they are not risk-free. Such smart drugs have only been developed relatively recently, and, says Sahakian (who has herself researched the effects of modafinil on healthy volunteers), it is therefore too early to feel confident that they are safe. "It's a real worry that students are taking these drugs, as we just don't know whether they are safe in the long term. They're so new. How could we know?" In addition to concerns about the drugs' physical effects, there are also moral issues. "Do we want to solve all our problems in this way?" Sahakian asks. "There are other ways of coping - like exercise, or sleep." Such methods would not only be physiologically better, but also psychologically. "It's nice to feel that what you have achieved is your achievement. Take a pill and you might not feel that," she says. For some, chemically enhanced achievement is reprehensible. "Students who are not taking them, feel (to do so) is cheating," says Sahakian. "They feel that (taking these) could just make the difference between a 2.1 and a first. At that point, students who don't want to take them start to feel coerced into doing so because everyone else is." But the accusation of bending the rules is denied unanimously. "I'm not cheating," says Makepeace. "Taking a pill is no different to having a cup of coffee. It's just more effective." Perera agrees: "I don't think this is cheating. I read a nice analogy, which said that people with a bad memory are no different to people who have bad eyesight. You let people with bad eyesight have glasses; why not let people with a bad memory have these pills?" At present, the actual status of such drug-taking remains undefined by universities, something that Sahakian hopes they will soon address. "Universities need to think about whether they want their students to be on drugs or not when they come into their exams. There needs to be some debate within the universities. Do we care about this? Is this cheating? Is it the way we want our society to be going?" Professor John Rallison, pro vice-chancellor for education at Cambridge University, said the university "does not approve of any non-medicinal drug-taking", and welfare officers at the university's union said that they were concerned about such usage. The view is echoed by Universities UK, the body representing the heads of British universities, which says it has "grave concerns about students taking drugs not prescribed to them", because it "poses health risks to those students". Instead, it advises pressurised students to seek help from university counselling services or the GP. A spokesman for Sheffield Hallam University said: "We are not aware of any student taking this drug and if any students do have difficulties with their studies we encourage them to make use of our support services." Given the habits of academics themselves, the topic is a sensitive one: according to a recent survey by Nature, whose readership tends to be academics and researchers, one in five respondents said that they had used smart drugs. Something of which Sahakian herself has personal experience. "I was at a conference in America recently," she says. "I'd just flown in that day from the UK. I saw I was timetabled to give a lecture that afternoon. I wanted to do a good job of it, but I was just feeling so jetlagged. I mentioned to a colleague how I felt and he immediately said to me, 'Oh, do you want to take some of my modafinil?'" She didn't, for the record, accept. All student names have been changed Captions: Modafinil is one of the new 'smart drugs' being used by students to help them keep going Photograph: Will Boase Staying alert is one reason students give for taking modafinil Alamy LOAD-DATE: April 6, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2010 Guardian Newspapers Limited All Rights Reserved 157 of 998 DOCUMENTS Indian Patents News April 2, 2010 Friday 6:30 AM EST American Inventors Develop Processes for the Preparation of Modafinil and Analogs Thereof LENGTH: 118 words New Delhi, April 2 -- Liang Sidney, Duchek John R and Schaffer Carl J of Mallinckrodt Inc, St. Louis, USA have developed processes for the preparation of modafinil and analogs thereof.Mallinckrodt Inc filed the patent application on June 9, 2008. The patent application number is 2877/CHENP/2008 A.According to the Controller General of Patents, Designs & Trade Marks, "The present invention generally relates to an improved process for preparing modafinil and analogs thereof. The process minimizes impurities and improves the overall yield by oxidizing a modafinil intermediate compound in a reaction mixture including an alcohol and an organic acid at a ratio of from about 1:1 to about 80:1 (by volume)." LOAD-DATE: May 4, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 Indian Patents News, distributed by Contify.com All Rights Reserved 158 of 998 DOCUMENTS PR Newswire March 29, 2010 Monday 4:47 PM EST Cephalon Receives Complete Response Letter for NUVIGIL for the Treatment of Excessive Sleepiness Associated with Jet Lag Disorder LENGTH: 1058 words DATELINE: FRAZER, Pa., March 29 FRAZER, Pa., March 29 /PRNewswire-FirstCall/ -- Cephalon, Inc. (Nasdaq: CEPH) today announced the company has received a Complete Response letter from the U.S. Food and Drug Administration (FDA) for its supplemental new drug application for NUVIGIL® (armodafinil) Tablets [C-IV] in the treatment of patients with excessive sleepiness associated with jet lag disorder resulting from eastbound travel. As the first company to study a treatment option to improve wakefulness associated with jet lag disorder, Cephalon worked closely with the FDA to design a special protocol assessment (SPA) that would evaluate the experience of a typical eastbound airline traveler. Clinical efficacy was evaluated using two primary endpoints: an objective assessment -- the Multiple Sleep Latency Test (MSLT), and a subjective assessment -- the Patient Global Impression of Severity (PGI-S). Patients taking NUVIGIL (150 mg/day) showed a statistically significant improvement over placebo as measured by the MSLT [p<0.0001] and the PGI-S [p=0.044]. The most common adverse events associated with NUVIGIL treatment (five percent or greater) were headache, nausea, insomnia, diarrhea and palpitations. There were no reports of serious rash observed in the trial participants, and no new safety signals were observed in the clinical trial. "Although we reached statistical significance on both primary endpoints, the Complete Response letter raised questions regarding the robustness of the PGI-S data," said Dr. Lesley Russell, Cephalon's Chief Medical Officer. "We have already reviewed this issue with the FDA and will be scheduling a meeting with the Agency in the near future to discuss it further." About NUVIGIL NUVIGIL, the longer-lasting isomer of modafinil, was launched in the United States in June 2009. It is indicated to improve wakefulness in patients with excessive sleepiness associated with treated obstructive sleep apnea (OSA), shift work disorder (SWD), or narcolepsy. NUVIGIL is not approved as a treatment for jet lag disorder or its associated symptoms. The NUVIGIL (armodafinil) label includes a bolded warning for serious or life-threatening rash, including Stevens-Johnson Syndrome, that has been reported in adults in association with the use of armodafinil and in adults and children in association with the use of modafinil, a racemic mixture of S and R modafinil (the latter is armodafinil, the active ingredient in NUVIGIL). NUVIGIL is not approved for use in pediatric patients for any indication. The most common adverse events in controlled clinical trials (five percent or greater) were headache, nausea, dizziness, and insomnia. Full prescribing information for NUVIGIL is available at www.NUVIGIL.com. About Cephalon, Inc. Cephalon is an international biopharmaceutical company dedicated to discovering, developing and bringing to market medications for difficult to treat and rare conditions. Since its inception in 1987, Cephalon has brought first-in-class and best-in-class medicines to patients around the world in several therapeutic areas. Cephalon has the distinction of being one of the world's fastest-growing biopharmaceutical companies, now among the Fortune 1000 and a member of the S&P 500 Index, employing approximately 3,000 people worldwide. Cephalon has a growing presence in Europe, the Middle East and Africa. The Cephalon European headquarters and pre-clinical development center are located in Maisons-Alfort, France, just outside of Paris. Key business units are located in England, Ireland, France, Germany, Italy, Spain, the Netherlands for the Benelux countries, and Poland for Eastern and Central European countries. The company's proprietary products in the United States include: NUVIGIL, TREANDA® (bendamustine hydrochloride) for Injection, AMRIX® (cyclobenzaprine hydrochloride extended-release capsules), FENTORA® (fentanyl buccal tablet) [C-II], PROVIGIL® (modafinil) Tablets [C-IV], TRISENOX® (arsenic trioxide) injection, GABITRIL® (tiagabine hydrochloride), and ACTIQ® (oral transmucosal fentanyl citrate) [C-II]. The company also markets numerous products internationally. Full prescribing information on its U.S. products is available at http://www.cephalon.com or by calling 1-800-896-5855. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs, development of potential pharmaceutical products, interpretation of clinical results, clinical development of NUVIGIL, prospects for and frequency of filing new indications for NUVIGIL, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, sales and earnings guidance, and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. Contacts: Media: Investor Relations: Candace Steele Flippin Chip Merritt 610-727-6231 (office) 610-738-6376 (office) csteele@cephalon.com cmerritt@cephalon.com SOURCE Cephalon, Inc. CONTACT:Media: Candace Steele Flippin, +1-610-727-6231 (office), csteele@cephalon.com; Investor Relations: Chip Merritt, +1-610-738-6376 (office), cmerritt@cephalon.com URL: http://www.prnewswire.com LOAD-DATE: March 30, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 PR Newswire Association LLC All Rights Reserved 159 of 998 DOCUMENTS Agence France Presse -- English March 19, 2010 Friday 9:11 PM GMT Cycling: US rider Clinger banned for two years LENGTH: 218 words DATELINE: colorado springs, Colorado, March 19 2010 David Clinger, runner-up in last year's US national road race championships, has been slapped with a two-year ban after testing positive for performance-enhancing drugs. The 32-year-old American tested positive for synthetic testosterone and modafinil in July at the 2009 national championships in Bend, Oregon, the US Anti-Doping Agency announced on Friday. "Synthetic testosterone is prohibited as an anabolic agent and modafinil is prohibited as a stimulant on the World Anti-Doping Agency Prohibited List," USADA said in a news release. This is the latest setback for Clinger, who is a former US Postal teammate of Lance Armstrong and Floyd Landis. He has been in and out of drug rehab facilities. He is also known for an unusual New Zealand Maori-inspired tattoo which covers his entire face like a mask. USADA said the suspension is retroactive to the date Clinger was first notified of the ban by US officials meaning he will be eligible to compete again in 19 months. His has also been stripped of his race results. Clinger told the discipline panel that he was taking the drugs on the advice of his personal doctor in Utah and that he declared the use of testosterone on the forms that accompanied his test sample. The disciplinary panel rejected USADA's request for a longer suspension than two years. gph/dj10 LOAD-DATE: March 20, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 Agence France Presse All Rights Reserved 160 of 998 DOCUMENTS Xinhua General News Service March 19, 2010 Friday 9:10 PM EST U.S. rider Clinger banned for two years SECTION: WORLD NEWS; Sports LENGTH: 179 words DATELINE: WASHINGTON March 19 David Clinger, runner-up in last year's U.S. national road race championships, has been banned for two years after testing positive for performance-enhancing drugs. The 32-year-old American tested positive for synthetic testosterone and modafinil in July at the 2009 national championships in Bend, Oregon, the US Anti-Doping Agency announced on Friday. "Synthetic testosterone is prohibited as an anabolic agent and modafinil is prohibited as a stimulant on the World Anti-Doping Agency Prohibited List," USADA said in a news release. USADA said the suspension is retroactive to the date Clinger was first notified of the ban by U.S. officials meaning he will be eligible to compete again in 19 months. He has also been stripped of his race results. Clinger told the discipline panel that he was taking the drugs on the advice of his personal doctor in Utah and that he declared the use of testosterone on the forms that accompanied his test sample. The disciplinary panel rejected USADA's request for a longer suspension than two years. LOAD-DATE: March 20, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 Xinhua News Agency 161 of 998 DOCUMENTS Xinhua General News Service March 19, 2010 Friday 1:18 AM EST U.S. rider Clinger banned for two years SECTION: WORLD NEWS; Sports LENGTH: 179 words DATELINE: WASHINGTON March 19 David Clinger, runner-up in last year's U.S. national road race championships, has been banned for two years after testing positive for performance-enhancing drugs. The 32-year-old American tested positive for synthetic testosterone and modafinil in July at the 2009 national championships in Bend, Oregon, the US Anti-Doping Agency announced on Friday. "Synthetic testosterone is prohibited as an anabolic agent and modafinil is prohibited as a stimulant on the World Anti-Doping Agency Prohibited List," USADA said in a news release. USADA said the suspension is retroactive to the date Clinger was first notified of the ban by U.S. officials meaning he will be eligible to compete again in 19 months. He has also been stripped of his race results. Clinger told the discipline panel that he was taking the drugs on the advice of his personal doctor in Utah and that he declared the use of testosterone on the forms that accompanied his test sample. The disciplinary panel rejected USADA's request for a longer suspension than two years. LOAD-DATE: March 21, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 Xinhua News Agency 162 of 998 DOCUMENTS Business Day (South Africa) March 17, 2010 Health News Edition NEUROLOGY. Perpetual motion for the brain BYLINE: Graeme Addison SECTION: HEALTH LENGTH: 1209 words NEUROLOGY Perpetual motion for the brain It may be time to sound a 'subculture alert' that there are people out there who think we should never sleep, but use our lives more productively by remaining awake and ever active. Are they right? investigates ADRUG called modafinil can keep you awake for many days and nights without apparently serious side effects. Considering that we humans spend up to a third of our lives sleeping, it seems only rational - the next step in our evolution - that we should attempt to extend our waking hours and get more done. There are those who believe that we need to sleep less, or not sleep at all. The usual suspects dosing themselves on stimulants such as caffeine and amphetamines include students cramming for exams, executives preparing for that big presentation, emergency workers at disaster scenes, and soldiers in battle. They - and others such as journalists on perpetual deadlines - are prime candidates for modafinil. The drug is a unique wake-promoting stimulant of the central nervous system, approved in the US in 1998 and in SA in 2004 as a treatment for narcolepsy (the tendency to fall asleep). It was discovered in the 1970s by Prof Micheal Jouvet, experimenting with antidepressants at the French firm Lafon. Students of Jouvet who tried the pill showed an "amazing" improvement in their work. It was speculated at the time that it could keep an army on its feet and fighting for three days and nights with no major negative side effects. Modafinil is one of only two drugs in a unique class called eugeroics, which literally means good arousal, and is a sold on prescription as Provigil, Modiodal and Alertec. Some users have been known to stay awake for up to four days and nights, recovering with only a normal eight-hour bout of sleep. In clinical trials the most commonly observed side effects in more than 5% of patients are headache, upper respiratory tract infection, nausea, nervousness, anxiety and insomnia. According to the Biogenesis Laboratories, which sells a variety of life-extension, anti-ageing, anti-depressant and cognitive enhancement drugs over the internet in SA, modafinil increases alertness and concentration, reducing the desire to nap, and yet at the same time displays no addictive or "coming-down" side-effects. It keeps you steadily awake for up to eight hours after swallowing a 100mg tablet. One participant in the online global Drugs Forum reported: "Small euphoria - seems to build when longer in the experience - getting the whole time absorbed into things, which have to be done (almost neurotic behaviour). Sleeplessness. More energy. Impulsive behavior." For that user modafinil lived up to its reputation as a mood-brightening psycho stimulant. The big question is where such stimulation may be taking us. Modafinil is probably not the last "go-pill" that will emerge from modern pharmacology. There is a real prospect of keeping people awake indefinitely. As with research into anti-ageing - promising death's end - the end of sleep would fundamentally change the nature of our species. What would we do with ourselves? For some, this lidless future - making us like snakes with ever-open eyes - is too horrible to contemplate. It would reconstruct our lives around activities lasting all day and night, pausing for rest and recovery only to think (consciously) about the next thing to do. The Swiss psychiatrist Calr Jung would turn in his grave, although he did say "that consciousness acts upon our nightly life just as much as the unconscious overshadows our daily life". Perhaps we could learn more about ourselves by simply staying awake. The fact is that medical science has struggled to explain why we need sleep anyway. According to the journal Science, the function of sleep is one of the 100 or so greatest unsolved mysteries in science. Theories range from brain "maintenance" - including memory consolidation and pruning - to reversing damage from oxidative stress suffered while awake. Dr Jerome Siegel, a University of California, Los Angeles, professor of psychiatry and director of the university's Centre for Sleep Research at the Semel Institute for Neuroscience and Human Behaviour, has studied sleep in a broad range of animals from the platypus to the walrus. In the online journal Nature Reviews Neuroscience last year, he concluded that sleep's primary function is to increase the efficiency of animals and minimise risk. We stay alert and active when we need to and relax our guard when there is less danger or less call for action. "We see sleep as lying on a continuum that ranges from these dormant states like torpor and hibernation, on to periods of continuous activity without any sleep, such as during migration, where birds can fly for days on end without stopping," said Siegel. Airmen, unfortunately, cannot fly for days for days on end. This problem has mightily exercised military researchers. But hopes that modafinil would be the solution have been dashed by a number of studies of its effectiveness. Harvard law student Douglas Kim pulled the findings together in a 2007 paper on "vigilance" as a military priority. "In certain studies, modafinil's efficacy as compared to caffeine and amphetamines were of questionable conclusion," he wrote. "Researchers also noticed modafinil produced unexpected side-effects including an increase in core temperature, an inability to discern when the drug has begun to perform, and an additional 'over-confidence' effect in self-reported questionnaires - all side-effects that are of real concern when superimposed on sustained military operations." If you ask busy people whether they would like to stay awake for long periods, you get some intriguing responses, as I did to my question on Facebook. "I would never give up sleeping, I need it too much," said one South African business executive now working in the US. He might well have quoted Shakespeare, whose nervously overwrought Macbeth feared that he was cursed to sleep no more. "You've got to love the ICU in hospital," wrote another, "it's the only place you actually get intensive nursing care but absolutely NO sleep." And a sportsman friend wrote: "Thankful for sleep... Best time of our lives sometimes." As to getting more done by not sleeping, a rather despairing note sounded in this response: "As an insomniac, I question that assumption." Efficiency and productivity may not be enhanced simply by staying awake, because the body and mind need to regenerate through sleep. Jung believed that in sleep our dreams reconnect us with the collective unconscious of our species, the myths and archetypes that underlie our wakeful reality and shape our lives. If so, we cannot do without it, and any attempt to drug ourselves into a state of perpetual sleeplessness will smash our psyche to pieces. To be cursed with sleep, or with sleeplessness: which is it to be? Birds know the answer, we don't - though perhaps only for now. The fact is that medical science has struggled to explain why we need sleep anyway AIMING EVER HIGHER: Night time is no time to nod off, say those who believe we should be spending more hours awake. Less time sleeping means more opportunity to make optimum use of our time and remain productive, they say. Picture: iSTOCKPHOTO LOAD-DATE: March 18, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2010 BDFM Publishers PTY Ltd. All Rights Reserved 163 of 998 DOCUMENTS Business Day (South Africa) March 17, 2010 Health News Edition NEUROLOGY. Perpetual motion for the brain BYLINE: Graeme Addison SECTION: HEALTH LENGTH: 1209 words NEUROLOGY Perpetual motion for the brain It may be time to sound a 'subculture alert' that there are people out there who think we should never sleep, but use our lives more productively by remaining awake and ever active. Are they right? investigates ADRUG called modafinil can keep you awake for many days and nights without apparently serious side effects. Considering that we humans spend up to a third of our lives sleeping, it seems only rational - the next step in our evolution - that we should attempt to extend our waking hours and get more done. There are those who believe that we need to sleep less, or not sleep at all. The usual suspects dosing themselves on stimulants such as caffeine and amphetamines include students cramming for exams, executives preparing for that big presentation, emergency workers at disaster scenes, and soldiers in battle. They - and others such as journalists on perpetual deadlines - are prime candidates for modafinil. The drug is a unique wake-promoting stimulant of the central nervous system, approved in the US in 1998 and in SA in 2004 as a treatment for narcolepsy (the tendency to fall asleep). It was discovered in the 1970s by Prof Micheal Jouvet, experimenting with antidepressants at the French firm Lafon. Students of Jouvet who tried the pill showed an "amazing" improvement in their work. It was speculated at the time that it could keep an army on its feet and fighting for three days and nights with no major negative side effects. Modafinil is one of only two drugs in a unique class called eugeroics, which literally means good arousal, and is a sold on prescription as Provigil, Modiodal and Alertec. Some users have been known to stay awake for up to four days and nights, recovering with only a normal eight-hour bout of sleep. In clinical trials the most commonly observed side effects in more than 5% of patients are headache, upper respiratory tract infection, nausea, nervousness, anxiety and insomnia. According to the Biogenesis Laboratories, which sells a variety of life-extension, anti-ageing, anti-depressant and cognitive enhancement drugs over the internet in SA, modafinil increases alertness and concentration, reducing the desire to nap, and yet at the same time displays no addictive or "coming-down" side-effects. It keeps you steadily awake for up to eight hours after swallowing a 100mg tablet. One participant in the online global Drugs Forum reported: "Small euphoria - seems to build when longer in the experience - getting the whole time absorbed into things, which have to be done (almost neurotic behaviour). Sleeplessness. More energy. Impulsive behavior." For that user modafinil lived up to its reputation as a mood-brightening psycho stimulant. The big question is where such stimulation may be taking us. Modafinil is probably not the last "go-pill" that will emerge from modern pharmacology. There is a real prospect of keeping people awake indefinitely. As with research into anti-ageing - promising death's end - the end of sleep would fundamentally change the nature of our species. What would we do with ourselves? For some, this lidless future - making us like snakes with ever-open eyes - is too horrible to contemplate. It would reconstruct our lives around activities lasting all day and night, pausing for rest and recovery only to think (consciously) about the next thing to do. The Swiss psychiatrist Calr Jung would turn in his grave, although he did say "that consciousness acts upon our nightly life just as much as the unconscious overshadows our daily life". Perhaps we could learn more about ourselves by simply staying awake. The fact is that medical science has struggled to explain why we need sleep anyway. According to the journal Science, the function of sleep is one of the 100 or so greatest unsolved mysteries in science. Theories range from brain "maintenance" - including memory consolidation and pruning - to reversing damage from oxidative stress suffered while awake. Dr Jerome Siegel, a University of California, Los Angeles, professor of psychiatry and director of the university's Centre for Sleep Research at the Semel Institute for Neuroscience and Human Behaviour, has studied sleep in a broad range of animals from the platypus to the walrus. In the online journal Nature Reviews Neuroscience last year, he concluded that sleep's primary function is to increase the efficiency of animals and minimise risk. We stay alert and active when we need to and relax our guard when there is less danger or less call for action. "We see sleep as lying on a continuum that ranges from these dormant states like torpor and hibernation, on to periods of continuous activity without any sleep, such as during migration, where birds can fly for days on end without stopping," said Siegel. Airmen, unfortunately, cannot fly for days for days on end. This problem has mightily exercised military researchers. But hopes that modafinil would be the solution have been dashed by a number of studies of its effectiveness. Harvard law student Douglas Kim pulled the findings together in a 2007 paper on "vigilance" as a military priority. "In certain studies, modafinil's efficacy as compared to caffeine and amphetamines were of questionable conclusion," he wrote. "Researchers also noticed modafinil produced unexpected side-effects including an increase in core temperature, an inability to discern when the drug has begun to perform, and an additional 'over-confidence' effect in self-reported questionnaires - all side-effects that are of real concern when superimposed on sustained military operations." If you ask busy people whether they would like to stay awake for long periods, you get some intriguing responses, as I did to my question on Facebook. "I would never give up sleeping, I need it too much," said one South African business executive now working in the US. He might well have quoted Shakespeare, whose nervously overwrought Macbeth feared that he was cursed to sleep no more. "You've got to love the ICU in hospital," wrote another, "it's the only place you actually get intensive nursing care but absolutely NO sleep." And a sportsman friend wrote: "Thankful for sleep... Best time of our lives sometimes." As to getting more done by not sleeping, a rather despairing note sounded in this response: "As an insomniac, I question that assumption." Efficiency and productivity may not be enhanced simply by staying awake, because the body and mind need to regenerate through sleep. Jung believed that in sleep our dreams reconnect us with the collective unconscious of our species, the myths and archetypes that underlie our wakeful reality and shape our lives. If so, we cannot do without it, and any attempt to drug ourselves into a state of perpetual sleeplessness will smash our psyche to pieces. To be cursed with sleep, or with sleeplessness: which is it to be? Birds know the answer, we don't - though perhaps only for now. The fact is that medical science has struggled to explain why we need sleep anyway AIMING EVER HIGHER: Night time is no time to nod off, say those who believe we should be spending more hours awake. Less time sleeping means more opportunity to make optimum use of our time and remain productive, they say. Picture: iSTOCKPHOTO LOAD-DATE: March 19, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2010 BDFM Publishers PTY Ltd. All Rights Reserved 164 of 998 DOCUMENTS Business Day (South Africa) March 17, 2010 Health News Edition NEUROLOGY. Perpetual motion for the brain BYLINE: Graeme Addison SECTION: HEALTH LENGTH: 1209 words NEUROLOGY Perpetual motion for the brain It may be time to sound a 'subculture alert' that there are people out there who think we should never sleep, but use our lives more productively by remaining awake and ever active. Are they right? investigates ADRUG called modafinil can keep you awake for many days and nights without apparently serious side effects. Considering that we humans spend up to a third of our lives sleeping, it seems only rational - the next step in our evolution - that we should attempt to extend our waking hours and get more done. There are those who believe that we need to sleep less, or not sleep at all. The usual suspects dosing themselves on stimulants such as caffeine and amphetamines include students cramming for exams, executives preparing for that big presentation, emergency workers at disaster scenes, and soldiers in battle. They - and others such as journalists on perpetual deadlines - are prime candidates for modafinil. The drug is a unique wake-promoting stimulant of the central nervous system, approved in the US in 1998 and in SA in 2004 as a treatment for narcolepsy (the tendency to fall asleep). It was discovered in the 1970s by Prof Micheal Jouvet, experimenting with antidepressants at the French firm Lafon. Students of Jouvet who tried the pill showed an "amazing" improvement in their work. It was speculated at the time that it could keep an army on its feet and fighting for three days and nights with no major negative side effects. Modafinil is one of only two drugs in a unique class called eugeroics, which literally means good arousal, and is a sold on prescription as Provigil, Modiodal and Alertec. Some users have been known to stay awake for up to four days and nights, recovering with only a normal eight-hour bout of sleep. In clinical trials the most commonly observed side effects in more than 5% of patients are headache, upper respiratory tract infection, nausea, nervousness, anxiety and insomnia. According to the Biogenesis Laboratories, which sells a variety of life-extension, anti-ageing, anti-depressant and cognitive enhancement drugs over the internet in SA, modafinil increases alertness and concentration, reducing the desire to nap, and yet at the same time displays no addictive or "coming-down" side-effects. It keeps you steadily awake for up to eight hours after swallowing a 100mg tablet. One participant in the online global Drugs Forum reported: "Small euphoria - seems to build when longer in the experience - getting the whole time absorbed into things, which have to be done (almost neurotic behaviour). Sleeplessness. More energy. Impulsive behavior." For that user modafinil lived up to its reputation as a mood-brightening psycho stimulant. The big question is where such stimulation may be taking us. Modafinil is probably not the last "go-pill" that will emerge from modern pharmacology. There is a real prospect of keeping people awake indefinitely. As with research into anti-ageing - promising death's end - the end of sleep would fundamentally change the nature of our species. What would we do with ourselves? For some, this lidless future - making us like snakes with ever-open eyes - is too horrible to contemplate. It would reconstruct our lives around activities lasting all day and night, pausing for rest and recovery only to think (consciously) about the next thing to do. The Swiss psychiatrist Calr Jung would turn in his grave, although he did say "that consciousness acts upon our nightly life just as much as the unconscious overshadows our daily life". Perhaps we could learn more about ourselves by simply staying awake. The fact is that medical science has struggled to explain why we need sleep anyway. According to the journal Science, the function of sleep is one of the 100 or so greatest unsolved mysteries in science. Theories range from brain "maintenance" - including memory consolidation and pruning - to reversing damage from oxidative stress suffered while awake. Dr Jerome Siegel, a University of California, Los Angeles, professor of psychiatry and director of the university's Centre for Sleep Research at the Semel Institute for Neuroscience and Human Behaviour, has studied sleep in a broad range of animals from the platypus to the walrus. In the online journal Nature Reviews Neuroscience last year, he concluded that sleep's primary function is to increase the efficiency of animals and minimise risk. We stay alert and active when we need to and relax our guard when there is less danger or less call for action. "We see sleep as lying on a continuum that ranges from these dormant states like torpor and hibernation, on to periods of continuous activity without any sleep, such as during migration, where birds can fly for days on end without stopping," said Siegel. Airmen, unfortunately, cannot fly for days for days on end. This problem has mightily exercised military researchers. But hopes that modafinil would be the solution have been dashed by a number of studies of its effectiveness. Harvard law student Douglas Kim pulled the findings together in a 2007 paper on "vigilance" as a military priority. "In certain studies, modafinil's efficacy as compared to caffeine and amphetamines were of questionable conclusion," he wrote. "Researchers also noticed modafinil produced unexpected side-effects including an increase in core temperature, an inability to discern when the drug has begun to perform, and an additional 'over-confidence' effect in self-reported questionnaires - all side-effects that are of real concern when superimposed on sustained military operations." If you ask busy people whether they would like to stay awake for long periods, you get some intriguing responses, as I did to my question on Facebook. "I would never give up sleeping, I need it too much," said one South African business executive now working in the US. He might well have quoted Shakespeare, whose nervously overwrought Macbeth feared that he was cursed to sleep no more. "You've got to love the ICU in hospital," wrote another, "it's the only place you actually get intensive nursing care but absolutely NO sleep." And a sportsman friend wrote: "Thankful for sleep... Best time of our lives sometimes." As to getting more done by not sleeping, a rather despairing note sounded in this response: "As an insomniac, I question that assumption." Efficiency and productivity may not be enhanced simply by staying awake, because the body and mind need to regenerate through sleep. Jung believed that in sleep our dreams reconnect us with the collective unconscious of our species, the myths and archetypes that underlie our wakeful reality and shape our lives. If so, we cannot do without it, and any attempt to drug ourselves into a state of perpetual sleeplessness will smash our psyche to pieces. To be cursed with sleep, or with sleeplessness: which is it to be? Birds know the answer, we don't - though perhaps only for now. The fact is that medical science has struggled to explain why we need sleep anyway AIMING EVER HIGHER: Night time is no time to nod off, say those who believe we should be spending more hours awake. Less time sleeping means more opportunity to make optimum use of our time and remain productive, they say. Picture: iSTOCKPHOTO LOAD-DATE: March 20, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2010 BDFM Publishers PTY Ltd. All Rights Reserved 165 of 998 DOCUMENTS Reuters Health Medical News March 15, 2010 Monday 9:00 PM EST Guideline urges treatment for nonmotor symptoms of Parkinson's disease SECTION: CLINICAL LENGTH: 579 words DATELINE: NEW YORK A new practice parameter from the American Academy of Neurology calls for doctors to identify and treat nonmotor symptoms in patients with Parkinson's disease (PD). Nonmotor symptoms - autonomic dysfunction, sleep disorders, psychological and cognitive problems, and sensory abnormalities - are major, often unrecognized causes of morbidity in PD. In 2006 and 2008, the Academy issued guidelines pertaining to cognitive and mood dysfunction in PD as well as treatment of sialorrhea with botulinum toxin. To evaluate treatment options for other nonmotor PD symptoms, Dr. Theresa A. Zesiewicz from the University of South Florida in Tampa and associates searched MEDLINE, EMBASE, and the Science Citation Index and identified 46 controlled trials published between 1966 and 2008. Most trials supporting specific treatments provided only level C evidence, the researchers report in the March 16th issue of Neurology. The only recommendation backed by level B evidence was the use of levodopa/carbidopa (Atamet, Sinemet) to treat periodic limb movements of sleep. One trial evaluated the efficacy of sildenafil (Viagra) in 12 patients with erectile dysfunction. Sildenafil was more effective than placebo at enabling men to achieve and maintain an erection, with minimal changes in blood pressure. The authors advise a complete medical evaluation to rule out other treatable causes of erectile dysfunction. For excessive daytime sleepiness, modafinil (Provigil) might be useful. However, modafinil might improve patients' perception of wakefulness without improving objective measures of sleepiness, creating a potential safety hazard if patients engage in activities such as driving. Methylphenidate (Ritalin) might help patients with fatigue, but the authors warn of the potential for abuse. They note that PD patients "have a risk for dopamine dysregulation syndrome and impulse control disorders that share many clinical and functional imaging features with addiction." Isosmotic macrogol (polyethylene glycol or Miralax) possibly improved constipation in one study. Increased water and dietary fiber intake have also been helpful. However, for many conditions considered - orthostatic hypotension, urinary incontinence, insomnia, rapid eye movement sleep behavior disorder, and anxiety -- the authors found insufficient evidence to support or refute treatments. Dr. Zesiewicz and associates advise physicians to diagnose nonmotor symptoms in PD using tools such as the NMS Quest study questionnaire and the updated version of the Unified Parkinson's Disease Rating Scale. Concluding, the investigators write, "There are few dedicated controlled trials of drugs to treat nonmotor symptoms in PD. Such trials are urgently required." However, co-author Dr. William J. Weiner commented in an interview with Reuters Health, "The truth is that when we do these very formal surveys of the literature looking for evidence in a rigorous manner, it's quite common that we can't find much evidence." That doesn't mean that many of the measures that physicians commonly use to treat nonmotor PD symptoms aren't helpful, he added. Dr. Weiner, from the University of Maryland Medical Center, Baltimore, continued, "It's also helpful for patients to know that they don't have another disease (when they develop these symptoms), so they don't have to see a cardiologist or a GI specialist or a urologist; that in fact it's part of what is going on with them." SOURCE: Neurology 2010;74:924-931. LOAD-DATE: March 16, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 Reuters Health All Rights Reserved 166 of 998 DOCUMENTS DAILY MAIL (London) March 9, 2010 Tuesday TEENAGERS ARE NOW BUYING ILLEGAL 'SMART DRUGS' ONLINE TO BOOST EXAM PERFORMANCE. BUT AS THIS SPECIAL REPORT SHOWS,THE EFFECT ON THEIR HEALTH CAN BE CATASTROPHIC BYLINE: BY STEVE BOGGAN AND TIM STEWART LENGTH: 1799 words JOSH has an exam and, like most of the other boys at his prestigious public school, he's keen to put his best foot forward. He's eaten breakfast and dressed smartly, but before he sets off for class, he reaches for a white pill and pops it into his mouth. He bought 30 of the tablets online for £40 from the U.S., but for all Josh knows they might well have been knocked up in an illegal backstreet 'pharmacy' in India. Still, the drug modafinil -- usually used to treat sleeping disorders -- has worked before for him and if it works again he is sure to get top marks. Welcome to the world of 'smart drugs', otherwise known as cognitive enhancement pharmaceuticals. This is a world where pupils as young as 15 self-medicate, participate in illegal online drug trafficking and swap notes on the best pill cocktails for good grades. Concern over smart drugs has been growing for some time among academics, politicians and pharmacologists, but it has been brought into sharp focus with the announcement that the former health minister, Lord Darzi of Denham, is heading a study at Imperial College, London, into their effects. This might seem odd because most of these drugs have been around for decades for the treatment of conditions such as Attention Deficit Hyperactivity Disorder (ADHD) and narcolepsy, and have been found to be safe. But no one has monitored their chaotic use in healthy young people taking inappropriate doses to boost their intellectual prowess. And some experts believe this kind of use in brains that are still developing could cause addiction and permanent damage. Josh is an intelligent, articulate 17-year-old, so you wonder why he needs extra help to feel smart. He has been taking modafinil (sold as the prescription-only drugs Provigil, Alertec, Modavigil and Modalert) since he was 16, but has friends who began using smart pharmaceuticals at 15. He lives in London and his parents are lawyers. 'I read about modafinil in a newspaper and then researched it on the internet and spoke to some of my friends about it,' he says. 'It appealed to me as an inexpensive method for highly concentrated revision, for which I would otherwise depend on coffee, tea or Red Bull. Modafinil gives you heightened alertness, stamina and productivity. I find it helpful for focus and memory. 'I find I can memorise a graph after drawing it once instead of several times. I would say it makes me 40 to 50 per cent more productive in a day, but it does not make me any cleverer. 'While revising for my last set of exams, I was taking 100mg of modafinil a day for six or seven days a week for three weeks. 'Around half-term, I stepped it up to 150mg to 200mg a day and in the last two or three weeks up to the exams I took 200mg to 300mg a day and worked 18-hour days. 'I find you can get by on four to six hours of sleep for up to three weeks and then, at the end, the body needs to rest and catch up. I take a whole day off and sleep for 24 hours. 'Taking it is no different from having other stimulants such as coffee, ProPlus caffeine tablets or Red Bull. It is no different from taking painkillers for a headache. 'I use it specifically for exams and will carry on at university. I would recommend it to anyone who is informed about it and knows what they are doing. 'I haven't told my parents about using modafinil. They wouldn't know what it is and they wouldn't approve of me using it.' Josh's use of modafinil is not unusual. A quick scan of student web forums uncovers a world where drug advice is swapped. The benefits of Ritalin and Adderall, which are meant to be used to treat ADHD, are compared with Provigil, Modalert and a group of drugs called ampakines -- prescription pharmaceuticals that are showing promise in the treatment of Alzheimer's and Parkinson's. The problem in telling students not to take them is that tests have shown these drugs can help with focus, memory, concentration and alertness by interacting in different ways with neurotransmitters -- chemical messengers -- in the brain. the ADHD treatments contain amphetamines, which can result in addiction, and there are suspicions that sleep disorder treatments such as modafinil could be addictive. Barbara Sahakian, Professor of Clinical Neuropsychology at Cambridge University, says scientists understand how drugs such as Ritalin work by stimulating levels of the neurotransmitters dopamine and noradrenaline in the brain. These affect mood, cognition and memory. 'However, there is an optimal dose for ideal performance,' she says. 'Levels beyond that could cause problems with addiction. With modafinil, no one really knows how exactly the drug acts in the brain to boost cognition.' Evidence is emerging, however, that modafinil -- long thought not to be addictive -- also affects the levels of dopamine. This is significant because dopamine production can lead to addictive behaviour. Sometimes referred to as the 'reward' drug, dopamine is released during experiences such as the enjoyment of sex, food and drugs. We are programmed to repeat rewarding experiences, a cycle that can result in addiction. A study published in the Journal of the American Medical Association last year looked at ten healthy men taking modafinil and found it did increase levels of dopamine. The research was conducted by the National Institute on Drug Abuse (Nida) in the U.S. '[Modafinil] has the signature that it could potentially be addictive,' says Nida's director Dr Nora Volkow. 'Studies have shown consistently that all of the drugs of abuse . . . have a common effect of increasing dopamine in the nucleus accumbens [area of the brain]. 'That is believed to be crucial for their reinforcing effect and ultimately their underlying potential for producing addiction.' The jury is still out on whether modafinil is addictive. Scientists regard tests on just ten people as being far from definitive. Sahakian has called on the Government to hold a public debate on the use of smart drugs. On the one hand, she feels they could be of real benefit to society if proven to be safe. On the other, she wonders whether in some dystopian future people will be pressured into taking them to work longer and harder. Already, there is evidence that students feel pressured into taking smart drugs to compete with highachieving classmates who are using them. And some pushy parents appear to be condoning their use. One third-year student studying computer science at London Metropolitan University told us that taking modafinil is a 'lifesaver' in helping him to complete assignments. 'I am aware of school children who have taken modafinil. They were aged between 16 and 18,' he says. 'Their father [a computer programmer], my friend, used to take it occasionally. The parents had extremely high expectations for their children and they were taking exams. 'My friend's daughter was advised to take modafinil by her classmates. Unfortunately, this was a terrible decision. 'She was taken to hospital after five days of sleep deprivation. She had high blood pressure, was anxious and experienced some kind of hallucinations and psychosis. 'She was taking extremely high doses of modafinil. I was told she had felt some kind of euphoria and kept taking more and more. It is proof that modafinil can be addictive for some people.' If Nida in the U.S. is correct and all these drugs affect dopamine levels in some way, then concern is likely to focus on students self-medicating inappropriate dosages and using them over a long time. Dr Daniel Amen, a psychiatrist and Fellow of the American Psychiatric Association, says that while treating young ADHD patients with carefully controlled doses of Ritalin can improve their lives immeasurably, unmonitored doses taken by healthy youngsters could be damaging. 'A therapeutic dose arrived at by careful monitoring by a physician might be anywhere from 5mg to 60mg a day,' he says. 'We know that can enhance brain function in many people by stimulating levels of dopamine. 'But where you have some of these students taking concentrations of 100mg to 500mg, that could cause some problems. 'The extra dopamine produced constricts blood flow to the brain and, over the long term, that could cause permanent damage. 'The adolescent brain, especially the pre-frontal cortex -- the most thoughtful part of the brain -- is developing rapidly. Anything that disrupts or interferes with this process can cause lasting problems.' There is debate on student forums over whether using smart drugs amounts to cheating. Some say it does, while others argue that those who want to ban them should be prepared to give up commonplace stimulants, such as caffeine and nicotine. Even academics are divided. Dr Anders Sandberg, a philosophy lecturer specialising in bioethics at Oxford University, tried modafinil as part of his research three years ago and now uses it openly. In common with students who take it, Dr Sandberg is on the legal side of an illegal transaction. Under the 1963 Medicines Act, it is an offence to supply a drug without a prescription, but not to buy one. 'When I take it, it is like having a little electric motor in the back of my head running through lists of things I need to do,' he says. 'Then, instead of putting them off until tomorrow, I go ahead and do them. 'I use the drugs only occasionally if I have a paper to write or need to fly long distances to attend a conference or deliver a speech. I find that instead of having jet-lag, I can focus on the job at hand.' But isn't that sending the wrong message to students? 'This is something I have spent a lot of time considering, but in general I believe people should have control over their own bodies,' he says. 'That right is important, but you need to use it appropriately and that's why youngsters shouldn't take responsibility for managing drugs, alcohol or enhancers. 'These drugs are like stepladders. If you need them to attain something that would otherwise be out of your reach, then use them. But if you can reach those heights anyway, then you're just being lazy.' However, health professionals take a dim view of anyone misusing drugs. 'Anyone taking prescription drugs without a prescription obtained through a consultation with a health professional is making a big mistake,' says Neal Patel, a pharmacist and spokesman for the Royal Pharmaceutical Society. 'It's dangerous to experiment with medicines and the sideeffects of cognitive enhancement drugs are significant -- they can cause abdominal pain, nausea, heart problems and changes in blood pressure. 'These side- effects are dose dependent -- the more you take, the greater your risk of being affected and seriously harmed.' Professor Sahakian and Dr Amen say there are other, less risky yet proven remedies for improving brain function: sleep, exercise and a healthy diet. Apparently, they work. LOAD-DATE: March 9, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Papers Copyright 2010 Associated Newspapers Ltd. All Rights Reserved 167 of 998 DOCUMENTS Irish Independent March 6, 2010 Saturday They call it the professional's pill SECTION: FEATURES LENGTH: 1264 words Why more middle-class people are taking a drug they believe will make them smarter Sandra is an air steward. She pops a tab every time she crosses the Atlantic to make sure she's perky on landing. Gerry uses them during exams to give his concentration a boost. Simon, a junior doctor, takes one during the night shift to keep sleep at bay and his brain sharp. You won't find their pill of choice on the shelves of your local head shop but there's growing evidence that high-flying professionals and stressed-out students are relying on brain-boosting drugs to quicken their thinking and keep them awake. This week in Britain, scientists urged the government to bring the closet phenomenon of so-called smart drugs into the open, claiming their use is spreading across all sectors of society from surgeons to soldiers. Researchers from Cambridge University warned that the drugs, which were designed to help people with neurological disorders like attention-deficit hyperactivity disorder, Alzheimer's and brain injury, are now being used for reasons far beyond their original purpose by uptight executives, multi-tasking mothers and exhausted shift-workers who need a chemical pick-me-up. No self-respecting GP would prescribe these powerful brain-changing drugs to a patient suffering from poor concentration or tiredness, so users are turning to the internet, where a multitude of websites offer them for sale. In Ireland, customs officers are at the coalface of this new craze, with increasing quantities of cognitive-enhancement drugs such as Modafinil and Ritalin being shipped into the country illegally every year. In 2008, 1,250 tablets of Modafinil, a sleep inhibitor, were seized at ports and airports, rising to 1,920 last year. In the first two months of this year, 170 tablets were found. Seizures of Ritalin, dubbed 'kiddie cocaine' in the US where it is doled outlike candy to school-going children, have been lower but significant all the same with more than 612 units found since 2007. Here, Modafinil is sold under the trade name Provigil. In November, its manufacturers Cephalon were granted permission by the Irish Medicines Board to market the drug for the treatment of excessive daytime sleepiness associated with sleep apnoea. Taoiseach Brian Cowen is among those who suffer from this condition, which periodically causes breathing to stop during sleep. Originally developed in France, Modafinil, which is also licensed to treat narcolepsy -- a disorder marked by sudden uncontrollable attacks of daytime sleep -- is the first of a new generation of wake-promoting drugs which targets the sleep/wake centres in the brain. It works by activating sleep-suppressing neurons fooling the mind into believing it is time to be alert. This pharmaceutical prototype has the power to keep a person awake and focussed for up to 90 hours running, without the jitteriness or poor concentration that other stimulants like amphetamines or caffeine are known to produce. Proponents say it works without causing a crash after its effects have worn off and does not create any sense of euphoria in the brain thereby limiting its potential for abuse. The use of Modafinil within the American military is well-documented where it has been approved for use on air force missions, allowing troops to stay awake for days at a time and complete operations as quickly as possible. In Britain, the drug was approved for use in 2002, and since then has surged in popularity. The number of prescriptions for stimulants like it has nearly doubled in recent years, rising from 458,000 in 2004 to 751,000 in 2008. A Nature magazine poll of 1,400 respondents, mostly scientists and academics, suggested that one in five had used 'smart drugs'. Fears that stay-awake pills are increasingly being used as 'lifestyle drugs' are strengthening, especially since their long-term effects on the brain are still unknown. Some neuroscientists also worry that drugs like this will turn humans into mechanistic beings who pop a pill when they need a brain boost rather than opting for a brisk walk or a good night's sleep. Pharmaceutical advances like this could make cosmetic neurology as popular as beauty enhancements, they claim. And there are ethical concerns about the unfair advantage such drugs give to users over their peers in academic settings. In the US, surveys show that an estimated 16-20pc of US college students take smart drugs to help their memory and keep them alert. The drugs may especially help in subjects like mathematics and science by aiding students to complete puzzles and remember long chains of digits. Last week, one of Britain's leading psychologists called for an official university-wide strategy to tackle student misuse of prescription drugs like Modafinil. Barbara Sahakian, professor of clinical neuropsychology at Cambridge University, whose work is at the forefront of research into cognitive enhancement drugs, has even raised the prospect of dope testing of exam students as a possible safeguard against their use. "This is something that universities really have to discuss," she says. "It has enormous implications. The coercion aspect is a strong one. Some students say they feel it is cheating and it puts pressure on them to feel they have to use drugs when they don't really want to. "You have to consider there are things that could be beneficial about such drugs because we have an ageing population: people will have to work for longer and their pensions may not be performing. "The big question is, are we all going to be taking drugs in the next 10 years and boosting our brain power in this way? And if we are, will we use them to have a shorter working week, so we can go home, spend more time with our families and have a good work/life balance? Or will we go headlong into a 24/7 society were we work all the time because we can work all the time'" Improving brain power and its ability to stay awake is certainly where drug companies think the future lies as the market for treatments for neurological and psychiatric illnesses continues to outstrip that for painkillers and cardiovascular drugs in the western world. Dozens of neuro-enhancing drugs are currently in the research pipeline and their use in the coming years is expected to soar. Advocates argue that smart drugs will remove disparities in society and give those who are mentally challenged a better chance of self-improvement and success. They also claim it is better for high-risk professionals like surgeons and pilots to take a medically-controlled tablet rather than dosing themselves up on caffeine and ending up with a shaky hand and a twitchy disposition But for those dealing with the downside of chemical consumption, the advent of smart drugs is a worrying prospect. "As with any stimulant that alters the central nervous system, you have to stop and think of the long-term consequences of using these drugs," says Dr Fiona Weldon, clinical director of the Rutland Centre, Dublin's leading addiction therapy centre. "We are unsure about the extent to which these drugs are being used in Ireland but it would be naive to think it isn't happening and it is something we should be very worried about," she says. "I've seen students become reliant on the likes of Ritalin. They claim it makes them work better but before you know it there is a dependency. "There is such a tendency now to seek out a quick chemical fix as the solution to our stresses but if you over-stimulate the brain in a false way, the system will eventually crash and the side effects are incredible." LOAD-DATE: March 6, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2010 Independent News and Media Ltd. All Rights Reserved 168 of 998 DOCUMENTS The Times (London) February 27, 2010 Saturday Edition 1; National Edition Get smart drugs out of the closet, scientists urge BYLINE: Lucy Bannerman SECTION: NEWS; Pg. 28,29 LENGTH: 574 words Scientists have urged the Government to bring the "closet phenomenon" of so-called smart drugs out into the open, suggesting that regulated use of the stimulants could help groups such as surgeons, soldiers, and jurors to maximise their benefit to society. The calls coincide with a new study, headed by the former health minister and surgeon Lord Darzi of Denham, that will monitor the effects of "cognitive enhancement drugs" on the memory, concentration and decisionmaking skills of healthy adults. There is little data on the long-term safety of the performance-enhancing effects of Ritalin and Modafinil, which are available only on prescription for those diagnosed with conditions such as attention deficit hyperactivity disorder (ADHD) or narcolepsy. Anecdotal evidence suggests, however, that the pills' illicit promise of increased brain power and long bouts of uninterrupted concentration is attracting numbers of healthy high-fliers. Professor Barbara Sahakian, a neuroscientist from the University of Cambridge, is working with Lord Darzi's team at Imperial College London. Making the drugs available over the counter would be one way of prompting the clinical trials, which she believes are needed to explore just how far they can improve the human mind. Until then, Professor Sahakian warns that ambitious executives, multitasking mothers and students under pressure will continue to take risks with drugs procured over the internet, or other people's prescriptions, while the rest of society risks losing out. "This is a closet phenomenon," she told The Times. "We know that people are doing these drugs anyway but we don't know about their long-term safety. The Government has a responsibility to think about what they should do about that. Maybe they should be letting pharmaceutical companies brand these medications via a safe route. Wouldn't that be better?" Government health statistics for England show that the number of prescriptions for stimulants such as Ritalin and Modafinil has nearly doubled in recent years - rising from 458,000 in 2004 to 751,000 in 2008. "I'm rather careful about my brain," said Dr Anders Sandberg, 37, as one might well expect from a philosophy lecturer who specialises in bioethics at the University of Oxford. He first took Modafinil three years ago, after consulting a pharmacologist friend, and procuring about thirty 50mg doses from a website. He now takes it on average once a month - "not chronically, but only on days when I decide, 'OK, I need to get something done'." Days when he has conferences, seminars, papers to write. He also wants to remove the stigma attached to those who seek artificial improvement for their attention span. "When the cellphone first arrived, we weren't sure when to use it. But we learnt to invent rules, so that it's generally not OK to use them in restaurants but it's OK walking outside. We need to achieve the same with enhancement drugs. We need the right culture surrounding it. And the only way we can do that is by being honest about its consumption, and face up to the fact it is going on." A spokeswoman for the Department of Health said a report had been commissioned in 2008 investigating the issue of cognitive-enhancing drugs. She said: "We strongly urge anyone thinking about taking a prescriptiononly medicine, not intended for their personal use, to consult their GP first." Online Health news, features and expert advice timesonline.co. uk/health LOAD-DATE: February 27, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: TIM Copyright 2010 Times Newspapers Limited All Rights Reserved 169 of 998 DOCUMENTS The Times (London) February 27, 2010 Saturday Edition 1; Ireland Get smart drugs out of the closet, scientists urge BYLINE: Lucy Bannerman SECTION: NEWS; Pg. 36,37 LENGTH: 574 words Scientists have urged the Government to bring the "closet phenomenon" of so-called smart drugs out into the open, suggesting that regulated use of the stimulants could help groups such as surgeons, soldiers, and jurors to maximise their benefit to society. The calls coincide with a new study, headed by the former health minister and surgeon Lord Darzi of Denham, that will monitor the effects of "cognitive enhancement drugs" on the memory, concentration and decisionmaking skills of healthy adults. There is little data on the long-term safety of the performance-enhancing effects of Ritalin and Modafinil, which are available only on prescription for those diagnosed with conditions such as attention deficit hyperactivity disorder (ADHD) or narcolepsy. Anecdotal evidence suggests, however, that the pills' illicit promise of increased brain power and long bouts of uninterrupted concentration is attracting numbers of healthy high-fliers. Professor Barbara Sahakian, a neuroscientist from the University of Cambridge, is working with Lord Darzi's team at Imperial College London. Making the drugs available over the counter would be one way of prompting the clinical trials, which she believes are needed to explore just how far they can improve the human mind. Until then, Professor Sahakian warns that ambitious executives, multitasking mothers and students under pressure will continue to take risks with drugs procured over the internet, or other people's prescriptions, while the rest of society risks losing out. "This is a closet phenomenon," she told The Times. "We know that people are doing these drugs anyway but we don't know about their long-term safety. The Government has a responsibility to think about what they should do about that. Maybe they should be letting pharmaceutical companies brand these medications via a safe route. Wouldn't that be better?" Government health statistics for England show that the number of prescriptions for stimulants such as Ritalin and Modafinil has nearly doubled in recent years - rising from 458,000 in 2004 to 751,000 in 2008. "I'm rather careful about my brain," said Dr Anders Sandberg, 37, as one might well expect from a philosophy lecturer who specialises in bioethics at the University of Oxford. He first took Modafinil three years ago, after consulting a pharmacologist friend, and procuring about thirty 50mg doses from a website. He now takes it on average once a month - "not chronically, but only on days when I decide, 'OK, I need to get something done'." Days when he has conferences, seminars, papers to write. He also wants to remove the stigma attached to those who seek artificial improvement for their attention span. "When the cellphone first arrived, we weren't sure when to use it. But we learnt to invent rules, so that it's generally not OK to use them in restaurants but it's OK walking outside. We need to achieve the same with enhancement drugs. We need the right culture surrounding it. And the only way we can do that is by being honest about its consumption, and face up to the fact it is going on." A spokeswoman for the Department of Health said a report had been commissioned in 2008 investigating the issue of cognitive-enhancing drugs. She said: "We strongly urge anyone thinking about taking a prescriptiononly medicine, not intended for their personal use, to consult their GP first." Online Health news, features and expert advice timesonline.co. uk/health LOAD-DATE: February 27, 2010 LANGUAGE: ENGLISH GRAPHIC: The Times writer David Aaronovich said that the Ritalin-type tablets he took brought unexpected benefits PUBLICATION-TYPE: Newspaper JOURNAL-CODE: TIM Copyright 2010 Times Newspapers Limited All Rights Reserved 170 of 998 DOCUMENTS Herald Sun (Australia) February 26, 2010 Friday 1 - FIRST Edition Dangerous increase in prescription drug abuse `Smart pills' alarm BYLINE: Felicity Williams social trends reporter SECTION: NEWS; Pg. 29 LENGTH: 476 words OVERWORKED Melbourne professionals and students are popping speed-like drugs in growing numbers to help them get through the day. The number of prescriptions for modafinil, a treatment for sleep disorders also known to improve alertness and concentration, has almost doubled in Victoria in the past three years. Prescription drug abusers are also engaging in the dangerous practice of using modafinil -- sold here as Modavigil -- without a doctor's authority by buying it on the black market. The Herald Sun can reveal that Melbourne professionals and students have openly discussed the effects, dosage, price and their experiences obtaining the drug without a prescription in an online drugs forum with a Russian domain name. A computer programmer in the discussion thread described the effect of modafinil as ``like amphetamine''. ``Modafinil seems to make me feel sharper . . . I don't know how else to describe it,'' he wrote. ``I usually take it when I feel I should be getting something done.'' Another user admitted he and his colleagues took the drugs before night meetings when he was selling commercial real estate. A student described it as ``the best study aid ever'' despite side-effects such as ``nasty headaches'' and ``feeling scattered''. According to the Pharmaceutical Benefits Scheme website, Victorian pharmacies dispensed 723 items of modafinil last year, up from 370 in 2007. It is also easy to obtain modafinil and other ``smart pills'' such as Ritalin, for hyperactivity, and donepezil, for dementia, without a prescription at online pharmacies. The Herald Sun arranged for the purchase and shipment to Australia of one packet of modafinil tablets but withdrew when the website requested credit card details. Australian Medical Association vice-president Dr Steve Hambleton said illicit use of prescription drugs as smart pills was a major concern. ``There are a range of side-effects, particularly when people aren't taking regular amounts,'' he said. Tweet with Felicity Williams about the latest trends twitter.com/flickwilliams MODAFINIL (Modavigil) Treats sleep disorders such as narcolepsy Used by prescription drug abusers to promote wakefulness Side-effects include dependency, rashes, mania, delusions, hallucinations, suicidal thoughts, high blood pressure, birth defects DONEPEZIL (Aricept) Treats Alzheimer's disease Used by prescription drug abusers to boost mental performance Side-effects include abnormally slow heart rate, fainting, diarrhoea, nausea, vomiting, headaches, insomnia May increase risk of stomach ulcers, seizures, asthma RITALIN Treats attention deficit hyperactivity disorder Used by prescription drug abusers to enhance concentration Side-effects include dependency, psychotic episodes, severe depression, suicidal thoughts, high blood pressure Linked to sudden death in children, teenagers and adults with serious heart problems LOAD-DATE: February 25, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: DHS Copyright 2010 Nationwide News Pty Limited All Rights Reserved 171 of 998 DOCUMENTS Guardian Unlimited February 23, 2010 Tuesday A Pandora's box full of smart drugs BYLINE: Ann Robinsonguardian.co.uk LENGTH: 737 words ABSTRACT Ann Robinson: We should think very carefully before we start routinely taking drugs such as Modafinil to boost cognitive function FULL TEXT Here's a thoroughly modern ethical dilemma to chew over. You go for a job interview but are pipped to the post by another person who seems wholly underwhelming and is less well qualified. The feedback is that she came across as more zappy and focused. Over coffee, she shares that she's popped a tab of before the interview. How does that make you feel? Or here's another one. Senior members of the academic department that you work in share their tip for being able to fly over to the US and deliver a lecture the same day while looking fresh and sounding perky. They regularly take the drug to counter jet lag and enhance their cognitive function. You're not keen, but as a junior member of the team, you want to perform as well as possible. So do you try to get your GP to prescribe some or, like most of your workmates, buy some on line? These challenges aren't theoretical but real. Cognitive-enhancing drugs, also known as "smart" drugs are already being used to help people with Alzheimer's disease, schizophrenia, attention deficit hyperactivity disorder (ADHD) and brain injury. But is there burgeoning use among university students and others wishing to boost their brain power? It is this that's posing the ethical dilemmas. , professor of clinical neuropsychology at Cambridge University, described how the smart drugs fit in to our quest to keep our minds functioning longer and better in our ageing population, in a , organised by Prospect magazine. The three drugs in common use are (Ritalin), (Provigil) and (Strattera). All boost neurotransmitter chemicals (noradrenaline, acetylcholine, dopamine) at the junction between nerves to improve transmission or electrical activity. Even modest improvements in cognitive function can make a big difference to people's lives. It can make the difference between someone with schizophrenia being able to live independently or not. Or a kid with ADHD being able to stop his impulsive behaviour and stay out of trouble at school. And there are huge financial implications in being able to reduce the cost of long-term care for people with Alzheimer's if a drug can slow their cognitive decline by even 1%. Professor Sahakian said that the smart drugs are just one approach to boosting cognitive function. Exercise (three brisk walks a week will do, she said) and learning new things throughout life are most important. And connecting with others, giving of yourself and maintaining your curiosity about life are the other cornerstones of mental wellbeing. She warns against the potential dangers of people under 20, whose brains are still developing, taking smart drugs like Ritalin unless they have a condition such as ADHD. But an estimated 16-20% of US college students take smart drugs and there is reason to believe its spreading to the UK. The field of is developing to look at challenges posed by advances in the neurosciences. Some arguments for smart drugs include removing disparity in society and boosting performance. In a lengthy operation, it is best to have one surgeon do the whole job and a tab of Modafinil may be better than caffeine which, in high doses, can cause tremor. The US army is interested in smart drugs to allow troops to complete military operations as quickly as possible. But the potential harms include the fact that we don't know about long-term effects, especially in developing brains. People may feel coerced into taking them. There's a potential for abuse and you may get unwanted effects like persistent memories. Is it cheating to take the drugs? Will it turn us into mechanistic beings who don't feel we've earned the right to feel proud of our achievements? Will working hard and being motivated become antiquated concepts? Will we become a homogenous society and will we lose creativity? The last concern is practical. There is no licence for prescribing smart drugs unless you have a specified condition. No self-respecting GP is likely to prescribe it. And buying drugs online is fraught with dangers. You have to check you have no contraindications, that it won't interact with any other medication and that what you get in the post is what it says on the box. LOAD-DATE: February 23, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2010 Guardian Unlimited All Rights Reserved 172 of 998 DOCUMENTS Reuters Health Medical News January 28, 2010 Thursday 9:00 PM EST Stimulants better than nonstimulants for adult ADHD: meta-analysis SECTION: CLINICAL LENGTH: 588 words DATELINE: NEW YORK Stimulant medications show greater efficacy than nonstimulants for treating attention-deficit/hyperactivity disorder (ADHD) in adults, according to a new meta-analysis. Study authors Dr. Stephen V. Faraone and Dr. Stephen J. Glatt note that stimulants have been the mainstay of ADHD pharmacotherapy for decades. Several nonstimulant medications have also been shown effective - tricyclic antidepressants, bupropion, modafinil, monoamine oxidase inhibitors, guanfacine, atomoxetine, and clonidine. However, it's been difficult to compare different drugs or drug classes due to the lack of head-to-head trials. Drs. Faraone and Glatt, both from SUNY Upstate Medical University in Syracuse, New York, searched the medical literature for double-blind, placebo-controlled studies of ADHD in adults published after 1979, in which subjects were followed for at least 2 weeks. They identified 18 articles that involved more than 2000 subjects and evaluated 13 drugs. In their report, which appeared online December 29 in the Journal of Clinical Psychiatry, effect size is expressed as the standardized mean difference, in which a 1-point difference is equivalent to 1 standard deviation on the outcome measure. Five trials studied 4 long-acting stimulants (mixed amphetamine salts extended release, osmotic-release oral system methylphenidate, dexmethylphenidate extended release, and lisdexamfetamine dimesylate) in 637 participants. The mean effect size was 0.73. The 3 short-acting stimulants evaluated in 7 trials (n = 459) were mixed amphetamine salts, dextroamphetamine, and methylphenidate. The effect size was 0.96. Nine trials with 968 subjects examined the efficacy of 6 nonstimulants (atomoxetine, bupropion SR, modafinil, bupropion XL, paroxetine, and an investigational drug ABT-418). The mean effect size was 0.39. There was significant heterogeneity among effect sizes, and evidence of publication bias, only in the trials of short-acting stimulants. Correction for publication bias revealed an effect size of 0.86, which did not differ significantly from that of long-acting stimulants. There was also no significant difference between methylphenidate- and amphetamine-based medications. On the other hand, the effect sizes for nonstimulant medications were significantly less than those for long-acting stimulants. After correcting for differences in study design, nonstimulants did not differ from short-acting stimulants. Dr. Faraone and Dr. Glatt note that the effect sizes are robust and similar to those reported for medication treatment studies of children with ADHD. Only one medication, paroxetine, was worse than placebo. Numbers needed to treat (NNT) ranged from 2 to 3 for long-acting stimulants, from 2 to 4 for short-acting stimulants, and from 2 to 5 for nonstimulants. Among nonstimulants, only modafinil had a NNT of less than 3. The authors point out that the response rates are less than those reported in the literature, because the latter are not placebo adjusted. "The NNT results...suggest that most patients will need more than 1 drug trial to achieve a positive outcome that cannot be attributed to a placebo effect." Still, in the absence of head-to-head trials, the researchers urge caution in comparing effects of different medications across studies. The study was funded by a grant from Shire US, whose products include lisdexamfetamine dimesylate (Vyvanse), methylphenidate transdermal (Daytrana), methylphenidate hydrochloride (Equasym), and guanfacine (Intuniv). SOURCE: J Clin Psychiatry 2009. LOAD-DATE: January 29, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 Reuters Health All Rights Reserved 173 of 998 DOCUMENTS US Fed News January 20, 2010 Wednesday 10:37 AM EST Patent No. 7,649,020 Issued on Jan. 19, Assigned to Cephalon France for Modafinil Polymorphic Forms (French Inventors) LENGTH: 187 words DATELINE: ALEXANDRIA, Va. ALEXANDRIA, Va., Jan. 21 -- Armand Frydman of Verrieres-le-Buisson, France, Veronique Broquaire of Noisy-le-Grand, France, Laurent Courvoisier of Laigneville, France, Franck Mallet of Blangy sur Bresle, France, Gerard Coquerel of Boos, France, and Michel Broquaire of Le Perreux, France, have developed modafinil polymorphic forms. The inventors were issued U.S. Patent No. 7,649,020 on Jan. 19. The patent has been assigned to Cephalon France, Maisons-Alfort, France. According to the abstract released by the U.S. Patent & Trademark Office: "Polymorphic forms of modafinil racemate, methods of preparation thereof, pharmaceutical compositions and methods of therapeutic treatment involving modafinil polymorphic forms." The original application was filed on Dec. 14, 2007. For further information please visit: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetah tml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=7649020&OS=7649020&R S=7649020 For more information about US Fed News contract awards please contact: Sarabjit Jagirdar, US Fed News, Email:- htsyndication@hindustantimes.com LOAD-DATE: January 21, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 HT Media Ltd. All Rights Reserved 174 of 998 DOCUMENTS Reuters Health Medical News January 19, 2010 Tuesday 9:00 PM EST No improvements in schizophrenia symptoms seen with modafinil SECTION: CLINICAL LENGTH: 410 words DATELINE: NEW YORK The "wakefulness promoting" agent modafinil does not appear to help schizophrenic patients who don't respond well to clozapine, researchers report in the December issue of the Journal of Clinical Psychiatry. Clozapine "mostly treats positive symptoms," the researchers explain, "with meager efficacy at best" for negative symptoms or cognitive deficits. Furthermore, "clozapine-induced sedation can worsen cognition and impair social and occupational functioning," lead investigator Dr. Oliver Freudenreich of Harvard Medical School, Boston, and colleagues point out. Modafinil, which is sold in the US as Provigil, is approved to treat narcolepsy and shift work sleep disorder. Three previous controlled trials that assessed the safety and efficacy of modafinil add-on therapy in schizophrenia had inconsistent results, according to Dr. Freudenreich and his associates. In a double-blind, placebo-controlled, flexible-dose pilot trial in 35 patients, the researchers evaluated the safety, tolerability, and effect of modafinil on negative symptoms, cognition, and wakefulness/fatigue. All subjects were outpatients with stable schizophrenia, and all were taking clozapine. For the 8-week study, they were randomized to receive up to 300 mg/day of modafinil (n=19) in addition to clozapine, or placebo (n=16). The patients were an average of 45.2 years old and their mean duration of illness was 19.5 years. Adherence was over 75% for most subjects. At the end of treatment, the average dose of modafinil was 250 mg/d. "Modafinil was well-tolerated, with no clear tolerability problem in this small sample," the researchers note. "We did not detect worsening of psychosis, one of the safety concerns that has been raised with modafinil." But, they add, there was no reduction in cognitive deficits, negative symptoms or wakefulness and fatigue with modafinil compared with placebo. "Our power to detect differences between modafinil and placebo was limited by sample size," the authors said, adding that larger trials might show a benefit with modafinil. They also caution that physicians who prescribe this agent on a case-by-case off-label basis should keep in mind that rare instances of psychosis, rashes, and Stevens-Johnson syndrome have been reported with modafinil use. The pilot trial was sponsored by Cephalon Inc, the manufacturer of modafinil. Two of the authors receive grant and research support from Cephalon. SOURCE: J Clin Psychiatry 2009;70:1674-1680. LOAD-DATE: January 20, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2010 Reuters Health All Rights Reserved 175 of 998 DOCUMENTS PR Newswire December 21, 2009 Monday 4:30 PM EST Cephalon Provides Update on Regulatory Review of NUVIGIL for the Treatment of Excessive Sleepiness Associated with Jet Lag Disorder; Company Expects FDA Decision by End of First Quarter 2010 LENGTH: 1014 words DATELINE: FRAZER, Pa., Dec. 21 FRAZER, Pa., Dec. 21 /PRNewswire-FirstCall/ -- Cephalon, Inc. (Nasdaq: CEPH) today announced that the U.S. Food and Drug Administration (FDA) has extended the action date to March 29, 2010, for its review of the supplemental New Drug Application (sNDA) for NUVIGIL® (armodafinil) Tablets [C-IV]. The sNDA is for the indication of improved wakefulness in patients with excessive sleepiness associated with jet lag disorder due to eastbound travel. "We will continue to work closely with the FDA to assist them in completing their review of our application in a timely manner and do not anticipate any further delays beyond the March 29, 2010, action date," said Dr. Lesley Russell, Chief Medical Officer at Cephalon. "We remain excited about this opportunity as there are no medications approved by the FDA to treat excessive sleepiness associated with eastbound jet lag disorder." This sNDA for NUVIGIL was filed with the FDA on June 29, 2009, and given the action date of December 29, 2009, under the Prescription Drug User Fee Act (PDUFA). The company submitted additional information within 90 days of the assigned action date. Subsequently, the FDA informed the company that the agency required more time for a full review of the submission and, therefore, would extend the action date by three months. About NUVIGIL NUVIGIL, the longer-lasting isomer of modafinil, was launched in the United States in June 2009. It is indicated to improve wakefulness in patients with excessive sleepiness associated with treated obstructive sleep apnea (OSA), shift work disorder (SWD), or narcolepsy. NUVIGIL is not approved as a treatment for jet lag disorder or its associated symptoms. The NUVIGIL label includes a bolded warning for serious or life-threatening rash, including Stevens-Johnson Syndrome, that has been reported in adults and children taking modafinil, a racemic mixture of S- and R-modafinil (the latter is armodafinil, the active ingredient in NUVIGIL). NUVIGIL is not approved for use in pediatric patients for any indication. The most common adverse events in controlled clinical trials (five percent or greater) were headache, nausea, dizziness, and insomnia. Full prescribing information for NUVIGIL is available at www.NUVIGIL.com. About Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and commercialization of many unique products in four core therapeutic areas: central nervous system, inflammatory diseases, pain and oncology. A member of the Fortune 1000 and the S&P 500 Index, Cephalon currently employs approximately 3,000 people in the United States and Europe. U.S. sites include the company's headquarters in Frazer, Pennsylvania, and offices, laboratories or manufacturing facilities in West Chester, Pennsylvania, Salt Lake City, Utah, and suburban Minneapolis, Minnesota. Cephalon has a growing presence in Europe, the Middle East and Africa. The Cephalon European headquarters and pre-clinical development center are located in Maisons-Alfort, France, just outside of Paris. Key business units are located in England, Ireland, France, Germany, Italy, Spain, the Netherlands for the Benelux countries, and Poland for Eastern and Central European countries. Cephalon Europe markets more than 30 products in four areas: central nervous system, pain, primary care and oncology. The company's proprietary products in the United States include: NUVIGIL, TREANDA® (bendamustine hydrochloride) for Injection, AMRIX® (cyclobenzaprine hydrochloride extended-release capsules), FENTORA® (fentanyl buccal tablet) [C-II], TRISENOX® (arsenic trioxide) injection, GABITRIL® (tiagabine hydrochloride), PROVIGIL® (modafinil) Tablets [C-IV] and ACTIQ® (oral transmucosal fentanyl citrate) [C-II]. The company also markets numerous products internationally. Full prescribing information on its U.S. products is available at http://www.cephalon.com or by calling 1-800-896-5855. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs, development of potential pharmaceutical products, interpretation of clinical results, clinical development of NUVIGIL, prospects for and frequency of filing new indications for NUVIGIL, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, sales and earnings guidance, and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. Contacts: Media: Investor Relations: Candace Steele Flippin Chip Merritt 610-727-6231 (office) 610-738-6376 (office) csteele@cephalon.com cmerritt@cephalon.com SOURCE Cephalon, Inc. CONTACT:Media, Candace Steele Flippin, +1-610-727-6231, csteele@cephalon.com, or Investor Relations, Chip Merritt, +1-610-738-6376, cmerritt@cephalon.com, both of Cephalon, Inc. URL: http://www.prnewswire.com LOAD-DATE: December 22, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2009 PR Newswire Association LLC All Rights Reserved 176 of 998 DOCUMENTS The Age (Melbourne, Australia) October 2, 2009 Friday First Edition Call for testing on 'smart drugs' BYLINE: JULIA MEDEW HEALTH REPORTER SECTION: NEWS; Pg. 7 LENGTH: 466 words INCREASING use of "smart drugs" among students aiming to improve their memory and cognitive function could prompt authorities to start drug-testing students before exams, an Australian researcher says. Vince Cakic, a researcher from the University of Sydney's school of psychology, said students were increasingly using psychostimulants â[#x20ac]" drugs usually prescribed for neuropsychiatric disorders and sleep disorders â[#x20ac]" to enhance their academic performance. He said drugs such as selegiline, usually prescribed for Parkinson's disease, were touted as a motivation enhancer, while others, such as modafinil and piracetam, were known for keeping people alert and improving their memory respectively. Collectively, the drugs are known as "nootropics" or "smart drugs", he said, because of the Greek words noo (mind) and troppo (to turn or change). Although research recently published in the US suggested modafinil was addictive, Mr Cakic said it was particularly popular among students because it kept them awake and alert without making them hyperactive. "I would say a lot of students are using that now," he said. "Memory enhancers like piracetam are also very popular." Mr Cakic said the drugs were easily purchased over the internet through online pharmacies in South-East Asia, Mexico and India, but he said amphetamines such as Dexedrine were harder to buy because they were controlled substances. In an article published in the Journal of Medical Ethics today, Mr Cakic said although some of the drugs had well-known side effects, including addictive qualities and the potential to aggravate mental illness, it was unclear how dangerous most of them were for healthy people long term. "It remains to be seen whether nootropics represent a pharmacological 'free lunch' or if the enhancement of some cognitive functions can only be realised at the expense of others," he wrote. Mr Cakic said increasing use among students could prompt people to treat them like performance-enhancing drugs in professional sport. If it was perceived they offered students an unfair advantage, drug tests could follow. Australian Drug Foundation chief executive John Rogerson said anecdotal reports suggested young people were talking more about these drugs, but he said there was no indication it was a big problem in Australia. "We haven't got evidence of this, but there's no doubt that kids are taking stimulants like Ritalin to get a short-term advantage," he said. "We would encourage young people to stay away from it." SO-CALLED SMART DRUGS METHYLPHENIDATE (Ritalin, Concerta) MODAFINIL (Provigil, Modavigil) AMPAKINES PIRACETAM (Nootropil, Avigilen) ERGOLOID (Hydergine, Cicanol) BETA-BLOCKERS (Propranolol) NOTE: THE AGE DOES NOT CONDONE THE USE OF ANY OF THESE DRUGS WITHOUT A PRESCRIPTION AND APPROPRIATE MEDICAL ADVICE. LOAD-DATE: October 1, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2009 The Age Company Limited All Rights Reserved 177 of 998 DOCUMENTS The Age (Melbourne, Australia) October 2, 2009 Friday Second Edition 'Smart' students could sit drug tests BYLINE: JULIA MEDEW, HEALTH REPORTER SECTION: NEWS; Pg. 3 LENGTH: 454 words INCREASING use of "smart drugs" among students aiming to improve their memory and cognitive function could prompt authorities to drug-test students before exams, an Australian researcher says. Vince Cakic, a researcher from the University of Sydney's school of psychology, said students were increasingly using psychostimulants â[#x20ac]" drugs usually prescribed for neuropsychiatric disorders and sleep disorders â[#x20ac]" to enhance their academic performance. He said drugs such as selegiline, usually prescribed for Parkinson's disease, were touted as a motivation enhancer, while others, such as modafinil and piracetam, were known for keeping people alert and improving their memory respectively. Collectively, the drugs are known as "nootropics" or "smart drugs". Although research recently published in the US suggested modafinil was addictive, Mr Cakic said it was particularly popular among students because it kept them awake and alert without making them hyperactive. "I would say that a lot of students are using that now," he said. "Memory enhancers like piracetam are also very popular." Mr Cakic said the drugs were easily purchased over the internet through online pharmacies in South-East Asia, Mexico and India, but he said amphetamines such as Dexedrine were harder to buy because they were controlled substances. In an article published in the Journal of Medical Ethics today, Mr Cakic said although some of the drugs had well-known side effects, including addictive qualities and the potential to aggravate mental illness, it was unclear how dangerous most of them were for healthy people long term. "It remains to be seen whether nootropics represent a pharmacological 'free lunch' or if the enhancement of some cognitive functions can only be realised at the expense of others," he wrote. Mr Cakic said increasing use among students could prompt people to view this issue in the same light as performance-enhancing drugs in professional sport. If it was perceived that drugs offered students an unfair advantage and were dangerous, drug tests could follow. Australian Drug Foundation chief executive John Rogerson said anecdotal reports suggested young people were talking more about these drugs, but he said there was no indication it was a big problem in Australia. "There's no doubt that kids are taking stimulants like Ritalin to get a short-term advantage," he said. "Some of this stuff is being bought off the internet, which is very risky," he said. SO-CALLED SMART DRUGS *METHYLPHENIDATE (Ritalin, Concerta) *MODAFINIL (Provigil, Modavigil) *AMPAKINES *PIRACETAM (Nootropil, Avigilen) *ERGOLOID (Hydergine, Cicanol) *BETA-BLOCKERS (Propranolol) NOTE: THE AGE DOES NOT CONDONE THE USE OF ANY OF THESE DRUGS WITHOUT A PRESCRIPTION LOAD-DATE: October 2, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2009 The Age Company Limited All Rights Reserved 178 of 998 DOCUMENTS MX Brisbane (Queensland, Australia) October 2, 2009 Friday 1 - BRIS Edition Sample exams - Call for urine tests to tackle `smart drug' BYLINE: Alex Dickinson SECTION: MX; Pg. 1 LENGTH: 308 words University students using ``smart drugs'' to get an edge in class could soon face sports-style urine tests before exams. Research from the University of Sydney has warned that students are increasingly using ``performance enhancing'' psychostimulants usually prescribed for Alzheimer's, Parkinson's or sleep disorders, to enhance their academic performance. Among those being taken are the ADD drug Ritalin, Aricept used to treat dementia and the ``wide-awake'' drug Modafinil. The drugs are being easily purchased over the internet through pharmacies in South-East Asia, Mexico and India. Researcher Vince Cakic, whose findings have been published in the Journal of Medical Ethics, said purchasing ``smartness in a bottle'' is likely to have broad appeal to students seeking to gain an advantage in an increasingly competitive world. He said the drugs are near-impossible to monitor, but a sports-style urine tests would detect them. ``One conjures to mind the scenario of students taken to one side, cup in hand, and asked to provide a urine sample to test officials,'' Cakic said. He said that Modafinil was very popular among students in the US because it kept them awake without making them hyperactive. ``So far, these drugs offer only a modest perk in performance, but more powerful versions are in the pharmaceutical pipeline and may well have a potent allure,'' Cakic said. But the proposal to set up urine tests before exams has angered student groups. General secretary of the Queensland University of Technology Student Guild, Kat Henderson, said urine tests on students was ``ridiculous''. ``There's nowhere in the world that a guild would allow the university to start drug-testing students,'' Henderson said. ``I've never heard of using drugs for concentration as being a big problem. To test students would be infringing on their basic rights.'' LOAD-DATE: October 2, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: MXB Copyright 2009 Nationwide News Pty Limited All Rights Reserved 179 of 998 DOCUMENTS PR Newswire September 24, 2009 Thursday 8:30 AM EST Cephalon Announces that FDA Grants Priority Review of its Supplemental New Drug Application for NUVIGIL as a Treatment for Excessive Sleepiness Associated with Jet Lag Disorder LENGTH: 957 words DATELINE: FRAZER, Pa., Sept. 24 FRAZER, Pa., Sept. 24 /PRNewswire-FirstCall/ -- Cephalon, Inc. (Nasdaq: CEPH) today announced the U.S. Food and Drug Administration (FDA) has granted a priority review for its supplemental New Drug Application (sNDA) for NUVIGIL(R) (armodafinil) Tablets [C-IV], which was filed in June of this year. The FDA decision on approval of NUVIGIL as a treatment for improving wakefulness in patients with excessive sleepiness associated with jet lag disorder due to eastbound travel is expected by December 29, 2009. There currently is no FDA-approved treatment for jet lag disorder. The NUVIGIL sNDA is based on data from a Phase III pivotal study that evaluated the efficacy and safety of NUVIGIL (50 or 150 mg/day) in 427 healthy adults over three days during travel from the United States to Europe. These data were presented earlier this year at the SLEEP 2009 23rd Annual Meeting of the Associated Professional Sleep Societies. About NUVIGIL NUVIGIL, the longer-lasting isomer of modafinil, was launched in the United States in June 2009 and is indicated to improve wakefulness in patients with excessive sleepiness associated with treated obstructive sleep apnea, shift work sleep disorder, also known as shift work disorder (SWD), and narcolepsy. NUVIGIL is not approved as a treatment for jet lag disorder or its associated symptoms. The NUVIGIL label includes a bolded warning for serious or life-threatening rash, including Stevens-Johnson syndrome, that has been reported in adults and children taking modafinil, a racemic mixture of S and R modafinil (the latter is armodafinil, the active ingredient in NUVIGIL). NUVIGIL is not approved for use in pediatric patients for any indication. The most common adverse events in controlled clinical trials (five percent or greater) were headache, nausea, dizziness and insomnia. Full prescribing information for NUVIGIL is available at www.NUVIGIL.com. About Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and commercialization of many unique products in four core therapeutic areas: central nervous system, inflammatory diseases, pain and oncology. A member of the Fortune 1000 and the S&P 500 Index, Cephalon currently employs approximately 3,000 people in the United States and Europe. U.S. sites include the company's headquarters in Frazer, Pennsylvania, and offices, laboratories or manufacturing facilities in West Chester, Pennsylvania, Salt Lake City, Utah, and suburban Minneapolis, Minnesota. Cephalon has a growing presence in Europe, the Middle East and Africa. The Cephalon European headquarters and pre-clinical development center are located in Maisons-Alfort, France, just outside of Paris. Key business units are located in England, Ireland, France, Germany, Italy, Spain, the Netherlands for the Benelux countries, and Poland for Eastern and Central European countries. Cephalon Europe markets more than 30 products in four areas: central nervous system, pain, primary care and oncology. The company's proprietary products in the United States include: NUVIGIL, TREANDA(R) (bendamustine hydrochloride) for Injection, AMRIX(R) (cyclobenzaprine hydrochloride extended-release capsules), FENTORA(R) (fentanyl buccal tablet) [C-II], TRISENOX(R) (arsenic trioxide) injection, GABITRIL(R) (tiagabine hydrochloride), PROVIGIL(R) (modafinil) Tablets [C-IV], and ACTIQ(R) (oral transmucosal fentanyl citrate) (C-II). The company also markets numerous products internationally. Full prescribing information on its U.S. products is available at www.cephalon.com or by calling 1-800-896-5855. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs, development of potential pharmaceutical products, interpretation of clinical results, clinical development of NUVIGIL, timing of FDA decisions, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, sales and earnings guidance, and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion.     Contacts:     Media     Sheryl Williams     610-738-6493     swilliam@cephalon.com     Investor Relations     Chip Merritt     (610) 738-6376     cmerritt@cephalon.com     Web Site:     www.cephalon.com SOURCE Cephalon, Inc. CONTACT:Media, Sheryl Williams, +1-610-738-6493, swilliam@cephalon.com, or Investor Relations, Chip Merritt, +1-610-738-6376, cmerritt@cephalon.com, both of Cephalon, Inc. URL: http://www.prnewswire.com LOAD-DATE: September 25, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2009 PR Newswire Association LLC All Rights Reserved 180 of 998 DOCUMENTS Independent Extra September 22, 2009 Tuesday First Edition The brain buzz you may live to regret; So-called 'smart drugs' have been seized upon by undergraduates as a means to stay alert and improve mental performance. But the long-term effects remain unknown. Rob Sharp investigates - and gets students' verdicts on the effects BYLINE: Rob Sharp SECTION: INDEPENDENT LIFE; Pg. 10 LENGTH: 1501 words Two mates in their mid-to-late 20s are joking around. One of them pulls a silver blister pack from his pocket. It contains a rare drug, two pills of which he pops from the shiny wrapper that he holds in his hand. He gives one pill to his pal. They stand still for a moment, consider what they are about to do, before placing the capsules into their mouths and washing them down with a swig of water. They complete the move with a couple of mock-grimaces. The drug in question is Modafinil, a form of prescription medication normally used to treat narcolepsy, but which is increasingly being abused by students across the US and UK for its stimulating properties: in small doses it can improve your memory, increase your focus and prevent you from falling asleep (proving especially handy in the run-up to exams). It is one of a group of cognitive enhancers or "smart pills" that also includes Ritalin and Adderall, both used to treat ADHD (attention-deficit/hyperactivity disorder), that have similar properties. A study by Cincinnati Children's Hospital published in the British Medical Journal last month indicated that use of these latter two drugs in the US has increased by 75 per cent between 1998 and 2005. What's more, a 2005 survey of more than 10,000 US university students found that 4 to 7 per cent of them had tried ADHD drugs at least once to pull pre-exam all-nighters. At some institutions, more than one in four students said they'd sampled the pills. The subject is relatively unstudied in the UK but the trend is the subject of a forthcoming documentary, Wasted Britain, set to air on Current TV on 28 September. "The problem is you don't know what you're getting," says Barbara Sahakian, professor of clinical neuropsychology at Cambridge University's psychiatry department. "We don't know about the effects of long-term use of drugs like Modafinil. We should wait for the studies to show the effect of it on healthy human beings. There are pressures on people but these quick fixes are not the way forward; education and exercise are both good ways of enhancing cognition, too." Perhaps what is so worrying about the Current TV programme is the means by which its participants, Steve Middleditch and Christian Boyd, first got hold of Modafinil. "When the producers first told me to buy it I had never heard of it," says Middleditch. "So I began doing some research on the internet. I discovered that with a few clicks I could get hold of it by filling in a phoney prescription online. I said I had jet lag." A week later a pack of 30 pills arrived, postmarked Mumbai. To conduct his experiment, Steve woke up one day at 3am to make himself fatigued, and took the pills at midday the following day. He describes the experience of taking the drug as odd, to say the least. "It's difficult to explain," he continues. "You get this massive buzz; it's a bit like drinking five cups of coffee in one go. You get a definite buzz off it. It affects areas of the brain rather than the heart. My hands were moving a bit. I definitely got the jitters. It's the sort of thing that not only keeps you awake, it keeps you blathering on. I certainly felt more focused. It was definitely stronger than I thought it would be." The effects of the drug are well-proven. In 2003, Cambridge University researchers found a single dose helped male university students perform in mental planning tests, accurately complete puzzles and remember long chains of digits; it has also been tested by the US and British forces to allow soldiers to complete all-night operations. Scientists believe Modafinil can give its user 48 hours of continuous wakefulness (though there are some side effects: headaches are the most common, though there are plenty of others). The most remarkable thing, however, is that its users don't have to pay back sleep "debt" - a standard eight hours is enough to compensate for no sleep on the previous night: could this mean a future of 22-hour days? Our bosses may hope so. "I would take Modafinil again because for me the problem is concentration and focus," says Boyd. "It allowed me to get down to what I wanted to do; I never felt like being distracted, so it was great." Philip Harvey, a professor at Emory University in Atlanta, says his work has been helped by Modafinil, which he takes to combat jet lag. Unlike in the UK, American doctors can prescribe the drug to night-shift workers as well as to narcoleptics. "I often fly to Europe to give talks," he says. "I used to travel the day before to give myself time to recover, but with Modafinil I can now give a talk the same day I arrive and feel like I've had a normal night's sleep." Modafinil is not a golden drug, though. Its other side-effects may include insomnia, agitation, anxiety, agitation, and heart problems. And then there are the ethics of taking something that might give you an unfair advantage over your peers. "It's all in your personal preference," concludes Middleditch. "But I don't think it is a good thing. I can see why some people might take them. We've all had a deadline and been knackered and that pill will help you reach that deadline. In some scenarios where people need it I can also agree with it - some troops in combat might use it, or a paramedic might need it to stay focused. Perhaps there's some warrant in that. But personally it's not something I would take again, but that's just my feeling because it doesn't feel right. You become this person that you are kind of not. It's a strange feeling - the day after you still have this strange sensation in your head." Ritalin and Adderall, which are defined by their active ingredients of mixed amphetamine salts and methylphenidate, as well as increasing concentration (in the right doses) can also be taken for the buzz they create. They are often used in combination with other drugs such as alcohol, or cocaine. Research conducted by Harry Sumnall, a psychopharmacologist at the Centre for Public Health at Liverpool's John Moores University, claims that research he has conducted in Merseyside shows that children with prescriptions for ADHD treatments were routinely selling their drugs; in some cases, so were their parents. "At least in the US they're looking out for the problem and routinely including Ritalin misuse in high school drugs surveys, for example," he says. "We might have to do the same here." These drugs are also less effective than Modafinil at enhancing performance. "The biggest issue with these drugs, certainly with the likes of Adderall, is that it is very difficult to know how much to take; very quickly they can go from enhancing your performance to making you of no use whatsoever," says John Marsden, a reader in addiction psychology at the Institute of Psychiatry. "Though the principal issue is that if people were using these drugs it might set in train a process where people were using them more and more and become addicted to them." 'Wasted Britain' is aired on Current TV (Sky channel 183/Virgin channel 155) on Monday 28 September Cognitive enhancers Is it smart to take them? Modafinil Modafinil often comes in the form of the branded Provigil and is a memory-enhancing and mood-brightening stimulant, which enhances wakefulness. It stimulates activity within the brain and spinal cord (central nervous system). It is used to treat narcolepsy and sleep apnoea. It was rejected in 2006 by the Food and Drug Administration in America for prescribing to children with ADHD, but it is prescribed in the UK. Some of the side effects include unstable moods, blurred vision and difficulty sleeping. Ritalin - Tablets of Ritalin, one of the most widely known drug used to treat ADHD in children, contain the active ingredient methylphenidate hydrochloride. This is a stimulant and it is also possible to buy methylphenidate tablets on their own in an unbranded form. As well as calming hyperactive kids, it is used illegally by students to boost concentration and effectiveness at exams. The drug is still illegal without prescription in the UK, and is lawfully rated as class B in this instance. Concerta This is another branded version of methylphenidate hydrochloride, which has very similar effects as Ritalin. It is one of the newer brands on the market used to treat children with ADHD. The side effects seem less pronounced in children than Ritalin but there are still many, such as abdominal pain, nervousness and hostility. It is used less than Ritalin by students but for the same effects. Adderall Contains both amphetamines and dextro-amphetamines (amphetamine salts) and is widely prescribed as a drug to treat ADHD. It has four component salts which are claimed to metabolise at different rates. Manufacturers suggest that this makes the effects smoother. It is also used to treat narcolepsy and sometimes severe depression. The patient or drug user experiences more intense and sustained periods of concentration. It can cause psychotic episodes in those with a history of psychosis, though this is rare. LOAD-DATE: September 21, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: IE Copyright 2009 Independent Print Ltd All Rights Reserved 181 of 998 DOCUMENTS US Fed News August 21, 2009 Friday 1:04 PM EST Patent No. 7,576,133 Issued on Aug. 18 for Modafinil Nasal Administration (Illinois Inventors) LENGTH: 116 words DATELINE: ALEXANDRIA, Va. ALEXANDRIA, Va., Aug. 21 -- Carl Henry Lawyer, Matthew Carl Lawyer and Edward Zadok Lawyer, all from Springfield, Ill., have developed a composition for nasal administration of modafinil. The inventors were issued U.S. Patent No. 7,576,133 on Aug. 18. According to the abstract released by the U.S. Patent & Trademark Office: "Systemic delivery of Modafinil to the nasal mucous membrane elicits rapid systemic therapeutic response with reduced side effects compared to current methods of administration." The original application was filed on March 7, 2003. For more information about US Fed News contract awards please contact: Sarabjit Jagirdar, US Fed News, Email:- htsyndication@hindustantimes.com LOAD-DATE: September 18, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2009 HT Media Ltd. All Rights Reserved 182 of 998 DOCUMENTS Clinical Advisor August 12, 2009 Agent battles excessive sleepiness SECTION: NEWS; Drug Updates from MPR LENGTH: 619 words HIGHLIGHT: Nuvigil promotes wakefulness in patients with various sleep disorders Product: Nuvigil Company: Cephalon Pharmacologic class: Wakefulness promoter Active ingredient: Armodafinil 50 mg, 150 mg, 250 mg; tabs. Indication: To improve wakefulness in patients with excessive sleepiness associated with obstructive sleep apnea/hypopnea syndrome (OSAHS), narcolepsy, and shift-work sleep disorder (SWSD). Adjunct to standard treatment for underlying airway obstruction in OSAHS. Pharmacology: Armodafinil is the R-enantiomer of modafinil (Provigil). Of the two enantiomers that comprise modafinil, the R-form is longer lasting. Both of these drugs have wakefulness- promoting effects similar to those of sympathomimetics such as amphetamines and methylphenidate. Clinical trials: Two 12-week studies were conducted to establish the safety and efficacy of armodafinil in OSAHS. In the first study, patients were given either armodafinil 150 mg or 250 mg/day, or placebo. The second trial compared the effects of armodafinil 150 mg/day and placebo. Both studies indicated that patients given armodafinil showed improvements in their ability to remain awake and in their overall clinical condition. The results of a 12-week study indicated that armodafinil was effective in improving wakefulness in patients with excessive sleepiness associated with narcolepsy. Patients treated with armodafinil 150 mg or 250 mg/day showed a significantly enhanced ability to remain awake, and more of the patients given armodafinil had an improved overall clinical condition than those given placebo. A 12-week trial was conducted to establish the efficacy of armodafinil in patients with chronic SWSD. Patients were randomized to receive either armodafinil 150 mg/day or placebo. Those given the study drug showed a significant prolongation in the time to sleep onset, as measured by a sleep latency test conducted during a simulated night shift at the final visit, compared with those given placebo. Also, more patients treated with armodafinil experienced an improvement in overall clinical condition, compared with patients given the placebo. Adults: > 17 years: OSAHS, narcolepsy: 150 mg or 250 mg once daily in the am. SWSD: 150 mg one hour before starting shift. Severe hepatic impairment: reduce dose. Children: <17 years: not recommended. Precautions: Discontinue if rash appears (unless clearly not drug-related), or if angioedema, anaphylaxis, or multi- organ hypersensitivity reaction occurs. OSAHS: treat underlying obstruction; maintain continuous positive airway pressure use if indicated. History of left ventricle hypertrophy or mitral valve prolapse syndrome (e.g., ischemic ECG changes, chest pain, arrhythmias associated with central nervous system [CNS] stimulants): not recommended. Recent MI. Unstable angina. Monitor BP. Psychosis. Depression. Mania. Severe hepatic or renal impairment. Re- evaluate periodically. Elderly (may need to reduce dose). Labor and delivery. Pregnancy (Cat. C). Nursing mothers. Interactions: May antagonize hormonal contraceptives; use alternative or additional contraception during and for one month after. Avoid alcohol. Caution with monoamine oxidase inhibitors. Armodafinil levels may be decreased by CYP3A4 inducers (e.g., carbamazepine, phenobarbital, rifampin) and increased by CYP3A4 inhibitors (e.g., ketoconazole, erythromycin). May reduce levels of drugs metabolized by CYP3A4 (e.g., cyclosporine). May increase levels of drugs metabolized by CYP2C9 (e.g., warfarin) or CYP2C19 (e.g., phenytoin, diazepam, propranolol). Adverse reactions: Headache, insomnia, other CNS effects, GI upset; rash (may be serious, e.g., Stevens-Johnson, toxic epidermal necrolysis). How supplied: Tabs-60 For more information, call 800.896.5855 or visit www.Nuvigil.com. LOAD-DATE: November 3, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Magazine JOURNAL-CODE: 6 Copyright 2009 Haymarket Media. All Rights Reserved 183 of 998 DOCUMENTS US Fed News August 3, 2009 Monday 11:07 AM EST Patent No.7,566,805 Issued on July 28, Assigned to Cephalon for Modafinil Compositions (Massachusetts Inventors) LENGTH: 156 words DATELINE: ALEXANDRIA, Va. ALEXANDRIA, Va., Aug. 3 -- Magali Bourghol Hickey of Medford, Mass., Matthew Peterson of Hopkinton, Mass., Orn Almarsson of Shrewsbury, Mass., and Mark Oliveira of Framingham, Mass., have developed a modafinil compositions. The inventors were issued U.S. Patent No. 7,566,805 on July 28. The patent has been assigned to Cephalon Inc., Frazer, Pa. According to the abstract released by the U.S. Patent & Trademark Office: "Co-crystals and solvates of racemic, enantiomerically pure, and enantiomerically mixed modafinil are formed and several important physical properties are modulated. The solubility, dissolution, bioavailability, dose response, and stability of modafinil can be modulated to improve efficacy in pharmaceutical compositions." The original application was filed on Sept. 4, 2004.For more information about US Fed News contract awards please contact: Sarabjit Jagirdar, US Fed News, Email:- htsyndication@hindustantimes.com LOAD-DATE: August 3, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2009 HT Media Ltd. All Rights Reserved 184 of 998 DOCUMENTS Pediatric News August 2009 Editorial Data Needed on Cognition-Enhancing Drugs BYLINE: Richard N. Rosenthal, M.D. SECTION: Pg. 14 Vol. 43 No. 8 ISSN: 0031-398X LENGTH: 853 words     DR. ROSENTHAL is chairman of psychiatry at St. Luke's-Roosevelt Hospital Center and professor of clinical psychiatry at Columbia University, both in New York, and a past president of the American Academy of Addiction Psychiatry. Dr. Rosenthal disclosed that he receives research grants from Titan Pharmaceuticals Inc. and Forest Research Institute. To respond to this editorial, e-mail Dr. Rosenthal at pdnews@elsevier.com    If we had drugs that would make people smarter, wouldn't that benefit society? And would using drugs in this way be a bad thing?    The reality is: We do have such drugs. And, more and more, we are hearing accounts of normal people taking agents to enhance their mental acuity and alertness at work and in school.    The journal Nature did a survey last year that looked at 1,400 of its scientist readers from 60 countries (Nature 2008;456:702-5). The survey found that 20% of them had used cognitive enhancement in the form of modafinil or methylphenidate or had used beta-blockers to calm them and help them focus when they had to give presentations. Interestingly, 80% of them were in favor of being able to obtain the drugs at their own discretion, as opposed to having to go to a doctor or visit the Internet to get a prescription.    Cognition-enhancing drugs give a competitive edge, and in our society the pressure to succeed is huge. Strikingly, one-third of those responding to the Nature survey said they would feel obligated to give cognition-enhancing drugs to their children if the other children in school were taking them.    Some of us may think that the use of such performance-enhancing drugs in "normal" people is wrong. Others see the practice as cheating. The use of a pill to make us smarter somehow goes against the Judeo-Christian ethic, which tells us there is no gain without pain-that gain without pain weakens our character. But does it automatically follow that taking a drug solely to satisfy a person's desires is objectionable?    The notion of improving performance using psychopharmacology is not a new one. Examples include the use of alcohol, caffeine, and herbs, as well as pharmaceutical agents.    In a study of commercial pilots, those who took 5 mg/day of the cholinesterase inhibitor donezepil (Aricept) for 1 month did better in flight simulation tests did than their counterparts who took placebo, especially in emergency situations. Think about that. If you are a passenger, wouldn't you rather have your pilot on donezepil?    Many people use caffeine for its stimulant properties. Caffeine improves concentration and increases the capacity for information processing in the brain. Glucose priming also enhances learning and memory, so coffee with sugar is a powerful combination. Is a sweet espresso an unfair advantage at work? If it reduces accidents in an industrial setting, why wouldn't you want people to consume caffeine?    Methylphenidate (Ritalin) improves concentration, working memory, and attention in people with attention-deficit/hyperactivity disorder. In healthy adults, it improves executive functioning. It's well known on college campuses for use as a study aid, but college students may ignore traditional dosing and snort it at high doses before taking exams or writing papers.    Modafinil (Provigil), approved for narcolepsy and shift-work sleep disorders, reduces attention deficits attributable to sleep deprivation. In normal adults, it significantly improves fatigue levels, motivation, vigilance, performance on digital pattern recognition, memory, and reaction time. Reportedly, modafinil is the entrepreneur's drug of choice in Silicon Valley.    There's a lot of nonmedical use of modafinil out there, and this begs the question about people using it this way-not just people, but also our colleagues.    The pharmaceutical industry is working to develop a drug aimed at inhibiting memory formation to prevent posttraumatic stress disorder after a traumatic event. This is primary prevention, and it is a good idea.    But what about using such a drug simply to prevent an unpleasant memory? Is that okay? How should use of cognition-enhancing drugs be regulated in healthy people? Should their use always be monitored by health care professionals?    These people are not patients; they are healthy members of society. Their rationale for using medication is for self-enhancement, not therapy. But many of these medications are supposed to be available only by prescription.    We need to do scientific work in this area. There may be evils associated with such use, such as increased social inequity. But there may also be real benefits to our society. I fear that if we do not attempt to answer some of these questions and create some guidelines, the government will do so. And when the government does it, the outcome often falls short.    Whatever our views on the matter, society is moving this way. The train has left the station, and there appears to be no conductor on board. Do we want to get on and steer, or do we want to stand by and let someone else deal with this increasingly important issue? LOAD-DATE: August 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: PDNEWS Copyright 2009 Elsevier Inc., International Medical News Group All Rights Reserved 185 of 998 DOCUMENTS Irish Independent July 7, 2009 Tuesday A stimulating debate SECTION: FEATURES LENGTH: 214 words Ritalin A stimulant drug introduced in 1956 for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children, it has become increasingly widely used, especially in the US. Recent reports have emerged of it being abused by students seeking aids to help them through their exams. Amphetamines The stimulant was first synthesised more than a century ago and has been used and abused to boost energy, increase wakefulness and prolong endurance. Its users have been as diverse as long distance lorry drivers wanting to ward off drowsiness and women trying to lose weight. Today it is prescribed for ADHD and narcolepsy, and has been investigated for its role in helping stroke victims re-learn motor skills. Donepezil Scientists in aviation medicine and in the military have been examining medicines which might increase alertness and concentration to minimise risk of pilot error and maximise endurance. Donepezil, used to treat dementia, has been shown to boost the performance of pilots on flight simulators. Modafinil Modafinil, a drug used to treat the sleep disorder narcolepsy, has also been tested on pilots and other members of the armed forces. Tests on helicopter pilots flying on simulators who had been deprived of sleep showed the drug boosted performance. LOAD-DATE: July 7, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2009 Independent News and Media Ltd. All Rights Reserved 186 of 998 DOCUMENTS US Fed News July 6, 2009 Monday 1:14 PM EST Patent No. 7,553,646 Issued on June 30, Assigned to University of Iowa Research Foundation for Synthesis Methods (Iowa Inventors) LENGTH: 186 words DATELINE: ALEXANDRIA, Va. ALEXANDRIA, Va., July 6 -- Horacio F. Olivo and Antonio Victor Osorio-Lozada, both of Iowa City, Iowa, have developed synthesis methods. The inventors were issued U.S. Patent No. 7,553,646 on June 30. The patent has been assigned to University of Iowa Research Foundation, Iowa City. According to the abstract released by the U.S. Patent & Trademark Office: "The present invention provides novel methods for the synthesis of racemic and enantiomers of modafinil via microbial oxidation-amidation transformation. The methods include the successive oxidation-amidation of benzhydrylsulfanyl carboxylic acid to produce racemic and enantiomers of modafinil using at least one microorganism of yeast, bacteria, or fungus. Also disclosed are pharmaceutical compositions of racemic and enantiomers of modafinil along with their use in the treatment of diseases, including attention deficit hyperactivity disorder and drug addiction." The original application was filed on July 27, 2006.For more information about US Fed News contract awards please contact: Sarabjit Jagirdar, US Fed News, Email:- htsyndication@hindustantimes.com LOAD-DATE: July 6, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2009 HT Media Ltd. All Rights Reserved 187 of 998 DOCUMENTS PR Newswire June 30, 2009 Tuesday 8:00 AM GMT Cephalon Submits NUVIGIL Supplemental New Drug Application for the Treatment of Excessive Sleepiness Associated with Jet Lag Disorder LENGTH: 1189 words DATELINE: FRAZER, Pa., June 30 FRAZER, Pa., June 30 /PRNewswire-FirstCall/ -- Cephalon, Inc. (Nasdaq: CEPH) today announced that it has submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) requesting approval of NUVIGIL(R) (armodafinil) Tablets [C-IV] for the indication of improved wakefulness in patients with excessive sleepiness associated with jet lag disorder resulting from eastbound travel. Jet lag disorder is an acute condition that occurs when a person's internal body clock becomes disrupted as a result of rapid travel across several time zones. Based on U.S. Bureau of Labor Statistics findings, an estimated 70 million American travelers experience jet lag annually. Currently, there are no FDA-approved medications to improve wakefulness in travelers who experience the excessive sleepiness commonly associated with long flights. "This supplemental New Drug Application for a new use of NUVIGIL is another important milestone for Cephalon. We hope that this will be the first of many new indications for NUVIGIL over the next five years," said Dr. Lesley Russell, Chief Medical Officer and Executive Vice President at Cephalon. The NUVIGIL sNDA for the treatment of excessive sleepiness associated with jet lag disorder is based on data from a Phase 3 study, recently presented at the SLEEP 2009 23rd Annual Meeting of the Associated Professional Sleep Societies in Seattle, Washington. The data from this novel placebo-controlled pivotal study, which involved overseas air travel, included an evaluation of the efficacy and safety of NUVIGIL (50 or 150 mg/day) in 427 healthy men and women who all had experienced jet lag symptoms at least once during the previous five years. Clinical efficacy was evaluated using two primary endpoints: an objective assessment -- the Multiple Sleep Latency Test (MSLT), and a subjective assessment -- the Patient Global Impression of Severity (PGI-S). Patients taking NUVIGIL (150 mg/day) showed a statistically significant improvement over placebo as measured by the MSLT [p<0.0001] and the PGI-S [p<0.05]. The most common adverse events associated with NUVIGIL treatment (five percent or greater) were headache, nausea, diarrhea, and palpitations. About NUVIGIL NUVIGIL, the longer-lasting form of modafinil, was launched in the United States in June 2009 and is indicated to improve wakefulness in patients with excessive sleepiness associated with treated obstructive sleep apnea (OSA), shift work sleep disorder, also known as shift work disorder (SWD), and narcolepsy. NUVIGIL is not currently indicated for the treatment of jet lag disorder or its associated symptoms. The NUVIGIL label includes a bolded warning for serious or life-threatening rash, including Stevens-Johnson Syndrome, that has been reported in adults and children taking modafinil, a racemic mixture of S- and R- modafinil (the latter is armodafinil, the active ingredient in NUVIGIL). NUVIGIL is not approved for use in pediatric patients for any indication. The most common adverse events in controlled clinical trials (five percent or greater) were headache, nausea, dizziness, and insomnia. Full prescribing information for NUVIGIL is available at www.NUVIGIL.com. About Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and commercialization of many unique products in four core therapeutic areas: central nervous system, inflammatory diseases, pain and oncology. A member of the Fortune 1000 and the S&P 500 Index, Cephalon currently employs approximately 3,000 people in the United States and Europe. U.S. sites include the company's headquarters in Frazer, Pennsylvania, and offices, laboratories or manufacturing facilities in West Chester, Pennsylvania, Salt Lake City, Utah, and suburban Minneapolis, Minnesota. Cephalon has a growing presence in Europe, the Middle East and Africa. The Cephalon European headquarters and pre-clinical development center are located in Maisons-Alfort, France, just outside of Paris. Key affiliates are located in England, Ireland, France, Germany, Italy, Spain, the Netherlands for the Benelux countries, and Poland for Eastern and Central European countries. Cephalon Europe markets more than 30 products in four areas: central nervous system, pain, primary care and oncology. The company's proprietary products in the United States include: NUVIGIL, TREANDA(R) (bendamustine hydrochloride) for Injection, AMRIX(R) (cyclobenzaprine hydrochloride extended-release capsules), FENTORA(R) (fentanyl buccal tablet) [C-II], TRISENOX(R) (arsenic trioxide) injection, GABITRIL(R) (tiagabine hydrochloride), PROVIGIL(R) (modafinil) Tablets [C-IV], and ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II]. The company also markets numerous products internationally. Full prescribing information on its U.S. products is available at http://www.cephalon.com or by calling 1-800-896-5855. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs, development of potential pharmaceutical products, interpretation of clinical results, clinical development of NUVIGIL, prospects for and frequency of filing new indications for NUVIGIL, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, sales and earnings guidance, and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion.     Contacts:     Media:                         Investor Relations:     Candace Steele                 Chip Merritt     610-727-6231 (office)          610-738-6376 (office)     csteele@cephalon.com           cmerritt@cephalon.com SOURCE Cephalon, Inc. CONTACT:Media, Candace Steele, +1-610-727-6231 (office), csteele@cephalon.com, or Investor Relations, Chip Merritt, +1-610-738-6376 (office), cmerritt@cephalon.com, both of Cephalon URL: http://www.prnewswire.com LOAD-DATE: July 1, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2009 PR Newswire Association LLC All Rights Reserved 188 of 998 DOCUMENTS US Fed News June 5, 2009 Friday 4:26 PM EST Patent No. 7,541,493 Issued on June 2, Assigned to Cephalon France for Modafinil Preparation Process (French Inventor) LENGTH: 162 words DATELINE: ALEXANDRIA, Va. ALEXANDRIA, Va., June 5 -- Sebastien Rose, Arsy, France, has developed a process for preparing modafinil with a defined granulometry. The inventor was issued U.S. Patent No. 7,541,493 on June 2. The patent has been assigned to Cephalon France, Maisons Alfort, France. According to the abstract released by the U.S. Patent & Trademark Office: "The invention relates to a process for preparing modafinil having a defined granulometry which comprises the steps of: a) preparing a solution of methyl diphenylmethylsulphinyl-acetate; b) contacting the solution obtained with NH3 at a predetermined temperature and a predetermined stirring; and c) isolating the modafinil formed, wherein said temperature and said stirring are predetermined in order to obtain said defined granulometry." The original application was filed on May 5, 2004.For more information about US Fed News contract awards please contact: Sarabjit Jagirdar, US Fed News, Email:- htsyndication@hindustantimes.com LOAD-DATE: June 5, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2009 HT Media Ltd. All Rights Reserved 189 of 998 DOCUMENTS CNS Drug News Pharmaceuticals June 3, 2009 Nuvigil available in US for treatment of excessive sleepiness LENGTH: 449 words Cephalon's Nuvigil (armodafinil) Tablets [C-IV], a longer-lasting formulation of modafinil, is now available in the US. It is indicated to improve wakefulness throughout the day for patients who struggle with excessive sleepiness associated with treated obstructive sleep apnoea, shift work sleep disorder and narcolepsy. Cephalon has finalised the commercialisation plans for the product and any patient with a Nuvigil prescription should now be able to obtain the medication from their pharmacy or have it filled within 24 hours. As part of the launch of Nuvigil, the company is introducing several new programmes designed to expand access for both patients and healthcare providers. To assist insured patients with co-pay costs for the drug, Cephalon will offer the Nuvigil Prescription Savings Program. Through this programme, eligible patients will receive a co-pay savings at the pharmacy to reduce their out-of-pocket costs to fill the prescription. Further, to help patients and healthcare providers navigate the authorisation and reimbursement process, Cephalon established the Nuvigil Reimbursement Hotline. The company is also working with managed care organisations in order to provide greater patient access for Nuvigil through health plans nationwide. In addition, this year Cephalon created the CephalonCares Foundation to provide free medication to eligible patients. Cephalon is also exploring the potential for Nuvigil to treat the symptoms associated with an array of medical disorders. The company recently announced results from a Phase III trial of the drug as a treatment for patients with excessive sleepiness associated with jet lag disorder. Those data are expected to be submitted as part of an sNDA later this year. In addition, the company has an extensive clinical development programme in place to further study the efficacy and safety of Nuvigil in bipolar depression, the negative symptoms of schizophrenia, cancer treatment-related fatigue and excessive sleepiness associated with traumatic brain injury. Nuvigil is indicated to improve wakefulness in patients with excessive sleepiness associated with treated obstructive sleep apnoea, shift work sleep disorder and narcolepsy. The Nuvigil label includes a bolded warning for serious or life-threatening rash, including Stevens-Johnson syndrome, that has been reported in adults and children taking modafinil, a racaemic mixture of S and R modafinil (the latter is armodafinil, the active ingredient in Nuvigil). Nuvigil is not approved for use in paediatric patients for any indication. The most common adverse events in controlled clinical trials (>5 per cent) were headache, nausea, dizziness and insomnia. LOAD-DATE: June 3, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2009 ESPICOM Business Intelligence Ltd. All Rights Reserved 190 of 998 DOCUMENTS CNS Drug News June 3, 2009 Nuvigil available in US for treatment of excessive sleepiness SECTION: NEWS LENGTH: 448 words Cephalon's Nuvigil (armodafinil) Tablets [C-IV], a longer-lasting formulation of modafinil, is now available in the US. It is indicated to improve wakefulness throughout the day for patients who struggle with excessive sleepiness associated with treated obstructive sleep apnoea, shift work sleep disorder and narcolepsy. Cephalon has finalised the commercialisation plans for the product and any patient with a Nuvigil prescription should now be able to obtain the medication from their pharmacy or have it filled within 24 hours. As part of the launch of Nuvigil, the company is introducing several new programmes designed to expand access for both patients and healthcare providers. To assist insured patients with co-pay costs for the drug, Cephalon will offer the Nuvigil Prescription Savings Program. Through this programme, eligible patients will receive a co-pay savings at the pharmacy to reduce their out-of-pocket costs to fill the prescription. Further, to help patients and healthcare providers navigate the authorisation and reimbursement process, Cephalon established the Nuvigil Reimbursement Hotline. The company is also working with managed care organisations in order to provide greater patient access for Nuvigil through health plans nationwide. In addition, this year Cephalon created the CephalonCares Foundation to provide free medication to eligible patients. Cephalon is also exploring the potential for Nuvigil to treat the symptoms associated with an array of medical disorders. The company recently announced results from a Phase III trial of the drug as a treatment for patients with excessive sleepiness associated with jet lag disorder. Those data are expected to be submitted as part of an sNDA later this year. In addition, the company has an extensive clinical development programme in place to further study the efficacy and safety of Nuvigil in bipolar depression, the negative symptoms of schizophrenia, cancer treatment-related fatigue and excessive sleepiness associated with traumatic brain injury. Nuvigil is indicated to improve wakefulness in patients with excessive sleepiness associated with treated obstructive sleep apnoea, shift work sleep disorder and narcolepsy. The Nuvigil label includes a bolded warning for serious or life-threatening rash, including Stevens-Johnson syndrome, that has been reported in adults and children taking modafinil, a racaemic mixture of S and R modafinil (the latter is armodafinil, the active ingredient in Nuvigil). Nuvigil is not approved for use in paediatric patients for any indication. The most common adverse events in controlled clinical trials (>5 per cent) were headache, nausea, dizziness and insomnia. LOAD-DATE: December 29, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter JOURNAL-CODE: CNS Drug News Copyright 2009 Espicom Business Intelligence All Rights Reserved 191 of 998 DOCUMENTS Internal Medicine News June 1, 2009 Editorial Data Needed on Cognitive-Enhancing Drugs BYLINE: Richard N. Rosenthal, M.D. SECTION: Pg. 9 Vol. 42 No. 11 ISSN: 1097-8690 LENGTH: 918 words    DR. ROSENTHAL is chairman of psychiatry at St. Luke's-Roosevelt Hospital Center, professor of clinical psychiatry at Columbia University, both in New York, and a past president of the American Academy of Addiction Psychiatry. Dr. Rosenthal disclosed that he receives research grants from Titan Pharmaceuticals Inc. and Forest Research Institute.    If we had drugs that would make people smarter, wouldn't that benefit society? And would using drugs in this way be a bad thing?    The reality is: We do have such drugs. And, more and more, we are hearing accounts of normal people taking agents to enhance their mental acuity and alertness at work and in school.    The journal Nature did a survey last year that looked at 1,400 of its scientist readers from 60 countries (Nature 2008;456:702-5). The survey found that 20% of them had used cognitive enhancement in the form of modafinil or methylphenidate or had used beta-blockers to calm them and help them focus when they had to give presentations. Interestingly, 80% of them were in favor of being able to obtain the drugs at their own discretion, as opposed to having to go to a doctor or through the Internet for a prescription.    Cognitive-enhancing drugs give a competitive edge, and in our society the pressure to succeed is huge. Strikingly, one-third of those responding to the Nature survey said they would feel obligated to give cognition-enhancing drugs to their children if the other children in school were taking them.    Some of us may think that the use of such performance-enhancing drugs in "normal" people is wrong. Others see the practice as cheating. The use of a pill to make us smarter somehow goes against the Judeo-Christian ethic, which tells us there is no gain without pain-that gain without pain weakens our character. But does it automatically follow that taking a drug solely to satisfy a person's desires is objectionable?    The notion of improving performance using psychopharmacology is not a new one. The use of alcohol, caffeine, and herbs, as well as pharmaceutical agents, are examples.    Another is the use of Viagra for erectile dysfunction. Is erectile dysfunction part of the normal male aging process? Is a lower free testosterone level because of decreased sex hormone-binding globulin in aging men pathologic? If erectile dysfunction is tied to normal aging, is it "cheating" to take Viagra? One purpose of medicine is to improve quality of life in addition to alleviating suffering. So, if we have the ability to enhance cognition, should we do it?    In a study of commercial pilots, those who took 5 mg per day of the cholinesterase inhibitor donezepil (Aricept) for 1 month did better in flight simulation tests did than their counterparts who took placebo, especially in emergency situations. Think about that. If you are a passenger, wouldn't you rather have your pilot on donezepil?    Many people use caffeine for its stimulant properties. Caffeine improves concentration and increases capacity for information processing in the brain. Glucose priming also enhances learning and memory, so coffee with sugar is a powerful combination. Is a sweet espresso an unfair advantage at work? If it reduces accidents in an industrial setting, why wouldn't you want people to consume caffeine?    Methylphenidate (Ritalin) improves concentration, working memory, and attention in people with attention-deficit/hyperactivity disorder. In healthy adults, it improves executive functioning. It's well known on college campuses for use as a study aid, but college students may ignore traditional dosing and snort it at high doses before taking exams or writing papers.    Modafinil (Provigil), approved for narcolepsy and shift-work sleep disorders, reduces attention deficits attributable to sleep deprivation. In normal adults, it significantly improves fatigue levels, motivation, vigilance, performance on digital pattern recognition, memory, and reaction time. Reportedly, modafinil is the entrepreneur's drug of choice in Silicon Valley. There's a lot of nonmedical use of modafinil out there, and this begs the question about people using it this way. Not just people, but also our colleagues.    The pharmaceutical industry is working to develop a drug aimed at inhibiting memory formation to prevent posttraumatic stress disorder after a traumatic event. This is primary prevention, and it is a good idea. But what about using such a drug simply to prevent an unpleasant memory? Is that okay?    How should use of cognitive-enhancing drugs be regulated in healthy people? Should their use always be monitored by health care professionals? These people are not patients; they are healthy members of society. Their rationale for using medication is for self-enhancement, not therapy. But many of these medications are supposed to be available only by prescription.    We need to do scientific work in this area. There may be evils associated with such use, such as increased social inequity. But there may also be real benefits to our society.    I fear that if we do not attempt to answer some of these questions and create some guidelines, the government will do so. And when the government does it, the outcome often falls short.    Whatever our views on the matter, society is moving this way. The train has left the station, and there appears to be no conductor on board. Do we want to get on and steer, or do we want to stand by and let someone else deal with this increasingly important issue? LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: IMNEWS Copyright 2009 Elsevier Inc., International Medical News Group All Rights Reserved 192 of 998 DOCUMENTS US Fed News May 12, 2009 Tuesday 11:39 AM EST Patent No. 7,528,172 Issued on May 5, Assigned to Cooper Health System for Improving Recovery Method (Pennsylvania Inventors) LENGTH: 145 words DATELINE: ALEXANDRIA, Va. ALEXANDRIA, Va., May 12 -- Ghassem E. Larijani of Villanova, Pa., and Michael E. Goldberg of Philadelphia, have developed a method for improving recovery after general anesthesia. The inventors were issued U.S. Patent No. 7,528,172 on May 5. The patent has been assigned to Cooper Health System Inc., Camden, N.J. According to the abstract released by the U.S. Patent & Trademark Office: "Compositions and methods for improving recovery following general anesthesia are provided. The composition comprises an effective dose of modafinil. Modafinil has been shown to reduce the symptoms associated with post-operative general anesthesia, improving the recovery form anesthesia." The original application was filed on Oct. 2, 2003.For more information about US Fed News contract awards please contact: Sarabjit Jagirdar, US Fed News, Email:- htsyndication@hindustantimes.com LOAD-DATE: May 12, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2009 HT Media Ltd. All Rights Reserved 193 of 998 DOCUMENTS The Sunday Times (London) May 3, 2009 Edition 1 Essay-enhancing drugs; More and more students are taking 'smart pills' to help boost their results in exams - but are they safe, asks Tariq Tahir BYLINE: Tariq Tahir SECTION: NEWS REVIEW;FEATURES; Pg. 9 LENGTH: 1004 words Gemma is a recent Oxford University graduate. As a student of experimental psychology, she wrote three essays a week, in addition to spending 40 hours in lectures and labs. At night she worked for the student newspaper. In her final year things began to pile up but the 22-year-old was reluctant to drop any of her activities. She started taking Modafinil to make possible a life that was fast becoming impossible. Modafinil is a stimulant most commonly prescribed as a prescription drug to treat sleeping disorders, particularly narcolepsy. But increasingly this drug, and two other stimulants, Ritalin and Adderall, are being bought illegally over the internet by high-achieving, overstretched students in British universities to sharpen their focus, concentration and memory. Like many other high-flyers who use so-called "study" or "smart" drugs, Gemma felt a desire to be on top of her game all the time. Modafinil helped her to stay awake long enough to complete her assignments. "I had a few American friends who regularly used Ritalin and sang its praises but I was suspicious of it," she says. "But my friend bought some Modafinil online, said it was fantastic and could keep you awake for ever so I bought some from him. "Taking Modafinil meant that I could just keep working. It didn't make me any more gifted but it meant that my day lasted anything up to 36 hours." The other popular stimulants, Ritalin and Adderall, are legally prescribed for children who have been given a diagnosis of attention-deficit hyperactivity disorder (ADHD). But since it has been demonstrated in scientific trials that these drugs can boost cognitive performance, their unofficial use has rocketed. Yet, even as students pop the pills and brag about their advantages in chat rooms, some experts are asking how much damage they are doing to their bodies. Others are speculating that, if the risks are found to be slight, the use of such drugs could become the norm for the brightest, most competitive young people in our society. Like many users Gemma soon discovered the downsides. She describes feeling shaky, although "this might just have been me not going to sleep. I didn't feel tired and I didn't feel hungry. It stopped my body clock. I lost all track of time and whether I was meant to be eating or not. I would have long bursts of concentration". More worryingly, she also experienced bouts of obsession. "One night I made 10 Facebook photo albums for no good reason other than the fact that I was set on doing it," she says. Tackling the problem is difficult. Figures that reveal who is taking what are not readily available. Last year the scientific journal Nature published the results of an online survey of 1,400 adults. It showed that 20% of readers had taken "smart drugs", but no definitive figures exist on the extent of their use in British universities. Research at the University of Michigan in the United States reveals that 8% of American undergraduates have used such drugs at one time or another to improve alertness. Other studies suggest the figure could be as high as one in six. Emmanuel Akpan-Inwang, a student union welfare officer at the London School of Economics, says that as students approach their exams at the end of the year many are experimenting with "anything that will enhance their performance. "Adderall is the most popular drug at the moment," he reveals. Such people include Claire, a 22-yearold final-year Cambridge University philosophy student. She opted to try Adderall, a drug that is composed of mixed amphetamine salts, in the run-up to her second-year exams last year. She had no difficulty getting hold of it. "I was sitting around in our college rooms with friends and someone mentioned that the engineering students had this drug that they used to help them study," she says. "A friend who was in the year above had a lot of it, which he had bought on the internet, and so he gave me some." She took a capsule the next day before going to the library and was delighted to sail through a highly productive session of study. "I really found my concentration levels went up," she says. "I thought, oh wow, I've been sitting in the library for five hours and haven't been distracted by people walking around like I usually am. It was very helpful." With her finals coming up in a few weeks, she is planning to use Adderall again to keep her concentration at peak levels. Nor are the prices prohibitive: Ritalin costs £290 for 150 10mg pills, Adderall £230 for 120 30mg capsules and Modafinil £75 for 100 200mg doses. Information on the risks of such drugs is highly anecdotal. Users report side effects such as headaches and depression, but no definitive research has been done on the long-term effects of their use on healthy people. This in itself is worrying many, including Barbara Sahakian, professor of neuropsychology at Cambridge University. Sahakian first became interested in the drugs when, arriving jet lagged at a conference in the United States, she was offered Modafinil. After speaking to her colleagues she discovered the extent to which it, and other similar drugs, were in circulation, both among her academic peers and their students. In a paper entitled Professor's Little Helper, she spelt out her concerns. "The trouble is that people in the UK are getting these drugs off the internet," she says. "That's worrying, because you are not really sure what you are getting. And even if the drug is pure, you may have another medical condition that means you shouldn't take it. A person having a bad reaction to one of these drugs is, I think, a horrible accident waiting to happen." For other academics, such as John Harris, professor of bioethics at Manchester University, it is only a matter of time before smart pills are available, without prescription, on the high street. "If these drugs are shown to be safe, I can see a time when bright, competitive people will be able to access them as easily as you can get the morning-after pill now," he says. Some names have been changed LOAD-DATE: May 4, 2009 LANGUAGE: ENGLISH GRAPHIC: Students take the drugs to avoid feeling drowsy TETRA IMAGES PUBLICATION-TYPE: Newspaper JOURNAL-CODE: STS Copyright 2009 Times Newspapers Limited All Rights Reserved 194 of 998 DOCUMENTS The Sunday Times (London) May 3, 2009 Edition 1 Drugs to write essays by; More and more students are taking 'smart pills' to help boost their results in exams - but are they safe, asks Tariq Tahir BYLINE: Tariq Tahir SECTION: ECOSSE;FEATURES; Pg. 12 LENGTH: 963 words Gemma is a recent Oxford University graduate. As a student of experimental psychology, she wrote three essays a week, in addition to spending 40 hours in lectures and labs. At night she worked for the student newspaper. In her final year, things began to pile up, but the 22-year-old was reluctant to drop any of her activities. She started taking Modafinil to make possible a life that was fast becoming impossible. Modafinil is a stimulant most commonly prescribed to treat sleeping disorders. But increasingly this drug, and two other stimulants, Ritalin and Adderall, are being bought illegally over the internet by highachieving, overstretched students in British and American universities to sharpen their focus, concentration and memory. Like many other high-flyers who use study drugs, Gemma felt a desire to be on top of her game all the time. For her, Modafinil helped her stay awake long enough to complete her assignments. "I had a few American friends who regularly used Ritalin and sang its praises but I was suspicious of it," she reveals. "But my friend bought some Modafinil online, said it was fantastic and could keep you awake forever so I bought some from him. "Taking Modafinil meant that I could just keep working. It didn't make me any more gifted but it meant that my working day lasted anything up to 36 hours." The other popular stimulants, Ritalin and Adderall, are legally prescribed for children who have been given a diagnosis of attention-deficit hyperactivity disorder (ADHD). But since it has been demonstrated in scientific trials that these "study" or "smart" drugs, as they have now become known, can boost cognitive performance, their unofficial use for non-medical purposes has rocketed. So as students pop the pills, and brag about their advantages in chat rooms, some experts are asking how much damage they are doing to their bodies. Others are speculating that, if the risks are found to be slight, the use of such drugs could become the norm for the brightest, most competitive young people in our society. Like many users, Gemma soon discovered the downsides. She describes feeling shaky, although "this might just have been me not going to sleep. I just didn't feel tired and I didn't feel hungry. It stopped my body clock. I lost all track of time and whether I was meant to be eating or not. I would have long bursts of concentration." More worryingly, she also experienced bouts of obsession. "One night I made 10 Facebook photo albums for no good reason other than the fact that I was set on doing it," she says. Tackling the problem is, however, difficult. Figures that reveal who is taking what are not readily available. Last year the scientific journal Nature published the results of an online survey of 1,400 adults that revealed that 20% of readers had taken smart drugs to sharpen their concentration or memory, but no definitive figures exist on the extent of smart drug use in British universities. Research at the University of Michigan reveals that 8% of American undergraduates have used such drugs at one time or another to improve alertness. Other studies suggest the figure could be as high as one in six.. Emmanuel Akpan-Inwang, a student union welfare officer at the London School of Economics, is only too aware of the level of use as students approach their exams at the end of the year. "Adderall is the most popular one at the moment," he reveals. "Most people will do anything they can to enhance their performance during the exam period." People such as Claire, a 22-year-old final-year Cambridge University philosophy student. She opted to experiment with Adderall, a drug that is composed of mixed amphetamine salts, in the run-up to her second-year exams last year. She had no difficulty getting hold of it. "I was sitting around in our college rooms with friends, talking about our exams, and someone mentioned that the engineering students had this drug that they used to help them study," she says. "A friend who was in the year above had a lot of it, which he had bought on the internet, and so he gave me some." She took some the next day before going to the library and was delighted to sail through a highly productive session of study. With her finals coming up in a few weeks, she's planning to use it again to keep her concentration at peak levels. Information on the risks of such drugs is equally anecdotal. Users report side effects such as headaches and depression, but no definitive research has been done on the long-term effects of their use on healthy people. This in itself is worrying many, such as Barbara Sahakian, professor of neuropsychology at Cambridge University. She first became interested in the drugs when, arriving jet lagged at a conference in America, she was offered Modafinil. After speaking to her colleagues she discovered the extent to which Modafinil, and other similar drugs, were in circulation among her academic colleagues and their students. In a paper entitled Professor's Little Helper, she spelt out her concerns. "The trouble is that people in the UK are getting these drugs off the internet," she says. "That's worrying, because you are not really sure what you are getting. And even if the drug is pure, you may have another medical condition that means you shouldn't take it. A person having a bad reaction to one of these drugs is, I think, a horrible accident waiting to happen." For other academics, however, such as John Harris, professor of bioethics at Manchester University, it is only a matter of time before smart pills are available on the high street. "If these drugs are shown to be safe, I can see a time when bright, competitive people will be able to access them as easily as you can get the morning-after pill now," he says. Some names have been changed LOAD-DATE: May 4, 2009 LANGUAGE: ENGLISH GRAPHIC: Students take the drugs to avoid feeling drowsy TETRA IMAGES PUBLICATION-TYPE: Newspaper JOURNAL-CODE: STS Copyright 2009 Times Newspapers Limited All Rights Reserved 195 of 998 DOCUMENTS Clinical Psychiatry News May 2009 Modafinil's Mechanism of Action Raises Abuse Risk BYLINE: Mary Ann Moon SECTION: Pg. 18 Vol. 37 No. 5 ISSN: 0270-6644 LENGTH: 213 words    The wake-promoting drug modafinil raises dopamine levels in the brain, data from a pilot study of 10 men show.    Until now, modafinil's mechanism of action has been uncertain, and it was thought to involve several other central nervous system substances but not dopamine. That hypothesis must now be reconsidered, said Dr. Nora D. Volkow of the National Institute on Drug Abuse, Bethesda, Md., and her associates.    More important, the drug's effect on dopamine means that it has a heightened potential for abuse. Given its growing popularity for a variety of uses, clinicians and patients alike must be made aware of the increased risk of addiction, the investigators noted.    The study subjects, who were aged 23-46 years, were given the 200-mg dose that is recommended to treat narcolepsy as well as the 400-mg dose that is thought to be beneficial for attention-deficit/hyperactivity disorder, at different times. They then underwent positron-emission tomography with different radiotracers to measure the effects on extracellular dopamine and dopamine transporters in the brain (JAMA 2009;301:1148-54).    Modafinil was found to increase dopamine in the brain by blocking dopamine transporters, Dr. Volkow and her colleagues said    The investigators had no conflicts. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: CPNEWS Copyright 2009 Elsevier Inc., International Medical News Group All Rights Reserved 196 of 998 DOCUMENTS Clinical Oncology Alert May 1, 2009 Pharmacology Watch LENGTH: 1371 words FDA Warning: Pharmaceuticals in "Natural" Products In this issue: Aspirin dose and cardioprotection; uncovering modafinil's abuse potential; proton-pump inhibitors and clopidogrel; FDA actions. Finding pharmaceuticals in natural products Some natural products are not so "natural" after all. The FDA has warned consumers for several months that a number of weight-loss products contain undeclared pharmaceutical ingredients. The newest products to join the list are Herbal Xenicol which contains cetilistat (a drug similar to orlistat that is not approved in this country), as well as Slimbionic and Xsvelten, both of which contain sibutramine (the prescription medication also known as Meridia®). The FDA's list of over-the-counter weight-loss agents that contain undeclared active pharmaceutical ingredients now includes 72 products. Some of the other undeclared pharmaceutical ingredients found in these products include fenproporex (an amphetamine derivative no longer available in this country), fluoxetine (Prozac®, an SSRI), furosemide (Lasix®, a loop diuretic), and even phenytoin (Dilantin®, an antiseizure medication). The FDA is seeking recalls on many of these products; however, some are available only on-line and previous recall efforts have proved inadequate. Pharmacology Watch In a related story, the FDA has announced a voluntary recall of Zencore Plus, the heavily marketed product for "natural male enhancement," which has been found to contain benzamidenafil, a new PDE5 inhibitor not yet available in this country. Benzamidenafil is similar in action to sildenafil (Viagra®) and tadalafil (Cialis®). PDE5 inhibitors are noted to have a drug interaction with nitrates, leading to potential life-threatening risk of sudden and profound drop in blood pressure. Zencore Plus is distributed by Hi-Tech Pharmaceuticals in Norcross, GA, and is widely sold in health food stores, by mail order, and by Internet sales. Aspirin dose and cardioprotection What is the best dose of aspirin for patients taking dual therapy with clopidogrel to prevent cardiovascular events? Investigators looked at 15,595 patients with cardiovascular disease or multiple risk factors in an observational analysis from a double-blind, placebo-controlled randomized trial. Patients were randomized to doses of aspirin less than 100 mg (75 mg or 81 mg), 100 mg, or greater than 100 mg (150 mg or 162 mg) with or without clopidogrel. The primary efficacy outcome was the composite of myocardial infarction, stroke, or cardiovascular death and the primary safety endpoint was severe life-threatening bleeding. In patients given aspirin alone, the hazard ratio for the efficacy and safety endpoints were the same regardless of aspirin dose. In patients given aspirin with clopidogrel, there was a statistically nonsignificant associated reduction in efficacy with aspirin doses over 100 mg, and a significantly higher increase in harm (hazard ratio, 1.30 with clopidogrel plus aspirin greater than 100 mg). The authors conclude that daily doses of aspirin greater than 100 mg were not associated with benefit and may be associated with harm in patients also taking clopidogrel. Therefore, daily doses of aspirin 75-81 mg optimize efficacy and safety in patients requiring long-term aspirin therapy, especially in patients receiving dual antiplatelet therapy (Ann Intern Med 2009;150:379-386). This is especially important given the recent U.S. Preventive Services Task Force recommendation that encourages men ages 45-79 years to take aspirin preventively when the potential benefit of a reduction of myocardial infarction outweighs the potential harm of an increase in gastrointestinal hemorrhage. Women ages 55-79 years are also encouraged to use aspirin when the potential benefit of a reduction in ischemic stroke outweighs the potential harm of increased gastrointestinal hemorrhage (Ann Intern Med 2009;150:396-404). PPIs and clopidogrel Increasing evidence suggests that proton pump inhibitors (PPIs) may attenuate the effect of clopidogrel on platelet aggregation. PPIs are often used prophylactically in patients with acute coronary syndrome (ACS), as patients on clopidogrel and aspirin may be at higher risk for GI bleeding. A new study from VA researchers was set up to determine if there are clinical implications from the interaction between PPIs and clopidogrel. In a retrospective cohort study of 8205 patients with ACS taking clopidogrel, 63.9% were also prescribed a PPI at discharge, during follow-up, or both. Death or rehospitalization for ACS occurred in 20.8% of patients taking clopidogrel without a PPI and 29.8% patients taking clopidogrel with a PPI. Use of clopidogrel plus a PPI was associated with an increased risk of death or rehospitalization for ACS compared with use of clopidogrel without a PPI (adjusted odds ratio, 1.25; 95% confidence interval, 1.11-1.41). Patients taking a combination of the two drugs were at higher risk for hospitalizations for ACS and revascularization procedures, but not for all-cause mortality. Patients taking a PPI without clopidogrel were not at higher risk for rehospitalization. The authors conclude that concomitant use of clopidogrel and a PPI after hospital discharge for ACS is associated with an increase risk of adverse outcomes, suggesting that PPIs may attenuate the benefits of clopidogrel, and that PPIs should only be used with clopidogrel if there is a clear indication, and not for routine prophylaxis (JAMA 2009;301:937-944). Modafinil's abuse potential Modafinil (Provigil®) is a wake-promoting medication used to treat narcolepsy and other sleep disorders. Recently, the drug has be used off-label to enhance cognition in psychiatric patients and even in healthy patients seeking a memory boost. Modafinil has been touted as having a low abuse potential; however, a new study questions that assumption. Most stimulant medications, such as methylphenidate and amphetamine, increase brain dopamine levels. Modafinil was thought to exert its effect in the brain on pathways other than dopamine, but now there is evidence that dopamine is involved. Researchers from the National Institute on Drug Abuse looked at 10 healthy male volunteers to measure the effects of modafinil at therapeutic dosing of 200 mg and 400 mg given orally. PET scans were used to measure the effect of modafinil on extracellular dopamine and dopamine transporters. Modafinil increased extracellular dopamine and showed evidence of occupancy of dopamine transporters, effects similar to drugs with the potential for abuse. The authors conclude that, considering the increasing use of modafinil, there needs to be heightened awareness for potential abuse of and dependence on modafinil in vulnerable populations (JAMA 2009;301:1148-1154). FDA Actions The FDA is requiring the manufacturers of metoclopramide (Reglan®) include a boxed warning on their labeling regarding the risk of long-term or high-dose use and tardive dyskinesia. Manufacturers will also be required to implement a risk evaluation and medication strategy (REMS) to ensure patients are provided with a medication guide that discusses the risk. Metoclopramide is approved for the treatment of gastric motility problems associated with GERD, diabetic gastroparesis, and nausea and vomiting. A new proton pump inhibitor has been approved by the FDA, bringing the number of PPIs on the market to six. Dexlansoprazole is the purified active isomer of lansoprazole (Pepcid®). The drug has a delayed-release formulation designed to provide two separate releases of the medication. It is approved for the treatment of GERD and erosive esophagitis. Takeda Pharmaceuticals will market dexlansoprazole as Kapidex[TM]. This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5468. E-mail: LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2009 AHC Media LLC All Rights Reserved 197 of 998 DOCUMENTS Critical Care Alert May 1, 2009 Pharmacology Watch: FDA Warning: Pharmaceuticals in "Natural" Products LENGTH: 1371 words FDA Warning: Pharmaceuticals in "Natural" Products In this issue: Aspirin dose and cardioprotection; uncovering modafinil's abuse potential; proton-pump inhibitors and clopidogrel; FDA actions. Pharmacology Watch Finding pharmaceuticals in natural products Some natural products are not so "natural" after all. The FDA has warned consumers for several months that a number of weight-loss products contain undeclared pharmaceutical ingredients. The newest products to join the list are Herbal Xenicol which contains cetilistat (a drug similar to orlistat that is not approved in this country), as well as Slimbionic and Xsvelten, both of which contain sibutramine (the prescription medication also known as Meridia®). The FDA's list of over-the-counter weight-loss agents that contain undeclared active pharmaceutical ingredients now includes 72 products. Some of the other undeclared pharmaceutical ingredients found in these products include fenproporex (an amphetamine derivative no longer available in this country), fluoxetine (Prozac®, an SSRI), furosemide (Lasix®, a loop diuretic), and even phenytoin (Dilantin®, an antiseizure medication). The FDA is seeking recalls on many of these products; however, some are available only on-line and previous recall efforts have proved inadequate. In a related story, the FDA has announced a voluntary recall of Zencore Plus, the heavily marketed product for "natural male enhancement," which has been found to contain benzamidenafil, a new PDE5 inhibitor not yet available in this country. Benzamidenafil is similar in action to sildenafil (Viagra®) and tadalafil (Cialis®). PDE5 inhibitors are noted to have a drug interaction with nitrates, leading to potential life-threatening risk of sudden and profound drop in blood pressure. Zencore Plus is distributed by Hi-Tech Pharmaceuticals in Norcross, GA, and is widely sold in health food stores, by mail order, and by Internet sales. Aspirin dose and cardioprotection What is the best dose of aspirin for patients taking dual therapy with clopidogrel to prevent cardiovascular events? Investigators looked at 15,595 patients with cardiovascular disease or multiple risk factors in an observational analysis from a double-blind, placebo-controlled randomized trial. Patients were randomized to doses of aspirin less than 100 mg (75 mg or 81 mg), 100 mg, or greater than 100 mg (150 mg or 162 mg) with or without clopidogrel. The primary efficacy outcome was the composite of myocardial infarction, stroke, or cardiovascular death and the primary safety endpoint was severe life-threatening bleeding. In patients given aspirin alone, the hazard ratio for the efficacy and safety endpoints were the same regardless of aspirin dose. In patients given aspirin with clopidogrel, there was a statistically nonsignificant associated reduction in efficacy with aspirin doses over 100 mg, and a significantly higher increase in harm (hazard ratio, 1.30 with clopidogrel plus aspirin greater than 100 mg). The authors conclude that daily doses of aspirin greater than 100 mg were not associated with benefit and may be associated with harm in patients also taking clopidogrel. Therefore, daily doses of aspirin 75-81 mg optimize efficacy and safety in patients requiring long-term aspirin therapy, especially in patients receiving dual antiplatelet therapy (Ann Intern Med 2009;150:379-386). This is especially important given the recent U.S. Preventive Services Task Force recommendation that encourages men ages 45-79 years to take aspirin preventively when the potential benefit of a reduction of myocardial infarction outweighs the potential harm of an increase in gastrointestinal hemorrhage. Women ages 55-79 years are also encouraged to use aspirin when the potential benefit of a reduction in ischemic stroke outweighs the potential harm of increased gastrointestinal hemorrhage (Ann Intern Med 2009;150:396-404). PPIs and clopidogrel Increasing evidence suggests that proton pump inhibitors (PPIs) may attenuate the effect of clopidogrel on platelet aggregation. PPIs are often used prophylactically in patients with acute coronary syndrome (ACS), as patients on clopidogrel and aspirin may be at higher risk for GI bleeding. A new study from VA researchers was set up to determine if there are clinical implications from the interaction between PPIs and clopidogrel. In a retrospective cohort study of 8205 patients with ACS taking clopidogrel, 63.9% were also prescribed a PPI at discharge, during follow-up, or both. Death or rehospitalization for ACS occurred in 20.8% of patients taking clopidogrel without a PPI and 29.8% patients taking clopidogrel with a PPI. Use of clopidogrel plus a PPI was associated with an increased risk of death or rehospitalization for ACS compared with use of clopidogrel without a PPI (adjusted odds ratio, 1.25; 95% confidence interval, 1.11-1.41). Patients taking a combination of the two drugs were at higher risk for hospitalizations for ACS and revascularization procedures, but not for all-cause mortality. Patients taking a PPI without clopidogrel were not at higher risk for rehospitalization. The authors conclude that concomitant use of clopidogrel and a PPI after hospital discharge for ACS is associated with an increase risk of adverse outcomes, suggesting that PPIs may attenuate the benefits of clopidogrel, and that PPIs should only be used with clopidogrel if there is a clear indication, and not for routine prophylaxis (JAMA 2009;301:937-944). Modafinil's abuse potential Modafinil (Provigil®) is a wake-promoting medication used to treat narcolepsy and other sleep disorders. Recently, the drug has be used off-label to enhance cognition in psychiatric patients and even in healthy patients seeking a memory boost. Modafinil has been touted as having a low abuse potential; however, a new study questions that assumption. Most stimulant medications, such as methylphenidate and amphetamine, increase brain dopamine levels. Modafinil was thought to exert its effect in the brain on pathways other than dopamine, but now there is evidence that dopamine is involved. Researchers from the National Institute on Drug Abuse looked at 10 healthy male volunteers to measure the effects of modafinil at therapeutic dosing of 200 mg and 400 mg given orally. PET scans were used to measure the effect of modafinil on extracellular dopamine and dopamine transporters. Modafinil increased extracellular dopamine and showed evidence of occupancy of dopamine transporters, effects similar to drugs with the potential for abuse. The authors conclude that, considering the increasing use of modafinil, there needs to be heightened awareness for potential abuse of and dependence on modafinil in vulnerable populations (JAMA 2009;301:1148-1154). FDA Actions The FDA is requiring the manufacturers of metoclopramide (Reglan®) include a boxed warning on their labeling regarding the risk of long-term or high-dose use and tardive dyskinesia. Manufacturers will also be required to implement a risk evaluation and medication strategy (REMS) to ensure patients are provided with a medication guide that discusses the risk. Metoclopramide is approved for the treatment of gastric motility problems associated with GERD, diabetic gastroparesis, and nausea and vomiting. A new proton pump inhibitor has been approved by the FDA, bringing the number of PPIs on the market to six. Dexlansoprazole is the purified active isomer of lansoprazole (Pepcid®). The drug has a delayed-release formulation designed to provide two separate releases of the medication. It is approved for the treatment of GERD and erosive esophagitis. Takeda Pharmaceuticals will market dexlansoprazole as Kapidex[TM]. This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5468. E-mail: LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2009 AHC Media LLC All Rights Reserved 198 of 998 DOCUMENTS Emergency Medicine Reports May 1, 2009 Modafinil's abuse potential LENGTH: 213 words Modafinil's abuse potential Modafinil (Provigil®) is a wake-promoting medication used to treat narcolepsy and other sleep disorders. Recently, the drug has be used off-label to enhance cognition in psychiatric patients and even in healthy patients seeking a memory boost. Modafinil has been touted as having a low abuse potential; however, a new study questions that assumption. Most stimulant medications, such as methylphenidate and amphetamine, increase brain dopamine levels. Modafinil was thought to exert its effect in the brain on pathways other than dopamine, but now there is evidence that dopamine is involved. Researchers from the National Institute on Drug Abuse looked at 10 healthy male volunteers to measure the effects of modafinil at therapeutic dosing of 200 mg and 400 mg given orally. PET scans were used to measure the effect of modafinil on extracellular dopamine and dopamine transporters. Modafinil increased extracellular dopamine and showed evidence of occupancy of dopamine transporters, effects similar to drugs with the potential for abuse. The authors conclude that, considering the increasing use of modafinil, there needs to be heightened awareness for potential abuse of and dependence on modafinil in vulnerable populations (JAMA 2009;301:1148-1154). LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2009 AHC Media LLC All Rights Reserved 199 of 998 DOCUMENTS Infectious Disease Alert May 1, 2009 Pharmacology Watch: FDA Warning: Pharmaceuticals in "Natural" Products LENGTH: 1371 words FDA Warning: Pharmaceuticals in "Natural" Products In this issue: Aspirin dose and cardioprotection; uncovering modafinil's abuse potential; proton-pump inhibitors and clopidogrel; FDA actions. Finding pharmaceuticals in natural products Some natural products are not so "natural" after all. The FDA has warned consumers for several months that a number of weight-loss products contain undeclared pharmaceutical ingredients. The newest products to join the list are Herbal Xenicol which contains cetilistat (a drug similar to orlistat that is not approved in this country), as well as Slimbionic and Xsvelten, both of which contain sibutramine (the prescription medication also known as Meridia®). The FDA's list of over-the-counter weight-loss agents that contain undeclared active pharmaceutical ingredients now includes 72 products. Some of the other undeclared pharmaceutical ingredients found in these products include fenproporex (an amphetamine derivative no longer available in this country), fluoxetine (Prozac®, an SSRI), furosemide (Lasix®, a loop diuretic), and even phenytoin (Dilantin®, an antiseizure medication). The FDA is seeking recalls on many of these products; however, some are available only on-line and previous recall efforts have proved inadequate. Pharmacology Watch In a related story, the FDA has announced a voluntary recall of Zencore Plus, the heavily marketed product for "natural male enhancement," which has been found to contain benzamidenafil, a new PDE5 inhibitor not yet available in this country. Benzamidenafil is similar in action to sildenafil (Viagra®) and tadalafil (Cialis®). PDE5 inhibitors are noted to have a drug interaction with nitrates, leading to potential life-threatening risk of sudden and profound drop in blood pressure. Zencore Plus is distributed by Hi-Tech Pharmaceuticals in Norcross, GA, and is widely sold in health food stores, by mail order, and by Internet sales. Aspirin dose and cardioprotection What is the best dose of aspirin for patients taking dual therapy with clopidogrel to prevent cardiovascular events? Investigators looked at 15,595 patients with cardiovascular disease or multiple risk factors in an observational analysis from a double-blind, placebo-controlled randomized trial. Patients were randomized to doses of aspirin less than 100 mg (75 mg or 81 mg), 100 mg, or greater than 100 mg (150 mg or 162 mg) with or without clopidogrel. The primary efficacy outcome was the composite of myocardial infarction, stroke, or cardiovascular death and the primary safety endpoint was severe life-threatening bleeding. In patients given aspirin alone, the hazard ratio for the efficacy and safety endpoints were the same regardless of aspirin dose. In patients given aspirin with clopidogrel, there was a statistically nonsignificant associated reduction in efficacy with aspirin doses over 100 mg, and a significantly higher increase in harm (hazard ratio, 1.30 with clopidogrel plus aspirin greater than 100 mg). The authors conclude that daily doses of aspirin greater than 100 mg were not associated with benefit and may be associated with harm in patients also taking clopidogrel. Therefore, daily doses of aspirin 75-81 mg optimize efficacy and safety in patients requiring long-term aspirin therapy, especially in patients receiving dual antiplatelet therapy (Ann Intern Med 2009;150:379-386). This is especially important given the recent U.S. Preventive Services Task Force recommendation that encourages men ages 45-79 years to take aspirin preventively when the potential benefit of a reduction of myocardial infarction outweighs the potential harm of an increase in gastrointestinal hemorrhage. Women ages 55-79 years are also encouraged to use aspirin when the potential benefit of a reduction in ischemic stroke outweighs the potential harm of increased gastrointestinal hemorrhage (Ann Intern Med 2009;150:396-404). PPIs and clopidogrel Increasing evidence suggests that proton pump inhibitors (PPIs) may attenuate the effect of clopidogrel on platelet aggregation. PPIs are often used prophylactically in patients with acute coronary syndrome (ACS), as patients on clopidogrel and aspirin may be at higher risk for GI bleeding. A new study from VA researchers was set up to determine if there are clinical implications from the interaction between PPIs and clopidogrel. In a retrospective cohort study of 8205 patients with ACS taking clopidogrel, 63.9% were also prescribed a PPI at discharge, during follow-up, or both. Death or rehospitalization for ACS occurred in 20.8% of patients taking clopidogrel without a PPI and 29.8% patients taking clopidogrel with a PPI. Use of clopidogrel plus a PPI was associated with an increased risk of death or rehospitalization for ACS compared with use of clopidogrel without a PPI (adjusted odds ratio, 1.25; 95% confidence interval, 1.11-1.41). Patients taking a combination of the two drugs were at higher risk for hospitalizations for ACS and revascularization procedures, but not for all-cause mortality. Patients taking a PPI without clopidogrel were not at higher risk for rehospitalization. The authors conclude that concomitant use of clopidogrel and a PPI after hospital discharge for ACS is associated with an increase risk of adverse outcomes, suggesting that PPIs may attenuate the benefits of clopidogrel, and that PPIs should only be used with clopidogrel if there is a clear indication, and not for routine prophylaxis (JAMA 2009;301:937-944). Modafinil's abuse potential Modafinil (Provigil®) is a wake-promoting medication used to treat narcolepsy and other sleep disorders. Recently, the drug has be used off-label to enhance cognition in psychiatric patients and even in healthy patients seeking a memory boost. Modafinil has been touted as having a low abuse potential; however, a new study questions that assumption. Most stimulant medications, such as methylphenidate and amphetamine, increase brain dopamine levels. Modafinil was thought to exert its effect in the brain on pathways other than dopamine, but now there is evidence that dopamine is involved. Researchers from the National Institute on Drug Abuse looked at 10 healthy male volunteers to measure the effects of modafinil at therapeutic dosing of 200 mg and 400 mg given orally. PET scans were used to measure the effect of modafinil on extracellular dopamine and dopamine transporters. Modafinil increased extracellular dopamine and showed evidence of occupancy of dopamine transporters, effects similar to drugs with the potential for abuse. The authors conclude that, considering the increasing use of modafinil, there needs to be heightened awareness for potential abuse of and dependence on modafinil in vulnerable populations (JAMA 2009;301:1148-1154). FDA Actions The FDA is requiring the manufacturers of metoclopramide (Reglan®) include a boxed warning on their labeling regarding the risk of long-term or high-dose use and tardive dyskinesia. Manufacturers will also be required to implement a risk evaluation and medication strategy (REMS) to ensure patients are provided with a medication guide that discusses the risk. Metoclopramide is approved for the treatment of gastric motility problems associated with GERD, diabetic gastroparesis, and nausea and vomiting. A new proton pump inhibitor has been approved by the FDA, bringing the number of PPIs on the market to six. Dexlansoprazole is the purified active isomer of lansoprazole (Pepcid®). The drug has a delayed-release formulation designed to provide two separate releases of the medication. It is approved for the treatment of GERD and erosive esophagitis. Takeda Pharmaceuticals will market dexlansoprazole as Kapidex[TM]. This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5468. E-mail: LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2009 AHC Media LLC All Rights Reserved 200 of 998 DOCUMENTS Neurology Alert May 1, 2009 Pharmacology Watch LENGTH: 1371 words FDA Warning: Pharmaceuticals in "Natural" Products In this issue: Aspirin dose and cardioprotection; uncovering modafinil's abuse potential; proton-pump inhibitors and clopidogrel; FDA actions. Finding pharmaceuticals in natural products Some natural products are not so "natural" after all. The FDA has warned consumers for several months that a number of weight-loss products contain undeclared pharmaceutical ingredients. The newest products to join the list are Herbal Xenicol which contains cetilistat (a drug similar to orlistat that is not approved in this country), as well as Slimbionic and Xsvelten, both of which contain sibutramine (the prescription medication also known as Meridia®). The FDA's list of over-the-counter weight-loss agents that contain undeclared active pharmaceutical ingredients now includes 72 products. Some of the other undeclared pharmaceutical ingredients found in these products include fenproporex (an amphetamine derivative no longer available in this country), fluoxetine (Prozac®, an SSRI), furosemide (Lasix®, a loop diuretic), and even phenytoin (Dilantin®, an antiseizure medication). The FDA is seeking recalls on many of these products; however, some are available only on-line and previous recall efforts have proved inadequate. Pharmacology Watch In a related story, the FDA has announced a voluntary recall of Zencore Plus, the heavily marketed product for "natural male enhancement," which has been found to contain benzamidenafil, a new PDE5 inhibitor not yet available in this country. Benzamidenafil is similar in action to sildenafil (Viagra®) and tadalafil (Cialis®). PDE5 inhibitors are noted to have a drug interaction with nitrates, leading to potential life-threatening risk of sudden and profound drop in blood pressure. Zencore Plus is distributed by Hi-Tech Pharmaceuticals in Norcross, GA, and is widely sold in health food stores, by mail order, and by Internet sales. Aspirin dose and cardioprotection What is the best dose of aspirin for patients taking dual therapy with clopidogrel to prevent cardiovascular events? Investigators looked at 15,595 patients with cardiovascular disease or multiple risk factors in an observational analysis from a double-blind, placebo-controlled randomized trial. Patients were randomized to doses of aspirin less than 100 mg (75 mg or 81 mg), 100 mg, or greater than 100 mg (150 mg or 162 mg) with or without clopidogrel. The primary efficacy outcome was the composite of myocardial infarction, stroke, or cardiovascular death and the primary safety endpoint was severe life-threatening bleeding. In patients given aspirin alone, the hazard ratio for the efficacy and safety endpoints were the same regardless of aspirin dose. In patients given aspirin with clopidogrel, there was a statistically nonsignificant associated reduction in efficacy with aspirin doses over 100 mg, and a significantly higher increase in harm (hazard ratio, 1.30 with clopidogrel plus aspirin greater than 100 mg). The authors conclude that daily doses of aspirin greater than 100 mg were not associated with benefit and may be associated with harm in patients also taking clopidogrel. Therefore, daily doses of aspirin 75-81 mg optimize efficacy and safety in patients requiring long-term aspirin therapy, especially in patients receiving dual antiplatelet therapy (Ann Intern Med 2009;150:379-386). This is especially important given the recent U.S. Preventive Services Task Force recommendation that encourages men ages 45-79 years to take aspirin preventively when the potential benefit of a reduction of myocardial infarction outweighs the potential harm of an increase in gastrointestinal hemorrhage. Women ages 55-79 years are also encouraged to use aspirin when the potential benefit of a reduction in ischemic stroke outweighs the potential harm of increased gastrointestinal hemorrhage (Ann Intern Med 2009;150:396-404). PPIs and clopidogrel Increasing evidence suggests that proton pump inhibitors (PPIs) may attenuate the effect of clopidogrel on platelet aggregation. PPIs are often used prophylactically in patients with acute coronary syndrome (ACS), as patients on clopidogrel and aspirin may be at higher risk for GI bleeding. A new study from VA researchers was set up to determine if there are clinical implications from the interaction between PPIs and clopidogrel. In a retrospective cohort study of 8205 patients with ACS taking clopidogrel, 63.9% were also prescribed a PPI at discharge, during follow-up, or both. Death or rehospitalization for ACS occurred in 20.8% of patients taking clopidogrel without a PPI and 29.8% patients taking clopidogrel with a PPI. Use of clopidogrel plus a PPI was associated with an increased risk of death or rehospitalization for ACS compared with use of clopidogrel without a PPI (adjusted odds ratio, 1.25; 95% confidence interval, 1.11-1.41). Patients taking a combination of the two drugs were at higher risk for hospitalizations for ACS and revascularization procedures, but not for all-cause mortality. Patients taking a PPI without clopidogrel were not at higher risk for rehospitalization. The authors conclude that concomitant use of clopidogrel and a PPI after hospital discharge for ACS is associated with an increase risk of adverse outcomes, suggesting that PPIs may attenuate the benefits of clopidogrel, and that PPIs should only be used with clopidogrel if there is a clear indication, and not for routine prophylaxis (JAMA 2009;301:937-944). Modafinil's abuse potential Modafinil (Provigil®) is a wake-promoting medication used to treat narcolepsy and other sleep disorders. Recently, the drug has be used off-label to enhance cognition in psychiatric patients and even in healthy patients seeking a memory boost. Modafinil has been touted as having a low abuse potential; however, a new study questions that assumption. Most stimulant medications, such as methylphenidate and amphetamine, increase brain dopamine levels. Modafinil was thought to exert its effect in the brain on pathways other than dopamine, but now there is evidence that dopamine is involved. Researchers from the National Institute on Drug Abuse looked at 10 healthy male volunteers to measure the effects of modafinil at therapeutic dosing of 200 mg and 400 mg given orally. PET scans were used to measure the effect of modafinil on extracellular dopamine and dopamine transporters. Modafinil increased extracellular dopamine and showed evidence of occupancy of dopamine transporters, effects similar to drugs with the potential for abuse. The authors conclude that, considering the increasing use of modafinil, there needs to be heightened awareness for potential abuse of and dependence on modafinil in vulnerable populations (JAMA 2009;301:1148-1154). FDA Actions The FDA is requiring the manufacturers of metoclopramide (Reglan®) include a boxed warning on their labeling regarding the risk of long-term or high-dose use and tardive dyskinesia. Manufacturers will also be required to implement a risk evaluation and medication strategy (REMS) to ensure patients are provided with a medication guide that discusses the risk. Metoclopramide is approved for the treatment of gastric motility problems associated with GERD, diabetic gastroparesis, and nausea and vomiting. A new proton pump inhibitor has been approved by the FDA, bringing the number of PPIs on the market to six. Dexlansoprazole is the purified active isomer of lansoprazole (Pepcid®). The drug has a delayed-release formulation designed to provide two separate releases of the medication. It is approved for the treatment of GERD and erosive esophagitis. Takeda Pharmaceuticals will market dexlansoprazole as Kapidex[TM]. This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5468. E-mail: LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2009 AHC Media LLC All Rights Reserved 201 of 998 DOCUMENTS OB/GYN Clinical Alert May 1, 2009 Pharmacology Watch: FDA Warning: Pharmaceuticals in LENGTH: 1371 words FDA Warning: Pharmaceuticals in "Natural" Products In this issue: Aspirin dose and cardioprotection; uncovering modafinil's abuse potential; proton-pump inhibitors and clopidogrel; FDA actions. Finding pharmaceuticals in natural products Some natural products are not so "natural" after all. The FDA has warned consumers for several months that a number of weight-loss products contain undeclared pharmaceutical ingredients. The newest products to join the list are Herbal Xenicol which contains cetilistat (a drug similar to orlistat that is not approved in this country), as well as Slimbionic and Xsvelten, both of which contain sibutramine (the prescription medication also known as Meridia®). The FDA's list of over-the-counter weight-loss agents that contain undeclared active pharmaceutical ingredients now includes 72 products. Some of the other undeclared pharmaceutical ingredients found in these products include fenproporex (an amphetamine derivative no longer available in this country), fluoxetine (Prozac®, an SSRI), furosemide (Lasix®, a loop diuretic), and even phenytoin (Dilantin®, an antiseizure medication). The FDA is seeking recalls on many of these products; however, some are available only on-line and previous recall efforts have proved inadequate. Pharmacology Watch In a related story, the FDA has announced a voluntary recall of Zencore Plus, the heavily marketed product for "natural male enhancement," which has been found to contain benzamidenafil, a new PDE5 inhibitor not yet available in this country. Benzamidenafil is similar in action to sildenafil (Viagra®) and tadalafil (Cialis®). PDE5 inhibitors are noted to have a drug interaction with nitrates, leading to potential life-threatening risk of sudden and profound drop in blood pressure. Zencore Plus is distributed by Hi-Tech Pharmaceuticals in Norcross, GA, and is widely sold in health food stores, by mail order, and by Internet sales. Aspirin dose and cardioprotection What is the best dose of aspirin for patients taking dual therapy with clopidogrel to prevent cardiovascular events? Investigators looked at 15,595 patients with cardiovascular disease or multiple risk factors in an observational analysis from a double-blind, placebo-controlled randomized trial. Patients were randomized to doses of aspirin less than 100 mg (75 mg or 81 mg), 100 mg, or greater than 100 mg (150 mg or 162 mg) with or without clopidogrel. The primary efficacy outcome was the composite of myocardial infarction, stroke, or cardiovascular death and the primary safety endpoint was severe life-threatening bleeding. In patients given aspirin alone, the hazard ratio for the efficacy and safety endpoints were the same regardless of aspirin dose. In patients given aspirin with clopidogrel, there was a statistically nonsignificant associated reduction in efficacy with aspirin doses over 100 mg, and a significantly higher increase in harm (hazard ratio, 1.30 with clopidogrel plus aspirin greater than 100 mg). The authors conclude that daily doses of aspirin greater than 100 mg were not associated with benefit and may be associated with harm in patients also taking clopidogrel. Therefore, daily doses of aspirin 75-81 mg optimize efficacy and safety in patients requiring long-term aspirin therapy, especially in patients receiving dual antiplatelet therapy (Ann Intern Med 2009;150:379-386). This is especially important given the recent U.S. Preventive Services Task Force recommendation that encourages men ages 45-79 years to take aspirin preventively when the potential benefit of a reduction of myocardial infarction outweighs the potential harm of an increase in gastrointestinal hemorrhage. Women ages 55-79 years are also encouraged to use aspirin when the potential benefit of a reduction in ischemic stroke outweighs the potential harm of increased gastrointestinal hemorrhage (Ann Intern Med 2009;150:396-404). PPIs and clopidogrel Increasing evidence suggests that proton pump inhibitors (PPIs) may attenuate the effect of clopidogrel on platelet aggregation. PPIs are often used prophylactically in patients with acute coronary syndrome (ACS), as patients on clopidogrel and aspirin may be at higher risk for GI bleeding. A new study from VA researchers was set up to determine if there are clinical implications from the interaction between PPIs and clopidogrel. In a retrospective cohort study of 8205 patients with ACS taking clopidogrel, 63.9% were also prescribed a PPI at discharge, during follow-up, or both. Death or rehospitalization for ACS occurred in 20.8% of patients taking clopidogrel without a PPI and 29.8% patients taking clopidogrel with a PPI. Use of clopidogrel plus a PPI was associated with an increased risk of death or rehospitalization for ACS compared with use of clopidogrel without a PPI (adjusted odds ratio, 1.25; 95% confidence interval, 1.11-1.41). Patients taking a combination of the two drugs were at higher risk for hospitalizations for ACS and revascularization procedures, but not for all-cause mortality. Patients taking a PPI without clopidogrel were not at higher risk for rehospitalization. The authors conclude that concomitant use of clopidogrel and a PPI after hospital discharge for ACS is associated with an increase risk of adverse outcomes, suggesting that PPIs may attenuate the benefits of clopidogrel, and that PPIs should only be used with clopidogrel if there is a clear indication, and not for routine prophylaxis (JAMA 2009;301:937-944). Modafinil's abuse potential Modafinil (Provigil®) is a wake-promoting medication used to treat narcolepsy and other sleep disorders. Recently, the drug has be used off-label to enhance cognition in psychiatric patients and even in healthy patients seeking a memory boost. Modafinil has been touted as having a low abuse potential; however, a new study questions that assumption. Most stimulant medications, such as methylphenidate and amphetamine, increase brain dopamine levels. Modafinil was thought to exert its effect in the brain on pathways other than dopamine, but now there is evidence that dopamine is involved. Researchers from the National Institute on Drug Abuse looked at 10 healthy male volunteers to measure the effects of modafinil at therapeutic dosing of 200 mg and 400 mg given orally. PET scans were used to measure the effect of modafinil on extracellular dopamine and dopamine transporters. Modafinil increased extracellular dopamine and showed evidence of occupancy of dopamine transporters, effects similar to drugs with the potential for abuse. The authors conclude that, considering the increasing use of modafinil, there needs to be heightened awareness for potential abuse of and dependence on modafinil in vulnerable populations (JAMA 2009;301:1148-1154). FDA Actions The FDA is requiring the manufacturers of metoclopramide (Reglan®) include a boxed warning on their labeling regarding the risk of long-term or high-dose use and tardive dyskinesia. Manufacturers will also be required to implement a risk evaluation and medication strategy (REMS) to ensure patients are provided with a medication guide that discusses the risk. Metoclopramide is approved for the treatment of gastric motility problems associated with GERD, diabetic gastroparesis, and nausea and vomiting. A new proton pump inhibitor has been approved by the FDA, bringing the number of PPIs on the market to six. Dexlansoprazole is the purified active isomer of lansoprazole (Pepcid®). The drug has a delayed-release formulation designed to provide two separate releases of the medication. It is approved for the treatment of GERD and erosive esophagitis. Takeda Pharmaceuticals will market dexlansoprazole as Kapidex[TM]. This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5468. E-mail: LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2009 AHC Media LLC All Rights Reserved 202 of 998 DOCUMENTS Primary Care Reports May 1, 2009 Pharmacology Watch LENGTH: 1371 words FDA Warning: Pharmaceuticals in "Natural" Products In this issue: Aspirin dose and cardioprotection; uncovering modafinil's abuse potential; proton-pump inhibitors and clopidogrel; FDA actions. Pharmacology Watch Finding pharmaceuticals in natural products Some natural products are not so "natural" after all. The FDA has warned consumers for several months that a number of weight-loss products contain undeclared pharmaceutical ingredients. The newest products to join the list are Herbal Xenicol which contains cetilistat (a drug similar to orlistat that is not approved in this country), as well as Slimbionic and Xsvelten, both of which contain sibutramine (the prescription medication also known as Meridia®). The FDA's list of over-the-counter weight-loss agents that contain undeclared active pharmaceutical ingredients now includes 72 products. Some of the other undeclared pharmaceutical ingredients found in these products include fenproporex (an amphetamine derivative no longer available in this country), fluoxetine (Prozac®, an SSRI), furosemide (Lasix®, a loop diuretic), and even phenytoin (Dilantin®, an antiseizure medication). The FDA is seeking recalls on many of these products; however, some are available only on-line and previous recall efforts have proved inadequate. In a related story, the FDA has announced a voluntary recall of Zencore Plus, the heavily marketed product for "natural male enhancement," which has been found to contain benzamidenafil, a new PDE5 inhibitor not yet available in this country. Benzamidenafil is similar in action to sildenafil (Viagra®) and tadalafil (Cialis®). PDE5 inhibitors are noted to have a drug interaction with nitrates, leading to potential life-threatening risk of sudden and profound drop in blood pressure. Zencore Plus is distributed by Hi-Tech Pharmaceuticals in Norcross, GA, and is widely sold in health food stores, by mail order, and by Internet sales. Aspirin dose and cardioprotection What is the best dose of aspirin for patients taking dual therapy with clopidogrel to prevent cardiovascular events? Investigators looked at 15,595 patients with cardiovascular disease or multiple risk factors in an observational analysis from a double-blind, placebo-controlled randomized trial. Patients were randomized to doses of aspirin less than 100 mg (75 mg or 81 mg), 100 mg, or greater than 100 mg (150 mg or 162 mg) with or without clopidogrel. The primary efficacy outcome was the composite of myocardial infarction, stroke, or cardiovascular death and the primary safety endpoint was severe life-threatening bleeding. In patients given aspirin alone, the hazard ratio for the efficacy and safety endpoints were the same regardless of aspirin dose. In patients given aspirin with clopidogrel, there was a statistically nonsignificant associated reduction in efficacy with aspirin doses over 100 mg, and a significantly higher increase in harm (hazard ratio, 1.30 with clopidogrel plus aspirin greater than 100 mg). The authors conclude that daily doses of aspirin greater than 100 mg were not associated with benefit and may be associated with harm in patients also taking clopidogrel. Therefore, daily doses of aspirin 75-81 mg optimize efficacy and safety in patients requiring long-term aspirin therapy, especially in patients receiving dual antiplatelet therapy (Ann Intern Med 2009;150:379-386). This is especially important given the recent U.S. Preventive Services Task Force recommendation that encourages men ages 45-79 years to take aspirin preventively when the potential benefit of a reduction of myocardial infarction outweighs the potential harm of an increase in gastrointestinal hemorrhage. Women ages 55-79 years are also encouraged to use aspirin when the potential benefit of a reduction in ischemic stroke outweighs the potential harm of increased gastrointestinal hemorrhage (Ann Intern Med 2009;150:396-404). PPIs and clopidogrel Increasing evidence suggests that proton pump inhibitors (PPIs) may attenuate the effect of clopidogrel on platelet aggregation. PPIs are often used prophylactically in patients with acute coronary syndrome (ACS), as patients on clopidogrel and aspirin may be at higher risk for GI bleeding. A new study from VA researchers was set up to determine if there are clinical implications from the interaction between PPIs and clopidogrel. In a retrospective cohort study of 8205 patients with ACS taking clopidogrel, 63.9% were also prescribed a PPI at discharge, during follow-up, or both. Death or rehospitalization for ACS occurred in 20.8% of patients taking clopidogrel without a PPI and 29.8% patients taking clopidogrel with a PPI. Use of clopidogrel plus a PPI was associated with an increased risk of death or rehospitalization for ACS compared with use of clopidogrel without a PPI (adjusted odds ratio, 1.25; 95% confidence interval, 1.11-1.41). Patients taking a combination of the two drugs were at higher risk for hospitalizations for ACS and revascularization procedures, but not for all-cause mortality. Patients taking a PPI without clopidogrel were not at higher risk for rehospitalization. The authors conclude that concomitant use of clopidogrel and a PPI after hospital discharge for ACS is associated with an increase risk of adverse outcomes, suggesting that PPIs may attenuate the benefits of clopidogrel, and that PPIs should only be used with clopidogrel if there is a clear indication, and not for routine prophylaxis (JAMA 2009;301:937-944). Modafinil's abuse potential Modafinil (Provigil®) is a wake-promoting medication used to treat narcolepsy and other sleep disorders. Recently, the drug has be used off-label to enhance cognition in psychiatric patients and even in healthy patients seeking a memory boost. Modafinil has been touted as having a low abuse potential; however, a new study questions that assumption. Most stimulant medications, such as methylphenidate and amphetamine, increase brain dopamine levels. Modafinil was thought to exert its effect in the brain on pathways other than dopamine, but now there is evidence that dopamine is involved. Researchers from the National Institute on Drug Abuse looked at 10 healthy male volunteers to measure the effects of modafinil at therapeutic dosing of 200 mg and 400 mg given orally. PET scans were used to measure the effect of modafinil on extracellular dopamine and dopamine transporters. Modafinil increased extracellular dopamine and showed evidence of occupancy of dopamine transporters, effects similar to drugs with the potential for abuse. The authors conclude that, considering the increasing use of modafinil, there needs to be heightened awareness for potential abuse of and dependence on modafinil in vulnerable populations (JAMA 2009;301:1148-1154). FDA Actions The FDA is requiring the manufacturers of metoclopramide (Reglan®) include a boxed warning on their labeling regarding the risk of long-term or high-dose use and tardive dyskinesia. Manufacturers will also be required to implement a risk evaluation and medication strategy (REMS) to ensure patients are provided with a medication guide that discusses the risk. Metoclopramide is approved for the treatment of gastric motility problems associated with GERD, diabetic gastroparesis, and nausea and vomiting. A new proton pump inhibitor has been approved by the FDA, bringing the number of PPIs on the market to six. Dexlansoprazole is the purified active isomer of lansoprazole (Pepcid®). The drug has a delayed-release formulation designed to provide two separate releases of the medication. It is approved for the treatment of GERD and erosive esophagitis. Takeda Pharmaceuticals will market dexlansoprazole as Kapidex[TM]. This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5468. E-mail: LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2009 AHC Media LLC All Rights Reserved 203 of 998 DOCUMENTS Travel Medicine Advisor May 1, 2009 Pharmacology Watch: FDA Warning: Pharmaceuticals in "Natural" Products LENGTH: 1371 words FDA Warning: Pharmaceuticals in "Natural" Products In this issue: Aspirin dose and cardioprotection; uncovering modafinil's abuse potential; proton-pump inhibitors and clopidogrel; FDA actions. Finding pharmaceuticals in natural products Some natural products are not so "natural" after all. The FDA has warned consumers for several months that a number of weight-loss products contain undeclared pharmaceutical ingredients. The newest products to join the list are Herbal Xenicol which contains cetilistat (a drug similar to orlistat that is not approved in this country), as well as Slimbionic and Xsvelten, both of which contain sibutramine (the prescription medication also known as Meridia®). The FDA's list of over-the-counter weight-loss agents that contain undeclared active pharmaceutical ingredients now includes 72 products. Some of the other undeclared pharmaceutical ingredients found in these products include fenproporex (an amphetamine derivative no longer available in this country), fluoxetine (Prozac®, an SSRI), furosemide (Lasix®, a loop diuretic), and even phenytoin (Dilantin®, an antiseizure medication). The FDA is seeking recalls on many of these products; however, some are available only on-line and previous recall efforts have proved inadequate. Pharmacology Watch In a related story, the FDA has announced a voluntary recall of Zencore Plus, the heavily marketed product for "natural male enhancement," which has been found to contain benzamidenafil, a new PDE5 inhibitor not yet available in this country. Benzamidenafil is similar in action to sildenafil (Viagra®) and tadalafil (Cialis®). PDE5 inhibitors are noted to have a drug interaction with nitrates, leading to potential life-threatening risk of sudden and profound drop in blood pressure. Zencore Plus is distributed by Hi-Tech Pharmaceuticals in Norcross, GA, and is widely sold in health food stores, by mail order, and by Internet sales. Aspirin dose and cardioprotection What is the best dose of aspirin for patients taking dual therapy with clopidogrel to prevent cardiovascular events? Investigators looked at 15,595 patients with cardiovascular disease or multiple risk factors in an observational analysis from a double-blind, placebo-controlled randomized trial. Patients were randomized to doses of aspirin less than 100 mg (75 mg or 81 mg), 100 mg, or greater than 100 mg (150 mg or 162 mg) with or without clopidogrel. The primary efficacy outcome was the composite of myocardial infarction, stroke, or cardiovascular death and the primary safety endpoint was severe life-threatening bleeding. In patients given aspirin alone, the hazard ratio for the efficacy and safety endpoints were the same regardless of aspirin dose. In patients given aspirin with clopidogrel, there was a statistically nonsignificant associated reduction in efficacy with aspirin doses over 100 mg, and a significantly higher increase in harm (hazard ratio, 1.30 with clopidogrel plus aspirin greater than 100 mg). The authors conclude that daily doses of aspirin greater than 100 mg were not associated with benefit and may be associated with harm in patients also taking clopidogrel. Therefore, daily doses of aspirin 75-81 mg optimize efficacy and safety in patients requiring long-term aspirin therapy, especially in patients receiving dual antiplatelet therapy (Ann Intern Med 2009;150:379-386). This is especially important given the recent U.S. Preventive Services Task Force recommendation that encourages men ages 45-79 years to take aspirin preventively when the potential benefit of a reduction of myocardial infarction outweighs the potential harm of an increase in gastrointestinal hemorrhage. Women ages 55-79 years are also encouraged to use aspirin when the potential benefit of a reduction in ischemic stroke outweighs the potential harm of increased gastrointestinal hemorrhage (Ann Intern Med 2009;150:396-404). PPIs and clopidogrel Increasing evidence suggests that proton pump inhibitors (PPIs) may attenuate the effect of clopidogrel on platelet aggregation. PPIs are often used prophylactically in patients with acute coronary syndrome (ACS), as patients on clopidogrel and aspirin may be at higher risk for GI bleeding. A new study from VA researchers was set up to determine if there are clinical implications from the interaction between PPIs and clopidogrel. In a retrospective cohort study of 8205 patients with ACS taking clopidogrel, 63.9% were also prescribed a PPI at discharge, during follow-up, or both. Death or rehospitalization for ACS occurred in 20.8% of patients taking clopidogrel without a PPI and 29.8% patients taking clopidogrel with a PPI. Use of clopidogrel plus a PPI was associated with an increased risk of death or rehospitalization for ACS compared with use of clopidogrel without a PPI (adjusted odds ratio, 1.25; 95% confidence interval, 1.11-1.41). Patients taking a combination of the two drugs were at higher risk for hospitalizations for ACS and revascularization procedures, but not for all-cause mortality. Patients taking a PPI without clopidogrel were not at higher risk for rehospitalization. The authors conclude that concomitant use of clopidogrel and a PPI after hospital discharge for ACS is associated with an increase risk of adverse outcomes, suggesting that PPIs may attenuate the benefits of clopidogrel, and that PPIs should only be used with clopidogrel if there is a clear indication, and not for routine prophylaxis (JAMA 2009;301:937-944). Modafinil's abuse potential Modafinil (Provigil®) is a wake-promoting medication used to treat narcolepsy and other sleep disorders. Recently, the drug has be used off-label to enhance cognition in psychiatric patients and even in healthy patients seeking a memory boost. Modafinil has been touted as having a low abuse potential; however, a new study questions that assumption. Most stimulant medications, such as methylphenidate and amphetamine, increase brain dopamine levels. Modafinil was thought to exert its effect in the brain on pathways other than dopamine, but now there is evidence that dopamine is involved. Researchers from the National Institute on Drug Abuse looked at 10 healthy male volunteers to measure the effects of modafinil at therapeutic dosing of 200 mg and 400 mg given orally. PET scans were used to measure the effect of modafinil on extracellular dopamine and dopamine transporters. Modafinil increased extracellular dopamine and showed evidence of occupancy of dopamine transporters, effects similar to drugs with the potential for abuse. The authors conclude that, considering the increasing use of modafinil, there needs to be heightened awareness for potential abuse of and dependence on modafinil in vulnerable populations (JAMA 2009;301:1148-1154). FDA Actions The FDA is requiring the manufacturers of metoclopramide (Reglan®) include a boxed warning on their labeling regarding the risk of long-term or high-dose use and tardive dyskinesia. Manufacturers will also be required to implement a risk evaluation and medication strategy (REMS) to ensure patients are provided with a medication guide that discusses the risk. Metoclopramide is approved for the treatment of gastric motility problems associated with GERD, diabetic gastroparesis, and nausea and vomiting. A new proton pump inhibitor has been approved by the FDA, bringing the number of PPIs on the market to six. Dexlansoprazole is the purified active isomer of lansoprazole (Pepcid®). The drug has a delayed-release formulation designed to provide two separate releases of the medication. It is approved for the treatment of GERD and erosive esophagitis. Takeda Pharmaceuticals will market dexlansoprazole as Kapidex[TM]. This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5468. E-mail: LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2009 AHC Media LLC All Rights Reserved 204 of 998 DOCUMENTS Pharmacy News (Australia) April 1, 2009 Sleep disorder drug open to abuse BYLINE: Mark Gertskis SECTION: LENGTH: 336 words A DRUG used to treat sleeping disorders and boost cognitive functions has the potential to be abused as an addictive stimulant. A new study in the Journal of the American Medical Association (JAMA) has revealed that modafinil, marketed as Modavigil in Australia, has the potential to be addictive due to its effect on levels of the dopamine hormone. "Modafinil blocked dopamine transporters and increased dopamine in the human brain (including the nucleus accumbens)," the study's authors wrote. "Because drugs that increase dopamine in the nucleus accumbens have the potential for abuse, and considering the increasing use of modafinil, these results highlight the need for heightened awareness for potential abuse of and dependence on modafinil in vulnerable populations." Modafinil is designed to improve daytime wakefulness in people suffering from narcolepsy, sleep apnoea and shift work sleep disorder. The study's authors noted that it is also being increasingly used as a cognitive enhancer for conditions such as attention deficit hyperactivity disorder. "Although initially launched as distinct from stimulants that increase extracellular dopamine by targeting dopamine transporters, recent preclinical studies suggest otherwise," the authors wrote. Modafinil consumer medicine information states, however, that the drug differs from other stimulants because it does not "overstimulate or produce a 'high' feeling". The drug's US manufacturer, Cephalon, said JAMA's findings were consistent with what was already known about modafinil, marketed as Provigil in the US. "We believe that there is a low relative potential for abuse with modafinil," a Cephalon statement said. "It has some potential for abuse and dependence. "It is important to note that the product label for Provigil advises physicians to follow patients closely, especially those with a history of drug and/or stimulant (e.g. methylphenidate, amphetamine or cocaine) abuse and to observe patients for signs of misuse or abuse or drug-seeking behavior." LOAD-DATE: June 24, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Magazine JOURNAL-CODE: PN Copyright 2009 Reed Business Information Ltd. All Rights Reserved 205 of 998 DOCUMENTS M2 PressWIRE March 30, 2009 Monday visiongain: Visiongain is proud to announce the release of the brand new report "Sleep Disorders: Market Analysis 2008-2018" LENGTH: 1035 words the release of the brand new report "Sleep Disorders: Market Analysis 2008-2018" More than 80 sleep disorders have been identified. They affect over 200 million people worldwide. The report focuses on the market for following sleep disorders: * Insomnia * Restless legs syndrome (RLS) * Narcolepsy and * Obstructive Sleep Apnoea / Hypopnea Syndrome (OSAHS) The market penetration for insomnia drugs has not reached saturation point. Opportunities remain. But with the introduction of several new products the market is set to see changes, but expansion. This expansion is based on increased general awareness physicians better comprehension of the significance of this disease and the positive role that a sleep medication prescription plays. At present time there are several prescription sleeping medications available to treat insomnia. The market-focus has been driven by the production of sleep medications with less side-effects and danger of overdose. Prescription benzodiazepines and newer non-benzodiazepine hypnotics developed in the 1990s, such as Imovane, Ambien and Sonata will continue to be the most prescribed. Benzodiazepines are widely used to treat an underlying neurological disorder which is often the underlying cause of insomnia, e.g. anxiety and depression. Visiongain predicts that market share by volume for insomnia in the US will change significantly from 2008 to 2018. Ambien IR lost its patent protection in April 2007, which opened to generic competition for Zolpidem. Ambien will remain the market leader for the short term, but what will over take it? A generic version of Ambien is expected to achieve strong market share by volume as there is a great demand for zolpidem tartrate for insomnia. The market share for insomnia treatment will gradually rise after 2012, which will be due to: * Market expansion of existing expensive medications into Europe and Japan in particular * Market penetration of new medications currently in pipeline. Other drugs dealt with in this report include: * Modafinil (Provigil) is the first in a new class of wake-promoting drugs and is currently approved in more than 20 countries for the treatment of excessive daytime sleepiness associated with narcolepsy. * Provigil is quickly replacing Ritalin, and other CNS stimulants, as the medication of choice for treating daytime sleepiness in narcolepsy. The FDA granted modafinil (Provigil) orphan drug status in 1993. * Modafinil was initially launched in the US in 1999 for the treatment of narcolepsy. In 2004, modafinil became FDA-approved prescription medicine for the treatment of excessive sleepiness associated with Obstructive Sleep Apnoea/Hypopnea Syndrome (OSAHS) and Shift Workers Sleep Disorder (SWSD). * Requip (ropinirole) became the first and only FDA-approved drug treatment for moderate to severe primary Restless Legs Syndrome (RLS) in 2005. Key findings that will broaden the scope of the sleep disorders market: * Over the next decade, the development and improvement of sleep disorders therapies will primarily depend on the success of burgeoning technology and innovative approaches. * It is possible to purchase prescription medications online without producing a prescription. Purchase of online sleep medications has increased and will continue to evolve over the next years. * The impact of DTC advertising has created an improved awareness of available insomnia treatment. * This is likely to increase as DTC advertising continues to prosper and the culture becomes more accepting towards insomnia treatment. Visiongain expects the market for sleep disorders to increase, driven by a growing awareness of sleep disorders and by campaigns to promote sleep medications, both by DTC advertising and consumer education. The relaxation of DTC marketing restrictions in the 1990s in the US set the stage for a flow for both branded and unbranded advertising and promotional programmes. Those regulations are prompting more responsible DTC advertising on the industry's part. * The FDA has requested that all manufacturers of sedative-hypnotic drug products, a class of drugs used to induce and/or maintain sleep, strengthen their product labelling to include stronger warnings concerning potential risks. * The Committee for Medicinal Products in Human Use (CHMP) of the European Medicines Agency (EMEA) approved Neurim's Circadin a prolonged-release melatonin as monotherapy for the short-term treatment of primary insomnia characterised by poor quality of sleep in patients aged 55 or over. Neurim is actively seeking strategic alliances for the major European markets. What questions does the report answer? * Which current or future therapies will drive the sleep disorders market from 2008 to 2018? * The key companies involved in the market and their analysis? * What is the patient identification rate for each of the therapeutic areas? * What is the present state of the disease awareness? * What R&D opportunities exist for 'new comers'? Why should you buy this report? * This report focuses on the marketed medications and the pipeline development for sleep disorders from 2008 to 2018. It also discusses the strength and weakness of products, along with the opportunities and threats facing the market. * The report describes world market situation for sleep disorders, namely insomnia, narcolepsy, RLS and OSAHS, with forecasts made for all key products. It also describes the insomnia market situation in the seven major world markets for sleep medications: the US, Japan, France, Germany, Italy, Spain and the UK, with forecasts for key products. * The report provides transcripts of visiongain's interviews with experts in the field of sleep disorders, which reviews the future direction of the sleep disorders treatment market. Visiongain ltd. Report.aspx?rid=274 Or http://www.visiongain.com CONTACT: Suvitha Damodaran, Visiongain ltd e-mail: suvitha.damodaran@visiongainglobal.com e-mail: info@visiongainglobal.com Tel: +44 (0)20 7549 9946 Tel: +44 (0)20 7336 6100 Fax: +44 (0) 20 7549 9930 WWW: http://www.visiongain.com ((M2 Communications Ltd disclaims all liability for information provided within Further information on http://www.presswire.net on the world wide web. Inquiries to info@m2.com)). LOAD-DATE: April 4, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire JOURNAL-CODE: M2P Copyright 2009 M2 PressWIRE All Rights Reserved 206 of 998 DOCUMENTS Flesh and Stone March 24, 2009 Tuesday 12:52 PM EST Neuro Scans LENGTH: 958 words Mar. 24, 2009 (Flesh and Stone delivered by Newstex) -- Stem cell ban lifted but researchers must remain vigilant to protect scientific integrity Earlier this month, President Obama through executive order lifted the ban on federal funding for embryonic stem cell research. The ban put in place by President Bush in 2001 limited research funding to approximately two dozen existing embryonic stem cells lines. The ban was viewed as politically motivated by many researchers and the public which overwhelmingly favored increased research that might lead to cures for diabetes, Alzheimers, Parkinsons, spinal cord injuries, and other neurological disorders. Some researchers insist America has lost almost a decade of research time that could have resulted in medical advancements. A possible silver lining to the ban is that many researchers developed new partnerships with colleagues in foreign institutions in order to continue their research. With the lifting of the ban, hundreds of lines developed since 2001 will be eligible for federal funding. Obama science advisor Harold Varmus, president of Memorial Sloan-Kettering Cancer Center in New York and former head of the National Institutes of Health, recently co-authored an editorial in Science on Obama's stem cell research and scientific integrity policies (registration required). In the editorial Varmus encourages scientists to stay involved in policy discussions because preserving scientific integrity in a highly politicized environment will require vigilance. When lifting the ban, Obama also pledged through a memorandum to appoint only credentialed experts to federal positions that involve evaluating scientific information. Wakefulness drug modafinil may be addictive Modafinil (Provigil), approved by the FDA for the treatment of narcolepsy, has also come into wider use as a cognitive performance enhancer as it was generally believed to be a safer alternative to amphetamines. A recent study by NIH and collaborating institutions published in JAMA, however, found that the drug blocked dopamine transporters and increased dopamine in the brain. These changes in the brains pleasure center could lead to dependence and abuse, say researchers. Using positron emission tomography (PET), researchers measured the effects of 200 mg and 400 mg, common therapeutic dosages given in pill form, on extracellular dopamine and on dopamine transporters in 10 healthy male brains. The study is preliminary, given such a small sample, but the findings warrant further study, especially since modafinil has been approved for use by the U.S. military beginning in 2003. Approved initially for certain Air Force personnel, returning Army and National Guard soldiers have said the drug is readily available to those in combat situations, and clinicians have concerns that returning soldiers may have developed a dependency on the drug. The drug is also increasing in popularity among college students and others who say the drug improves performance, enhances mood and allows better concentration. Citation: JAMA. 2009;301(11):1148-1154. Closer to a consensus on when brain death occurs? The medical community, particularly neurologists, have been grappling with the definition of brain death and striving to reach a consensus on when brain death occurs for decades. JAMA first published a landmark article that quantitatively defined the clinical and laboratory criteria used to measure the presence of brain death in 1968. But different protocols at different institutions left openings for disagreements and legal entanglements. The work took on new urgency in 2005 when the Terry Schiavo case became a national political wedge issue. Not limited to medical experts and ethicists, the case galvanized religious activists, conservative politicians, and celebrities who grandstanded before an eager media. Adding to the high drama, President Bush made a midnight flight from his ranch in Crawford, Texas, to Washington, DC, to sign a law passed by an emotionally charged Congress that forced doctors to re-insert the feeding tube that had kept Schiavo alive in a vegetative state for 15 years. After all Congressional and legal maneuvers were exhausted, Florida judge George Greer ruled that Schiavo could be removed from life support as her legal guardian had requested for seven years. Schiavo died from dehydration on March 30, 2005. After intense study, an ad hoc committee of experts from Harvard Medical School has just issued a new definition on when brain death occurs: Consciousness, Coma, and Brain Death"2009, A Definition of Irreversible Coma: Report of the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death. Will it be the final word? Left: CAT scan of normal brain. Right: Terri Schiavo's 2002 CAT scan provided by Ronald E. Cranford, MD, then assistant chief of neurology at the Hennepin County Medical Center, Minneapolis. (The image is fair use, since the doctor released his image to the public.) Wrapping it up with a bow tie workshop The American Academy of Neurology, known for hosting an intense dawn to dusk (and beyond) annual meeting, is gearing up for its 61st in Seattle, April 25-May 2. While the conference attendees work hard, they also know how to have competitive fun at the wildly popular NeuroBowl quiz show and Neuro Idol talent show. The organization does, on occasion, poke a little fun at itself. This year the AAN is hosting a oebow-tying booth at the meeting in honor of the bowtie which, along with pale blue blazers, is ubiquitous among neurologists. Ill be attending the meeting and filing stories for some free lance clients and doing some news blogging from the meeting here on Flesh & Stone. Newstex ID: FLST-0001-33400535 LOAD-DATE: March 24, 2009 LANGUAGE: ENGLISH NOTES: The views expressed on blogs distributed by Newstex and its re-distributors ("Blogs on Demand®") are solely the author's and not necessarily the views of Newstex or its re-distributors. Posts from such authors are provided "AS IS", with no warranties, and confer no rights. The material and information provided in Blogs on Demand® are for general information only and should not, in any respect, be relied on as professional advice. No content on such Blogs on Demand® is "read and approved" before it is posted. Accordingly, neither Newstex nor its re-distributors make any claims, promises or guarantees about the accuracy, completeness, or adequacy of the information contained therein or linked to from such blogs, nor take responsibility for any aspect of such blog content. All content on Blogs on Demand® shall be construed as author-based content and commentary. Accordingly, no warranties or other guarantees will be offered as to the quality of the opinions, commentary or anything else offered on such Blogs on Demand®. Reader's comments reflect their individual opinion and their publication within Blogs on Demand® shall not infer or connote an endorsement by Newstex or its re-distributors of such reader's comments or views. Newstex and its re-distributors expressly reserve the right to delete posts and comments at its and their sole discretion. PUBLICATION-TYPE: Web Blog Copyright 2009 Newstex LLC All Rights Reserved Newstex Web Blogs Copyright 2009 Flesh and Stone 207 of 998 DOCUMENTS The Times & Transcript (New Brunswick) March 23, 2009 Monday 'Smart drug' may be addictive; Study suggests Provigil may be habit- forming SECTION: LIFE; Pg. D2 LENGTH: 339 words A so-called "smart drug" popular with young people may carry more of an addiction risk than thought, a small government study suggests. Scans of 10 healthy men showed that the prescription drug Provigil caused changes in the brain's pleasure centre, very much like potentially habit- forming classic stimulants. Modafinil, the drug's generic name, is sometimes used as an illegal study aid by college students. "It would be wonderful if one could take a drug and be smarter, faster or have more energy," said Dr. Nora Volkow, director of the National Institute on Drug Abuse, who led the study with a Brookhaven National Laboratory scientist. "But that is like fairy tales. We currently have nothing that has those benefits without side-effects." The study, appearing in the Journal of the American Medical Association, may bust the myth that the drug is safe for healthy people, experts said. Provigil is approved to treat excessive daytime sleepiness caused by narcolepsy. On the market since 1999, it's the flagship product of Cephalon Inc. of Frazer, Pa., and it sales topped $1 billion last year. The company is developing a spin-off called Nuvigil. Modafinil's reputation as a brain enhancer stems from an air force study that found it improved the performance of sleep-deprived fighter pilots. College students buy and sell it illegally, as they do Ritalin and Adderall, to stay alert while studying. The men in the study were 23 to 46 years old. They received either a dummy pill or modafinil. Effects were measured by PET scans, which showed that the drug increased dopamine, the brain's "feel-good" neurotransmitters. Modafinil once was thought to be safer than conventional stimulants because it was believed that it did not engage the brain's dopamine system, which is linked with addiction. Studies in mice and monkeys suggested otherwise. The new study is the first human evidence that a typical dose of modafinil affects dopamine in the brain as much as a dose of Ritalin, a controlled substance with clear potential for dependence. LOAD-DATE: March 23, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2009 CanWest Interactive, a division of CanWest MediaWorks Publications Inc. All Rights Reserved 208 of 998 DOCUMENTS The Philadelphia Inquirer March 18, 2009 Wednesday CITY-D Edition Study says Provigil may be addictive; It affected the brain just as other addictive drugs did, the research found. BYLINE: By Miriam Hill; Inquirer Staff Writer SECTION: BUSINESS; P-com Biz; Pg. C01 LENGTH: 619 words Smart drugs may not be so smart after all. A new federal government study steps up concerns that Cephalon Inc.'s top-selling drug, Provigil, is addictive. The research arrives amid reports that college students and some professionals increasingly pop Provigil, Adderal and Ritalin to improve focus and stay awake. Many people now call these pills "brain boosters" or "smart drugs." The findings, published yesterday in the Journal of the American Medical Association, found that taking Provigil caused changes in the pleasure centers of the brains of 10 men. The changes resembled those caused by other addictive drugs, such as amphetamines, said Nora Volkow, director of the National Institute on Drug Abuse, who led the study with a Brookhaven National Laboratory scientist. Cephalon is based in Frazer. A recent article in the journal Nature said people without medical problems should be able to use these drugs to work harder and longer. "The Nature article was cavalier, equating it to dangers of drinking coffee, and that was incorrect," she said. "The implication that these drugs are safe, I think, is very misleading." Provigil is approved to treat excessive drowsiness associated with narcolepsy, obstructive sleep apnea, and shift-work sleep disorder. University of Pennsylvania brain scientist Martha Farah co-authored the Nature paper. Yesterday, she told the Associated Press that the new study "goes to show that we need a little caution and a little humility when we're messing around with our brain chemistry." She added that "even now, after all the years that [Provigil] has been on the market, we are still learning things about it that are relevant to its safety." The Provigil label has included information about the risk of abuse and addiction since the U.S. Food and Drug Administration approved the drug in 1998, Cephalon's chief scientific officer Jeffry Vaught said. He said the company agreed with Volkow that doctors should not prescribe Provigil to healthy people. Provigil's U.S. sales totaled $943 million last year, according to data provider IMS Health. Analysts have estimated that 80 percent of Provigil prescriptions are for "off-label" treatment of sleepiness and fatigue from illnesses such as depression, Parkinson's disease and multiple sclerosis. The company is developing a longer-acting version of the drug, called Nuvigil. Yesterday, Cephalon shares jumped 9.3 percent, to close at $69.06 each, after the company reported that Nuvigil met key study goals in a Phase II clinical trial involving adults with bipolar disorder. Volkow and her group studied 10 men 23 to 46 years old. They received either a dummy pill or modafinil - the generic name for Provigil. PET scans showed higher levels of dopamine among those who took modafinil. Modafinil also increased dopamine in the nucleus accumbens, a part of the brain believed to be involved with addiction. Volkow said her research was the first evidence that Provigil affects dopamine transporters in human brains. Although the study was small, Volkow said the clear correlation between Provigil and dopamine levels in the scans was good evidence. Earlier research had showed the same results in mice and monkeys. In a September agreement with the Philadelphia office of the U.S. Attorney, Cephalon said it would pay $425 million to settle criminal and civil charges that it illegally marketed three of its drugs, including Provigil, for so-called off-label uses. Doctors can prescribe a drug for any use, but drug companies can market them only for uses approved by the U.S. Food and Drug Administration. Marketing them for other purposes is known as "off-label." Contact staff writer Miriam Hill at 215-854-5520 or hillmb@phillynews.com. LOAD-DATE: March 18, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2009 Philadelphia Newspapers, LLC All Rights Reserved 209 of 998 DOCUMENTS Reuters Health Medical News March 18, 2009 Wednesday 9:00 PM EST Modafinil has addictive potential in vulnerable populations SECTION: CLINICAL LENGTH: 273 words DATELINE: NEW YORK Modafinil, a wake-promoting drug initially used to treat narcolepsy, increases extracellular dopamine -- an effect that increases the drug's potential for abuse -- results of a pilot study indicate. "The growing use of modafinil in clinical medicine and as a cognitive enhancing agent and the uncertainties surrounding the mechanisms underlying its pharmacological effects highlight the need to better understand its mechanisms of action," the research team explains in the Journal of the American Medical Association for March 18. Led by Dr. Nora D. Volkow at the National Institute on Drug Abuse in Bethesda, Maryland, the investigators measured the effects of modafinil in 10 healthy men. Positron emission tomography was used to compare the effects of modafinil (therapeutic doses of 200 mg or 400 mg) versus placebo on extracellular dopamine and on dopamine transporters. Results showed that modafinil produces elevations in brain dopamine through blockade of dopamine transporters similar in magnitude to those produced by methylphenidate, which is used to treat attention deficit/hyperactivity disorder. "The dopamine-enhancing effects of modafinil in the nucleus accumbens may help explain reports of its abuse, since this pharmacological effect is considered crucial for drug reinforcement," Dr. Volkow and colleagues write. Despite the fact that "modafinil is much less potent as a reinforcer than stimulant drugs, and reports of modafinil abuse are rare and much less frequent than those for stimulant drugs," the team warns that "risk for addiction in vulnerable persons merits heightened awareness." SOURCE: JAMA 2009;301:1148-1154. LOAD-DATE: March 19, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2009 Reuters Health All Rights Reserved 210 of 998 DOCUMENTS St. Louis Post-Dispatch (Missouri) March 18, 2009 Wednesday THIRD EDITION MEDICAL DIGEST BYLINE: FROM NEWS SERVICES SECTION: NEWS; Pg. A2 LENGTH: 372 words DATELINE: 0 Study questions safety of Modafinil A so-called "smart drug" popular with young people may carry more of an addiction risk than thought, a small government study suggests. Scans of 10 healthy men showed that the prescription drug Provigil caused changes in the brain's pleasure center, very much like potentially habit-forming classic stimulants. Modafinil, the drug's generic name, is sometimes used as an illegal study aid by college students. "It would be wonderful if one could take a drug and be smarter, faster or have more energy," said Dr. Nora Volkow, director of the National Institute on Drug Abuse, who led the study with a Brookhaven National Laboratory scientist. "But that is like fairy tales. We currently have nothing that has those benefits without side effects." The study, appearing in today's Journal of the American Medical Association, may bust the myth that the drug is safe for healthy people, experts said. 'Observation stay' being questioned Hospitals are using a little-known category of medical care called the "observation stay" more than ever, and patients are reporting that they weren't aware that many standard hospital services are not covered by insurance when a patient is admitted on this basis. Paula Biever filed a complaint with Medicare and the Minnesota attorney general's office when her father, 79, was billed $17,820 over an observation stay. Experts say hospitals are turning to "observation stays" when they believe a patient is too sick to go home but not sick enough to meet guidelines for admittance. Medicare officials said observation care is supposed to be for a day, but that longer stays are happening. Medicare is looking into it. Briefly - Obesity problems: Being obese can take years off your life and in some cases may be as dangerous as smoking, according to a study being published today in the medical journal Lancet that was paid for by Britain's Medical Research Council, the British Heart Foundation, Cancer Research UK and others. - Brain waves: Brain waves generated when trying to hear were sharply reduced in people with schizophrenia, suggesting a connection, according to a study by researchers at Harvard-affiliated McLean Hospital published in the Schizophrenia Bulletin. LOAD-DATE: March 18, 2009 LANGUAGE: ENGLISH NOTES: medical Digest DOCUMENT-TYPE: BRIEF PUBLICATION-TYPE: Newspaper Copyright 2009 St. Louis Post-Dispatch, Inc. All Rights Reserved 211 of 998 DOCUMENTS USA TODAY March 18, 2009 Wednesday FINAL EDITION A warning on off-label use of sleep-disorder drug; Modafinil meant for snoozing, not for 'smarts' BYLINE: Rita Rubin SECTION: LIFE; Pg. 6D LENGTH: 454 words A drug approved to help people with sleep disorders stay awake during the day is also being used off-label by healthy people who think it helps them perform better on the job or at school. But new research into how the medication affects the brain suggests the risk of abuse or addiction, while low, might be greater than previously thought. The conventional wisdom has been that modafinil is different from other stimulant drugs, such as amphetamines or methylphenidate -- marketed as Ritalin for attention deficit hyperactivity disorder -- in that it doesn't increase dopamine in the brain, researchers write in the Journal of the American Medical Association. Dopamine is a neurotransmitter that carries messages from nerve cell to nerve cell or other tissues. Drugs that increase dopamine have the potential for abuse. Modafinil, marketed as Provigil, has been available in the USA since 1999. Like benzodiazipines such as Valium, it is a Schedule IV controlled substance, with relatively low abuse potential. In the new study, scientists used positron emission tomography, or PET, to scan the brains of 10 healthy men given 200 milligrams of modafinil, the recommended daily dose for treating sleep disorders, or 400 milligrams. Both doses raise dopamine levels as much as methylphenidate does, but not as much as amphetamines do. Lead author Nora Volkow, director of the National Institute on Drug Abuse, says she hopes the pilot study will lead to more research. Volkow says no one knows how many people are using modafinil off-label as a "cognitive enhancer" to improve their thinking ability and work for hours on end. "It's not like anyone has done a proper survey to actually document that," Volkow says. The potential for abuse isn't the only reason healthy people shouldn't take modafinil or other "smart drugs," she says. They can have serious effects, such as brief psychotic episodes, she says, and there's little evidence they improve cognition. Jeffry Vaught, chief scientific officer for the medication's maker, Cephalon, calls modafinil "a very serious medication for serious medical disease. This is for pathological sleep disruption, not for people who've stayed awake for 24 hours." Animal studies have long suggested that modafinil raises dopamine in humans' brains, Vaught says, but "to date, we've just not seen any signals that there's a problem" with abuse or addiction. Although Volkow says no cases of modafinil addiction have been reported in the scientific literature, psychiatrist Stefan Kruszewski of Harrisburg, Pa., says he is treating his third case. "I had two doctors back-to-back who were addicted to modafinil, so I became alarmed," Kruszewski says. Both of them also were alcoholics, he says. LOAD-DATE: March 18, 2009 LANGUAGE: ENGLISH GRAPHIC: PHOTO, B/W, National Institute on Drug Abuse PUBLICATION-TYPE: NEWSPAPER Copyright 2009 Gannett Company, Inc. All Rights Reserved 212 of 998 DOCUMENTS Associated Press Online March 18, 2009 Wednesday 12:05 AM GMT Study: 'Smart drug' Provigil may be habit-forming BYLINE: By CARLA K. JOHNSON, AP Medical Writer SECTION: DOMESTIC NEWS LENGTH: 577 words DATELINE: CHICAGO A so-called "smart drug" popular with young people may carry more of an addiction risk than thought, a small government study suggests. Scans of 10 healthy men showed that the prescription drug Provigil caused changes in the brain's pleasure center, very much like potentially habit-forming classic stimulants. Modafinil, the drug's generic name, is sometimes used as an illegal study aid by college students. "It would be wonderful if one could take a drug and be smarter, faster or have more energy," said Dr. Nora Volkow, director of the National Institute on Drug Abuse, who led the study with a Brookhaven National Laboratory scientist. "But that is like fairy tales. We currently have nothing that has those benefits without side effects." The study, appearing in Wednesday's Journal of the American Medical Association, may bust the myth that the drug is safe for healthy people, experts said. Provigil is approved to treat excessive daytime sleepiness caused by narcolepsy. On the market since 1999, it's the flagship product of Cephalon Inc. of Frazer, Pa., and its sales approached $1 billion last year. The company is developing a spin-off called Nuvigil. Modafinil's reputation as a brain enhancer stems from an Air Force study that found it improved the performance of sleep-deprived fighter pilots. College students buy and sell it illegally, as they do Ritalin and Adderall, to stay alert while studying. Several scientists recently wrote in the journal Nature that healthy people should have the right to boost their brains with pills like Provigil. One author of that commentary, brain scientist Martha Farah of the University of Pennsylvania, said the new study "goes to show that we need a little caution and a little humility when we're messing around with our brain chemistry." "But even now, after all the years that it has been on the market, we are still learning things about it that are relevant to its safety," Farah said. The men in the study were 23 to 46 years old. They received either a dummy pill or modafinil. Effects were measured by PET scans, which showed that the drug increased dopamine, the brain's "feel-good" neurotransmitters. Modafinil once was thought to be safer than conventional stimulants because it was believed that it did not engage the brain's dopamine system, which is linked with addiction. Studies in mice and monkeys suggested otherwise. The new study is the first human evidence that a typical dose of modafinil affects dopamine in the brain as much as a dose of Ritalin, a controlled substance with clear potential for dependence. Volkow said modafinil acts slowly when swallowed and is difficult to inject, making it less likely to be abused. Its high price, about $10 per pill compared to Ritalin at $2 per pill, also makes it less attractive to people seeking a high. That may change when generics become available in 2012, Volkow said. Jeffry Vaught, chief science officer for Cephalon, said the company has seen no evidence the drug is highly abused. "If abuse is a problem with modafinil, it's minimal at best," Vaught said. "We're not seeing it used at rave scenes." Prescribing information for the drug warns of severe rashes and other side effects such as headache, nausea and anxiety. Cephalon doesn't support the drug's use as a cognitive enhancer. "There's no substitute for sleep," Vaught said. On the Net: JAMA: http://jama.ama-assn.org (This version CORRECTS that Provigil's sales "approached" $1 billion.)) LOAD-DATE: March 18, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2009 Associated Press All Rights Reserved 213 of 998 DOCUMENTS The Associated Press State & Local Wire March 18, 2009 Wednesday 7:28 AM GMT Study: 'Smart drug' Provigil may be habit-forming BYLINE: By CARLA K. JOHNSON, AP Medical Writer SECTION: STATE AND REGIONAL LENGTH: 565 words DATELINE: CHICAGO A so-called "smart drug" popular with young people may carry more of an addiction risk than thought, a small government study suggests. Scans of 10 healthy men showed that the prescription drug Provigil caused changes in the brain's pleasure center, very much like potentially habit-forming classic stimulants. Modafinil, the drug's generic name, is sometimes used as an illegal study aid by college students. "It would be wonderful if one could take a drug and be smarter, faster or have more energy," said Dr. Nora Volkow, director of the National Institute on Drug Abuse, who led the study with a Brookhaven National Laboratory scientist. "But that is like fairy tales. We currently have nothing that has those benefits without side effects." The study, appearing in Wednesday's Journal of the American Medical Association, may bust the myth that the drug is safe for healthy people, experts said. Provigil is approved to treat excessive daytime sleepiness caused by narcolepsy. On the market since 1999, it's the flagship product of Cephalon Inc. of Frazer, Pa., and its sales approached $1 billion last year. The company is developing a spin-off called Nuvigil. Modafinil's reputation as a brain enhancer stems from an Air Force study that found it improved the performance of sleep-deprived fighter pilots. College students buy and sell it illegally, as they do Ritalin and Adderall, to stay alert while studying. Several scientists recently wrote in the journal Nature that healthy people should have the right to boost their brains with pills like Provigil. One author of that commentary, brain scientist Martha Farah of the University of Pennsylvania, said the new study "goes to show that we need a little caution and a little humility when we're messing around with our brain chemistry." "But even now, after all the years that it has been on the market, we are still learning things about it that are relevant to its safety," Farah said. The men in the study were 23 to 46 years old. They received either a dummy pill or modafinil. Effects were measured by PET scans, which showed that the drug increased dopamine, the brain's "feel-good" neurotransmitters. Modafinil once was thought to be safer than conventional stimulants because it was believed that it did not engage the brain's dopamine system, which is linked with addiction. Studies in mice and monkeys suggested otherwise. The new study is the first human evidence that a typical dose of modafinil affects dopamine in the brain as much as a dose of Ritalin, a controlled substance with clear potential for dependence. Volkow said modafinil acts slowly when swallowed and is difficult to inject, making it less likely to be abused. Its high price, about $10 per pill compared to Ritalin at $2 per pill, also makes it less attractive to people seeking a high. That may change when generics become available in 2012, Volkow said. Jeffry Vaught, chief science officer for Cephalon, said the company has seen no evidence the drug is highly abused. "If abuse is a problem with modafinil, it's minimal at best," Vaught said. "We're not seeing it used at rave scenes." Prescribing information for the drug warns of severe rashes and other side effects such as headache, nausea and anxiety. Cephalon doesn't support the drug's use as a cognitive enhancer. "There's no substitute for sleep," Vaught said. On the Net: JAMA: http://jama.ama-assn.org LOAD-DATE: March 19, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2009 Associated Press All Rights Reserved 214 of 998 DOCUMENTS Associated Press Financial Wire March 17, 2009 Tuesday 8:08 PM GMT Study: 'Smart drug' Provigil may be habit-forming BYLINE: By CARLA K. JOHNSON, AP Medical Writer SECTION: BUSINESS NEWS LENGTH: 565 words DATELINE: CHICAGO A so-called "smart drug" popular with young people may carry more of an addiction risk than thought, a small government study suggests. Scans of 10 healthy men showed that the prescription drug Provigil caused changes in the brain's pleasure center, very much like potentially habit-forming classic stimulants. Modafinil, the drug's generic name, is sometimes used as an illegal study aid by college students. "It would be wonderful if one could take a drug and be smarter, faster or have more energy," said Dr. Nora Volkow, director of the National Institute on Drug Abuse, who led the study with a Brookhaven National Laboratory scientist. "But that is like fairy tales. We currently have nothing that has those benefits without side effects." The study, appearing in Wednesday's Journal of the American Medical Association, may bust the myth that the drug is safe for healthy people, experts said. Provigil is approved to treat excessive daytime sleepiness caused by narcolepsy. On the market since 1999, it's the flagship product of Cephalon Inc. of Frazer, Pa., and its sales approached $1 billion last year. The company is developing a spin-off called Nuvigil. Modafinil's reputation as a brain enhancer stems from an Air Force study that found it improved the performance of sleep-deprived fighter pilots. College students buy and sell it illegally, as they do Ritalin and Adderall, to stay alert while studying. Several scientists recently wrote in the journal Nature that healthy people should have the right to boost their brains with pills like Provigil. One author of that commentary, brain scientist Martha Farah of the University of Pennsylvania, said the new study "goes to show that we need a little caution and a little humility when we're messing around with our brain chemistry." "But even now, after all the years that it has been on the market, we are still learning things about it that are relevant to its safety," Farah said. The men in the study were 23 to 46 years old. They received either a dummy pill or modafinil. Effects were measured by PET scans, which showed that the drug increased dopamine, the brain's "feel-good" neurotransmitters. Modafinil once was thought to be safer than conventional stimulants because it was believed that it did not engage the brain's dopamine system, which is linked with addiction. Studies in mice and monkeys suggested otherwise. The new study is the first human evidence that a typical dose of modafinil affects dopamine in the brain as much as a dose of Ritalin, a controlled substance with clear potential for dependence. Volkow said modafinil acts slowly when swallowed and is difficult to inject, making it less likely to be abused. Its high price, about $10 per pill compared to Ritalin at $2 per pill, also makes it less attractive to people seeking a high. That may change when generics become available in 2012, Volkow said. Jeffry Vaught, chief science officer for Cephalon, said the company has seen no evidence the drug is highly abused. "If abuse is a problem with modafinil, it's minimal at best," Vaught said. "We're not seeing it used at rave scenes." Prescribing information for the drug warns of severe rashes and other side effects such as headache, nausea and anxiety. Cephalon doesn't support the drug's use as a cognitive enhancer. "There's no substitute for sleep," Vaught said. On the Net: JAMA: http://jama.ama-assn.org LOAD-DATE: March 18, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2009 Associated Press All Rights Reserved 215 of 998 DOCUMENTS The Associated Press March 17, 2009 Tuesday Study: 'Smart drug' Provigil may be habit-forming BYLINE: By CARLA K. JOHNSON, AP Medical Writer SECTION: BUSINESS NEWS LENGTH: 565 words DATELINE: CHICAGO A so-called "smart drug" popular with young people may carry more of an addiction risk than thought, a small government study suggests. Scans of 10 healthy men showed that the prescription drug Provigil caused changes in the brain's pleasure center, very much like potentially habit-forming classic stimulants. Modafinil, the drug's generic name, is sometimes used as an illegal study aid by college students. "It would be wonderful if one could take a drug and be smarter, faster or have more energy," said Dr. Nora Volkow, director of the National Institute on Drug Abuse, who led the study with a Brookhaven National Laboratory scientist. "But that is like fairy tales. We currently have nothing that has those benefits without side effects." The study, appearing in Wednesday's Journal of the American Medical Association, may bust the myth that the drug is safe for healthy people, experts said. Provigil is approved to treat excessive daytime sleepiness caused by narcolepsy. On the market since 1999, it's the flagship product of Cephalon Inc. of Frazer, Pa., and its sales approached $1 billion last year. The company is developing a spin-off called Nuvigil. Modafinil's reputation as a brain enhancer stems from an Air Force study that found it improved the performance of sleep-deprived fighter pilots. College students buy and sell it illegally, as they do Ritalin and Adderall, to stay alert while studying. Several scientists recently wrote in the journal Nature that healthy people should have the right to boost their brains with pills like Provigil. One author of that commentary, brain scientist Martha Farah of the University of Pennsylvania, said the new study "goes to show that we need a little caution and a little humility when we're messing around with our brain chemistry." "But even now, after all the years that it has been on the market, we are still learning things about it that are relevant to its safety," Farah said. The men in the study were 23 to 46 years old. They received either a dummy pill or modafinil. Effects were measured by PET scans, which showed that the drug increased dopamine, the brain's "feel-good" neurotransmitters. Modafinil once was thought to be safer than conventional stimulants because it was believed that it did not engage the brain's dopamine system, which is linked with addiction. Studies in mice and monkeys suggested otherwise. The new study is the first human evidence that a typical dose of modafinil affects dopamine in the brain as much as a dose of Ritalin, a controlled substance with clear potential for dependence. Volkow said modafinil acts slowly when swallowed and is difficult to inject, making it less likely to be abused. Its high price, about $10 per pill compared to Ritalin at $2 per pill, also makes it less attractive to people seeking a high. That may change when generics become available in 2012, Volkow said. Jeffry Vaught, chief science officer for Cephalon, said the company has seen no evidence the drug is highly abused. "If abuse is a problem with modafinil, it's minimal at best," Vaught said. "We're not seeing it used at rave scenes." Prescribing information for the drug warns of severe rashes and other side effects such as headache, nausea and anxiety. Cephalon doesn't support the drug's use as a cognitive enhancer. "There's no substitute for sleep," Vaught said. On the Net: JAMA: http://jama.ama-assn.org LOAD-DATE: March 18, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2009 Associated Press All Rights Reserved 216 of 998 DOCUMENTS Elsevier Global Medical News March 17, 2009 Tuesday 05:25 PM GMT Modafinil Boosts Brain Dopamine, Raising Addiction Risk BYLINE: By Mary Ann Moon, Elsevier Global Medical News LENGTH: 378 words The wake-promoting drug modafinil, often used off-label to boost cognitive performance in attention-deficit/hyperactivity disorder and even in healthy individuals, was found to raise dopamine levels in the brain, according to a report in the March 18 issue of JAMA. Until now, modafinil's mechanism of action has been uncertain, and it was thought to involve several other central nervous system substances but not dopamine. That hypothesis must now be reconsidered, said Dr. Nora D. Volkow of the National Institute on Drug Abuse, Bethesda, Md., and her associates. More important, the drug's effect on dopamine means that it has a heightened potential for abuse. Given its growing popularity for a variety of uses, clinicians and patients alike must be made aware of the increased risk of addiction, the investigators noted. They assessed modafinil's effects on the brain in a pilot study of 10 healthy men aged 23-46 years. The study subjects were given the 200-mg dose that is recommended to treat narcolepsy as well as the 400-mg dose that is thought to be beneficial for attention-deficit/hyperactivity disorder, at different times. They then underwent positron emission tomography with different radiotracers to measure the effects on extracellular dopamine and dopamine transporters in the brain. Modafinil was found to increase dopamine in the brain by blocking dopamine transporters. The elevations in dopamine were comparable with those produced by therapeutic doses of methylphenidate, Dr. Volkow and her colleagues said (JAMA 2009;301:1148-54). Modafinil was developed as a drug that "could have a nondopaminergic target for its wake-promoting effects." However, these findings, together with preclinical study results, document that modafinil has clear dopamine-enhancing effects, they added. Modafinil appears to be "much less potent as a reinforcer" than stimulant drugs are, making its abuse less common. "Nevertheless, considering the broadening use of modafinil and the results in this study showing that it increases dopamine in the nucleus accumbens at therapeutic doses, its potential for abuse should not be disregarded," the investigators noted. Dr. Volkow and her associates had no financial disclosures to make in relation to the study. Nora D. Volkow LOAD-DATE: June 10, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: NewsWire Copyright 2009 Elsevier Inc., International Medical News Group All Rights Reserved 217 of 998 DOCUMENTS States News Service March 17, 2009 Tuesday NARCOLEPSY DRUG BEING USED TO IMPROVE COGNITIVE PERFORMANCE AFFECTS BRAIN DOPAMINE ACTIVITY BYLINE: States News Service LENGTH: 642 words DATELINE: CHICAGO The following information was released by Brookhaven National Laboratory: Preliminary research in healthy men suggests that the narcolepsy drug modafinil, increasingly being used to enhance cognitive abilities, affects the activity of dopamine in the brain in a way that may create the potential for abuse and dependence, according to a study in the March 18 issue of JAMA. Brookhaven senior chemist Joanna Fowler: "Like cocaine and methylphenidate, Modafinil blocks dopamine transporters thereby increasing dopamine levels in the brain. This study raises awareness about Modafinil's potential for abuse and addiction in vulnerable populations and signals the need to monitor its use." Modafinil, a wake-promoting drug used in the treatment of sleep disorders, may enhance cognition and is used off-label for the treatment of cognitive dysfunction in some psychiatric disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder [ADHD]). The Physicians' Desk Reference cautions that it can produce psychoactive and euphoric effects typical of central nervous system stimulant drugs, and there is debate surrounding its potential for abuse, according to background information in the article. The mechanisms of action of modafinil are not well understood but are believed to differ from those of stimulant medications (such as methylphenidate and amphetamine), which increase dopamine (a neurotransmitter in the brain essential for the normal functioning of the central nervous system) in the brain by targeting the dopamine transporters, a mechanism that underlies the abuse potential of these drugs. However, there is growing evidence that dopamine may also play a role in the mode of action of modafinil. Nora D. Volkow, M.D., of the National Institute on Alcohol Abuse and Alcoholism, Bethesda, Md., and colleagues at Brookhaven National Laboratory conducted a study to test whether modafinil, at therapeutic doses, would elevate extracellular (located or occurring outside of cells) dopamine in the brain by blocking the dopamine transporter. The study included 10 healthy men, between the ages of 23-46 years, who received either placebo or modafinil: 200 mg, the dose recommended for narcolepsy; or 400 mg, a dose shown to be beneficial for the treatment of ADHD. The effects of modafinil on extracellular dopamine and on dopamine transporters were measured by positron emission tomography (a radiographic technique used to examine biochemical activity in tissue). The researchers found: In this pilot study, modafinil acutely increased dopamine levels and blocked dopamine transporters in the human brain. Because drugs that increase dopamine have the potential for abuse, and considering the increasing use of modafinil for multiple purposes, these results suggest that risk for addiction in vulnerable persons merits heightened awareness. PET images of the brain show that subjects given modafinil had lower levels of the radiotracer [11C]raclopride bound to dopamine receptors than subjects given a placebo. Red represents the highest amount of binding. This signal indicates higher levels of dopamine release in the modafinil subjects. (Dopamine competes with the radiotracer so higher levels of dopamine "push" the tracers out.) Modafinil also increased dopamine in the nucleus accumbens, a brain region critical for the rewarding effects of drugs of abuse. Modafinil was developed with an expectation that a medication could have a non-dopaminergic target for its wake-promoting effects. However, the current findings in humans, along with preclinical studies, documenting the indispensable role of dopamine in the wake-promoting effects of modafinil, support modafinil's dopamine-enhancing effects as a mechanism for its therapeutic actions. (JAMA. 2009;301[11]:1148-1154. Available pre-embargo to the media at http://www.jamamedia.org) LOAD-DATE: April 29, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2009 States News Service 218 of 998 DOCUMENTS Associated Press Worldstream March 17, 2009 Tuesday 8:16 PM GMT Study: 'Smart drug' Provigil may be habit-forming BYLINE: By CARLA K. JOHNSON, AP Medical Writer SECTION: DOMESTIC NEWS LENGTH: 566 words DATELINE: CHICAGO A so-called "smart drug" popular with young people may carry more of an addiction risk than thought, a small government study suggests. Scans of 10 healthy men showed that the prescription drug Provigil caused changes in the brain's pleasure center, very much like potentially habit-forming classic stimulants. Modafinil, the drug's generic name, is sometimes used as an illegal study aid by college students. "It would be wonderful if one could take a drug and be smarter, faster or have more energy," said Dr. Nora Volkow, director of the National Institute on Drug Abuse, who led the study with a Brookhaven National Laboratory scientist. "But that is like fairy tales. We currently have nothing that has those benefits without side effects." The study, appearing in Wednesday's Journal of the American Medical Association, may bust the myth that the drug is safe for healthy people, experts said. Provigil is approved to treat excessive daytime sleepiness caused by narcolepsy. On the market since 1999, it's the flagship product of Cephalon Inc. of Frazer, Pennsylvania, and it sales approached $1 billion last year. The company is developing a spin-off called Nuvigil. Modafinil's reputation as a brain enhancer stems from an Air Force study that found it improved the performance of sleep-deprived fighter pilots. College students buy and sell it illegally, as they do Ritalin and Adderall, to stay alert while studying. Several scientists recently wrote in the journal Nature that healthy people should have the right to boost their brains with pills like Provigil. One author of that commentary, brain scientist Martha Farah of the University of Pennsylvania, said the new study "goes to show that we need a little caution and a little humility when we're messing around with our brain chemistry." "But even now, after all the years that it has been on the market, we are still learning things about it that are relevant to its safety," Farah said. The men in the study were 23 to 46 years old. They received either a dummy pill or modafinil. Effects were measured by PET scans, which showed that the drug increased dopamine, the brain's "feel-good" neurotransmitters. Modafinil once was thought to be safer than conventional stimulants because it was believed that it did not engage the brain's dopamine system, which is linked with addiction. Studies in mice and monkeys suggested otherwise. The new study is the first human evidence that a typical dose of modafinil affects dopamine in the brain as much as a dose of Ritalin, a controlled substance with clear potential for dependence. Volkow said modafinil acts slowly when swallowed and is difficult to inject, making it less likely to be abused. Its high price, about $10 per pill compared to Ritalin at $2 per pill, also makes it less attractive to people seeking a high. That may change when generics become available in 2012, Volkow said. Jeffry Vaught, chief science officer for Cephalon, said the company has seen no evidence the drug is highly abused. "If abuse is a problem with modafinil, it's minimal at best," Vaught said. "We're not seeing it used at rave scenes." Prescribing information for the drug warns of severe rashes and other side effects such as headache, nausea and anxiety. Cephalon doesn't support the drug's use as a cognitive enhancer. "There's no substitute for sleep," Vaught said. On the Net: JAMA: http://jama.ama-assn.org LOAD-DATE: March 18, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2009 Associated Press All Rights Reserved 219 of 998 DOCUMENTS The Associated Press State & Local Wire March 17, 2009 Tuesday 8:26 PM GMT Study: 'Smart drug' Provigil may be habit-forming BYLINE: By CARLA K. JOHNSON, AP Medical Writer SECTION: STATE AND REGIONAL LENGTH: 565 words DATELINE: CHICAGO A so-called "smart drug" popular with young people may carry more of an addiction risk than thought, a small government study suggests. Scans of 10 healthy men showed that the prescription drug Provigil caused changes in the brain's pleasure center, very much like potentially habit-forming classic stimulants. Modafinil, the drug's generic name, is sometimes used as an illegal study aid by college students. "It would be wonderful if one could take a drug and be smarter, faster or have more energy," said Dr. Nora Volkow, director of the National Institute on Drug Abuse, who led the study with a Brookhaven National Laboratory scientist. "But that is like fairy tales. We currently have nothing that has those benefits without side effects." The study, appearing in Wednesday's Journal of the American Medical Association, may bust the myth that the drug is safe for healthy people, experts said. Provigil is approved to treat excessive daytime sleepiness caused by narcolepsy. On the market since 1999, it's the flagship product of Cephalon Inc. of Frazer, Pa., and its sales approached $1 billion last year. The company is developing a spin-off called Nuvigil. Modafinil's reputation as a brain enhancer stems from an Air Force study that found it improved the performance of sleep-deprived fighter pilots. College students buy and sell it illegally, as they do Ritalin and Adderall, to stay alert while studying. Several scientists recently wrote in the journal Nature that healthy people should have the right to boost their brains with pills like Provigil. One author of that commentary, brain scientist Martha Farah of the University of Pennsylvania, said the new study "goes to show that we need a little caution and a little humility when we're messing around with our brain chemistry." "But even now, after all the years that it has been on the market, we are still learning things about it that are relevant to its safety," Farah said. The men in the study were 23 to 46 years old. They received either a dummy pill or modafinil. Effects were measured by PET scans, which showed that the drug increased dopamine, the brain's "feel-good" neurotransmitters. Modafinil once was thought to be safer than conventional stimulants because it was believed that it did not engage the brain's dopamine system, which is linked with addiction. Studies in mice and monkeys suggested otherwise. The new study is the first human evidence that a typical dose of modafinil affects dopamine in the brain as much as a dose of Ritalin, a controlled substance with clear potential for dependence. Volkow said modafinil acts slowly when swallowed and is difficult to inject, making it less likely to be abused. Its high price, about $10 per pill compared to Ritalin at $2 per pill, also makes it less attractive to people seeking a high. That may change when generics become available in 2012, Volkow said. Jeffry Vaught, chief science officer for Cephalon, said the company has seen no evidence the drug is highly abused. "If abuse is a problem with modafinil, it's minimal at best," Vaught said. "We're not seeing it used at rave scenes." Prescribing information for the drug warns of severe rashes and other side effects such as headache, nausea and anxiety. Cephalon doesn't support the drug's use as a cognitive enhancer. "There's no substitute for sleep," Vaught said. On the Net: JAMA: http://jama.ama-assn.org LOAD-DATE: March 18, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2009 Associated Press All Rights Reserved 220 of 998 DOCUMENTS Business Wire February 10, 2009 Tuesday 2:40 PM GMT Research and Markets: Narcolepsy - Entry-Point to a Lucrative Fatigue-Associated Market - Provigil (Modafinil), Expected To Launch In 2012 LENGTH: 484 words DATELINE: DUBLIN, Ireland Research and Markets( http://www.researchandmarkets.com/research/30c8d6/stakeholder_opinio ) has announced the addition of the " Stakeholder Opinions: Narcolepsy - Entry-point to a Lucrative Fatigue-Associated Market " report to their offering. Introduction Narcolepsy is a chronic sleep disorder, which affects fewer than 500,000 sufferers across the seven major markets (7MM). The narcolepsy market value has grown considerably since 2004 to reach $230m in 2007 driven largely by the significant penetration of Provigil (modafinil; Cephalon) and Xyrem (sodium oxybate; Jazz Pharma) and the associated increase in the awareness of the disorder. Scope · Patient potential including disease definition, etiology, prevalence, diagnosis, and treatment guideline review. · Review of the key unmet needs in the treatment of narcolepsy as identified by key opinion leaders interviewed for the report. · Analysis of narcolepsy market IMS sales data from 2004 to 2007 for major marketed narcolepsy drugs: Provigil and Xyrem. · Pipeline analysis with detailed profile for Nuvigil (armodafinil, Cephalon) and the theory behind potential label expansions beyond narcolepsy. Highlights Although generic versions of Cephalons market leading treatment, Provigil ( modafinil), are expected to launch in 2012, Cephalon is expected to retain a significant position in the narcolepsy market by switching patients over from Provigil to its follow-up product, Nuvigil (armodafinil). Despite Xyrems (sodium oxybate) proven efficacy and its broader narcolepsy coverage than Provigil, Xyrems sales continue to be limited because of its black box warning, restricted distribution and comparatively high price. Targeting narcolepsy as a primary indication and then expanding Provigils label coverage to other sleep disorders has proven commercially successful for Cephalon. Datamonitor believes companies could take this strategy a step further by using narcolepsy as an entry point to access the broader fatigue- or sleepiness-associated market. Reasons to Purchase · Quantify the narcolepsy market value in the US, 5EU and Japan and identify the drivers and resistors in this market. · Understand key opinion leader (KOL) views on topical issues in the current and future treatment of narcolepsy and associated disorders. · Appreciate the potential of off-label prescribing and indication expansions for treatments possessing narcolepsy as the primary indication. Key Topics Covered: · CHAPTER 1 EXECUTIVE SUMMARY · CHAPTER 2 MARKET DEFINITION AND OVERVIEW · CHAPTER 3 DISEASE OVERVIEW · CHAPTER 4 UNMET NEEDS · CHAPTER 5 BRAND DYNAMICS · CHAPTER 6 PIPELINE ANALYSIS · BIBLIOGRAPHY · APPENDIX · List of Tables · List of Figures For more information visit http://www.researchandmarkets.com/research/30c8d6/stakeholder_opinio . Source: Datamonitor CONTACT: Research and Markets Laura Wood Senior Manager press@researchandmarkets.com Fax from USA: 646-607-1907 Fax from rest of the world: +353-1-481-1716 URL: http://www.businesswire.com LOAD-DATE: February 11, 2009 LANGUAGE: ENGLISH DISTRIBUTION: Business Editors PUBLICATION-TYPE: Newswire Copyright 2009 Business Wire, Inc. 221 of 998 DOCUMENTS M2 PressWIRE February 10, 2009 Tuesday Research and Markets: Narcolepsy - Entry-Point to a Lucrative Fatigue-Associated Market - Provigil (Modafinil), Expected To Launch In 2012 LENGTH: 540 words Entry-Point to a Lucrative Fatigue-Associated Market - Provigil (Modafinil), Expected To Launch In 2012 Dublin - Research and Markets(http://www.researchandmarkets.com/research/f49f45/stakeholder_op inio) has announced the addition of the "Stakeholder Opinions: Narcolepsy - Entry-point to a Lucrative Fatigue-Associated Market" report to their offering. Introduction Narcolepsy is a chronic sleep disorder, which affects fewer than 500,000 sufferers across the seven major markets (7MM). The narcolepsy market value has grown considerably since 2004 to reach $ 230m in 2007 driven largely by the significant penetration of Provigil (modafinil; Cephalon) and Xyrem (sodium oxybate; Jazz Pharma) and the associated increase in the awareness of the disorder. Scope - Patient Patient potential including disease definition, etiology, prevalence, diagnosis, and treatment guideline review. - Review of the key unmet needs in the treatment of narcolepsy as identified by key opinion leaders interviewed for the report. - Analysis of narcolepsy market IMS sales data from 2004 to 2007 for major marketed narcolepsy drugs: Provigil and Xyrem. - Pipeline analysis with detailed profile for Nuvigil (armodafinil, Cephalon) and the theory behind potential label expansions beyond narcolepsy. Highlights Although generic versions of Cephalons market leading treatment, Provigil (modafinil), are expected to launch in 2012, Cephalon is expected to retain a significant position in the narcolepsy market by switching patients over from Provigil to its follow-up product, Nuvigil (armodafinil). Despite Xyrems (sodium oxybate) proven efficacy and its broader narcolepsy coverage than Provigil, Xyrems sales continue to be limited because of its black box warning, restricted distribution and comparatively high price. Targeting narcolepsy as a primary indication and then expanding Provigils label coverage to other sleep disorders has proven commercially successful for Cephalon. Datamonitor believes companies could take this strategy a step further by using narcolepsy as an entry point to access the broader fatigue- or sleepiness-associated market. Reasons to Purchase - Quantify the narcolepsy market value in the US, 5EU and Japan and identify the drivers and resistors in this market. - Understand key opinion leader (KOL) views on topical issues in the current and future treatment of narcolepsy and associated disorders. - Appreciate the potential of off-label prescribing and indication expansions for treatments possessing narcolepsy as the primary indication. Key Topics Covered: - CHAPTER 1 EXECUTIVE SUMMARY - CHAPTER 2 MARKET DEFINITION AND OVERVIEW - CHAPTER 3 DISEASE OVERVIEW - CHAPTER 4 UNMET NEEDS - CHAPTER 5 BRAND DYNAMICS - CHAPTER 6 PIPELINE ANALYSIS - BIBLIOGRAPHY - APPENDIX - List of Tables - List of Figures For more information visit http://www.researchandmarkets.com/research/f49f45/stakeholder_opinio Source: Datamonitor CONTACT: Laura Wood, Senior Manager, Research and Markets Fax: +1 646 607 1907 (US) Fax: +353 1 481 1716 (Rest of World) e-mail: press@researchandmarkets.com ((M2 Communications Ltd disclaims all liability for information provided within Further information on http://www.presswire.net on the world wide web. Inquiries to info@m2.com)). LOAD-DATE: February 12, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire JOURNAL-CODE: M2P Copyright 2009 M2 PressWIRE All Rights Reserved 222 of 998 DOCUMENTS Guardian Unlimited January 13, 2009 The not-so-clever pills LENGTH: 494 words HIGHLIGHT: Robert Fox: Cognitive-enhancement pills are nothing new - and neither is their power to disappoint us The generalised use of Modafinil, the "clever pill" advocated in Nature magazine last month and by its online editor Adam Rutherford on this website, may not be quite so clever as it appears. In the Nature article, Professor Henry Greely marshals a distinguished panel of experts and co-writers to argue that cognitive-enhancement drugs are so generally used by students in the US, occasionally illegally, that it is time to put them on a sensible footing. If need be, the authors suggest, there should be licensing or regulation. The article claims that some 7% of all US college students now use Ritalin, a drug prescribed for attention-deficiency hyperactivity disorder (ADHD), to help them concentrate and stay alert while studying for exams. Another favourite is the pharmaceutical psychostimulant sold under the commercial name of Adderall, also prescribed for ADHD cases. It is suggested that on some campuses up to 25% of all students are using one of these two stimulants. Greely and Rutherford argue that a wider use of Modafinil, commonly sold as Provigil for narcolepsy and similar cases, can only be beneficial to concentration, learning and study. There seem to be few side-effects, if any, and such use should be for self-improvement and the better education of humanity in general. After all, he rightly suggests, humanity has always tried to master and adapt nature for its own benefit. Greely, the Director of Stanford Law School's Center for Law and Biosciences, suggests that dishing out cognitive-enhancing drugs to students isn't necessarily tipping the level playing field of competition in the same way as giving performance-enhancing drugs to athletes. After all, he suggests, differences in schooling and previous learning experience, also make for inequality between examinees. Fair enough, but from a little research I'm not entirely convinced about the invidious comparison with performance-enhancers, for different reasons. Of course, we have been through the arguments about the liberal and libertarian approaches to recreational and mind-expanding drugs since the priestesses got stoned at the shrine of Apollo at Delphi and da Quincy and Coleridge got high on opium. In our own day we have a cult of psychotropic drugs. Aldous Huxley cautiously suggested that mescaline might open the doors of perception to greater spiritual awareness and unity with creation - and gave the name to Jim Morrison's visionaries The Doors. Hunter S Thompson took on a load of pills to fuel his quest for the American dream in Fear and Loathing in Las Vegas. All of them thought the drugs made them better and powerful performers and thinkers. Coleridge was doing fine as he sketched his path through Xanadu, Alph the sacred river and the sunless sea, until the man from Porlock broke in on the spell. The muse fled and Kubla Khan remains a fragmented, broken spell. The problem is that the man from Porlock is always lurking in the corner to be a spoil-sport. LOAD-DATE: January 13, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2009 Guardian Unlimited (© Guardian Newspapers Limited) All rights reserved 223 of 998 DOCUMENTS Daily Mail (London) January 6, 2009 Tuesday 1ST Edition CAN A PILL MAKE YOU BRAINIER?; Students and the military are using drugs to boost their brainpower. But do they work -- and are they safe? This intrepid writer decided to find out BYLINE: ANGUS WATSON SECTION: Pg. 45 LENGTH: 1423 words A PILL that makes you more intelligent, boosts your memory, improves your concentration and reduces tiredness? It sounds like the stuff of science fiction. In fact, it is already available, and academics in America and Britain have apparently been taking it for years. Last week, John Harris, a professor of bioethics at the University of Manchester, said students should be allowed to take 'smart' drugs (or 'Viagra for the brain', as they've been dubbed) to boost their academic performance. He claimed a sizeable body of evidence showed that pills such as Ritalin, which is prescribed for ADHD (Attention- Deficit/Hyperactivity Disorder), Adderall, another ADHD drug, and Modafinil significantly improved concentration and should be available without prescription. Modafinil -- better known as Provigil -- is the pill the academics have been taking. Officially, it's used to treat conditions that cause daytime sleepiness, such as narcolepsy. But off-prescription, it's being used, not only by academics and students, but reportedly by the U.S. and UK military, to improve mental energy. There are no figures on the numbers of people using Modafinil as an off-prescription stimulant (it can be obtained through the internet). However, according to my sources, and judging by the large chunk of the internet devoted to the subject, the use -- or abuse -- of Modafinil is widespread. 'Plenty of people use Modafinil,' agrees Barbara Sahakian, professor of Clinical Neuropsychology at the University of Cambridge. 'I know an Oxford University professor who takes it fortnightly for one day of really hard work and a colleague at Cambridge who takes it at parties, while another takes it for jet-lag.' Nobody is certain how Modafinil works, according to Sahakian. It does seem clear, however, that it specifically tackles drowsiness without affecting other parts of the brain. This sets it apart from other stimulants such as amphetamines, which make you less tired, but can also compel you to talk too much. Working at home as a freelance writer, I'm OK in the mornings, but my afternoon work ethic would shame a siesta-loving Spaniard. A pill to increase my post-lunch productivity would be marvellous. I decided to see for myself if Modafinil worked. THE fact that it definitely does something to one's brain, but nobody's quite sure what, was a niggling worry. It didn't help when I talked to Baroness Susan Greenfield, the neuroscientist, about my plans to take it. 'You're taking a risk,' she said firmly. 'Our brains are hugely delicate and responsive to drugs. If you take too much vitamin C, it's excreted in your urine. That's not the case with brain-altering drugs. Any influence -- especially the direct chemical manipulation that you're suggesting -- could have a long-term, negative effect on brain cells. You're risking your life.' So trying Modafinil might damage my brain for ever. And there were other potential, and more immediate side-effects. I read of a vast range of possible nasties, including headaches, nausea, nervousness, diarrhoea, back pain, reduced appetite and abnormal ejaculation. It was all pretty frightening. But a reckless part of me wondered if it was all worthwhile if the pills did make me branier. First there was the problem of getting prescription-only drugs without being ill. I asked a doctor friend if she'd write me a prescription. She said I was an idiot. So I ordered them online, but they never came. Finally, I tried a randomly picked doctor. Fortunately, his standards weren't as high as my friend's, and he gave me a prescription for a £5 'admin fee'. The guilt of using an ill-gained prescription wore off when the chemist charged me £75 for 30 100mg tablets. He explained, that's how much privately-prescribed drugs cost. The label gave no dosage advice, but the internet suggested 200mg daily. I'd told the doctor this was my plan, and he agreed that it seemed reasonable. I decided to start with a 100mg pill at 9am. Given all those potential sideeffects I reasoned it would be best to be wary. I popped the pill and began a big writing project I'd been putting off. An hour later I wasn't dead -- I was perfectly happy, although I had no appetite for breakfast. Perhaps I was working harder -- it was difficult to tell since I usually work well in the morning. By 10am, I was still alive and sane, and, apart from my lack of appetite, all seemed normal. So I took a second 100mg pill. Half an hour later I was lightheaded and euphoric. I began singing along to the radio and my computer keyboard felt oddly fizzy, as if I had pins and needles in my fingertips. At 10am, alone in my flat, it felt like I'd downed four glasses of champagne. Modafinil was meant to improve my work ethic and focus, but there was no way I could concentrate. My mind was rushing, so much so that I got a little scared. I worried that I might have a heart attack, or perhaps my head might explode. So I went for a walk by the Thames. I've always found that watching ducks can allay pretty much any affliction, and this was no exception. I calmed down, came home, forced myself to eat and felt better. My mind was still on overdrive but it was my most productive working afternoon -- ever. That evening, I had dinner with a friend. I was conscious of being chatty, but also witty and incisive. Before we parted, I told her about the Modafinil trial. 'You were a little more obnoxious than usual,' she commented. Back home, I found myself standing in the bathroom doing a sudoku puzzle at 1.30am, and didn't get to sleep until 2am. Next morning I took 200mg in one go. Soon I felt a bit sick, muddle-headed, panicky and sweaty. But I calmed down, and did a good morning's work. A night later, I met my new girlfriend's friends for the first time in a trendy restaurant. I was extremely talkative as I knocked back gallons of wine, and became astonishingly extrovert, dancing with people and coercing a group of reluctant revellers to sing Under Pressure by Queen. I remember nothing of the taxi ride home. The next morning, I had a horrendous hangover but was cheered by reports from my girlfriend, who said her friends thought I was the life and soul of the party. Was that a euphemism for loudmouth buffoon, I asked? 'No, really, you were fun', she insisted. I recovered by Sunday and, settling into the Modafinil, my work took off. Panic disappeared, I felt absolutely fine. Concentration and output sky-rocketed and I felt fantastic. In fact, during my two weeks of Modafinil-enhanced life I did tons of good work, gained two new regular slots in newspapers, lost 4lb in weight and cleared an Augean stable of admin. But I'm not sure Modafinil really increases your memory or makes you more intelligent. It makes you think you're more intelligent. I took part in a pub quiz -- we won -- but despite, rather than because of me. I was convinced I was right every time, but was consistently wrong. WHAT'S the driest place in the world? 'Atacama Desert!' I cried, full of confidence. 'Isn't it Antarctica?', asked someone. 'No, no, Atacama,' I insisted patronisingly. Of course, the answer was Antarctica. And then there are those lingering health doubts. It's said that Turkish leader Kemal Ataturk only functioned after he overcame his crushing shyness with vast quantities of the spirit of Raki. And he defeated every major European power and founded modern Turkey. So it worked for him. But he did die of cirrhosis at the age of 58. Another danger comes with buying the Modafinil online. As with all illegally supplied drugs, you have no control over what you're getting. You could be sold something useless or, worse, dangerous. And then there's that fundamental question: is false brain enhancement morally acceptable? And if it is, could it also ever be made safe? Neuroscientist Greenfield thinks not. 'Drugs will always have sideeffects. If you want to improve your output, you should look at your lifestyle and goals. Not take drugs.' Professor Sahakian treads a middle ground. 'There are better ways to enhance ourselves, such as education and exercise. If there are clean drugs that could make work easier and improve our lives, that would be great, but we'd have to be careful not to push ourselves to unpleasant limits.' Cephalon, who manufacture Provigil, said it only supported approved uses for the drug. It is 'naturally opposed to all forms of purchases which are not under the control of physicians such as online sales,' their spokesman added. So -- expensive, 'illegal' and a potential health risk. Think I'll stick to early nights instead.. LOAD-DATE: January 6, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Papers Copyright 2009 Associated Newspapers Ltd. All Rights Reserved 224 of 998 DOCUMENTS The International Herald Tribune November 3, 2008 Monday Narcoleptic allowed to race again; Cycling BYLINE: Samuel Abt - The New York Times Media Group SECTION: SPORT; Pg. 20 LENGTH: 609 words Rise and shine, up and at 'em: After four years of legal and medical battles, Franck Bouyer can return to work. ''I can dream again,'' he said with no hint of irony. Bouyer's problem has been that of course he can dream - anywhere, at any time - since he is a victim of narcolepsy, or sleeping sickness. The genetic disease, which is marked by unpredictable episodes of sleep during normal waking hours and disturbed sleep at night, afflicts about one in 200,000 people. Except for Bouyer, none of them is a professional bicycle racer. That job is impossible for a narcoleptic without medical treatment since Bouyer works amid a pack of other men on bicycles. Let the sandman call and Bouyer swerve, the result can be a mass crash. Although that has not happened yet, he has been known to fall asleep during a training ride and wake up sprawled in the courtyard of a farm. Once or twice, feeling himself nodding off, he has had to pull to the side of the road during a race. ''With medicine, no problem,'' he said in a telephone interview this week from his home in western France. ''Without medicine, lots of problems.'' But the medicine that is commonly used to treat narcolepsy is modafinil, which is on the list of drugs prohibited by the International Cycling Union because they enhance performance. So Bouyer has been caught between two arguments: For safety's sake, doctors for the French Cycling Federation refused to issue him a license unless he was using modafinil, but the highest governors of the sport refused to let him race if he did use the drug. Back and forth the legal battle went, with the International Cycling Union barring Bouyer, the World Anti-Doping Agency first ruling against him and then for him and the Court of Arbitration for Sport turning down his appeal. ''It went on so long,'' he said this week. ''So much time, so much money. It killed my career.'' Now 34 years old, Bouyer has long been a solid midlevel rider. Since he turned professional in 1995 and joined the first of six French teams, he has finished, albeit far back, five Tours de France. He has had his share of victories, though. In 2001, he won the Tour of the Limousin and in 2002, the Tour of the Vendée, both French races. His best year was 2004, when he won Paris-Camembert and a stage in the Circuit of the Sarthe. That was also the year, however, that he learned he had narcolepsy. Since then, he has raced only briefly late in 2005 and early in 2006 while the legal battles were in abeyance. His breakthrough occurred early this year when a doctor prescribed another medicine, Xyrem, to treat his disease. It worked as well as modafinil and was not on the list of prohibited drugs, according to the International Cycling Union when Bouyer phoned its doctors. ''So that was that,'' he said. ''I applied for my racing license in July and got it. Since August, I've been training constantly.'' Why did nobody prescribe the legal drug years ago? Good question, said Bouyer, unable to answer it. He will join his Bouygues Télécom teammates this week at a training camp and will be a paid rider for the first time in two years. ''It's really strange,'' Bouyer said, ''I thought it was all over and now I'll be back. Such a long wait.'' He has no great hopes for immediate success, not after years away from the sport. ''Lance Armstrong might be able to do that,'' he said, ''but I don't have his motor. I hope to be riding at a correct level, mostly for the pleasure of it all. Yes, for the satisfaction of competing again.'' As for the races he will enter next year, it's too early to decide, but he will give it a lot of thought, he said. In other words, he'll sleep on it. LOAD-DATE: November 3, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2008 International Herald Tribune All Rights Reserved 225 of 998 DOCUMENTS The Times (South Africa) October 20, 2008 Monday Stay wired awake BYLINE: Caspar Greeff SECTION: LIFESTYLE & LEISURE; Pg. 20 LENGTH: 422 words POKER is not yet an Olympic sport, which means that players are not monitored by the World Anti-Doping Agency, nor are they subject to the rules of the World Anti-Doping Code. This is a pity because I am sure that two of the more senior members of our Thursday night poker school (both of them are 87- years- old) are on performance-enhancing drugs. How else do they win all my money week after week? One poker player who openly admits his use of stimulants is former computer programmer Paul "Dot Com" Phillips, who has career winnings of more than $2.3-million. Phillips told Slate magazine: "I've long been an enthusiastic believer in better living through chemistry. That's why, when I was diagnosed with attention-deficit hyperactive disorder two years ago, I didn't hesitate to fill a prescription for Adderall. A few months later, I won almost $500000 in a World Poker Tour event, then another $1.1-million in another WPT event soon after." "With Adderall in my system, I am like an information sponge, able to process data from several players at once while considering my next action. It improved my patience. "This year, I have a new chemical weapon: Modafinil. It stimulates wakefulness and enhances focus but without the side effects of an amphetamine - for me, reduced appetite and insomnia. With Modafinil, I feel well-rested even on limited sleep. Through judicious use of both I can operate at my full potential for days on end." Modafinil, also called Provigil, is a nootropic or cognitive enhancer used in the treatment of narcolepsy, shift work sleep disorder and obstructive sleep apnea. It is also described as a "memory-improving and mood-brightening psychostimulant". The US military has given Modafinil to its air force pilots in the Gulf War and Iraq, and the French government admits that the Foreign Legion has used it during " covert operations". Modafinil expert Trevor Robbins, professor of cognitive neuroscience at Cambridge University, says: "It works like a mental manager. It's great on tasks requiring reflection and planning, plus it inhibits impulsiveness - and blurting out the wrong thing." What are the side effects? The website provigil.com warns: "If you experience chest pain, depression, anxiety, hallucinations, psychosis, mania, thoughts of suicide, aggression, or other mental problems, stop taking Provigil [Modafinil] and call your doctor or get emergency treatment." Funny, I get all those symptoms every time I lose money at poker, and that's without any performance-enhancing stimulant. LOAD-DATE: June 2, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: The Times Copyright 2008 AVUSA Media LTD All Rights Reserved 226 of 998 DOCUMENTS US Fed News September 19, 2008 Friday 6:05 AM EST French Inventors Develop Therapeutic Treatment Method BYLINE: US Fed News LENGTH: 192 words DATELINE: Alexandria, Va. ALEXANDRIA, Va., Sept. 19 -- Veronique Broquaire of Noisy-le-Grand, France, Ludovic Broquaire of Frejus, France, Laurent Courvoisier of Laigneville, France, Gerard Coquerel of Boos, France, Franck Mallet of Blangy sur Bresle, France, and Michel Broquaire of Le Perreux, France, have developed a therapeutic treatment system. According to the abstract released by the U.S. Patent & Trademark Office: " Modafinil polymorphic forms of modafinil racemate, methods of preparation thereof, pharmaceutical compositions and methods of therapeutic treatment involving modafinil polymorphic forms." The inventors were issued U.S. Patent No. on July 29. The patent has been assigned to Cephalon France, Maisons Alfort, France. The original application was filed on Oct. 12, 2005, and is available at: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=% 2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=7,405,323.PN.&OS=PN/7,405,323&RS= PN/7,405,323. For more information about US Fed News federal patent awards please contact: Myron Struck, Managing Editor/US Bureau, US Fed News, Direct: 703/866-4708, Cell: 703/304-1897, Myron@targetednews.com LOAD-DATE: September 19, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2008 HT Media Ltd. All Rights Reserved 227 of 998 DOCUMENTS US Fed News September 19, 2008 Friday 6:05 AM EST French Inventors Develop Therapeutic Treatment Method BYLINE: US Fed News LENGTH: 193 words DATELINE: Alexandria, Va. ALEXANDRIA, Va., Sept. 19 -- Veronique Broquaire of Noisy-le-Grand, France, Ludovic Broquaire of Frejus, France, Laurent Courvoisier of Laigneville, France, Gerard Coquerel of Boos, France, Franck Mallet of Blangy sur Bresle, France, and Michel Broquaire of Le Perreux, France, have developed a therapeutic treatment system. According to the abstract released by the U.S. Patent & Trademark Office: " Modafinil polymorphic forms of modafinil racemate, methods of preparation thereof, pharmaceutical compositions and methods of therapeutic treatment involving modafinil polymorphic forms." The inventors were issued U.S. Patent No. 7,405,323 on July 29. The patent has been assigned to Cephalon France, Maisons Alfort, France. The original application was filed on Oct. 12, 2005, and is available at: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=% 2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=7,405,323.PN.&OS=PN/7,405,323&RS= PN/7,405,323. For more information about US Fed News federal patent awards please contact: Myron Struck, Managing Editor/US Bureau, US Fed News, Direct: 703/866-4708, Cell: 703/304-1897, Myron@targetednews.com LOAD-DATE: September 19, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2008 HT Media Ltd. All Rights Reserved 228 of 998 DOCUMENTS Daily Mail (London) August 19, 2008 Tuesday 1ST Edition Fears for 'smart pill' generation BYLINE: Sarah Harris SECTION: Pg. 60 LENGTH: 761 words THE A-level and GCSE exam season is over for another year. Pupils -- and parents -- will be relieved that the stress, last-minute cramming and hard work is behind them. Last week saw record A-level results. The pattern is expected to be repeated this Thursday when hundreds of thousands of GCSE pupils discover how well they did. But experts are questioning how far pupils and their families are prepared to go to get the best results. Rising numbers of stressed students are feared to be popping so-called 'smart pills' to boost their exam performance. They are taking drugs used to treat hyperactive children and people with sleep problems to improve their brain power, despite being healthy. Doctors have warned that parents may be tempted to condone or even encourage this risky practice to give their youngsters a competitive edge. The British Medical Association claims that despite a lack of information about the possible long-term side-effects, 'there is already evidence of demand' for these cognitive enhancers in the UK. The problem is thought to be spreading due to the growth of online pharmacies selling Ritalin and Modafinil -- the most popular cognitive enhancers -- from 60p per pill without prescription. Experts believe parents are also duping doctors into giving them Ritalin for their children on prescription when there is no medical justification for using the drug. The number of prescriptions given to pupils for behaviour-altering drugs such as Ritalin and Modafinil has risen tenfold in the past decade, from around 48,000 in 1996-7 to more than 450,000 last year. Ritalin is used to calm and focus children with attention deficit hyperactivity disorder (ADHD). It increases alertness and improves concentration and memory. Modafinil is sold to treat narcolepsy (characterised by sudden attacks of sleepiness), but it can also stave off tiredness in those without a diagnosed sleep disorder. The BMA has warned that - cognitive enhancers are already being used 'surreptitiously' by students in the States as study aids. In a recent report, it says: 'Modern-day UK society is highly competitive. Children are judged from a young age on the basis of success in examinations, competition for university places, for openings in prestigious and highly paid professions, and pressure to succeed in one's chosen pursuits. ' In such an environment, it is perhaps not surprising that anything that gives an individual a competitive edge over his or her peers is seen as beneficial.' AND THE BMA says there is a 'strong advantage' for parents in trying to ensure their child, rather than somebody else's, gains an in-demand university place. 'So, those who could afford the interventions for their children would have a competitive advantage,' the report says. 'The result may well be pressure on parents to choose cognitive enhancers, and those who abstain risk holding their children back.' It asks 'whether we want to live in a society in which the use of cognitive enhancements are routine'. The use of brain-boosting drugs is rife among students in the U.S. Research by the National Institute on Drug Abuse found 2.5 per cent of eighth graders (13- to 14-year-olds) and 5.1per cent of 12th graders (17- to 18-year-olds) took 'smart pills' either for the 'rush' or as a study aid. Other studies show that on some U.S. campuses, 16 per cent of students are taking the drugs. Experts say that a similar problem is 'almost certainly happening here' among the student population. Barbara Sahakian, a professor of clinical neuropsychology at Cambridge University and author of studies into cognitive enhancers, says that prescriptions of Ritalin are increasing in the UK. She explains: 'When doctors see children, it's only for a short period of time. They're taking information provided by the parent about how they behave at school and home. It's self-reporting and it is open to abuse. For those children with ADHD it is a very effective form of treatment, but it shouldn't be used for all children.' Paul Cooper, professor of education at Leicester University, says teachers have told him that parents are buying Ritalin for their children off the internet. This is a 'dangerous risk' as they do not know if the drug is genuine or has been adulterated. They may also administer the wrong dose or mix it with other medicines. 'I think it's likely that parents are using Ritalin to try to improve their children's performance,' he says. 'If you think about the pressures that students and their parents are under -- short of outright cheating, I think they will go to extreme lengths.' LOAD-DATE: August 26, 2008 LANGUAGE: ENGLISH GRAPHIC: Under pressure: The use of brain-boosting drugs is on the increase PUBLICATION-TYPE: Papers Copyright 2008 Associated Newspapers Ltd. All Rights Reserved 229 of 998 DOCUMENTS Clinical Psychiatry News August 2008 Modafinil Reduces Severe Cancer Fatigue BYLINE: Kerri Wachter, Senior Writer SECTION: Pg. 52 Vol. 36 No. 8 ISSN: 0270-6644 LENGTH: 362 words    CHICAGO - The wakefulness-promoting drug modafinil reduced self-reported severe fatigue, according to a study of more than 600 cancer patients undergoing chemotherapy that was presented at the annual meeting of the American Society of Clinical Oncology.    Gary R. Morrow, Ph.D., of the University of Rochester (N.Y.) and his colleagues randomized 631 patients undergoing four cycles of chemotherapy to receive either 200 mg modafinil (Provigil) daily or placebo.    Among those with severe fatigue at baseline, patients on modafinil had significantly greater reductions in fatigue, compared with those on placebo.    Participants were asked to rate their level of fatigue at baseline (during the second cycle of chemotherapy) and during the final cycle. They rated fatigue on a 10-point scale: mild (1-4), moderate (5-6), and severe (7-10).    A total of 67 patients reported mild fatigue at baseline; 106 and 458 reported moderate and severe fatigue, respectively..    Among patients with mild and moderate fatigue, modafinil also reduced fatigue, compared with placebo, but the differences were not significant. This was not surprising, Dr. Morrow said during a press briefing. "With side effects, quite often the potency of the effect is somewhat dependent on where you began," he said.    Modafinil-a nonamphetamine stimulant-is currently indicated for the treatment of excessive sleepiness resulting from obstructive sleep apnea, shift-work sleep disorder, and narcolepsy. Last year, researchers also at the University of Rochester reported success with modafinil in treating "chemo brain," a reduction in cognitive function that has been associated with chemotherapy.    There may be some overlap between chemo brain and fatigue, Dr. Morrow said in an interview. Problems with executive function are commonly described in chemo brain. Cancer-related fatigue appears to particularly affect tasks associated with executive function. Cancer patients complain of not being able to "get around" to doing things they know they should do.    Cephalon Inc. provided modafinil and placebo for the trial. Dr. Morrow reported that he has no relevant financial relationships. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: CPNEWS Copyright 2008 Elsevier Inc., International Medical News Group All Rights Reserved 230 of 998 DOCUMENTS Internal Medicine News August 1, 2008 Modafinil Helps Reduce Severe Cancer-Related Fatigue BYLINE: Kerri Wachter, Senior Writer SECTION: Pg. 33 Vol. 41 No. 15 ISSN: 1097-8690 LENGTH: 361 words    CHICAGO - The wakefulness-promoting drug modafinil (Provigil) reduced self-reported severe fatigue, according to a study of more than 600 cancer patients undergoing chemotherapy that was presented at the annual meeting of the American Society of Clinical Oncology.    Gary R. Morrow, Ph.D., of the University of Rochester (N.Y.) and his colleagues randomized 631 patients undergoing four cycles of chemotherapy to receive either 200 mg modafinil daily or placebo. Among those with severe fatigue at baseline, patients on modafinil had significantly greater reductions in fatigue, compared with those on placebo.    The participants were asked to rate their level of fatigue at baseline (during the second cycle of chemotherapy) and during the final cycle. They rated fatigue on a 10-point scale: mild (1-4), moderate (5-6), and severe (7-10). A total of 67 patients reported mild fatigue at baseline; 106 and 458 reported moderate and severe fatigue, respectively.    Among patients with mild and moderate fatigue, modafinil also reduced fatigue, compared with placebo, but the differences were not significant. This was not surprising, Dr. Morrow said during a press briefing. "With side effects, quite often the potency of the effect is somewhat dependent on where you began," he said.    Modafinil-a nonamphetamine stimulant-is currently indicated for the treatment of excessive sleepiness resulting from obstructive sleep apnea, shift-work sleep disorder, and narcolepsy. Last year, researchers also at the University of Rochester reported success with modafinil in treating "chemo brain," a reduction in cognitive function that has been associated with chemotherapy.    There may be some overlap between chemo brain and fatigue, Dr. Morrow said in an interview. Problems with executive function are commonly described in chemo brain. Cancer-related fatigue appears to particularly affect tasks associated with executive function. Cancer patients complain of not being able to "get around" to doing things they know they should do.    Cephalon Inc. provided modafinil and placebo for the trial. Dr. Morrow reported that he has no relevant financial relationships. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: IMNEWS Copyright 2008 Elsevier Inc., International Medical News Group All Rights Reserved 231 of 998 DOCUMENTS The Sunday Times (London) July 20, 2008 There's a buzz about Modafinil BYLINE: Fleur Britten SECTION: FEATURES; Style; Pg.36 LENGTH: 1335 words There's a buzz about Modafinil, the 'smart' drug that is meant to make you sharper, brighter and more energised, but the idea of popping a pill to boost your brain - without any nasty side effects - is a little hard to swallow. Fleur Britten plays guinea pig Is your memory so perforated that you fear early-onset Alzheimer's? Your attention so centrifugal that you've self-diagnosed attention deficit hyperactivity disorder (ADHD)? Perhaps you don't have time to sleep, or maybe you would just like to function as a super-you. The sci-fi solution we have all been waiting for is already here, and it's circulating in student unions and school. These days, the kids are all on "smart drugs". A group of pharmaceuticals designed for sufferers of narcolepsy, Alzheimer's and ADHD, smart drugs are increasingly being used "off label" (unsupervised, as a lifestyle choice) by healthy people, who procure them from online pharmacies, friendly physicians and illicit prescription sales. "This stuff is being passed around all the time," says one male A-level student with something of a smart-drug habit - "this stuff" largely being Ritalin, usually prescribed for children with ADHD, and Modafinil, which is used to treat narcolepsy. Students are rejoicing and cramming for exams with smart-drug- fuelled all-nighters. One told me that he buys his from a mate who sells on his larger-than-necessary prescription; another offered to put me in touch with her "very kind doctor". The government, meanwhile, is sweating. It recently commissioned a report on brain science that concluded more work is needed. What students and the government both know is that in Ritalin improves attention, memory and cognitive flexibility in healthy subjects; Modafinil improves attention, memory, planning and decision- making and leaves you in a state of wakefulness without the wired bit, liability of addiction or "obvious toxic effects". So what's not to like? Imbued with visions of a new, improved me, I visit that conveniently unregulated online pharmacy. Ritalin costs £ 58 for 10 pills; Modafinil, £ 10 for 10. No questions asked, no electrocardiograph tests required. I plump for cheapo Modafinil. My sister, a doctor, phones with a warning: "I've been discussing your drugs trial with a colleague, and we don't think it's safe to experiment with your brain like this." I fall silent as she explains there are scant statistics on Modafinil's long-term effects, even fewer on the effects on healthy subjects. Plus, as with all neurological drugs, there can be atypical side effects. And a new report claims three in five medicines bought online are fake, some dangerously so. A dodgy package arrives in the post. Wrapped in low-grade manila, wonkily stamped "Mumbai - India", is a loose strip of 10 x 200mg legit-looking Modafinil pills (the website was recommended by a genuine American pharmacy that refused to ship to the UK). There are no instructions, no warnings of harmful contraindications, only this: "Dosage: as directed by the neurologist/ psychiatrist/specialist." I turn to my old friend the internet to check the dose (one or two pills) and side effects (insomnia, decreased appetite, anxiety, headache and rapid heartbeat). Some, of course, may see these cons as pros. First thing the next morning, down it goes, and I await the "eureka!" moment. It never comes, but an hour later, I feel undoubtedly alert. Actually, I feel pretty normal (no cleverer, no less hungry), if a little edgy. A persistent, dry headache develops, like I have drunk one too many coffees (after all, caffeine and Modafinil both stimulate the central nervous system), but where my attention usually drifts, today it can't. Streams of consciousness babble endlessly; I feel spirited and industrious. The steady energy endures with no 4pm fogs, and I fantasise about Thatcher-style productivity. Perhaps this is the key to the mythological 25-hour day? There are stories of off-label users finally conquering their intellectual Everests (lifelong battles with War and Peace); the American poker player Paul Phillips claimed that when he was prescribed Modafinil, it helped him win more than £ 1.7m. One A-level student told me: "On Ritalin and Modafinil, no matter what you're doing, you're interested. I studied politics, which usually I couldn't give a toss about. Four hours in, you have the choice to work or not, and you prefer to work. I screwed around all year and then worked really hard for my exams - on drugs. Some say it's cheating, but it's not like in sport, where you can be banned for taking steroids." According to the Department of Health, buying these drugs from illegal organisations is not against the law, as they are legal. It is time to find out what is going on in my head, so I call the Modafinil expert, Trevor Robbins, professor of cognitive neuroscience at Cambridge University and one of the academics behind the government's recent brain science report. He is unambiguously excited. "It works like a mental manager, optimising the performance of several different faculties," he says. "It's great on tasks requiring reflection and planning, plus it inhibits impulsiveness - and blurting out the wrong thing." Does he see it as cheating? "Coffee is a cognition enhancer," he argues. "People don't think of them as the same, but they're both chemicals. It's like taking a vitamin pill." Except that Modafinil is much more sophisticated and active. But where was super-me? "Modafinil operates on an inverted U-shaped curve," Robbins says. "If you're already functioning at the top of it, you can only go down." Depressing. He adds that some may not be genetically optimal for enhancement. Has Robbins tried Modafinil? "Never. I perform optimally already." Disturbingly, nobody knows exactly how Modafinil works, although it's generally considered safe (provided, of course, you're not taking the fakes). Made by Cephalon, it's been licensed for narcolepsy (as Provigil) for 10 years in the UK. In America, where the licensing regulations are more lenient, plenty of academics have it on repeat prescription. Cephalon refuses to answer my questions about off-label use, saying it has no direct involvement with tests on healthy volunteers, nor any plans for over-the-counter sales. It was after dark that Modafinil's potential for 48-hour wakefulness appeared - annoyingly. (I was only after the "smart" bit.) Wide-eyed at 2am, I reached for a sleeping pill. And another. Predisposed to poor sleep, I ended up taking three times the normal dose, yet getting barely two hours' kip. Many claim to sleep fine and that there is no sleep debt after all-nighters, provided you get eight hours' kip the following night. I'm not convinced. The next day, I'm still alert, but I need an extra jolt of caffeine. By 6pm, I'm broken. I see that upper- downer cycle winking at me: Exhausted? Take this little pill. Can't sleep? Try this. And I did, a few days later, this time on a hangover. With the stuffing already knocked out of me, I wondered whether Modafinil could be the ultimate hangover cure. But no - I had the same sleep issues (none, all night) and a whole new hangover to deal with. The day after, I felt heavy, woolly and strung out, with a stubborn, brittle headache - not dissimilar to the aftermath of a drugs bender. Unsurprisingly. According to the US military, sequential dosing has diminishing returns: Modafinil can work for 48 hours, but then people need sleep. After all, people eventually die from sleep deprivation. As far as I can work out, it doesn't do to mess with your circadian cycle: power pills are no substitute for real sleep. But in these time-obsessed days, off-label use is predicted to rise, and more cognition-enhancing drugs are in development. I haven't touched my stash since, but if I were a truckie or on the eve of exams, I could be tempted. But you would be foolish to treat smart drugs like the new coffee. 1 FOTOFIT LOAD-DATE: July 25, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: sb Copyright 2008 Times Newspapers Limited All Rights Reserved 232 of 998 DOCUMENTS Pallimed July 2, 2008 Wednesday 2:03 PM EST 2008 ASCO: methadone, genetics, modafinil BYLINE: Drew Rosielle MD LENGTH: 289 words Jul. 2, 2008 (Pallimed delivered by Newstex) -- The 2008 American Society of Clinical Oncology meeting was last month. Every year the palliative care, supportive care, and end-of-life care abstracts are worth browsing (abstracts here).I wanted to particularly point out 3:First is a case series about one center's experience with initiating and rotating to methadone in outpatients. Very little has been published about rotating to methadone in the outpatient setting despite it being a relatively common practice (that's my sense at least) - most of the publications about methadone rotations have been in inpatients. The data presented here suggest it's safe (no one falling over dead from torsades) and has salutary effects on pain.Second is one looking at genetic polymorphisms (of cytokine genes) and their associations with pain and opioid dose (certain polymorphisms in this lung cancer population were associated both with pain and opioid dose). I'm probably prematurely excited about the growing trickle of research (in actual real live humans in pain) into the genetic basis of the variable response to opioids, but there you go.Third, outcome data from a randomized, placebo controlled trial of modafinil for cancer-related fatigue was presented. Patients were all initiating chemotherapy, and those who reported severe fatigue (but not mild or moderate) seemed to benefit from modafinil over placebo. The magnitude of the benefit, while statistically significant, is unclear from the abstract. I've used modafinil occasionally, with (of course) mixed results; these are the first placebo controlled data I've seen on it in our population. I'm curious as to readers' experience with it. Newstex ID: PALL-0001-26407116 LOAD-DATE: July 3, 2008 LANGUAGE: ENGLISH NOTES: The views expressed on blogs distributed by Newstex and its re-distributors ("Blogs on Demand®") are solely the author's and not necessarily the views of Newstex or its re-distributors. Posts from such authors are provided "AS IS", with no warranties, and confer no rights. The material and information provided in Blogs on Demand® are for general information only and should not, in any respect, be relied on as professional advice. No content on such Blogs on Demand® is "read and approved" before it is posted. Accordingly, neither Newstex nor its re-distributors make any claims, promises or guarantees about the accuracy, completeness, or adequacy of the information contained therein or linked to from such blogs, nor take responsibility for any aspect of such blog content. All content on Blogs on Demand® shall be construed as author-based content and commentary. Accordingly, no warranties or other guarantees will be offered as to the quality of the opinions, commentary or anything else offered on such Blogs on Demand®. Reader's comments reflect their individual opinion and their publication within Blogs on Demand® shall not infer or connote an endorsement by Newstex or its re-distributors of such reader's comments or views. Newstex and its re-distributors expressly reserve the right to delete posts and comments at its and their sole discretion. PUBLICATION-TYPE: Web Blog Copyright 2008 Newstex LLC All Rights Reserved Newstex Web Blogs Copyright 2008 Pallimed 233 of 998 DOCUMENTS Family Practice News July 1, 2008 Modafinil Reduces Severe Cancer-Related Fatigue BYLINE: Kerri Wachter, Senior Writer SECTION: Pg. 45 Vol. 38 No. 13 ISSN: 0300-7073 LENGTH: 307 words    CHICAGO - The wakefulness-promoting drug modafinil (Provigil) reduced self-reported severe fatigue, according to a study presented at the annual meeting of the American Society of Clinical Oncology.    Gary R. Morrow, Ph.D., of the University of Rochester (N.Y.) and his colleagues randomized 631 patients undergoing four cycles of chemotherapy to receive either 200 mg modafinil daily or placebo. Among those with severe fatigue at baseline, patients on modafinil had significantly greater reductions in fatigue, compared with those on placebo.    The subjects were asked to rate their level of fatigue at baseline (during the second cycle of chemotherapy) and during the final cycle. They rated fatigue on a 10-point scale: mild (1-4), moderate (5-6), and severe (7-10). A total of 67 patients reported mild fatigue at baseline; 106 and 458 reported moderate and severe fatigue, respectively.    In patients with mild and moderate fatigue, modafinil also reduced fatigue, compared with placebo, but the differences were not significant.    Modafinil, a nonamphetamine stimulant, is indicated for the treatment of excessive sleepiness resulting from obstructive sleep apnea, shift-work, and narcolepsy. Last year, researchers also at the University of Rochester reported success with modafinil in treating "chemo brain," a reduction in cognitive function associated with chemotherapy.    There may be some overlap between chemo brain and fatigue. Problems with executive function are commonly described in chemo brain. Cancer-related fatigue appears to particularly affect tasks associated with executive function. Cancer patients often complain of not being able to do things they know they should do, Dr. Morrow said.    Cephalon Inc. provided modafinil and placebo for the trial. Dr. Morrow said he has no relevant financial relationships. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: FPNEWS Copyright 2008 Elsevier Inc., International Medical News Group All Rights Reserved 234 of 998 DOCUMENTS Ob/Gyn. News June 15, 2008 Modafinil May Cut Fatigue In Patients During Chemo BYLINE: Kerri Wachter, Senior Writer SECTION: Pg. 14 Vol. 43 No. 12 ISSN: 0029-7437 LENGTH: 361 words    CHICAGO - The wakefulness-promoting drug modafinil (Provigil) reduced self-reported severe fatigue, according to a study of more than 600 cancer patients undergoing chemotherapy that was presented at the annual meeting of the American Society of Clinical Oncology.    Gary R. Morrow, Ph.D., of the University of Rochester (N.Y.) and his colleagues randomized 631 patients undergoing four cycles of chemotherapy to receive either 200 mg modafinil daily or placebo. Among those with severe fatigue at baseline, patients on modafinil had significantly greater reductions in fatigue, compared with those on placebo.    Participants were asked to rate their level of fatigue at baseline (during the second cycle of chemotherapy) and during the final cycle. They rated fatigue on a 10-point scale: mild (1-4), moderate (5-6), and severe (7-10). A total of 67 patients reported mild fatigue at baseline; 106 and 458 reported moderate and severe fatigue, respectively.    Among patients with mild and moderate fatigue, modafinil also reduced fatigue, compared with placebo, but the differences were not significant. This was not surprising, Dr. Morrow said during a press briefing. "With side effects, quite often the potency of the effect is somewhat dependent on where you began," he said.    Modafinil-a nonamphetamine stimulant-is currently indicated for the treatment of excessive sleepiness resulting from obstructive sleep apnea, shift-work sleep disorder, and narcolepsy.    Last year, researchers also at the University of Rochester reported success with modafinil in treating "chemo brain," a reduction in cognitive function that has been associated with chemotherapy.    There may be some overlap between chemo brain and fatigue, Dr. Morrow said in an interview. Problems with executive function are commonly described in chemo brain. Cancer-related fatigue appears to particularly affect tasks associated with executive function. Cancer patients complain of not being able to "get around" to doing things they know they should do.    Cephalon Inc. provided modafinil and placebo for the trial. Dr. Morrow reported that he has no relevant financial relationships. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: OBNEWS Copyright 2008 Elsevier Inc., International Medical News Group All Rights Reserved 235 of 998 DOCUMENTS The Age (Melbourne, Australia) June 6, 2008 Friday First Edition 'Smart drugs' need smarter risk-handling; 'What if you could go into Starbucks and ask for your latte with a shot of (smart drug) modafinil?' BYLINE: Nick Miller, Health Editor SECTION: NEWS; Pg. 3 LENGTH: 844 words "SMART drugs" could be the fluoride of the new millennium, says a visiting expert. But they could also be a social scourge as we dope ourselves and our children to work harder and longer, warned Cambridge University professor Barbara Sahakian, who is visiting Melbourne for the 2008 Alfred Deakin Lectures. Academics, students and high-octane executives are already seeking a new generation of pills that improve cognition, planning skills and memory, with minimal side effects. "This could be the way of the future," Professor Sahakian said. "What if you could go into Starbucks and ask for your latte with a shot of (smart drug) modafinil?" Other experts have even suggested cognitive enhancers be put in the water alongside fluoride, she said. Developed to treat disorders such as narcolepsy or Alzheimer's, some new drugs were found to improve cognition in normal, healthy people. Those in the know are buying drugs such as modafinil through under-regulated internet pharmacies, or friendly doctors who bend strict prescription rules. They are handed around at conferences and swapped before exams. A recent Nature magazine survey found one-fifth of its readers had used smart drugs to boost their concentration or memory. "We're not always working at our best - young mothers with babies, people travelling all the time," Professor Sahakian said. "I went to a meeting in Florida and I said to a colleague 'I'm suffering from jetlag', and he said to me 'would you like some of my modafinil?' A lot of my colleagues (are) using it." Newer smart drugs are proving safer than predecessors such as Ritalin. "New drugs such as modafinil have a much lower side effects profile and don't seem to have a substance abuse potential. It really is something a healthy human might be tempted to try." But that temptation can lead to danger. Many people are sourcing smart drugs from internet pharmacies, unsure what they are getting and without advice about their effect on existing conditions and medication. "I'm keen to have some kind of governmental regulatory approach, so people are getting safe and effective cognitive drugs," Professor Sahakian said. Beyond medical safety, society might be hurt by smart drugs. "What if some people can afford cognitive-enhancing drugs, but other people can't?" she said. "What happens to the work-life balance . . . are we going to improve that using these drugs, to get a good day's work and come home early? Or are we just going to work more?" Professor Sahakian also worries that the focus on "quick fix" pills ignores the cognitive benefits of exercise and education. On the other hand, these drugs could keep an ageing population mentally active. There are at least 40 new cognitive drugs in development, such as "ampakines" that seem to boost memory. Modafinil is available on Australia's Pharmaceutical Benefits Scheme when prescribed for severe sleep disorders. The makers warn it has been associated with severe rashes in children. There may also be unknown side effects. "We don't know about the long-term effects (of modafinil) in the developing brain," Professor Sahakian said. If smart drugs became popular parents would feel pressure to give them to children, especially if schoolmates used them. Drug educator Paul Dillon said in the past 12 to 18 months he had noticed a sharp increase in interest from high school students in drugs that could help them study. "I have had quite a substantial number of questions from year 11s and 12s asking about Ritalin and its effects," he said. "They say 'a friend is using it to study'. Ritalin has always been used in non-medical ways, to get a 'buzz', but this is something new. You have to ask why - is it because of greater pressure to achieve?" There was a risk, especially with young people, if they didn't get the desired effect from one pill they would take 10 the next time, he said. Professor Sahakian delivers tonight's Deakin lecture: www.deakinlectures.net SMART DRUGS METHYLPHENIDATE (Drug names Ritalin, Concerta) A stimulant commonly used to treat attention deficit disorders and chronic fatigue. Healthy users believe it helps them focus on tasks and stay awake. MODAFINIL (Drug names Provigil, Modavigil) Another stimulant with less severe side-effects than Ritalin. Prescribed to treat severe sleep problems. Some studies suggest it improves short-term memory, concentration and pattern recognition. AMPAKINES Still experimental, drugs such as CX717 are believed to affect the neurotransmitter glutamate, possibly improving cognitive function and memory. PIRACETAM (Drug names Nootropil, Avigilen) Normally used to treat alcoholism, dementia or stroke. May improve memory and learning in healthy people. ERGOLOID (Drug names Hydergine, Cicanol) An anti-dementia treatment believed to promote alertness, memory and cognitive abilities. BETA-BLOCKERS (Propranolol, for example) An old treatment for high blood pressure, sometimes used to prevent anxiety in public speakers and musicians. NOTE: The Age does not condone the use of any of these drugs without a prescription and appropriate medical advice. LOAD-DATE: June 5, 2008 LANGUAGE: ENGLISH GRAPHIC: PHOTO: Cambridge University Professor Barbara Sahakian, who says emerging "smart" drugs could be the new fluoride or a scourge if misused. PICTURE: JASON SOUTH PUBLICATION-TYPE: Newspaper Copyright 2008 The Age Company Limited All Rights Reserved 236 of 998 DOCUMENTS The Age (Melbourne, Australia) June 6, 2008 Friday Second Edition 'Smart drugs' need smarter risk-handling; 'What if you could go into Starbucks and ask for your latte with a shot of (smart drug) modafinil?' BYLINE: Nick Miller, Health Editor SECTION: NEWS; Pg. 3 LENGTH: 839 words "SMART drugs" could be the fluoride of the new millennium, says a visiting expert. But they could also be a social scourge as we dope ourselves and our children to work harder and longer, warned Cambridge University professor Barbara Sahakian, who is visiting Melbourne for the 2008 Alfred Deakin Lectures. Academics, students and high-octane executives are already seeking a new generation of pills that improve cognition, planning skills and memory, with minimal side effects. "This could be the way of the future," Professor Sahakian said. "What if you could go into Starbucks and ask for your latte with a shot of (smart drug) modafinil?" Other experts have even suggested cognitive enhancers be put in the water alongside fluoride, she said. Developed to treat disorders such as narcolepsy or Alzheimer's, some new drugs were found to improve cognition in healthy people. Those in the know are buying drugs such as modafinil through under-regulated internet pharmacies, or friendly doctors who bend strict prescription rules. They are handed around at conferences and swapped before exams. A recent Nature magazine survey found one-fifth of its readers had used smart drugs to boost their concentration or memory. "We're not always working at our best - young mothers with babies, people travelling all the time," Professor Sahakian said. "I went to a meeting in Florida and I said to a colleague 'I'm suffering from jetlag', and he said to me 'would you like some of my modafinil?' A lot of my colleagues (are) using it." Newer smart drugs are proving safer than predecessors such as Ritalin. "New drugs such as modafinil have a much lower side effects profile and don't seem to have a substance abuse potential. It really is something a healthy human might be tempted to try." But that temptation can lead to danger. Many people are sourcing smart drugs from internet pharmacies, unsure what they are getting and without advice about their effect on existing conditions and medication. "I'm keen to have some kind of governmental regulatory approach, so people are getting safe and effective cognitive drugs," Professor Sahakian said. Beyond medical safety, society might be hurt by smart drugs. "What if some people can afford cognitive-enhancing drugs, but other people can't?" she said. "What happens to the work-life balance . . . are we going to improve that using these drugs, to get a good day's work and come home early? Or are we just going to work more?" Professor Sahakian also worries that the focus on "quick fix" pills ignores the cognitive benefits of exercise and education. On the other hand, these drugs could keep an ageing population mentally active. There are at least 40 new cognitive drugs in development, such as "ampakines" that seem to boost memory. Modafinil is available on Australia's Pharmaceutical Benefits Scheme when prescribed for severe sleep disorders. The makers warn it has been associated with severe rashes in children. There may also be unknown side effects. "We don't know about the long-term effects (of modafinil) in the developing brain," Professor Sahakian said. If smart drugs became popular parents would feel pressure to give them to children, especially if schoolmates used them. Drug educator Paul Dillon said in the past 12 to 18 months he had noticed a sharp increase in interest from high school students in drugs that could help them study. "I have had quite a substantial number of questions from year 11s and 12s asking about Ritalin and its effects," he said. "They say 'a friend is using it to study'. Ritalin has always been used in non-medical ways, to get a 'buzz', but this is something new. You have to ask why - is it because of greater pressure to achieve?" There was a risk, especially with young people, if they didn't get the desired effect from one pill they would take 10 the next time, he said. Professor Sahakian delivers tonight's Deakin lecture: www.deakinlectures.net SMART DRUGS METHYLPHENIDATE (Drug names Ritalin, Concerta) A stimulant commonly used to treat attention deficit disorders and chronic fatigue. Healthy users believe it helps them focus on tasks and stay awake. MODAFINIL (Drug names Provigil, Modavigil) Another stimulant with less severe side-effects than Ritalin. Prescribed to treat severe sleep problems. Some studies suggest it improves short-term memory, concentration and pattern recognition. AMPAKINES Still experimental, drugs such as CX717 are believed to affect the neurotransmitter glutamate, possibly improving cognitive function and memory. PIRACETAM (Drug names Nootropil, Avigilen) Normally used to treat alcoholism, dementia or stroke. May improve memory and learning in healthy people. ERGOLOID (Drug names Hydergine, Cicanol) An anti-dementia treatment believed to promote alertness, memory and cognitive abilities. BETA-BLOCKERS (Propranolol, for example) An old treatment for high blood pressure, sometimes used to prevent anxiety in public speakers and musicians. NOTE: These drugs should not be used without a prescription and appropriate medical advice. LOAD-DATE: June 5, 2008 LANGUAGE: ENGLISH GRAPHIC: PHOTO: Cambridge University Professor Barbara Sahakian, who says emerging "smart" drugs could be the new fluoride or a scourge if misused. PICTURE: JASON SOUTH PUBLICATION-TYPE: Newspaper Copyright 2008 The Age Company Limited All Rights Reserved 237 of 998 DOCUMENTS Clinical Psychiatry News June 2008 APA Meeting News Modafinil May Keep Weight Gain From Olanzapine to Minimum BYLINE: Kerri Wachter, Senior Writer SECTION: Pg. 20 Vol. 36 No. 6 ISSN: 0270-6644 LENGTH: 435 words    WASHINGTON - The wakefulness drug modafinil appears to reduce weight gain associated with the use of the atypical antipsychotic olanzapine, based on a study of healthy subjects presented at the annual meeting of the American Psychiatric Association.    Participants concurrently on olanzapine (Zyprexa) and modafinil (Provigil) gained roughly half the weight of those on olanzapine and placebo, reported James Roerig, Pharm.D., of the University of North Dakota, Grand Forks. Dr. Roerig reported that this study was supported through an investigator-initiated trial grant from Eli Lilly & Co., maker of olanzapine.    The etiology behind atypical antipsychotic-associated weight gain is unclear. Olanzapine is known to block the histamine H1 receptor. A significant increase in AMP-activated protein kinase (AMPK) has been associated with the antagonism of H1 receptors by olanzapine. AMPK is associated with the control of appetite and mediation of the effects of leptin and insulin. Modafinil is approved for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome, and shift work sleep disorder. The mechanism of action for modafinil is unclear, but research suggests that it acts on receptors that in turn act on histamine receptors.    For this study, the researchers recruited 50 healthy control volunteers. At baseline, their weight was recorded and they underwent a feeding laboratory assessment. All participants were titrated up to 10 mg/day olanzapine over 5 days. They were also randomized to receive placebo or modafinil, titrated to 200 mg/day over 5 days.    Because of adverse events, 10 patients dropped out-which left 20 patients in each study arm. At the end of 3 weeks, the participants were weighed and underwent another feeding laboratory assessment.    During the feeding laboratory assessment, participants were given a 550-kcal breakfast and a 600-kcal lunch. For dinner, they were given a choice of unlimited amounts of three food items; they were told to eat until they were not hungry. During the dinner session, patients were assessed for energy intake, sleepiness, hunger/satiety, and adverse events.    The placebo group showed a significantly greater increase in body mass index than did the modafinil group, Dr. Roerig said. This difference was significant at week 1 and until the end of the trial. Likewise, the placebo group gained more weight (2.67 kg on average) than the modafinil group (1.33 kg on average). This difference was significant at weeks 1 and 2 but only approached significance at week 3. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: CPNEWS Copyright 2008 Elsevier Inc., International Medical News Group All Rights Reserved 238 of 998 DOCUMENTS Clinical Neurology News June 2008 Modafinil Reduced Severe Fatigue in Cancer Patients BYLINE: Kerri Wachter, Senior Writer SECTION: Pg. 11 Vol. 4 No. 6 ISSN: 1553-3212 LENGTH: 381 words    CHICAGO - The wakefulness-promoting drug modafinil (marketed as Provigil) reduced self-reported severe fatigue, according to a recent study of more than 600 cancer patients who were undergoing chemotherapy.    Gary R. Morrow, Ph.D., of the University of Rochester (N.Y.) and his colleagues randomized 631 patients undergoing four cycles of chemotherapy to receive either 200 mg modafinil daily or placebo. Among those with severe fatigue at baseline, patients on modafinil had significantly greater reductions in fatigue, compared with those on placebo.    Dr. Morrow presented his study's findings at the annual meeting of the American Society of Clinical Oncology.    Study participants were asked to rate their level of fatigue at baseline (during the second cycle of chemotherapy) and during the final cycle.    They rated fatigue on a 10-point scale: mild (1-4), moderate (5-6), and severe (7-10).    A total of 67 patients reported mild fatigue at baseline; 106 and 458 reported moderate and severe fatigue, respectively.    Among patients with mild and moderate fatigue, modafinil also reduced fatigue, compared with placebo, but the differences were not significant.    This was not surprising, Dr. Morrow commented during a press briefing.    "With side effects, quite often the potency of the effect is somewhat dependent on where you began," he said.    Modafinil-a nonamphetamine stimulant-is currently indicated for the treatment of excessive sleepiness resulting from obstructive sleep apnea, shift-work sleep disorder, and narcolepsy. Last year, researchers also at the University of Rochester reported success with modafinil in treating "chemobrain," a reduction in cognitive function that has been associated with chemotherapy.    There may be some overlap between chemobrain and fatigue, Dr. Morrow said in an interview. Problems with executive function are commonly described in chemobrain.    Cancer-related fatigue appears to particularly affect tasks associated with executive function.    Cancer patients complain of not being able to "get around" to doing things they know they should do.    The pharmaceutical company Cephalon Inc. provided modafinil and placebo for the trial.    Dr. Morrow reported that he has no relevant financial relationships to disclose. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: CNNEWS Copyright 2008 Elsevier Inc., International Medical News Group All Rights Reserved 239 of 998 DOCUMENTS The Sunday Times (London) May 25, 2008 Dopers in the dock BYLINE: David Walsh, Chief Sports Writer SECTION: SPORT; Sport; Pg.21 LENGTH: 1148 words The trial of coach Trevor Graham is revealing just how widespread drugs in athletics were How did Michael Johnson feel as he read reports of Antonio Pettigrew's testimony in a San Francisco courtroom last week? Pettigrew was a witness in the case against athletics coach Trevor Graham, who is accused of lying to federal investigators. During his testimony, Pettigrew explained he had been put in touch with a drug supplier, Angel "Memo" Heredia, by Graham and that he continued receiving banned substances from Heredia until 2001. Johnson would have paid attention to Pettigrew's evidence because not only were they rivals on the track, they raced together on US relay teams. Regarded as the greatest of all 400m runners, Johnson's final race was the 4x400m relay in Sydney on September 30, 2000, where he anchored the US team to a clear victory. Pettigrew ran the second leg in that final and played his part in Johnson receiving the baton with an insurmountable lead. By his own admission, Pettigrew was doping at the time. One wonders if Johnson now feels that the last medal is tainted and unworthy of a place among his collection of 19 championship golds. The other two members of that 400m relay team in Sydney were the twins, Calvin and Alvin Harrison, who were given doping bans in 2004 for offences committed after the 2000 Olympics. Calvin tested positive for modafinil, a stimulant once used by athletes connected to the Balco laboratory run by Victor Conte, while Alvin was shown to have used EPO, the steroid tetrahydro-gestrinone (THG), testosterone, human growth hormone, insulin and modafinil. Alvin was given a four-year ban and became the first male athlete to be sanctioned without having failed a drug test. Johnson will know how this story is likely to unfold. Jim Scherr, chief executive of the United States Olympic Committee, weighed up Pettigrew's evidence. "If an athlete who ran in the finals knowingly and purposefully engaged in cheating, the medals won by the entire team are tarnished and, in our view, should be returned." There is a precedent for this sorry episode. At the same 2000 Olympics in Sydney, the women's 4x400m relay was won by a US team containing Marion Jones, who has since admitted she doped before the Games. Last month the International Olympic Committee (IOC) stripped that US team of its medals. They must now do the same with the US men's team and declare second-placed Nigeria as the gold medallists. Johnson never tested positive for doping, nor has he been implicated in any doping controversy, and since his retirement in 2000 he has been consistently critical of those who use drugs. What does he now think about the gold he won in that Sydney relay? At least one of his teammates was cheating at the time and given how well the Harrisons were running in Sydney, he may wonder if they started down the doping road before the 2000 Olympics. The bottom line is clear: that 4x400m gold medal is tarnished and worthless. The only good that can come from this is that by returning it, Johnson can say he wants nothing to do with any award or victory achieved with the help of drugs. It would be nice, too, if the 400m world record-holder returned that medal voluntarily, before the IOC order him to. Of course, the International Association of Athletics Federations (IAAF) and the IOC dislike talk of medals being returned and history being rewritten because there is no end to the problem. If all doping-affected results were re-evaluated and the cheats removed, there would be no time to organise the Games. When the IOC decided to strip the US women of their medals in the 4x100m and 4x400m relays (Jones was also in the 4x100m relay team) from the Sydney Olympics, they took a decision that involved more than 30 athletes in a process that would see some lose their medals, others change the colour of theirs and still others receive medals more than seven years after they had missed out. Three months before the start of the Beijing Olympics, the Graham trial is the last thing sports officials wanted. The Balco investigation is continuing to do significant damage to sport's battered image. It is not just athletics that has suffered in the fallout to the Balco investigation but also baseball and American football. Such was the cynicism that underpinned Conte's operation and the sheer scale of his doping programme that the investigation was always going to have serious consequences, but the situation has been exacerbated by athletes and their coaches believing they could tell the same lies to federal investigators that for years they have been telling to the public. That is why Jones ended up in prison, why the US cyclist Tammy Thomas awaits sentencing after her perjury conviction, why Graham is facing perjury charges. Graham's case is typical. He has been one of America's most successful track coaches and when it was discovered he was the person who tipped off US anti doping authorities about Conte's operation in San Francisco, he was praised for what seemed a strong anti-doping statement. But during the course of the Balco investigation, federal agents received information that suggested Graham was helping his athletes to dope. They interviewed him and agreed to his request for immunity from prosecution provided he was truthful. According to his testimony, Graham was never involved in doping. After speaking with other witnesses, in particular the Mexican-born steroid dealer Heredia, the investigators concluded that Graham had lied and charged him with perjury. For the first four days of last week, a jury in San Francisco heard the case against Graham and it was substantial. He had told the government investigators he had never met Heredia and had not spoken to him on the phone since 1997. A photograph showed Heredia and Graham together in Heredia's apartment in 1996, and phone records indicated Graham had spoken more than 100 times to the supplier since 1997. If the prosecution's case against Graham rested solely on Heredia's evidence, it would be difficult to prove because Heredia supplied drugs to many athletes and was not truthful in his initial interview with federal officers. The case against Graham, however, rests as much on the testimony of his former athletes. Pettigrew testified that Graham suggested he should consider using EPO and human growth hormone and that he would introduce him to a supplier Heredia), while Jerome Young, also a member of America's tarnished 4x400m team at the 2000 Olympics, told the court Graham introduced him to EPO. Dennis Mitchell, who won 4x100m gold for America at the 1992 Olympics, testified that Graham injected him with human growth hormone and Duane Ross, a retired American hurdler, said he fell out with Graham because he refused to use performance-enhancing drugs. The case resumes on Tuesday. LOAD-DATE: May 26, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: st Copyright 2008 Times Newspapers Limited All Rights Reserved 240 of 998 DOCUMENTS Canadian Corporate Newswire May 12, 2008 Monday 11:13 PM EST Get a Deep Insight into the Sleep Disorders Market Analysis 2008-2018 LENGTH: 2262 words LONDON, UNITED KINGDOM--(Marketwire - May 12, 2008) - Reportlinker.com announces that a new market research report related to the Pharmaceutical industry industry is available in its catalogue. Sleep Disorders Market Analysis 2008-2018 http://www.reportlinker.com/p089492/Sleep-Disorders-Market-Analysis-2008-201 8.html More than 80 sleep disorders have been identified. They affect over 200 million people worldwide. The report focuses on the market for following sleep disorders: - Insomnia - Restless legs syndrome (RLS) - Narcolepsy and - Obstructive Sleep Apnoea / Hypopnea Syndrome (OSAHS) The market penetration for insomnia drugs has not reached saturation point. Opportunities remain. But with the introduction of several new products the market is set to see changes, but expansion. This expansion is based on increased general awareness physicians better comprehension of the significance of this disease and the positive role that a sleep medication prescription plays. At present time there are several prescription sleeping medications available to treat insomnia. The market-focus has been driven by the production of sleep medications with less side-effects and danger of overdose. Prescription benzodiazepines and newer non-benzodiazepine hypnotics developed in the 1990s, such as Imovane, Ambien and Sonata will continue to be the most prescribed. Benzodiazepines are widely used to treat an underlying neurological disorder which is often the underlying cause of insomnia, e.g. anxiety and depression. Visiongain predicts that market share by volume for insomnia in the US will change significantly from 2008 to 2018. Ambien IR lost its patent protection in April 2007, which opened to generic competition for Zolpidem. Ambien will remain the market leader for the short term, but what will over take it? A generic version of Ambien is expected to achieve strong market share by volume as there is a great demand for zolpidem tartrate for insomnia. The market share for insomnia treatment will gradually rise after 2012, which will be due to: - Market expansion of existing expensive medications into Europe and Japan in particular - Market penetration of new medications currently in pipeline. Other drugs dealt with in this report include: - Modafinil (Provigil) is the first in a new class of wake-promoting drugs and is currently approved in more than 20 countries for the treatment of excessive daytime sleepiness associated with narcolepsy. Provigil is quickly replacing Ritalin, and other CNS stimulants, as the medication of choice for treating daytime sleepiness in narcolepsy. The FDA granted modafinil (Provigil) orphan drug status in 1993. Modafinil was initially launched in the US in 1999 for the treatment of narcolepsy. In 2004, modafinil became FDA-approved prescription medicine for the treatment of excessive sleepiness associated with Obstructive Sleep Apnoea/Hypopnea Syndrome (OSAHS) and Shift Workers Sleep Disorder (SWSD). - Requip (ropinirole) became the first and only FDA-approved drug treatment for moderate to severe primary Restless Legs Syndrome (RLS) in 2005. Key findings that will broaden the scope of the sleep disorders market: - Over the next decade, the development and improvement of sleep disorders therapies will primarily depend on the success of burgeoning technology and innovative approaches. - It is possible to purchase prescription medications online without producing a prescription. Purchase of online sleep medications has increased and will continue to evolve over the next years. - The impact of DTC advertising has created an improved awareness of available insomnia treatment. This is likely to increase as DTC advertising continues to prosper and the culture becomes more accepting towards insomnia treatment. Visiongain expects the market for sleep disorders to increase, driven by a growing awareness of sleep disorders and by campaigns to promote sleep medications, both by DTC advertising and consumer education. The relaxation of DTC marketing restrictions in the 1990s in the US set the stage for a flow for both branded and unbranded advertising and promotional programmes. Those regulations are prompting more responsible DTC advertising on the industry's part. - The FDA has requested that all manufacturers of sedative-hypnotic drug products, a class of drugs used to induce and/or maintain sleep, strengthen their product labelling to include stronger warnings concerning potential risks. - The Committee for Medicinal Products in Human Use (CHMP) of the European Medicines Agency (EMEA) approved Neurim's Circadin a prolonged-release melatonin as monotherapy for the short-term treatment of primary insomnia characterised by poor quality of sleep in patients aged 55 or over. Neurim is actively seeking strategic alliances for the major European markets. What questions does the report answer? - Which current or future therapies will drive the sleep disorders market from 2008 to 2018? - The key companies involved in the market and their analysis? - What is the patient identification rate for each of the therapeutic areas? - What is the present state of the disease awareness? - What R&D opportunities exist for 'new comers'? Why should you buy this report? - This report focuses on the marketed medications and the pipeline development for sleep disorders from 2008 to 2018. It also discusses the strength and weakness of products, along with the opportunities and threats facing the market. - The report describes world market situation for sleep disorders, namely insomnia, narcolepsy, RLS and OSAHS, with forecasts made for all key products. It also describes the insomnia market situation in the seven major world markets for sleep medications: the US, Japan, France, Germany, Italy, Spain and the UK, with forecasts for key products. - The report provides transcripts of visiongain's interviews with experts in the field of sleep disorders, which reviews the future direction of the sleep disorders treatment market. Unique benefits to you when you order this report - You can access your report whichever country you are in without using harddrive space - Primary research throughout. You will not find this information anywhere else - Full searchable report when you buy the company or corporate editions - Copies can be printed off for offline reading - Packed with charts, analysis, figures, graphs and table Please Note: Reports are sold based on the user licenses indicated. The Publisher delivers the report in Flash format via the publisher website, allowing viewing and printing capabilities only. Within one to two business days after placing the order, the Publisher will email the client with information on accessing their purchase. Prior to initiating fulfillment of an order, the client will be required to sign a document detailing the purchase terms for a publication from this publisher. 1 Executive Summary: Pharmaceutical Treatment of Sleep Disorders 2008-2018 1.1 Current Prospects of Sleep Disorders Market 1.1.1 Market Growth Estimate 1.1.2 Generic Pharmaceutical Market 1.1.3 Market Expansion 1.1.4 Market Demand for Short Elimination Half-Life 1.1.5 Medications Targeting M1 and M2 Receptors 1.1.6 Medications Targeting 5HT2A Receptor Receptors 1.1.7 Product Line Extension Activities 1.1.8 Effect of Direct-To-Consumer Advertising (DTCA) 1.1.9 Safety Measures for Online Consumers 1.2 Aim, Scope, and Format Of This Report 2 Introduction to Sleep Disorders and their Pharmaceutical Treatment 2.1 Introduction to Sleep Disorders 2.2 Overview of Chapter 2.3 Introduction to Insomnia 2.4 Discovery of Barbiturates 2.5 Market Entry for Non-Barbiturates 2.6 Arrival of Benzodiazepines 2.7 Non-benzodiazepines the Revolutionary Compound 2.7.1 Prescription Medicines and OTCs 2.8 Pharmacodynamics of Hypnotics 2.9 Introducing New Scope for Insomnia 2.10 Many Forms of Sleep Disturbances 2.10.1 Sleep Deprivation 2.11 Shift Workers Sleep Disorder (SWSD) 2.11.1 Melatonin 2.11.2 Valerian 2.12 Treatment for insomnia in Depression 2.13 Restless Legs Syndrome 2.13.1 Off-label Prescription for Restless Legs Syndrome 2.14 Other Medical Conditions 2.15 Narcolepsy 2.15.1 Xyrem for Cataplexy 2.15.2 Orphan Disease Status 2.15.3 Other Medications for Cataplexy 2.16 Obstructive Sleep Apnea / Hypopnea Syndrome (OSAHS) 2.17 Insomnia - A Common Disease 2.18 Patient Identification Rate 3 Analysis of Current Market for Insomnia 3.1 Market Share for World Insomnia Market 3.2 Market Dominance Continues for Ambien 3.3 Lunesta as Ambien's Contender 3.4 Sonata Continues to Form Niche Market 3.5 Imovane / Amoban Go Down in Insomnia Market 3.6 Benzodiazepines Survived as Low Priced Sleep Aid 3.6.1 Lendormin (brotizolam) 3.6.2 Halcion (triazolam) 3.6.3 Noctamid (Lormetazepam) 3.6.4 Doral (quazepam) 3.6.5 Dalmane (flurazepam) 3.6.6 Rohypnol (flunitrazepam) 3.6.7 Restoril (temazepam) 3.6.8 Eurodin or ProSom (estazolam) 3.6.9 Rhythmy (rilmazafone) 3.6.10 Rhythmy (rilmazafone) 3.6.10 Valium (diazepam) 3.7 Rozerem Market Up-and-Coming 4 Insomnia Market Analysis by World Regions 4.1 US has the Highest Market Share for Insomnia Treatments 4.2 Europe as a Significant Market for Insomnia Treatments 4.3 The Japanese Market for Insomnia is Expanding 5 Market Developments for Narcolepsy, Shift Work Sleep Disorder, and  Restless Legs Syndrome 5.1 Provigil Wins Label Extension 5.2 Adrafinil is a Isomer of Provigil 5.3 Ritalin/ Ritalin SR 5.4 Concerta is an Extension Version of Ritalin 5.5 Adderall as Stimulant 5.6 Xyrem for Cataplexy and Excessive Daytime Sleepiness 5.7 Recent FDA Activities for Restless Legs Syndrome 6 Products in Development for Sleep Disorders 6.1 FDA Approves Generic Ambien 6.2 Circadin a Prolonged-Release Melatonin 6.3 GHB analogue Generally Regarded as Safe 6.4 Clinical Trial Product List for Insomnia 6.5 Indiplon for Insomnia in Pre-Registration Stage 6.6 Caraco's Prospect in Narcolepsy Market 6.7 Lundbeck Faces Setback in Insomnia Market 6.8 Phase III Trial Begins on Posidorm for Insomnia 6.9 Hope for Physiological Sleep with Almorexant 6.10 5HT2A Antagonist for Insomnia 6.11 Agonist at the Serotonin 5-HT1A Receptor 6.12 VEC-162 Future Contender for Rozerem 6.13 Zolpidem as Oral Spray 6.14 Cephalon Adds Nuvigil Alongside Provigil 6.15 Dopamine Patch for RLS 6.16 Transported Prodrug of Gabapentin 7 Recommendations for Ideal Pharmaceutical Treatment for Sleep Disorders 7.1 Firsthand Interview for Expert Opinion 1 7.1.1 Prospect for Sleep Disorders Market 7.1.2 Prospect for Generic Market 7.1.3 Product Line Extension 7.1.4 Prospect for Niche Market 7.1.5 Future of Benzodiazepines Market 7.1.6 Future of Controlled Drug Market 7.1.7 Effect of Direct-to-Consumer Market 7.1.8 Future of Non-Hypnotics Medications 7.1.9 Future Medications for Sleep Apnoea 7.1.10 Prospect for Hypnotics as OTCs 7.1.12 Unmet Needs for Sleep Disorders Market 7.2 Firsthand Interview for Expert Opinion 2 7.2.1 Drug Therapies for the Future 7.2.2 Technological Advance in Sleep Disorders Treatment 7.2.3 New Effective Sleep Medications 7.2.4 Future of Sleep Disorders Market in the Developed Nations 7.2.5 Unmet Needs for Sleep Disorders Treatment 7.2.6 Favourable Medication for the Coming Decade 7.2.7 Side-Effect Profile for Future Drug Development 7.2.8 Sleep Disorders Market in Developing Nations 8 Market Force and Limitation of Sleep Disorders Market 8.1 Table for SWOT Analysis of Sleep Disorders Market 8.2 Market Analysis of Products Unapproved for Sleep Disorders by Regulatory Bodies and Niche Market 8.2.1 Unapproved Insomnia Medications: Benadryl, Unisom, Tylenol PM, Nytol 8.2.3 Purchase of Prescription Medications Online 8.3 Drug Safety Issues and Side-Effects of Drugs 8.3.1 Hypnotics are not Without Side-Effects 8.3.2 Labelling to include Potential Risks 8.3.3 Rohypnol and Xyrem have Potential for Abuse 8.4.4 Consumer Led Campaign 8.4 Unmet needs of Pharmaceutical Treatment for Sleep Disorders 8.5 Non-product Related Drivers and Restraints 8.5.1 National Policies Recommendations 8.5.2 National Policies Advising Prescription of Particular Drugs 8.5.3 Agreed Guidelines 8.5.4 Market Status Quo 8.6 Success of Direct-to-Consumer Advertising 9 Conclusions 9.1 Insomnia Market Will Show High Growth 9.2 Other Sleep Disorders of Interest 9.3 Life-Cycle Management 9.4 New Markets More Details Organisations mentioned in the report Abbott Actelion Alliance American Insomnia Association Andx Apotex Arena Astellas Avant Aventis Bayer Boehringer Ingelheim Caraco Carlsbad Cephalon Dr. Reddy's Elan Eli Lilly Drug Enforcement Administration (DEA) European Patent Office FDA Genpharm GlaxoSmithKline Hoffman-Roche Hypnion Ipsen Johnson & Johnson King Lek Lundbeck Mallinckrodt Merck Mutual MHRA Mylan National Sleep Foundation NCSDR Neurim Neurocrine Neurogen NHLBI NICE NIH NovaDel Novartis Orphan Pfizer Pharmaceutical Researchers and Manufacturers of America (PhRMA) Questcor Ranbaxy Roche Rhone-Poulenc Rorer Roxane Royal Pharmaceutical Society of Great Britain (RPSGB) Sanofi-Aventis Schering-Plough Sepracor Shionogi Shire Skye Synthon Takeda Teva Tikvah UCB Valeant Vanda Watson Wyeth XenoPort To order this report: Sleep Disorders Market Analysis 2008-2018 http://www.reportlinker.com/p089492/Sleep-Disorders-Market-Analysis-2008-201 8.html More market research reports here! FOR FURTHER INFORMATION PLEASE CONTACT: Reportlinker.com Nicolas (718) 887-3024 Email: nbo@reportlinker.com Healthcare - Healthcare, Medical and Healthcare - Surgery and Treatments LOAD-DATE: May 12, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2008 PIMS Canada, Inc., doing business as CCNMatthews All Rights Reserved 241 of 998 DOCUMENTS Market Wire May 12, 2008 Monday 8:12 PM GMT Get a Deep Insight into the Sleep Disorders Market Analysis 2008-2018 LENGTH: 2222 words DATELINE: LONDON, UNITED KINGDOM; May 12, 2008 Reportlinker.com announces that a new market research report related to the Pharmaceutical industry industry is available in its catalogue. Sleep Disorders Market Analysis 2008-2018 http://www.reportlinker.com/p089492/Sleep-Disorders-Market-Analysis-2008-2018.ht ml More than 80 sleep disorders have been identified. They affect over 200 million people worldwide. The report focuses on the market for following sleep disorders: - Insomnia - Restless legs syndrome (RLS) - Narcolepsy and - Obstructive Sleep Apnoea / Hypopnea Syndrome (OSAHS) The market penetration for insomnia drugs has not reached saturation point. Opportunities remain. But with the introduction of several new products the market is set to see changes, but expansion. This expansion is based on increased general awareness physicians better comprehension of the significance of this disease and the positive role that a sleep medication prescription plays. At present time there are several prescription sleeping medications available to treat insomnia. The market-focus has been driven by the production of sleep medications with less side-effects and danger of overdose. Prescription benzodiazepines and newer non-benzodiazepine hypnotics developed in the 1990s, such as Imovane, Ambien and Sonata will continue to be the most prescribed. Benzodiazepines are widely used to treat an underlying neurological disorder which is often the underlying cause of insomnia, e.g. anxiety and depression. Visiongain predicts that market share by volume for insomnia in the US will change significantly from 2008 to 2018. Ambien IR lost its patent protection in April 2007, which opened to generic competition for Zolpidem. Ambien will remain the market leader for the short term, but what will over take it? A generic version of Ambien is expected to achieve strong market share by volume as there is a great demand for zolpidem tartrate for insomnia. The market share for insomnia treatment will gradually rise after 2012, which will be due to: - Market expansion of existing expensive medications into Europe and Japan in particular - Market penetration of new medications currently in pipeline. Other drugs dealt with in this report include: - Modafinil (Provigil) is the first in a new class of wake-promoting drugs and is currently approved in more than 20 countries for the treatment of excessive daytime sleepiness associated with narcolepsy. Provigil is quickly replacing Ritalin, and other CNS stimulants, as the medication of choice for treating daytime sleepiness in narcolepsy. The FDA granted modafinil (Provigil) orphan drug status in 1993. Modafinil was initially launched in the US in 1999 for the treatment of narcolepsy. In 2004, modafinil became FDA-approved prescription medicine for the treatment of excessive sleepiness associated with Obstructive Sleep Apnoea/Hypopnea Syndrome (OSAHS) and Shift Workers Sleep Disorder (SWSD). - Requip (ropinirole) became the first and only FDA-approved drug treatment for moderate to severe primary Restless Legs Syndrome (RLS) in 2005. Key findings that will broaden the scope of the sleep disorders market: - Over the next decade, the development and improvement of sleep disorders therapies will primarily depend on the success of burgeoning technology and innovative approaches. - It is possible to purchase prescription medications online without producing a prescription. Purchase of online sleep medications has increased and will continue to evolve over the next years. - The impact of DTC advertising has created an improved awareness of available insomnia treatment. This is likely to increase as DTC advertising continues to prosper and the culture becomes more accepting towards insomnia treatment. Visiongain expects the market for sleep disorders to increase, driven by a growing awareness of sleep disorders and by campaigns to promote sleep medications, both by DTC advertising and consumer education. The relaxation of DTC marketing restrictions in the 1990s in the US set the stage for a flow for both branded and unbranded advertising and promotional programmes. Those regulations are prompting more responsible DTC advertising on the industry's part. - The FDA has requested that all manufacturers of sedative-hypnotic drug products, a class of drugs used to induce and/or maintain sleep, strengthen their product labelling to include stronger warnings concerning potential risks. - The Committee for Medicinal Products in Human Use (CHMP) of the European Medicines Agency (EMEA) approved Neurim's Circadin a prolonged-release melatonin as monotherapy for the short-term treatment of primary insomnia characterised by poor quality of sleep in patients aged 55 or over. Neurim is actively seeking strategic alliances for the major European markets. What questions does the report answer? - Which current or future therapies will drive the sleep disorders market from 2008 to 2018? - The key companies involved in the market and their analysis? - What is the patient identification rate for each of the therapeutic areas? - What is the present state of the disease awareness? - What R&D opportunities exist for 'new comers'? Why should you buy this report? - This report focuses on the marketed medications and the pipeline development for sleep disorders from 2008 to 2018. It also discusses the strength and weakness of products, along with the opportunities and threats facing the market. - The report describes world market situation for sleep disorders, namely insomnia, narcolepsy, RLS and OSAHS, with forecasts made for all key products. It also describes the insomnia market situation in the seven major world markets for sleep medications: the US, Japan, France, Germany, Italy, Spain and the UK, with forecasts for key products. - The report provides transcripts of visiongain's interviews with experts in the field of sleep disorders, which reviews the future direction of the sleep disorders treatment market. Unique benefits to you when you order this report - You can access your report whichever country you are in without using harddrive space - Primary research throughout. You will not find this information anywhere else - Full searchable report when you buy the company or corporate editions - Copies can be printed off for offline reading - Packed with charts, analysis, figures, graphs and table Please Note: Reports are sold based on the user licenses indicated. The Publisher delivers the report in Flash format via the publisher website, allowing viewing and printing capabilities only. Within one to two business days after placing the order, the Publisher will email the client with information on accessing their purchase. Prior to initiating fulfillment of an order, the client will be required to sign a document detailing the purchase terms for a publication from this publisher.  1 Executive Summary: Pharmaceutical Treatment of Sleep Disorders 2008-2018  1.1 Current Prospects of Sleep Disorders Market  1.1.1 Market Growth Estimate  1.1.2 Generic Pharmaceutical Market  1.1.3 Market Expansion  1.1.4 Market Demand for Short Elimination Half-Life  1.1.5 Medications Targeting M1 and M2 Receptors  1.1.6 Medications Targeting 5HT2A Receptor Receptors  1.1.7 Product Line Extension Activities  1.1.8 Effect of Direct-To-Consumer Advertising (DTCA)  1.1.9 Safety Measures for Online Consumers  1.2 Aim, Scope, and Format Of This Report  2 Introduction to Sleep Disorders and their Pharmaceutical Treatment  2.1 Introduction to Sleep Disorders  2.2 Overview of Chapter  2.3 Introduction to Insomnia  2.4 Discovery of Barbiturates  2.5 Market Entry for Non-Barbiturates  2.6 Arrival of Benzodiazepines  2.7 Non-benzodiazepines the Revolutionary Compound  2.7.1 Prescription Medicines and OTCs  2.8 Pharmacodynamics of Hypnotics  2.9 Introducing New Scope for Insomnia  2.10 Many Forms of Sleep Disturbances  2.10.1 Sleep Deprivation  2.11 Shift Workers Sleep Disorder (SWSD)  2.11.1 Melatonin  2.11.2 Valerian  2.12 Treatment for insomnia in Depression  2.13 Restless Legs Syndrome  2.13.1 Off-label Prescription for Restless Legs Syndrome  2.14 Other Medical Conditions  2.15 Narcolepsy  2.15.1 Xyrem for Cataplexy  2.15.2 Orphan Disease Status  2.15.3 Other Medications for Cataplexy  2.16 Obstructive Sleep Apnea / Hypopnea Syndrome (OSAHS)  2.17 Insomnia - A Common Disease  2.18 Patient Identification Rate  3 Analysis of Current Market for Insomnia  3.1 Market Share for World Insomnia Market  3.2 Market Dominance Continues for Ambien  3.3 Lunesta as Ambien's Contender  3.4 Sonata Continues to Form Niche Market  3.5 Imovane / Amoban Go Down in Insomnia Market  3.6 Benzodiazepines Survived as Low Priced Sleep Aid  3.6.1 Lendormin (brotizolam)  3.6.2 Halcion (triazolam)  3.6.3 Noctamid (Lormetazepam)  3.6.4 Doral (quazepam)  3.6.5 Dalmane (flurazepam)  3.6.6 Rohypnol (flunitrazepam)  3.6.7 Restoril (temazepam)  3.6.8 Eurodin or ProSom (estazolam)  3.6.9 Rhythmy (rilmazafone)  3.6.10 Rhythmy (rilmazafone)  3.6.10 Valium (diazepam)  3.7 Rozerem Market Up-and-Coming  4 Insomnia Market Analysis by World Regions  4.1 US has the Highest Market Share for Insomnia Treatments  4.2 Europe as a Significant Market for Insomnia Treatments  4.3 The Japanese Market for Insomnia is Expanding  5 Market Developments for Narcolepsy, Shift Work Sleep Disorder, and   Restless Legs Syndrome  5.1 Provigil Wins Label Extension  5.2 Adrafinil is a Isomer of Provigil  5.3 Ritalin/ Ritalin SR  5.4 Concerta is an Extension Version of Ritalin  5.5 Adderall as Stimulant  5.6 Xyrem for Cataplexy and Excessive Daytime Sleepiness  5.7 Recent FDA Activities for Restless Legs Syndrome  6 Products in Development for Sleep Disorders  6.1 FDA Approves Generic Ambien6.2 Circadin a Prolonged-Release Melatonin  6.3 GHB analogue Generally Regarded as Safe  6.4 Clinical Trial Product List for Insomnia  6.5 Indiplon for Insomnia in Pre-Registration Stage  6.6 Caraco's Prospect in Narcolepsy Market  6.7 Lundbeck Faces Setback in Insomnia Market  6.8 Phase III Trial Begins on Posidorm for Insomnia  6.9 Hope for Physiological Sleep with Almorexant  6.10 5HT2A Antagonist for Insomnia  6.11 Agonist at the Serotonin 5-HT1A Receptor  6.12 VEC-162 Future Contender for Rozerem  6.13 Zolpidem as Oral Spray  6.14 Cephalon Adds Nuvigil Alongside Provigil  6.15 Dopamine Patch for RLS  6.16 Transported Prodrug of Gabapentin  7 Recommendations for Ideal Pharmaceutical Treatment for Sleep Disorders  7.1 Firsthand Interview for Expert Opinion 1  7.1.1 Prospect for Sleep Disorders Market  7.1.2 Prospect for Generic Market  7.1.3 Product Line Extension  7.1.4 Prospect for Niche Market  7.1.5 Future of Benzodiazepines Market  7.1.6 Future of Controlled Drug Market  7.1.7 Effect of Direct-to-Consumer Market  7.1.8 Future of Non-Hypnotics Medications  7.1.9 Future Medications for Sleep Apnoea  7.1.10 Prospect for Hypnotics as OTCs  7.1.12 Unmet Needs for Sleep Disorders Market  7.2 Firsthand Interview for Expert Opinion 2  7.2.1 Drug Therapies for the Future  7.2.2 Technological Advance in Sleep Disorders Treatment  7.2.3 New Effective Sleep Medications  7.2.4 Future of Sleep Disorders Market in the Developed Nations  7.2.5 Unmet Needs for Sleep Disorders Treatment  7.2.6 Favourable Medication for the Coming Decade  7.2.7 Side-Effect Profile for Future Drug Development  7.2.8 Sleep Disorders Market in Developing Nations  8 Market Force and Limitation of Sleep Disorders Market  8.1 Table for SWOT Analysis of Sleep Disorders Market  8.2 Market Analysis of Products Unapproved for Sleep Disorders by  Regulatory Bodies and Niche Market  8.2.1 Unapproved Insomnia Medications: Benadryl,  Unisom, Tylenol PM, Nytol  8.2.3 Purchase of Prescription Medications Online  8.3 Drug Safety Issues and Side-Effects of Drugs  8.3.1 Hypnotics are not Without Side-Effects  8.3.2 Labelling to include Potential Risks  8.3.3 Rohypnol and Xyrem have Potential for Abuse  8.4.4 Consumer Led Campaign  8.4 Unmet needs of Pharmaceutical Treatment for Sleep Disorders  8.5 Non-product Related Drivers and Restraints  8.5.1 National Policies Recommendations  8.5.2 National Policies Advising Prescription of Particular Drugs  8.5.3 Agreed Guidelines  8.5.4 Market Status Quo  8.6 Success of Direct-to-Consumer Advertising  9 Conclusions  9.1 Insomnia Market Will Show High Growth  9.2 Other Sleep Disorders of Interest  9.3 Life-Cycle Management  9.4 New Markets  More Details  Organisations mentioned in the report  Abbott  Actelion  Alliance  American Insomnia Association  Andx  Apotex  Arena  Astellas  Avant  Aventis  Bayer  Boehringer Ingelheim  Caraco  Carlsbad  Cephalon  Dr. Reddy's  Elan  Eli Lilly  Drug Enforcement Administration (DEA)  European Patent Office  FDA  Genpharm  GlaxoSmithKline  Hoffman-Roche  Hypnion  Ipsen  Johnson & Johnson  King  Lek  Lundbeck  Mallinckrodt  Merck  Mutual  MHRA  Mylan  National Sleep Foundation  NCSDR  Neurim  Neurocrine  Neurogen  NHLBI  NICE  NIH  NovaDel  Novartis  Orphan  Pfizer  Pharmaceutical Researchers and Manufacturers of America (PhRMA)  Questcor  Ranbaxy  Roche  Rhone-Poulenc Rorer  Roxane  Royal Pharmaceutical Society of Great Britain (RPSGB)  Sanofi-Aventis  Schering-Plough  Sepracor  Shionogi  Shire  Skye  Synthon  Takeda  Teva  Tikvah  UCB  Valeant  Vanda  Watson  Wyeth  XenoPort To order this report: Sleep Disorders Market Analysis 2008-2018 http://www.reportlinker.com/p089492/Sleep-Disorders-Market-Analysis-2008-2018.ht ml More market research reports here!  Contacts:  Reportlinker.com  Nicolas  (718) 887-3024  Email: nbo@reportlinker.com SOURCE: Reportlinker.com LOAD-DATE: May 13, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2008 Market Wire, Incorporated All Rights Reserved 242 of 998 DOCUMENTS The Evening Standard (London) May 6, 2008 Tuesday Can a pill boost your brain?; They call it Viagra for the mind. Modafinil is a drug designed for narcoleptics that's now being abused by students to improve their memories - and their IQs. This is what happened when our writer took it for a fortnight ... BYLINE: JOHANN HARI SECTION: A; Pg. 22 LENGTH: 1572 words SOME time in March, in the drizzle, I realised my brain was burned out. Like a rusty engine, I could hear it chug-chug and splutter but it would never quite run at top speed. I had just come back from a month-long worktrip to Bangladesh, and I had an Everest of work in front of me. It was all fascinating and urgent but I was plodding though it at half my normal speed. I needed to be performing at my best; instead, I was at my worst. I stared at the London rain and slogged on. That's when I stumbled across a small story in an American scientific magazine. It said there was a spiky debate across America's universities about the increasing use by students of a drug called modafinil. It was, they said, Viagra for the brain. Originally designed for narcoleptics in the Seventies, clinical trials had uncovered something odd: if you give it to non-narcoleptics, they just become smarter. Their memory and concentration improve, as does their IQ. It's not an amphetamine or a stimulant, the article explained. It doesn't make you high, or wired. It seems to work by restricting the parts of your brain that make you sluggish or sleepy. No significant negative effects have been discovered. Now students are using it in the run-up to exams as a "smart drug" a steroid for the mind. It sounded perfect. A few clicks online and I found I could order it from a foreign pharmacy, for just £30 for a month's supply. I called a friend who is a GP; she'd heard of people using the drug, and went away and looked up the details. "I think it's a stupid thing to do because you shouldn't ever take drugs you don't need," she said when she called back. "Do I think it'll seriously harm you? No, I don't. But you'd be much better off taking a long holiday than narcolepsy pills." Then she warned me: "There is one known side-effect." Oh damn, I thought. A downside. "It often causes people to lose weight." Are you mad? You become cleverer and thinner? I whipped out my Visa card immediately. A week later, the little white pills arrived in the post. I sat down and took one 200mg tablet with a glass of water. It didn't seem odd: for years, I took an antidepressant. Then I pottered about the flat for an hour before sitting down on the settee. I picked up a book about quantum physics and super-string theory I had been meaning to read for ages, for a column I was thinking of writing. Five hours later, I realised I had hit the last page. I looked up. It was getting dark. I was hungry. I hadn't noticed anything, except the words I was reading, and they came in cool, clear passages; I didn't stop or stumble once. PERPLEXED, I got up, made a sandwich and was overcome with the urge to write an article that had been kicking around my subconscious for months. It rushed out of me in a few hours, and was better than usual. My mood wasn't any different; I wasn't high. My heart wasn't beating any faster. I was just able to glide into a state of deep, cool, effortless concentration. It was as if I had opened a window in my brain and all the stuffy air had seeped out, to be replaced by a calm breeze. Once that article was finished, I wanted to do more. I wrote another piece, all of it springing out of my mind effortlessly. Then I went to dinner with friends. At the end, my mate Jess turned to me and said, "You seem very thoughtful tonight." That night, I couldn't sleep. I wasn't restless but I kept thinking very clearly, and I wanted to write it all down. I remembered there's a long history of people in high-pressure jobs using stimulants when their brains lost their sponginess: Anthony Eden was taking Benzedrine all through the Suez Crisis, and Jean-Paul Sartre wrote several of his novels while pumped on mescaline. Admittedly, these precedents aren't encouraging: Eden had a breakdown, and Sartre's brain was so cooked that for the rest of his life, he had the recurring fear he was being followed by a giant lobster. Am I making a stupid mistake? The next morning I woke up and felt immediately alert. Normally it takes a coffee and an hour to kick-start my brain; today I'm ready to go from the second I rise. And so it continues like this, for five days: I inhale books and exhale articles effortlessly. My friends all say I seem more contemplative, less rushed which is odd, because I'm doing more than normal. I keep waiting for an exhausted crash, and it doesn't seem to come. When the American journalist David Plotz took modafinil, he said it should be given a slogan. Just as Valium was marketed as "the housewife's little helper", he said this should be sold as "the boss's little helper". It makes you work better and harder than before. It's hard to explain modafinil's effects beyond that. Normally, one day out of seven I have a day when I'm working at my best I've slept really well, and everything comes easily and fast. modafinil makes every day into that kind of day. It's as if I have been upgraded to a new operating system: Johann 3.0. On discussion boards, I talk to American student doctors taking the drug, who say they feel the same way. "I keep thinking where's the catch?" one says. It turns out it is being given to US soldiers, too. It was then that I noticed I wasn't very hungry. I am normally porcine; my ex once seriously considered having a trough made for me. But on modafinil, I was filled up by a bowl of soup and a piece of bread. I would feel stuffed halfway through my normal meals. A friend howled: "Who are you, and what have you done with the real Johann?" Is all this just the placebo effect: I expect it to do this to me, so it does? Perhaps. But in the clinical trials, it worked much better than the placebo. But then I began to worry again. We don't know the long-term effects of this drug. What if it causes your brain to deplete its resources and wear out? My wonderful grandmother has dementia, her life and personality dissolving in lost memories; no short-term concentration is worth that. A friend says to me, "Why do you always feel like you're not good enough, and you need some kind of chemical enhancement?" It makes me wonder. So after five days on, I decided to take three days off, to see what would happen. It was easy. I sagged back to my former somewhat-depleted state, as though the modafinil had never happened. I worked in my usual stop-start bursts. I ate my usual portions-and-a-half. I stared sadly at the pack of pills, and every time I hit a mental stumbling block, I had to discipline myself not to crack out a modafinil. As soon as my three days were up and I started again, my brain revved back into super-speed and my stomach began to shrivel. But this time I began to worry about the ethics of it all. If this drug had been available during my A-levels or finals, I would have been the first to guzzle it down. But isn't that cheating? What's the difference between modafinil for students and steroids for athletes? And if this drug becomes as popular as, say, antidepressants or Ritalin, won't there be a social pressure for workers to take it, and for parents to drug away their child's disobedience? Professor Anjan Chatterjee says: "This age of cosmetic neurology is coming, and we need to know it's coming." The use of modafinil and its progeny will be mainstream and mainlined in just a few years, he argues, and this made me feel excited and anxious. As the end of my final five days approached, I had to decide what to do. Do I order another pack? Do I think all my thoughts at a faster pace from here on in with the power of modafinil? I finally concluded that taking narcolepsy drugs when you don't have narcolepsy is just stupid. Our lack of knowledge about what it does to your brain was, in the end, a dealbreaker for me. So I have made a pact with myself. I am keeping a pack for the days when I am really knackered and have to work fast and fluently but I won't take more than two or three a month. As I put the tablets aside, I look out over my flat. My desk is piled high with the vast quantities of work I have pumped out. My cupboards are full of uneaten food. The whole place is freakishly clean. Ah, modafinil, you are a gorgeous temptress. With a sad sigh, I close the bathroom cabinet and stumble back to my slow, patchy life, with my slow, patchy brain. ¡ Johann Hari writes for The Independent.. A DOCTOR'S WARNING "MODAFINIL (trade name Provigil) is a brain stimulant drug and the accepted first-line treatment for narcolepsy, a rare condition where the chemical 'switch' that turns sleep on and off is not working properly. Narcoleptics fall asleep in the daytime but also wake frequently at night. "No one knows precisely how modafinil works, not even the company (Cephalon) that developed it. It probably keeps people awake by acting on deep-seated parts of the brain. "Side-effects from modafinil are few although there have been some reports of liver dysfunction. But buying prescription drugs over the internet with no medical control is fraught with hazards. Cognitive ability may be impaired and an untoward event could occur. A case is bound to pop up sooner or later when something awful happens because of someone staying awake too long using stimulants. " Restricted sleep is part of the 24/7 society and there is lots of research beginning to look at the effects on the immune system. But for now the message is 'you mess with these drugs at your peril'." Dr Peter Venn, director of sleep studies at Queen Victoria Hospital, West Sussex.. LOAD-DATE: May 6, 2008 LANGUAGE: ENGLISH GRAPHIC: Cleverer by half: with Progivil, Hari could read fast and absorb ideas effortlessly PUBLICATION-TYPE: Newspaper Copyright 2008 Associated Newspapers Ltd. All Rights Reserved 243 of 998 DOCUMENTS The Pharmaceutical Journal May 2, 2008 Caution in use alert / SPC changes / Prescription products BYLINE: Old_manager LENGTH: 622 words HIGHLIGHT: Prescription Products Meningitec Meningitec (meningococcal serogroup C oligosaccharide conjugate vaccine [adsorbed]; Wyeth) is now available in prefilled syringes. The 10 x 0.5ml vials are no longer available. Childhood immunisation programme supplies are available from Movianto UK on 0870 871 1891. Prescription Products Meningitec Meningitec (meningococcal serogroup C oligosaccharide conjugate vaccine [adsorbed]; Wyeth) is now available in prefilled syringes. The 10 x 0.5ml vials are no longer available. Childhood immunisation programme supplies are available from Movianto UK on 0870 871 1891. Net price: 10 x 0.5ml prefilled syringe, £75 Legal category: POM Pentasa Pentasa 2g sachets (mesalazine prolonged release granules) are now available from Ferring Pharmaceuticals. Net price: 60 x 2g sachets, £72.05 Legal category: POM SPC changes Accessing SPCs The summaries of product characteristics and patient information leaflets for medicines licensed in the UK are available online Corticosteroids The summaries of product characteristics for Medrone (methylprednisolone; Pharmacia) tablets, Solu-Medrone (methylprednisolone sodium succinate; Pharmacia) injections and Solu-Cortef (hydrocortisone sodium succinate; Pharmacia) injection have been updated to include a warning about potential psychiatric side effects occurring with systemic steroids. Hepsera In lamivudine-resistant patients, Hepsera (adefovir dipivoxil; Gilead) should be used in combination with lamivudine, not as monotherapy, to reduce the risk of resistance, the summary of product characteristics for Hepsera now states. It adds: "In order to reduce the risk of resistance in patients receiving adefovir dipivoxil monotherapy, a modification of treatment should be considered if serum HBV DNA remains above 1,000 copies/ml at or beyond one year of treatment." The SPC also warns that resistance to Hepsera can result in viral load rebound, which could result in exacerbation of hepatitis B and, if hepatic function is reduced, lead to liver decompensation and mortality. Virological response should be monitored closely and if viral rebound occurs resistance testing should be performed. Renal failure, Fanconi syndrome, hypophosphatemia, proximal renal tubulopathy and associated myopathy and osteomalacia have been added to the list of undesirable effects (frequency not known) from post-marketing surveillance. Provigil Serious rash requiring admission to hospital and discontinuation of treatment has been reported with the use of Provigil (modafinil; Cephalon), occurring one to five weeks after treatment initiation, the summary of product characteristics for Provigil now states. Isolated cases of serious rash have been reported after prolonged treatment (eg, three months), the SPC adds. It also says that patients with major anxiety should only receive treatment with Provigil in a specialist unit. Psychiatric adverse experiences, including suicidal ideation, have been reported in patients treated with modafinil. In such circumstances, modafinil should be discontinued and not restarted. Caution should be exercised in administering modafinil to patients with a history of psychosis, depression or mania, the SPC says. Sandimmun Patients on Sandimmun (ciclosporin; Novartis) concentrate for infusion should be warned to avoid excess ultraviolet light exposure in view of the potential risk of skin malignancy, the product's summary of product characteristics now says. The SPC also now states that renal function should be monitored with particular care in elderly patients and that caution should be exercised when co-administering lercanidipine with ciclosporin. LOAD-DATE: November 10, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Journal Copyright 2008 PJ Online All Rights Reserved 244 of 998 DOCUMENTS Clinical Psychiatry News May 2008 Options Expanding For Bipolar Disorder BYLINE: Bruce Jancin, Denver Bureau SECTION: Pg. 10 Vol. 36 No. 5 ISSN: 0270-6644 LENGTH: 775 words    VIENNA - A growing list of innovative therapies with novel mechanisms of action in bipolar disorder is available for tough-to-treat cases, Dr. Benedikt L. Amann said at the annual congress of the European College of Neuropsychopharmacology.    All of these candidates have demonstrated promise in open-label or small, controlled, proof-of-concept studies, but they all clearly require larger confirmatory trials. In the interim, psychiatrists are likely to find some of these agents beneficial for off-label use in the many patients with bipolar disorder who respond inadequately to current guideline-directed treatments, said Dr. Amann of the University of Barcelona.    Although he discussed promising new therapies for mania, he gave greater emphasis to progress in the treatment of bipolar depressive episodes because the need is more pressing.    "We do very well with our manic patients on a symptomatic level, but we still do very badly with depressive patients," he observed. Options for Bipolar Depression    The wakefulness drug modafinil (Provigil) improved symptoms of bipolar depression in a recent randomized, placebo-controlled, 85-patient, multicenter study.    All enrollees were inadequately responsive to a mood stabilizer. By week 2, the modafinil-treated group, on a mean dosage of 177 mg/day, showed significantly greater improvement than did controls on the clinician-rated Inventory of Depressive Symptomatology. The remission rate at the end of the 6-week trial was 39% in the modafinil group, compared with 18% with placebo. There was no difference between the two groups in treatment-emergent mania or hypomania (Am. J. Psychiatry 2007;164:1242-9).    In Dr. Amann's 2-year, open-label study of 30 patients with refractory severe bipolar depression, the nutritional supplement chromium was associated with a mean 40% decrease in Montgomery-Åsberg Depression Rating Scale (MADRS) scores (J. Clin. Psychopharmacol. 2007;27:104-6). Like the modafinil trial, the chromium study was funded by the Stanley Medical Research Institute.    In the first double-blind, placebo-controlled trial conducted of a potential treatment for acute bipolar II depression, pramipexole (Mirapex) showed significant benefit, with 60% of patients treated to a target dosage of 1-3 mg/day demonstrating a greater than 50% reduction in MADRS scores after 6 weeks, compared with 9% of those on placebo. One patient on pramipexole and two on placebo developed hypomanic symptoms (Biol. Psychiatry 2004;56:54-60).    Pramipexole, a neurotrophic dopamine agonist with selectivity for the D2 receptor subfamily, is approved by the Food and Drug Administration for the treatment of Parkinson's disease. Results of the 21-patient bipolar depression study, led by investigators at the National Institute of Mental Health, implicate the dopaminergic system in the pathophysiology of bipolar depression. Novel Mania Treatments    What do lithium and valproate share besides an antimanic effect? The two structurally dissimilar agents inhibit protein kinase C, an enzyme which regulates pre- and postsynaptic neurotransmission. So does tamoxifen, the estrogen receptor modifier used by huge numbers of women for primary or secondary prevention of breast cancer. Indeed, tamoxifen is also the only selective protein kinase C inhibitor that crosses the blood-brain barrier.    That insight prompted NIMH investigators to conduct a double-blind, placebo-controlled, 3-week pilot study in 16 bipolar patients with acute mania or a mixed state. The response rates, as assessed by the Young Mania Rating Scale, were 63% with tamoxifen at 20-140 mg/day and 13% for placebo (Bipolar Disord. 2007;9:561-70).    "Protein kinase C will probably become an important enzyme in the future in bipolar disorder," Dr. Amann predicted. "Its activation impairs cognition. ... And inhibitors of protein kinase C in the limbic system appear to be relevant to the treatment of mania."    The atypical antipsychotic zotepine, which is marketed in Europe and elsewhere but not in the United States, showed a rapid therapeutic effect in Dr. Amann's open-label pilot study of 12 patients with severe acute mania. Two patients dropped out after 2 days, but 9 of the remaining 10 were classified as responders, with 5 patients experiencing at least a 50% reduction in the Young Mania Rating Scale score within 4 days (Bipolar Disord. 2005;7:471-6).    With regard to mood stabilizers, he asserted that, despite intensive studies of anticonvulsants and atypical antipsychotics in the last decade, nothing has been shown to be more effective than lithium.    "The real mood stabilizer is waiting to be found," he observed. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: CPNEWS Copyright 2008 Elsevier Inc., International Medical News Group All Rights Reserved 245 of 998 DOCUMENTS Family Practice News May 1, 2008 Modafinil Improves ADHD Symptoms in Different Subtypes BYLINE: Heidi Splete, Senior Writer SECTION: Pg. 29 Vol. 38 No. 9 ISSN: 0300-7073 LENGTH: 568 words    Modafinil significantly improved symptoms in children with inattentive and combined subtypes of attention-deficit/hyperactivity disorder, based on data from 638 children aged 6-17 years.    Pooled results from one 7-week study and two 9-week studies showed that modafinil was well tolerated and improved attention-deficit hyperactivity disorder (ADHD) symptoms both at home and in school. The studies were funded by Cephalon Inc., which markets modafinil as Provigil in the United States.    Dr. Joseph Biederman of Massachusetts General Hospital, Boston, and Dr. Steven R. Pliszka of the University of Texas Health Science Center, San Antonio, reviewed the pooled data to analyze the effectiveness of modafinil on three ADHD subtypes: inattentive, combined, and hyperactive impulsive (J. Pediatr. 2008;152:394-9). Few studies have examined the effectiveness of drug treatments for ADHD by subtype.    In the 7-week study, children were randomized to receive 340 mg or 425 mg of modafinil or a placebo daily. In the 9-week studies, children were randomized to receive a flexible dose from 170 mg to 425 mg or a placebo daily. A total of 423 children received modafinil and 215 received a placebo.    The researchers used the ADHD-RS-IV School Version, which includes teacher and investigator ratings to assess symptoms.    Children in the inattentive and combined subgroups who received modafinil showed significant improvements in the ADHD-RS-IV School Version total scores, compared with placebo patients. Children in the hyperactive-impulsive subgroup who received modafinil showed a greater improvement in total scores (demonstrated by lower numbers) than placebo patients, but this difference was not statistically significant.    The average score for modafinil patients across all subgroups was 57 at the study's end versus 73 for placebo patients. Results were similar for scores on the ADHD-RS-IV Home Version, which were detailed in a separate analysis.    Forty-eight percent of the inattentive subgroup who received modafinil versus 15% of those who were given a placebo received "much improved" or "very much improved" ratings from investigators. Similarly, 44% of the combined subgroup who received modafinil versus 18% of those who received placebo were rated "much improved" or "very much improved" by the investigators.    Children in the inattentive and combined subtype groups who received modafinil showed significant improvements in subscale scores for cognitive problems/inattention, hyperactivity, and the ADHD index, compared with placebo patients.    The combined subtype of ADHD is the most commonly diagnosed and is most often associated with psychiatric comorbidity and other behavioral, social, and academic problems, the researchers noted. A total of 65% of the children met criteria for the combined ADHD subtype, and this group had the largest percentage (18%) of children who were ranked "severely ill" or "extremely ill" at baseline.    Dr. Biederman receives research support from multiple drug companies, including this study's sponsor, Cephalon (for whom he also serves as a speaker and a member of the advisory board). He also serves as a speaker and advisory board member for many other pharmaceutical companies.    Dr. Pliszka receives research support from Cephalon and Eli Lilly & Co., and serves on speakers bureaus sponsored by Shire Pharmaceuticals and McNeil. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: FPNEWS Copyright 2008 Elsevier Inc., International Medical News Group All Rights Reserved 246 of 998 DOCUMENTS US Fed News April 14, 2008 Monday 2:41 AM EST Missouri Inventor Develops Benzhydrylthioacetamide Preparation Process BYLINE: US Fed News LENGTH: 234 words DATELINE: Alexandria, Va. ALEXANDRIA, Va., April 14 -- Sidney Liang of Olivette, Mo., has developed a benzhydrylthioacetamide preparation process. According to the U.S. Patent & Trademark Office: "The present invention is directed to an improved process for preparing modafinil wherein benzhydrylthioacetate is prepared in high yield and purity by the reaction of a haloacetate with the reaction product of thiourea and benzhydrol." An abstract of the invention, released by the Patent Office, said: "The reaction employing the haloacetate is conducted in a solvent comprising an organic solvent such as methanol having dissolved therein an organic base or an inorganic basic salt such as sodium bicarbonate. The resulting benzhydrylthioacetate can be amidated and then oxidized to provide the pharmaceutical grade modafinil in high yield and purity." The inventor was issued U.S. Patent No. 7,345,188 on March 18. The patent has been assigned to Mallinckrodt Inc., Hazelwood, Mo. The original application was filed on Oct. 22, 2004, and is available at: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=% 2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=7,345,188.PN.&OS=PN/7,345,188&RS= PN/7,345,188. For more information about US Fed News federal patent awards please contact: Myron Struck, Managing Editor/US Bureau, US Fed News, Direct: 703/866-4708, Cell: 703/304-1897, Myron@targetednews.com LOAD-DATE: April 14, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2008 HT Media Ltd. All Rights Reserved 247 of 998 DOCUMENTS Irish Independent April 9, 2008 Wednesday Just like Viagra for your brain... SECTION: FEATURES LENGTH: 987 words Professionals use them for jet lag, students to pass exams, soldiers to stay alert. Brain-enhancing drugs are the latest fix -- and they're legal. By Simon Usborne Do you face a mid-afternoon lull that even a double espresso cannot break? Is jetlag the bane of your life, or does that pile of revision seem insurmountable? Or perhaps you're just fed up yawning your way out of the pub at 9.30pm. Whether modern life leaves you struggling to keep up or just totally exhausted, the answer could be as simple as popping a pill. Using drugs to improve performance in sport is nothing new -- expect doping to be a hot topic at this summer's Beijing Olympics -- but what about pills that do nothing to enhance biceps, glutes or abs, and instead target the body's most powerful 'muscle' -- the brain? The idea that pills could boost memory or allow weary workers to put in 24-hour shifts evokes the dystopia of Aldous Huxley's 1932 science-fiction novel Brave New World, in which humanity depends on a government-prescribed "happy" drug called Soma. Some scientists are warning that a generation of artificially enhanced thinkers could soon become science-fact, as an increasing number of people, from stockbrokers and soldiers to students and shelf-stackers, look for something moreeffective than caffeine to boost performance. The medicines they use are called cognitive- or brain-enhancing drugs. But you won't find a dedicated shelf in your local pharmacy. Instead, healthy people are popping prescription pills designed to treat conditions such as attention deficit hyperactivitydisorder (ADHD), narcolepsy or even Alzheimer's. The drugs of choice are Ritalin and Modafinil. Prescribed to ADHD sufferers to help calm them down, Ritalin, dubbed 'kiddie coke' by some, can boost concentration and alertness in healthy people. Modafinil, meanwhile, is designed to combat narcolepsy, but it can also stave off tiredness in those without a diagnosed sleep disorder. A 2005 survey of more than 10,000 US university students found that 4pc-7pc of them had tried ADHD drugs at least once to pull pre-exam all-nighters. At some institutions, more than one in four students said they'd sampled the pills. Anecdotal evidence suggests as many as three in four classical musicians in the US take beta blockers such as Inderal, which block adrenaline receptors in the brain, helping to control conditions such as high blood pressureor stage fright in jitterymusicians. Philip Harvey, a professor at Emory University in Atlanta, says his work has been transformed by Modafinil, which he takes to combat jet lag. Unlike here, American doctors can prescribe the drug to night-shift workers as well as to narcoleptics. "I often fly to Europe to give talks," Harvey says. "I used to travel the day before to give myself time to recover, but with Modafinil I can now give a talk the same day I arrive and feel like I've had a normal night's sleep." Harvey says he has no urge to take the drug more frequently, but many do. And it's easy to understand why. In 2003, scientists at Cambridge University found a single dose of Modafinil helped healthy male university students perform better at mental planning tests, complete puzzles more accurately and remember longer chains of digits. The drug has also been tested by British and American armed forces, where it has been shown to help soldiers stay alert during night-time operations. Scientists say that the drug allows 48 hours of continuous wakefulness with few side effects, mild headaches being the most common. Perhaps the most remarkable thing about Modafinil is that users don't have to pay back sleep 'debt' -- a standard eight hours is apparently enough to make up for no sleep the night before. Such impressive results have led some scientists to predict a world with little or no need for sleep, where drugs will allow us to put in 22-hour days. Little wonder, then, that the drugs companies are reportedly racing to develop the world's first marketed brain-enhancing drugs. If, or when, they do, they could make the launch of the impotence drug Viagra look like a damp squib. "It could change society as we know it," says Barbara Sahakian, a psychiatrist at Cambridge University, who has studied cognitive-enhancing drugs. "The drive for the self-enhancement of brain power is likely to be as strong, if not stronger, as in the realms of enhancement of beauty or sexual function." But that is not necessarily a good thing, Sahakian warns. "One concern I have is the lack of regulation when people buy these drugs on the internet, where they can't be absolutely certain what they are getting, or whether they should be taking them. More seriously, we have to ask how this might affect society. We control drug-use in sport, so will we do the same for students who take drugs before exams, forexample? "And if some students or workers take them, will theothers feel pressure to do the same to keep up? "We also have to ask what this says about us -- why is it that we are always looking for the quickest way around the problem? And why do we so often look to the answer in drugs rather than trying psychological therapies -- or just making more time to sleep?" Whether or not these questions can be answered, brain enhancers look set to challenge caffeine as the pick-me-up of choice in the world's offices, classrooms and war zones. Last year Foresight, a British government think-tank, said drugs such as Modafinil could be "as common as coffee" within a decade or two. That will delight hard-working professionals such as Philip Harvey, who want to improve their work-life balance.But Barbara Sahakian's parting words are cautionary: "One person might say cognitive enhancing drugs are good because they allow us to get home early because we finish our work sooner, but others worry that we are working towards a 24-hours-a-day society pushed to the limits of human endurance." LOAD-DATE: April 9, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2008 Independent News and Media Ltd. All Rights Reserved 248 of 998 DOCUMENTS Reuters Health Medical News April 9, 2008 Wednesday 9:00 PM EST Use of cognition-enhancing drugs common among academics SECTION: HUMAN INTEREST LENGTH: 503 words DATELINE: NEW YORK An informal survey of individuals who read the journal Nature reveals that roughly one in five use prescription agents to improve their focus, concentration, or memory. As reported in the April 10th issue of the journal, 1400 people from 60 countries responded to the online survey. The subjects were asked specifically about the use of three drugs: 1.) methylphenidate (Ritalin), which is used to treat ADHD, but is considered on college campuses as a "study aid"; 2.) modafinil (Provigil), which is prescribed for sleep disorders, but is used off-label to fight general fatigue or jet lag; 3.) beta blockers, anti-arrhythmic agents that are also known for their anti-anxiety effect. Brendan Maher, a feature and commentary editor with Nature, analyzed the results and found that among those "who choose to use," methylphenidate was the most popular agent: 62% of users reported taking it. Modafinil was taken by 44% of users and beta blockers by 15%. Thus, many of the subjects were using more than one agent. When asked about use of other agents, many of the subjects reported taking Adderall, an amphetamine similar to methylphenidate. Other drugs used included centrophenoxine, piractem, Dexedrine, and alternative medicines, including ginkgo and omega-3 fatty acids. Use of cognition-enhancing drugs did not vary by age group, the report indicates. Maher said this may be surprising to some people since prior research has suggested increased usage in 18- to 25-years-olds. Improving concentration was the main reason cited for using these drugs with enhancing focus on a specific task being a close second. Usage patterns were evenly split between daily, weekly, monthly, or no more than once a year. Unpleasant side effects, including headache and jitteriness, among others, were reported by roughly half of users. The emergence of side effects did not correlate with decreased frequency of use, however. Four-fifths of respondents believed that healthy adults should be permitted to take cognition-enhancing agents if they want to and 69% said they would risk mild adverse effects to take the drugs themselves. Eighty-six percent of respondents said that children under 16 years should be restricted from using these drugs, yet one-third of respondents said they would feel pressured to give their child these agents if other children were taking them. In a related commentary, Dr. Barbara Sahakian and Dr. Sharon Morein-Zamir, UK researchers whose 2007 study of cognition-enhancing drug use prompted the current survey, caution that "although the appeal of pharmaceutical cognitive enhancers...is understandable, potential users, both healthy and diseased, must consider the pros and cons of their choices." Drs. Sahakian and Morein-Zamir, neuroscientists with the University of Cambridge, add that "scientists, doctors, and policy-makers should provide easy access to information about the advantages and dangers of using cognitive-enhancing drugs and set out clear guidelines for their future use." LOAD-DATE: April 10, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2008 Reuters Health All Rights Reserved 249 of 998 DOCUMENTS Independent Extra April 8, 2008 Tuesday First Edition Like Viagra for your brain; Professionals use them for jet lag, students to pass exams, soldiers to stay alert. Brain-enhancing drugs are the latest fix - and they're legal. By Simon Usborne BYLINE: Simon Usborne SECTION: EXTRA; Pg. 12 LENGTH: 1014 words Do you face a mid-afternoon lull that even a double espresso cannot break? Is jet lag the bane of your life, or does that pile of revision seem insurmountable? Or perhaps you're just fed up yawning your way out of the pub at 9.30pm. Whether modern life leaves you struggling to keep up or just totally exhausted, the answer could be as simple as popping a pill. Using drugs to improve performance in sport is nothing new - expect doping to be a hot topic at this summer's Beijing Olympics - but what about pills that do nothing to enhance biceps, glutes, or abs, and instead target the body's most powerful "muscle" - the brain? The idea that pills could boost memory or allow weary workers to put in 24-hour shifts evokes the dystopia of Aldous Huxley's 1932 science-fiction novel Brave New World, in which humanity depends on a government-prescribed "happy" drug called Soma. Some scientists are warning that a generation of artificially enhanced thinkers could soon become science-fact, as an increasing number of people, from stockbrokers and soldiers to students and shelf-stackers, look for something more effective than caffeine to boost performance. The medicines they use are called cognitive- or brain-enhancing drugs. But you won't find a dedicated shelf in your local chemist's. Instead, healthy people are popping prescription pills designed to treat conditions such as attention deficit hyperactivity disorder (ADHD), narcolepsy or even Alzheimer's. The drugs of choice are Ritalin and Modafinil. Prescribed to ADHD sufferers to help calm them down, Ritalin, dubbed "kiddie coke" by some, can boost concentration and alertness in healthy people. Modafinil, meanwhile, is designed to combat narcolepsy, but it can also stave off tiredness in those without a diagnosed sleep disorder. The British Medical Association believes this kind of drug abuse is growing rapidly, as healthy pill-poppers dupe doctors into writing prescriptions, or buy medicines from unlicensed online pharmacies, usually based abroad. The true scale of the problem in the UK is unknown but studies in America suggest brain-boosting drug use is rife. A 2005 survey of more than 10,000 US university students found that 4-7 per cent of them had tried ADHD drugs at least once to pull pre-exam all-nighters. At some institutions, more than one in four students said they'd sampled the pills. Anecdotal evidence suggests as many as three in four classical musicians in the US take beta blockers such as Inderal, which block adrenalin receptors in the brain, helping to control conditions such as high blood pressure, or stage fright in jittery musicians. Philip Harvey, a professor at Emory University in Atlanta, says his work has been transformed by Modafinil, which he takes to combat jet lag. Unlike in the UK, American doctors can prescribe the drug to night-shift workers as well as to narcoleptics. "I often fly to Europe to give talks," Harvey says. "I used to travel the day before to give myself time to recover, but with Modafinil I can now give a talk the same day I arrive and feel like I've had a normal night's sleep." Harvey says he has no urge to take the drug more frequently, but many do. And it's not difficult to understand why. In 2003, scientists at Cambridge University found a single dose of Modafinil helped healthy male university students perform better at mental planning tests, complete puzzles more accurately and remember longer chains of digits. The drug has also been tested by British and American armed forces, where it has been shown to help soldiers stay alert during night-time operations. Scientists say that the drug allows 48 hours of continuous wakefulness with few side effects, mild headaches being the most common. Perhaps the most remarkable thing about Modafinil is that users don't have to pay back sleep "debt"; a standard eight hours is apparently enough to make up for no sleep the night before. Such impressive results have led some scientists to predict a world with little or no need for sleep, where drugs will allow us to put in 22-hour days. Little wonder, then, that the drugs companies are reportedly racing to develop the world's first marketed brain- enhancing drugs. If, or when, they do, they could make the launch of the impotence drug Viagra look like a damp squib. "It could change society as we know it," says Barbara Sahakian, a psychiatrist at Cambridge University, who has studied cognitive-enhancing drugs. "The drive for the self-enhancement of brain power is likely to be as strong if not stronger as in the realms of enhancement of beauty or sexual function." But that is not necessarily a good thing, Sahakian warns. "One concern I have is the lack of regulation when people buy these drugs on the internet, where they can't be absolutely certain what they are getting, or whether they should be taking them. More seriously, we have to ask how this might affect society. We control drug use in sport, so will we do the same for students who take drugs before exams, for example? And if some students or workers take them, will the others feel pressure to do the same to keep up? "We also have to ask what this says about us - why is it that we are always looking for the quickest way around the problem? And why do we so often look to the answer in drugs rather than trying psychological therapies - or just making more time to sleep?" Whether or not these questions can be answered, brain enhancers look set to challenge caffeine as the pick-me-up of choice in the world's offices, classrooms and war zones. Last year, Foresight, a Government think tank, said drugs such as Modafinil could be "as common as coffee" within a decade or two. That will delight hard-working professionals like Philip Harvey, who want to improve their work-life balance. But Barbara Sahakian's parting words are cautionary: "One person might say cognitive enhancing drugs are good because they allow us to get home early because we finish our work sooner, but others worry that we are working towards a 24-hours-a-day society pushed to the limits of human endurance." LOAD-DATE: April 8, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: IE Copyright 2008 Independent Print Ltd All Rights Reserved 250 of 998 DOCUMENTS Drug Formulary Review April 1, 2008 Drug Criteria & Outcomes: An Awakening to Narcolepsy LENGTH: 871 words Drug Criteria & Outcomes An Awakening to Narcolepsy By Lori Lawson, PharmD Candidate, Harrison School of Pharmacy, Auburn University Narcolepsy is a chronic neurological disorder, mistakenly thought to occur only rarely. However, approximately 5% of patients seen at the American Academy of Sleep Medicine in the United States have this disease and it is estimated that as many as one in 2,000 Americans have narcolepsy.1,2 Narcolepsy is characterized by uncontrollable sleepiness and intermittent manifestations of REM sleep at periods when a person should normally be awake. Most patients also experience cataplexy, which is partial or generalized loss of skeletal muscle tone and power in response to emotion, especially amusement, anger, and elation. Other common symptoms include: sleep paralysis, hypnagogic hallucinations (vivid, dream-like experiences at the start of sleep), disturbed nocturnal sleep, and automatic behavior.3 This disease has many clinical facets. Sleep attacks can occur at any time and can be very disabling. Patients may involuntarily fall asleep while driving, eating, working, or talking. Hence, this is a dangerous disease that could lead to accidents and loss of employment. Researchers have identified a potential biochemical basis of narcolepsy. In humans, hypocretin, a neurotransmitter, is reduced or undetectable in many but not all patients with narcolepsy associated with cataplexy. Research data on hypocretin continue to be accumulate and in the future hypocretin therapy may be an option. Treatment options Treatment can make a significant difference in these patients' lives. The excessive daytime sleepiness is most commonly treated with stimulants. In 1999, the FDA approved modafinil (Provigil®), a novel stimulant with an unclear mechanism of action that may increase hypocretin activity. Apart from modafinil, all stimulants are centrally acting sympathomimetic agents that increase the release of monoamines in the synaptic cleft and block their reuptake.4 Modafinil is now considered first-line treatment for narcolepsy.2 Modafinil is not a psychostimulant and it does not cause psychomotor agitation, disruption of night-time sleep, inappropriate mood shifts, or the potential for addiction. In June 2007, the FDA approved the active isomer of modafinil, armodafinil (Nuvigil ®), also indicated for narcolepsy. Armodafinil has very similar pharmacokinetics, dosing, and adverse effects as compared to modafinil, and at this time, armodafinil appears to have no clinical advantages over modafinil.5,6 Other stimulants used to treat excessive daytime sleepiness include amphetamine, methamphetamine, dextroamphetmaine, and methylphenidate.1 These drugs can cause insomnia, hypertension, palpitations, and irritability. However, many patients tolerate these drugs without significant side effects. Tolerance to these medications may also occur, necessitating an increase in dose to achieve the same control of symptoms.2 The goal of stimulant therapy is to treat to near normal alertness with minimal adverse effects. Dosages should be started out low and increased as needed and as tolerated. Many physicians are weary of increasing the dose for fear of inducing tolerance or dependence. While tolerance does occur in some patients, abuse is rare in patients who do not have a history.4 Selegiline, a monoamine oxidase inhibitor, is an effective treatment for all narcoleptic symptoms. However, experience with the high doses needed for narcolepsy is limited and diet-induced hypertension is a danger at effective doses.1 Unfortunately, stimulants do not treat cataplexy effectively. Common drug therapies include tricyclic antidepressants such as protriptyline, imipramine, and clomipramine, and selective serotonin reuptake inhibitors such as fluoxetine and paroxetine. Sodium oxybate or gammahydroxybutyrate (GHB) was granted FDA approval in 2002 for the treatment of cataplexy and daytime sleepiness in patients with narcolepsy. It is an old sedative drug with considerable abuse potential, and is available only from one national specialty pharmacy on a named-patient basis. Sodium oxybate is a neurotransmitter found in the brain, and research demonstrates that nightly administration of sodium oxybate helps produce sleep patterns more closely resembling normal sleep patterns.2 Nonpharmacological therapies include maintaining regular sleep and wake times, avoiding shift work, and working in a stimulating environment. It is often said that naps throughout the day are helpful, but objective data are contradictory.1 References · Littner M, Johnson S, McCall V, et al. Practice parameters for the treatment of narcolepsy: An update for 2000. Sleep 2001;24:451-466. · Feldman N. Narcolepsy. South Med J 2003;96:277-282. · Zeman A, Britton T, Douglas N, et al. Narcolepsy and excessive daytime sleepiness. BMJ 2004;329:724-728. · Krahn L, Black J, Silber H. Narcolepsy: New understanding of irresistible sleep. Mayo Clin Proc 2001;76:185-194. · Lexi-Drugs. Hudson, OH: Lexi-Comp, Inc.; 2007. · Harsh J, Hyaduk R, Wesnes K, et al. The efficacy and safety of armodafinil as treatment for adults with excessive sleepiness associated with narcolepsy. Curr Med Res Opin 2006;22:761-774. LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2008 AHC Media LLC All Rights Reserved 251 of 998 DOCUMENTS io9 March 25, 2008 Tuesday 5:28 PM EST Provigil is the Cocaine of the Twenty-First Century [Pharmaceuticals] LENGTH: 367 words Mar. 25, 2008 (io9 delivered by Newstex) -- Provigil (AKA modafinil) has been called a wonder drug: it can keep you awake and alert for hours without side-effects, and it's even recommended as "the professor's little helper" by neuroscience researchers writing in the prestigious journal Nature. Provigil, approved by the US food and drug administration for the treatment of narcolepsy, is often prescribed "off label" for ailments like severe jet lag, ADHD, and even problems with sleep cycles. But this drug, which is supposed to be a non-addictive stimulant because it doesn't get you high, turns out to be potentially as euphoria-inducing and addictive as cocaine. In March 2006, researcher Stefan Kruszewski wrote in The American Journal of Psychiatry: Modanifil is reinforcing, as evidenced by its self-administration in monkeys previously trained to self-administer cocaine. And back in 2002, an article published in Behavioral Pharmacology states: Modafinil and cocaine dose-dependently increased heart rate and blood pressure. The results of the present study suggest that modafinil has minimal abuse potential, but should be viewed cautiously because of the relatively small sample size. Future studies should further characterize the abuse potential of modafinil using other behavioral arrangements, such as drug discrimination or drug self-administration. A full characterization of the abuse potential of modafinil will become important as the use of this drug increases. Other reports suggest that Provigil isn't addictive at all, and would in fact work well as a cure for methamphetamine addiction. Here's a snippet from a 2006 article from Current Psychiatry Reports: In early trials, several candidate medications--bupropion, modafinil, and, to a lesser extent, baclofen--have shown promise in treating aspects of methamphetamine dependence, including aiding memory function necessary to more effectively participate in and benefit from behavioral therapies. With more and more people getting prescriptions for Provigil, and the drug fast catching up with Viagra for most spammy ads online, shouldn't someone be investigating just how addictive it is? Newstex ID: GAWK-0015-24015631 LOAD-DATE: March 25, 2008 LANGUAGE: ENGLISH NOTES: The views expressed on blogs distributed by Newstex and its re-distributors ("Blogs via Newstex") are solely the author's and not necessarily the views of Newstex or its re-distributors. Posts from such authors are provided "AS IS", with no warranties, and confer no rights. The material and information provided in Blogs via Newstex are for general information only and should not, in any respect, be relied on as professional advice. No content on such Blogs via Newstex is "read and approved" before it is posted. Accordingly, neither Newstex nor its re-distributors make any claims, promises or guarantees about the accuracy, completeness, or adequacy of the information contained therein or linked to from such blogs, nor take responsibility for any aspect of such blog content. All content on Blogs via Newstex shall be construed as author-based content and commentary. Accordingly, no warranties or other guarantees will be offered as to the quality of the opinions, commentary or anything else offered on such Blogs via Newstex. Reader's comments reflect their individual opinion and their publication within Blogs via Newstex shall not infer or connote an endorsement by Newstex or its re-distributors of such reader's comments or views. Newstex and its re-distributors expressly reserve the right to delete posts and comments at its and their sole discretion. PUBLICATION-TYPE: Web Blog Copyright 2008 Newstex LLC All Rights Reserved Newstex Web Blogs Copyright 2008 io9 252 of 998 DOCUMENTS World Generic Markets Pharmaceuticals February 22, 2008 FTC files complaint against Cephalon charging unlawful blockage of generic modafinil LENGTH: 327 words The FTC has filed a complaint against Cephalon in the US District Court for the District of Columbia, alleging that the company has undertaken a course of anticompetitive conduct to prevent competition against its proprietary drug, Provigil (modafinil), thus denying patients access to generic equivalents. The complaint challenges the validity of certain agreements entered into by the company in late 2005 and early 2006 to settle modafinil patent infringement litigation; it seeks to permanently enjoin the company from maintaining or enforcing these agreements. According to the complaint, Cephalon entered into agreements with four generic drug manufacturers that each planned to sell a generic version of Provigil: Teva Pharmaceutical Industries, Ranbaxy Laboratories, Mylan Pharmaceuticals and Barr Laboratories. These companies had challenged the only remaining patent covering modafinil, which related to the size of particles used in the product. The complaint charges that Cephalon was able to induce each of the generic companies to abandon its patent challenge and agree to refrain from selling a generic version of the drug until 2012, by agreeing to pay the companies a total amount in excess of $200US million. The FTC is seeking a permanent injunction against Cephalon that would allow generic modafinil entry before 2012. Furthermore, it is seeking a final court judgement against the company, declaring that its course of conduct, including its agreements, violates Section 5(a) of the FTC Act and barring Cephalon from engaging in similar or related conduct in the future. In response, Cephalon has stated that it stands by the strength and validity of its modafinil patents and the legal basis for the settlements; the company clarified that it is prepared to vigorously defend itself in this matter. Modafinil is approved to treat excessive sleepiness in patients with sleep apnoea, narcolepsy and shift-work sleep disorder. 13th February 2008 LOAD-DATE: February 22, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2008 ESPICOM Business Intelligence Ltd. All Rights Reserved 253 of 998 DOCUMENTS The Sun (England) February 21, 2008 Thursday Would you trust a pill to make you smart? BYLINE: Pat Hagan SECTION: SUN HEALTH LENGTH: 1121 words DRUGS WITH DESIGNS ON YOUR MIND FORGET morning caffeine boosts. In future, we could all be popping brain-boosting "smart" pills to give us the edge in school and at work. In fact, thousands of people are already using powerful prescription medicines to sharpen their minds. But experts are warning too little is known about the long-term effects of the new generation of smart pills. Oxford University students swotting through the night for exams confess to downing Ritalin, the drug used to treat hyperactivity in kids. They say it boosts concentration and attention span. Some education experts say they know parents who buy the drug on the internet and feed it to their kids to try to beef up exam results. Meanwhile, pilots, soldiers and shift workers are turning to a pill called modafinil (Provigil) to stay awake. The drug was originally developed to treat narcolepsy, a condition where people suddenly fall asleep dozens of times a day. Tests show that, as well as keeping the brain awake for up to 40 hours at a time, it can actually BOOST short-term memory and the ability to plan properly. Battle Even jet-lagged scientists attending conferences are reported to use the drug to pep up their presentations. Psychiatrist Professor Philip Harvey takes modafinil to ward off jet lag. He says: "It makes me feel alert, like I had more sleep." The medic, from Emory University in Atlanta, Georgia, claims the drug doesn't create a high like other stimulants but does focus the mind. The Ministry of Defence is said to have given it to soldiers exhausted by battle. Other drugs that perk up brain cells include amphetamines and ampakines, a new class of medicines that bolster memory. However, thousands of users are thought to be buying them on the internet without getting clearance from their GPs. The British Medical Association believes a growing number of healthy people are using brain-boosting drugs that should only be taken on prescription, buying stimulants like Ritalin for as little as 67p a pill. Apart from potential long-term side-effects, this raises the risk of dangerous interactions with other medicines. A report last year by Government think-tank Foresight said brain boosters like modafinil could be "as common as coffee" within 20 years. The Government has asked the Academy of Medical Sciences to investigate the use of so-called "intelligence drugs". Professor Barbara Sahakian, from Cambridge University, says if studies prove drugs like modafinil are safe, adults could one day buy them over the counter to help them cope with long hours. That would be safer than buying them from unknown suppliers on the internet. Party She says: "I know scientists who buy modafinil on the internet and take it a few hours before a presentation. But some then start to use it when they are busy. One even took it to stay up late for a party. It may be that one day you could go into Boots and buy these pills. "As we get more effective drugs, people will definitely want to use them. But it may be that you have to be over 16 to get them because we have to be careful about the long-term effects on the developing brain." In the US, research at the University of Michigan shows just over eight per cent of undergraduates have used prescription stimulants. And the National Institute On Drug Abuse found one in twenty 17 and 18-year olds had used amphetamines. But how exactly do "smart pills" increase brain power and what are the risks in taking them? Sun Health investigates, and looks at other mind-boosting solutions. HOW TO BOOST YOUR BRAIN SMART DRUGS Amphetamines: Used for: Little medical use these days, apart from Dexedrine, a drug given to help people with narcolepsy. Affect on brain: Stimulates the brain through increased heart rate, promoting alertness. An estimated 72million amphetamine tablets were issued to British Forces during the Second World War. Side-effects: Long-term use can lead to delusions, panic attacks and paranoia. Ritalin: Used for: Hyper- activity in children. Affect on brain: Increases activity of chemicals in parts of the brain that control attention and behaviour. Studies also show just one pill boosts mental performance in healthy, young male students. Side-effects: Although generally safe, some people can suffer severe liver problems. Cost: About 67p a pill on the internet. Modafinil: Used for: Narcolepsy, the sudden onset of sleep. Affect on brain: Keeps the brain awake for up to 40 hours at a time with high levels of concentration. Side-effects: Very few but can cause dizziness and blurred vision. Cost: About £ 1.43 per pill on the internet. Ampakines: Used for: Experimental drugs that could treat Alzheimer's and jet lag. Affect on brain: They boost the activity of glutamate, a chemical that helps the brain store and retrieve memories. Even a small dose can protect the brain against sleep loss. Side-effects: Not yet known Cost: Not yet available. NATURAL BRAIN BOOSTERS Smart pills may be one way to give your brain cells a lift. But there are other reliable methods that don't rely on a chemical cocktail found in a pill. Fish oils: Oils rich in Omega-3 are thought to aid learning and concentration by keeping nerve connections in the brain healthy. A major trial involving 1,000 young offenders is about to launch in the UK to see if fish oil capsules and other supplements will improve behaviour by bolstering brain activity. Caffeine: Strong coffee and caffeine-rich drinks like Red Bull can give the brain a short-term boost. Israeli scientists found caffeine makes existing brain cells swell and new ones grow. It may also protect the female brain against dementia. French researchers found that women over 65 who drank more than three coffees a day suffered less memory loss. Vitamins: Certain vitamins may be crucial in keeping the brain healthy. Scientists at Johns Hopkins University in the US found taking vitamins C and E together seemed to have the most powerful effect, protecting brain cells against damage by highly destructive molecules called free radicals. Folic acid: A daily dose of folic acid boosts the ageing brain, according to a study last year in The Lancet. Men and women aged 50 to 70 who took daily supplements had similar mental abilities to people five years younger. COMPUTER GAMES Kids who play on computer games before lessons do better in exams. Scottish pupils as young as nine who spent 20 minutes each day on the Nintendo Dr Kawashima Brain Training games made dramatic improvements in maths tests. EXERCISE Children who exercise regularly get better exam results. Exeter University researchers found that 79 per cent of 11-year-olds with better than average English results exercised at least three times a week. Among below average pupils, only 38 per cent exercised. LOAD-DATE: February 21, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2008 NEWS GROUP NEWSPAPERS LTD All Rights Reserved 254 of 998 DOCUMENTS Generic Line February 20, 2008 Wednesday FTC Accuses Cephalon of Buying Off Generic Competition SECTION: Vol. 25 No. 4 LENGTH: 1225 words Cephalon's "anticompetitive conduct" aimed at protecting sales of its top-selling product, which involved paying four firms to refrain from selling generic Provigil until 2012, extended the company's monopoly on the drug beyond the scope of its patent protection and cost patients and payers millions of dollars a year, the FTC alleged in a complaint against the company. But the FTC hasn't filed suit against any of the generic companies involved in the agreements -- Teva Pharmaceuticals, Ranbaxy Pharmaceuticals, Mylan and Barr Laboratories -- because the allegations focus more on the monopolistic actions of Cephalon, rather than the nature of the deals, an FTC staffer told Generic Line. However, FTC Commissioner Jon Leibowitz issued a statement dissenting in part with the 5-0 vote approving the Feb. 13 complaint, saying he would have initiated action against the generic firms as well unless they chose to relinquish their 180-day exclusivity on generic Provigil (modafinil), allowing other companies to receive final approval and launch before 2012. Provigil, originally approved in 1998, is indicated for improving wakefulness in adults who experience excessive sleepiness due to obstructive sleep apnea, shift work sleep disorder or narcolepsy. The drug is unique among wakefulness treatments and is considered the gold standard for treating excessive sleepiness, according to the FTC's complaint, filed in the U.S. District Court for the District of Columbia. Cephalon's recent earnings announcement showed that Provigil had U.S. sales of more than $800 million in 2007. Because Cephalon's compound patent for modafinil expired in 2001, Provigil is only protected by the '516 formulation patent relating to particle size that generic companies could easily design around, the FTC said. In 2002, Teva, Ranbaxy, Mylan and Barr simultaneously submitted abbreviated new drug applications (ANDAs) for generic Provigil with Paragraph IV certifications that the '516 patent was invalid or that their products would not infringe on the patent, which expires in 2015. As first filers, the four companies would share 180-day exclusivity for generic Provigil, and under the Hatch-Waxman Act, the FDA would not be able to approve any other generic versions of the drug until the exclusivity ended. Cephalon filed separate patent infringement suits against the generic drugmakers in 2003, triggering a 30-month stay of approval of the ANDAs. The FTC said in its complaint that Cephalon would likely not have prevailed in litigation against all four companies. However, before the litigation could conclude, Cephalon set about settling with each of the defendants. Cephalon agreed to allow the generic companies to launch their products in April 2012, but the company "had to provide other inducements to the first filers to secure their agreement to refrain from competing," the FTC wrote. The company achieved this by entering into seemingly separate transactions with the generic firms worth more than $200 million total, the agency said. For example, Teva agreed not to launch generic Provigil until April 2012 in exchange for a license agreement relating to Teva's modafinil patents and patent applications worth up to $125 million in Provigil royalties. Cephalon also agreed to buy modafinil active pharmaceutical ingredient from Teva at prices higher than what it was already paying. The FTC alleged that Cephalon did not need the license or supply agreement because it was already successfully making and selling Provigil. Cephalon executed similar deals with the other generic firms. Cephalon said in a statement that the settlement agreements sought to allow generic Provigil entry three years prior to the expiration of the drug's patent protection, but the FTC argued that some or all of the first filers would have launched their generics in 2006 at the end of the 30-month stay or upon a favorable ruling. The agency noted that many parties had expected to see generic Provigil entry in 2006, and Cephalon even made plans to launch an authorized generic and introduce its successor product, Nuvigil (armodafinil). Therefore, the FTC concluded that Cephalon harmed consumers, "abused" the Hatch-Waxman Act and violated the FTC Act. Not only did the agreements eliminate potential competition from the four generic firms involved, they prevented any other generic drugmakers from obtaining approval for and launching generic Provigil. "Cephalon prevented competition to Provigil by agreeing to share its future monopoly profits with generic drugmakers poised to enter the market, in exchange for delayed generic entry," FTC Bureau of Competition Director Jeffrey Schmidt said in a statement. "Such conduct is at the core of what the antitrust laws proscribe." The FTC asked the court to issue a permanent injunction preventing Cephalon from enforcing the settlement agreements or from entering into similar deals in the future. Cephalon said it is "prepared to vigorously defend itself in this matter and expects to prevail." In his statement, Leibowitz said the lawsuit would probably go on for years, and he recommended that Congress act on legislation -- the Preserve Access to Affordable Generics Act, S. 316 and H.R. 1432 -- that would ban settlements involving payments in exchange for delayed generic entry. "Morever, as it is drafting much-needed legislation to create a pathway for generic biologics, Congress should try to ensure that it does not create a loophole that lets pharmaceutical companies conspire to exploit consumers through yet a new avenue of pay-for-delay deals," he wrote. "Sadly, pay-for-delay settlements, if not stopped, will continue to grow exponentially -- costing consumers and the federal government (which pays more than 30 percent of prescription drug costs) literally billions of dollars in excess charges." GPhA does not support the Preserve Access to Affordable Generics Act, and last year after the House Energy and Commerce Committee held a hearing on H.R. 1432, the group asked Congress to continue to allow patent settlement agreements to be reviewed by the FTC on a case-by-case basis. "Limiting a generic company's ability to settle patent disputes would lead to fewer patent challenges and, in the end, delay market entry with a substantial loss in savings for consumers," the group said. Call to Give Up Exclusivity Leibowitz suggested in his statement that Congress ask Teva, Mylan, Ranbaxy and Barr whether they are willing to waive their 180-day exclusivity periods, which he argued have "very little financial value to them when the benefits of waivers to American consumers seem so substantial." He noted that if the companies wait four more years to launch generic Provigil, they will be competing with the drug's successor product, Nuvigil, and even more generics. "So why would a generic company refuse to relinquish its exclusivity when that exclusivity arguable has little value to the generic but creates near iron-clad protection of Cephalon's Provigil monopoly?" he wrote. "Here, the non-relinquishing generics appear to be sending a clear signal to PhRMA companies: You can do business with us in the future; we will protect your monopolies." Teva, Mylan and Ranbaxy said they had no comment on the suit. Barr could not be reached for comment by press time. -- Breda Lund Release date: Feb. 20, 2008 LOAD-DATE: February 20, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2008 Washington Business Information, Inc. All Rights Reserved 255 of 998 DOCUMENTS FDAnews Drug Daily Bulletin February 18, 2008 Monday FTC Accuses Cephalon of Buying Off Generic Competition SECTION: Vol. 5 No. 33 LENGTH: 285 words Cephalon's "anticompetitive conduct" to protect its top-selling product, which involved paying four firms to refrain from selling generic versions of Provigil until 2012, extended the company's monopoly on the drug beyond the scope of its patent protection and cost patients and payers millions of dollars a year, the FTC alleges in a complaint against the company. Provigil (modafinil), originally approved in 1998, is indicated for improving wakefulness in adults who experience excessive sleepiness due to obstructive sleep apnea, shift work sleep disorder or narcolepsy. Because Cephalon's compound patent for modafinil expired in 2001, Provigil is only protected by the '516 formulation patent relating to particle size that generic companies could easily design around, the FTC says. Teva Pharmaceuticals, Ranbaxy Pharmaceuticals, Mylan and Barr Laboratories simultaneously submitted abbreviated new drug applications (ANDAs) for generic Provigil in 2002 with Paragraph IV certifications that the '516 patent was invalid or that their products would not infringe on the patent, which expires in 2015. Cephalon filed separate patent infringement suits against the generic drugmakers in 2003, triggering a 30-month stay of approval of the ANDAs. The FTC says in its complaint that Cephalon would not have prevailed in litigation against all four companies. However, before the litigation could conclude, Cephalon set about settling with each of the defendants. Cephalon agreed to allow the generic companies to launch their products in April 2012, but the company "had to provide other inducements to the first filers to secure their agreement to refrain from competing," the FTC writes. Release date: Feb. 18, 2008 LOAD-DATE: February 15, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2008 Washington Business Information, Inc. All Rights Reserved 256 of 998 DOCUMENTS Washington Drug Letter February 18, 2008 Monday FTC Accuses Cephalon of Buying Off Generic Competition SECTION: Vol. 40 No. 7 LENGTH: 914 words Cephalon's "anticompetitive conduct" to protect its top-selling product, which involved paying four firms to refrain from selling generic versions of Provigil until 2012, extended the company's monopoly on the drug beyond the scope of its patent protection and cost patients and payers millions of dollars a year, the FTC alleges in a complaint against the company. Provigil (modafinil), originally approved in 1998, is indicated for improving wakefulness in adults who experience excessive sleepiness due to obstructive sleep apnea, shift work sleep disorder or narcolepsy. The drug is unique among wakefulness treatments and is considered the gold standard for treating excessive sleepiness, according to the FTC's Feb. 13 complaint, filed in the U.S. District Court for the District of Columbia. Cephalon's recent earnings announcement showed that Provigil had U.S. sales of more than $800 million in 2007. Because Cephalon's compound patent for modafinil expired in 2001, Provigil is only protected by the '516 formulation patent relating to particle size that generic companies could easily design around, the FTC says. In fact, in 2002 Teva Pharmaceuticals, Ranbaxy Pharmaceuticals, Mylan and Barr Laboratories simultaneously submitted abbreviated new drug applications (ANDAs) for generic Provigil with Paragraph IV certifications that the '516 patent was invalid or that their products would not infringe on the patent, which expires in 2015. As first filers, the four companies would have shared 180-day exclusivity for generic Provigil, and under Hatch-Waxman, the FDA would not have been able to approve any other generic versions of the drug until the exclusivity expired. Cephalon filed separate patent infringement suits against the generic drugmakers in 2003, triggering a 30-month stay of approval of the ANDAs. The FTC says in its complaint that Cephalon would not have prevailed in litigation against all four companies. However, before the litigation could conclude, Cephalon set about settling with each of the defendants. Cephalon agreed to allow the generic companies to launch their products in April 2012, but the company "had to provide other inducements to the first filers to secure their agreement to refrain from competing," the FTC writes. Deals Delaying Generic Entry The company achieved this by entering into seemingly separate transactions with the generic firms worth more than $200 million total, the agency says. For example, Teva agreed not to launch generic Provigil until April 2012 in exchange for a license agreement relating to Teva's modafinil patents and patent applications worth up to $125 million in Provigil royalties. Cephalon also agreed to buy modafinil active pharmaceutical ingredient from Teva at prices higher than what it was already paying. The FTC alleges that Cephalon did not need the license or supply agreement because it was already successfully making and selling Provigil. Cephalon executed similar deals with the other generic firms. Cephalon says in a statement that the settlement agreements seek to allow generic Provigil entry three years prior to the expiration of the drug's patent protection, but the FTC argues that some or all of the first filers would have launched their generics in June 2006 at the end of the 30-month stay or upon a favorable ruling. The agency notes that many parties had expected to see generic Provigil entry in 2006, and Cephalon had made plans to launch an authorized generic and introduce its successor product, Nuvigil (armodafinil). Therefore, the FTC concludes that Cephalon harmed consumers, "abused" the Hatch-Waxman Act and violated the FTC Act. Not only did the agreements eliminate potential competition from the four generic firms involved, they prevented any other generic drugmakers from obtaining approval for and launching generic Provigil. "Cephalon prevented competition to Provigil by agreeing to share its future monopoly profits with generic drugmakers poised to enter the market, in exchange for delayed generic entry," FTC Bureau of Competition Director Jeffrey Schmidt says in a statement. "Such conduct is at the core of what the antitrust laws proscribe." The FTC asks the court to issue a permanent injunction preventing Cephalon from enforcing the settlement agreements or from executing similar deals in the future. Cephalon says it is "prepared to vigorously defend itself in this matter and expects to prevail." While the FTC vote approving the complaint was 5-0, Commissioner Jon Leibowitz issued a statement dissenting in part. He says he would have named the generic companies as defendants in the case unless they chose to relinquish their 180-day exclusivity, allowing other companies that have received tentative approval for their generic Provigil ANDAs to receive final approval and launch. He recommends that Congress act on legislation -- the Preserve Access to Affordable Generics Act, S. 316 and H.R. 1432 -- that would ban settlements involving payments in exchange for delayed generic entry. He also suggests that Congress "consider asking these [generic companies] whether they are willing to waive [180-day exclusivity] that arguably has very little financial value to them when the benefits of waivers to American consumers seem so substantial -- and if not, why not." Teva said it had no comment on the status of its agreement with Cephalon. Ranbaxy, Mylan and Barr could not be reached for comment by press time. -- Breda Lund Release date: Feb. 18, 2008 LOAD-DATE: February 15, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2008 Washington Business Information, Inc. All Rights Reserved 257 of 998 DOCUMENTS Drug Industry Daily February 15, 2008 Friday FTC Accuses Cephalon of Buying Off Generic Competition SECTION: Vol. 7 No. 32 LENGTH: 918 words Cephalon's "anticompetitive conduct" to protect its top-selling product, which involved paying four firms to refrain from selling generic versions of Provigil until 2012, extended the company's monopoly on the drug beyond the scope of its patent protection and cost patients and payers millions of dollars a year, the FTC alleges in a complaint against the company. Provigil (modafinil), originally approved in 1998, is indicated for improving wakefulness in adults who experience excessive sleepiness due to obstructive sleep apnea, shift work sleep disorder or narcolepsy. The drug is unique among wakefulness treatments and is considered the gold standard for treating excessive sleepiness, according to the FTC's Feb. 13 complaint, filed in the U.S. District Court for the District of Columbia. Cephalon's recent earnings announcement showed that Provigil had U.S. sales of more than $800 million in 2007. Because Cephalon's compound patent for modafinil expired in 2001, Provigil is only protected by the '516 formulation patent relating to particle size that generic companies could easily design around, the FTC said. In fact, in 2002 Teva Pharmaceuticals, Ranbaxy Pharmaceuticals, Mylan and Barr Laboratories simultaneously submitted abbreviated new drug applications (ANDAs) for generic Provigil with Paragraph IV certifications that the '516 patent was invalid or that their products would not infringe on the patent, which expires in 2015. As first filers, the four companies would have shared 180-day exclusivity for generic Provigil, and under Hatch-Waxman, the FDA would not have been able to approve any other generic versions of the drug until the exclusivity expired. Cephalon filed separate patent infringement suits against the generic drugmakers in 2003, triggering a 30-month stay of approval of the ANDAs. The FTC said in its complaint that Cephalon would not have prevailed in litigation against all four companies. However, before the litigation could conclude, Cephalon set about settling with each of the defendants. Cephalon agreed to allow the generic companies to launch their products in April 2012, but the company "had to provide other inducements to the first filers to secure their agreement to refrain from competing," the FTC wrote. Deals Delaying Generic Entry The company achieved this by entering into seemingly separate transactions with the generic firms worth more than $200 million total, the agency said. For example, Teva agreed not to launch generic Provigil until April 2012 in exchange for a license agreement relating to Teva's modafinil patents and patent applications worth up to $125 million in Provigil royalties. Cephalon also agreed to buy modafinil active pharmaceutical ingredient from Teva at prices higher than what it was already paying. The FTC alleged that Cephalon did not need the license or supply agreement because it was already successfully making and selling Provigil. Cephalon executed similar deals with the other generic firms. Cephalon said in a statement that the settlement agreements seek to allow generic Provigil entry three years prior to the expiration of the drug's patent protection, but the FTC argued that some or all of the first filers would have launched their generics in June 2006 at the end of the 30-month stay or upon a favorable ruling. The agency noted that many parties had expected to see generic Provigil entry in 2006, and Cephalon had made plans to launch an authorized generic and introduce its successor product, Nuvigil (armodafinil). Therefore, the FTC concluded that Cephalon harmed consumers, "abused" the Hatch-Waxman Act and violated the FTC Act. Not only did the agreements eliminate potential competition from the four generic firms involved, they prevented any other generic drugmakers from obtaining approval for and launching generic Provigil. "Cephalon prevented competition to Provigil by agreeing to share its future monopoly profits with generic drugmakers poised to enter the market, in exchange for delayed generic entry," FTC Bureau of Competition Director Jeffrey Schmidt said in a statement. "Such conduct is at the core of what the antitrust laws proscribe." The FTC asked the court to issue a permanent injunction preventing Cephalon from enforcing the settlement agreements or from executing similar deals in the future. Cephalon said it is "prepared to vigorously defend itself in this matter and expects to prevail." Generics Off the Hook While the FTC vote approving the complaint was 5-0, Commissioner Jon Leibowitz issued a statement dissenting in part. He said he would have named the generic companies as defendants in the case unless they chose to relinquish their 180-day exclusivity, allowing other companies that have received tentative approval for their generic Provigil ANDAs to receive final approval and launch. He recommended that Congress act on legislation -- the Preserve Access to Affordable Generics Act, S. 316 and H.R. 1432 -- that would ban settlements involving payments in exchange for delayed generic entry. He also suggested that Congress "consider asking these [generic companies] whether they are willing to waive [180-day exclusivity] that arguably has very little financial value to them when the benefits of waivers to American consumers seem so substantial -- and if not, why not." Teva said it had no comment on the status of its agreement with Cephalon. Ranbaxy, Mylan and Barr could not be reached for comment by press time. -- Breda Lund Release date: Feb. 15, 2008 LOAD-DATE: February 14, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2008 Washington Business Information, Inc. All Rights Reserved 258 of 998 DOCUMENTS Daily Mail (London) February 12, 2008 Tuesday ADHD drug can tackle tinnitus; GOOD HEALTH SECTION: 1ST; Pg. 48 LENGTH: 123 words A DRUG used to treat hyperactivity and sleep disorders is being prescribed to people with tinnitus. Patients with the condition are being given a two-week course of daily modafinil as part of a clinical trial at Arkansas University, in the U.S. Researchers believe that brain activity associated with tinnitus buzzing, whistling, ringing or hissing in the ear can be reduced by the therapy. It may also help with associated insomnia and depression. Modafinil is already being used to treat narcolepsy, an extreme form of daytime sleepiness, and attention deficit hyperactive disorder. How it works on tinnitus is not yet clear, but in narcolepsy it changes the amounts of chemicals in the area of the brain that controls sleep and wakefulness.. LOAD-DATE: February 13, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Papers Copyright 2008 Associated Newspapers Ltd. All Rights Reserved 259 of 998 DOCUMENTS Clinical Psychiatry News February 2008 Modafinil Helps Some Cocaine Dependence BYLINE: Bruce Jancin, Denver Bureau SECTION: Pgs. 40-41 Vol. 36 No. 2 ISSN: 0270-6644 LENGTH: 595 words    VIENNA - Modafinil has now been found to be effective for the treatment of cocaine dependence in two randomized clinical trials, Frank J. Vocci, Ph.D., reported at the annual congress of the European College of Neuropsychopharmacology.    The caveat is that modafinil (Provigil) does not appear to work in individuals who are both cocaine and alcohol dependent, which is a common situation among cocaine users, said Dr. Vocci, director of the division of pharmacotherapies and medical consequences of drug abuse at the National Institute of Mental Health, Bethesda, Md.    Modafinil is approved by the Food and Drug Administration to promote wakefulness in adults who have excessive daytime sleepiness that is associated with sleep apnea/hypopnea syndrome, narcolepsy, or shift work sleep disorder.    The drug has several effects making it of interest as a potential treatment for cocaine dependence, including increases in brain glutamate and gamma amino butyric acid (GABA).    In laboratory studies, modafinil produced clinical effects opposite to those seen in cocaine withdrawal, reduced cocaine self-administration, diminished cocaine-induced euphoria, attenuated the cardiovascular effects of large doses of cocaine, and showed no untoward effects in combination with the drug of abuse. However, "we still don't have any idea how it's working [as a treatment for cocaine dependence] in terms of mechanisms," Dr. Vocci said.    The first clinical trial to demonstrate efficacy was an 8-week, randomized double-blind study involving 62 treatment-seeking cocaine-dependent patients at the University of Pennsylvania. Participants received a single daily morning dose of 400 mg of modafinil or placebo plus twice-weekly manual-guided cognitive-behavioral therapy (CBT).    The primary outcome-the mean proportion of clean urine samples during the 8 weeks-was 42% in the modafinil group and 24% with placebo. Moreover, 33% of the patients in the modafinil arm achieved 3 consecutive weeks of clean urine samples at some point during the study period, compared with 13% of the controls.    There were, however, no significant differences between the two study groups in any secondary outcome measures, including craving scores and patient-reported cocaine use (Neuropsychopharmacology 2005;30:205-11).    In a recently completed, not yet published phase II multicenter double-blind trial, 210 cocaine-dependent patients were randomized to receive modafinil at 200 mg or 400 mg once daily or placebo for 12 weeks. All subjects received manualized CBT once a week. A total of 122 participants completed the study.    The primary outcome measure was the maximum number of consecutive days without cocaine use as determined by urine testing and patient self-report.    The mean maximum was 8.8 days with placebo, 12.6 days with 200 mg/day of modafinil, and 12 days with modafinil at 400 mg daily.    That is a less robust treatment effect than had been seen in the earlier single-center trial. But patients with comorbid alcohol dependence were excluded from that earlier trial while roughly 40% in the larger trial were both cocaine and alcohol dependent.    Upon closer analysis of the multicenter trial data, researchers found a statistically significant benefit for modafinil in reducing cocaine use that was confined to the non-alcohol-dependent subgroup, Dr. Vocci said.    Both trials were funded by the National Institute on Drug Abuse.    Despite several decades of research, there remains no approved pharmacotherapy for cocaine dependence. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: CPNEWS Copyright 2008 Elsevier Inc., International Medical News Group All Rights Reserved 260 of 998 DOCUMENTS The Chronicle of Higher Education January 11, 2008 Friday Mind-Boosting Drugs in the Faculty Lounge Create Controversy BYLINE: RICHARD MONASTERSKY SECTION: THE FACULTY; Pg. 14 Vol. 54 No. 18 LENGTH: 884 words While caffeine reigns as the supreme drug of the professoriate, some university faculty members have started popping "smart" pills to enhance their mental energy and ability to work long hours, according to two University of Cambridge scientists. In a commentary published in the journal Nature last month, Barbara Sahakian and Sharon Morein-Zamir revealed the results of their informal survey of a handful of colleagues who study drugs that help people perform better mentally. Ms. Morein-Zamir said they asked "fewer than 10" colleagues who have done research on cognitive-enhancing drugs, such as Provigil, which is approved in the United States to treat narcolepsy and other severe sleep disorders. "We know that some people, academics -- they could be philosophers or ethicists or people who do neuroscience -- they chose to take some of these drugs," said Ms. Morein-Zamir. But brain boosting raises hackles in some parts of academe. "It smells to me a lot like taking steroids for physical prowess," said Barbara Prudhomme White, an associate professor of occupational therapy at the University of New Hampshire, who has studied the abuse of Ritalin by college students. After recent revelations about the use of performance-enhancing drugs in professional baseball, she sees parallels between athletes and assistant professors. "You're expected to publish and teach, and the stakes are high. So young professors have to work their tails off to get that golden nugget of tenure." The poll was not meant to be a comprehensive study, said Ms. Morein-Zamir, a research associate at Cambridge. Rather, the essay, "Professor's Little Helper," was intended to provoke a public discussion of whether society in general, and universities in particular, should regulate the use of available compounds and medications that might be developed in the future. "If a drug helps you be more alert but also make better decisions, how does society feel about that?" she asked. The colleagues they contacted had not used stimulants such as Ritalin or Adderall but had used Provigil, known generically as modafinil. Although it is approved only to treat sleep-related disorders, there have been hints that modafinil can also improve cognitive performance. In 2003, Ms. Sahakian and colleagues reported that normal subjects performed better on certain types of cognitive tests and felt more alert after taking modafinil, compared with people who had taken a placebo. Soldiers in Iraq, according to reports, have also used the drug. The Thinking Man's Drug When the Cambridge researchers asked their colleagues why they used modafinil, the answers included "to stay awake, to stay focused, to be on the ball, for sustained hard thinking, to stay focused for extended amounts of time," said Ms. Morein-Zamir. One academic in the United States obtained the drug from a primary-care doctor and uses it to combat jet lag. A British researcher, who got modafinil via an Internet site, said he used it fortnightly to enhance productivity and for important intellectual challenges. Although the drug is not approved to treat jet lag, many doctors are apparently willing to prescribe it for that purpose. "I would say it's fairly common, by which I mean that I know several people who use it occasionally for purposes of counteracting jet lag," said Martha J. Farah, a professor of psychology at the University of Pennsylvania. She notes that she has used it herself on two overseas trips. "Many academics do take it for that purpose, often after getting a prescription from their physician." Neuroscientists may be the early adopters in academe because they know more about the drug. And some go beyond using it for jet lag. After Ms. Farah gave a talk on cognitive-enhancing drugs, a graduate student approached her to say that he takes modafinil at the end of each week to finish all his work. The drug enables him to work all night. Ms. Farah said that she was tempted to use the drug regularly, but that she decided against it. "This is a little too good to be true," she said. "I think as society becomes more experienced with these medications, we'll have a better sense of what are their hidden downsides." For example, she notes, cheating the body of sleep suppresses the immune system and impairs brain function. "There's no reason to believe that modafinil is protecting you from these really bad effects." In fact, although cognitive-enhancing drugs have been on the market for decades, it sometimes takes that long for side effects to become apparent. A major study published in August showed that children with ADHD who had taken stimulants grew less than children with ADHD who did not take the drugs. Modafinil is widely regarded as having fewer side effects than stimulants like Ritalin, but the Food and Drug Administration warned doctors in October about some rare but potentially life-threatening conditions associated with the drug: skin rashes, hypersensitivity that can damage organs, and adverse psychiatric reactions. Even with such warnings, the allure of chemicals that confer an advantage may be hard to resist for academics, given the pressures they face. If there were a cognitive-enhancing drug that did not have side effects, said Ms. Prudhomme White, "would I be tempted? Damn right I would. Who wouldn't be?" LOAD-DATE: January 8, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2008 The Chronicle of Higher Education All Rights Reserved 261 of 998 DOCUMENTS The Herald (Glasgow) January 3, 2008 Thursday Final Edition Brain-boosting drugs could soon become the smart choice; SCIENCE NOTEBOOK BYLINE: James Morgan SECTION: FEATURES; Pg. 17 LENGTH: 874 words DURING a quiet moment in the pub over Christmas, a friend of mine leaned over and whispered in my ear. "Do you know where I can get my hands on some smart pills?" Like me, the friend . . . who works for an engineering firm . . . had heard the rumours about modafinil, one of a powerful new breed of brainboosting drugs that enhance concentration, memory and mental aptitude. Medicines which were designed to treat brain injury, dementia and ADHD are now becoming popular pick-me ups. Businessmen take them to beat jet lag, academics pop them to sharpen their minds and shift workers take them to stay alert. Online you can find web chat rooms full of glowing testimonies from users, but as the popularity of smart pills spirals, experts are warning that, with no real knowledge of long-term health risks, users are making themselves guinea pigs. In a recent commentary in the journal Nature, Professor Barbara Sahakian and Dr Sharon Morein-Zamir called for a national debate on "cognitive enhancers" and their potential impact on society. Are smart pills "unfair", they ask, and should we do anything to regulate them? To address their questions, we should begin by looking at currently available cognitive enhancers. Perhaps the nearest thing we have to the ideal "smart pill" is modafinil, a drug designed to treat narcolepsy, which is reportedly being used by businessmen and others to overcome tiredness. "We know that a number of our scientific colleagues in the US and the UK already use modafinil to counteract the effects of jetlag, to enhance productivity or mental energy, or to deal with demanding and important intellectual challenges" says Sahakian. Recent paparazzi shots revealed a packet of a brand of modafinil . . . Provigil . . . in Britney Spears's handbag. Although there are side effects . . . headaches and nausea . . . they appear to be mild. One survey found that as many as 10% of students at American universities are using Ritalin and Adderall . . . ADHD drugs . . . to improve their performance. Ritalin helps hyperactive children to focus on one thing at a time, but when used in otherwise healthy adults it makes them feel more alert and full of energy . . . unsurprising when you find out that the active ingredient is amphetamine. However, its side effects include sleeplessness, loss of appetite and in rare cases, hallucinations. Other so-called smart pills include Aricept (donepezil), an Alzheimer's drug, which studies found could improve the memory of fighter pilots learning new moves on a flight simulator. Finally and potentially the most powerful of all are ampakines, a new untested class of drug designed to boost memory and improve alertness, without giving users the dreaded caffeine shakes. Does that sound tempting? Most of us can imagine a situation at work where we would benefit from a little cognitive enhancement. And is that really such a crime? "People have all sorts of natural advantages . . . some are cleverer, stronger or more beautiful than others, " says Michael Gazzaniga, president of the Cognitive Neuroscience Institute in America. "If we can boost our abilities to make up for the ones Mother Nature didn't give us, what is wrong with that?" After all, as the Nature authors point out: "Most readers would not consider that having a double shot of espresso or a soft drink containing caffeine would confer an unfair advantage at work. [So] does it matter if it is delivered as a pill or a drink?" Indeed, they argue that there are situations in which the use of drugs to improve concentration or planning "may be tolerated, if not encouraged", such as by "airtraffic controllers, surgeons and nurses who work long shifts, airport-security screeners, or by soldiers in active combat". However, they are quick to point out the f lipside. "Universities may have to decide whether to ban drug use altogether, or to tolerate it in some situations . . . whether to enable all-night study sessions or to boost alertness during lectures, " they say. Their biggest concern is for children. The long-term effects of many cognitive enhancers on the developing brains is still unknown. So what form should any regulation take? Should they only be available on prescription? "We believe it would be difficult to stop the spread in use of cognitive enhancers given a global market in pharmaceuticals with increasingly easy online access. They call on scientists, doctors and policymakers to "provide easy access to information about the advantages and dangers of using cognitive-enhancing drugs and set out clear guidelines for their future use." A softer approach is possible, they say, because at present, cognitive enhancers are "relatively safe" and yield "only moderate effects". But, with increasingly sophisticated and even genetically-tailored treatments, truly smart drugs with dangerous large effects on cognition will become feasible. "Fears have been raised of an overworked 24/7 society pushed to the limits of human endurance, or of direct and indirect coercion into taking such drugs, " they say. "If other colleagues at work, or children at your child's school, are taking cognitive-enhancing drugs, will you feel pressure to take them yourself?" For many, this is no longer a theoretical question. LOAD-DATE: January 8, 2008 LANGUAGE: ENGLISH GRAPHIC: CLEVER THINKING: Use of mind enhancing drugs is on the rise. PUBLICATION-TYPE: Newspaper JOURNAL-CODE: GH Copyright 2008 Newsquest Media Group All Rights Reserved 262 of 998 DOCUMENTS Clinical Psychiatry News January 2008 News From The FDA Revised Modafinil Label Cites Psychiatric Risks BYLINE: Elizabeth Mechcatie, Senior Writer SECTION: Pg. 3 Vol. 36 No. 1 ISSN: 0270-6644 LENGTH: 660 words    Warnings about serious rashes-including Stevens-Johnson syndrome and hypersensitivity reactions-as well as psychiatric symptoms have been added to the label of modafinil, according to a MedWatch notice issued by the Food and Drug Administration.    Modafinil, described as a "wakefulness-promoting agent," is marketed as Provigil by Cephalon Inc., and was first approved as a treatment for narcolepsy in 1998. It is approved for improving wakefulness in adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome, and shift-work sleep disorder. It is not approved for any pediatric indications, the advisory emphasizes, although some reports have been in children.    The MedWatch notice and a "Dear Healthcare Professional" letter issued by Cephalon late last year, describe worldwide postmarketing reports of life-threatening rash, including toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) in adults and children. There have also been postmarketing reports of angioedema and multiorgan hypersensitivity reactions.    The reporting rate-which is considered an underestimate, because postmarketing reports of adverse events tend to be underreported-of TEN and Stevens-Johnson syndrome (SJS) associated with modafinil use is higher than the background incidence rate, according to the letter. The background in the general population is estimated at 1-2 million cases per million person-years.    The potential for benign rashes-which have been associated with modafinil use-to develop into serious rashes cannot be reliably predicted, so "modafinil should ordinarily be discontinued at the first sign of rash, unless the rash is clearly not drug-related," the letter says. However, stopping treatment "may not prevent a rash from becoming life-threatening or permanently disabling or disfiguring."    Because of postmarketing reports of angioedema, the letter says that patients should be advised to stop treatment and "immediately report to their physician any signs of symptoms suggesting angioedema or anaphylaxis," which includes swelling of the face, eyes, lips, tongue, or larynx; difficult breathing or swallowing; and hoarseness. There have also been postmarketing reports of multiorgan hypersensitivity reactions, including at least one fatal case, which have occurred "in close temporal association to the initiation of modafinil." Modafinil should be discontinued if such a rash is suspected.    The letter also recommends that discontinuation of the drug should be considered in patients who develop psychiatric symptoms during treatment, because mania, anxiety, hallucinations, and suicidal ideation are among the psychiatric adverse reactions reported in people treated with modafinil. In addition, "caution should be exercised" when the drug is prescribed to patients with a history of psychosis, depression, or mania.    Cephalon had pursued approval of modafinil as a treatment for attention-deficit/hyperactivity disorder in children and adolescents, but in March 2006, the FDA's Psychopharmacologic Drugs Advisory Panel agreed that the drug was not safe for treating children and adolescents, largely because of concerns about its potential to cause SJS in this population. Last summer, Cephalon announced that it had received a "non-approvable" letter from the FDA for this indication and had stopped developing the drug.    The "Dear Healthcare Professional" letter says that in studies, the incidence of rash resulting in discontinuation of the drug in pediatric patients (younger than age 17 years) was 0.8% (13 of 1,585); these cases included one case of possible SJS and one case of what appeared to be a multiorgan hypersensitivity reaction.    Adverse reactions should be reported to the FDA's MedWatch program at 800-332-1088 or www.fda.gov/medwatch. For more information, visit www.fda.gov/medwatch/safety/2007/safety07.htm#Provigil. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: CPNEWS Copyright 2008 Elsevier Inc., International Medical News Group All Rights Reserved 263 of 998 DOCUMENTS The Herald (Glasgow) January 1, 2008 Tuesday Final Edition Brain-boosting drugs could soon become the smart choice; SCIENCE NOTEBOOK BYLINE: James Morgan SECTION: FEATURES; Pg. 17 LENGTH: 874 words DURING a quiet moment in the pub over Christmas, a friend of mine leaned over and whispered in my ear. "Do you know where I can get my hands on some smart pills?" Like me, the friend . . . who works for an engineering firm . . . had heard the rumours about modafinil, one of a powerful new breed of brainboosting drugs that enhance concentration, memory and mental aptitude. Medicines which were designed to treat brain injury, dementia and ADHD are now becoming popular pick-me ups. Businessmen take them to beat jet lag, academics pop them to sharpen their minds and shift workers take them to stay alert. Online you can find web chat rooms full of glowing testimonies from users, but as the popularity of smart pills spirals, experts are warning that, with no real knowledge of long-term health risks, users are making themselves guinea pigs. In a recent commentary in the journal Nature, Professor Barbara Sahakian and Dr Sharon Morein-Zamir called for a national debate on "cognitive enhancers" and their potential impact on society. Are smart pills "unfair", they ask, and should we do anything to regulate them? To address their questions, we should begin by looking at currently available cognitive enhancers. Perhaps the nearest thing we have to the ideal "smart pill" is modafinil, a drug designed to treat narcolepsy, which is reportedly being used by businessmen and others to overcome tiredness. "We know that a number of our scientific colleagues in the US and the UK already use modafinil to counteract the effects of jetlag, to enhance productivity or mental energy, or to deal with demanding and important intellectual challenges" says Sahakian. Recent paparazzi shots revealed a packet of a brand of modafinil . . . Provigil . . . in Britney Spears's handbag. Although there are side effects . . . headaches and nausea . . . they appear to be mild. One survey found that as many as 10% of students at American universities are using Ritalin and Adderall . . . ADHD drugs . . . to improve their performance. Ritalin helps hyperactive children to focus on one thing at a time, but when used in otherwise healthy adults it makes them feel more alert and full of energy . . . unsurprising when you find out that the active ingredient is amphetamine. However, its side effects include sleeplessness, loss of appetite and in rare cases, hallucinations. Other so-called smart pills include Aricept (donepezil), an Alzheimer's drug, which studies found could improve the memory of fighter pilots learning new moves on a flight simulator. Finally and potentially the most powerful of all are ampakines, a new untested class of drug designed to boost memory and improve alertness, without giving users the dreaded caffeine shakes. Does that sound tempting? Most of us can imagine a situation at work where we would benefit from a little cognitive enhancement. And is that really such a crime? "People have all sorts of natural advantages . . . some are cleverer, stronger or more beautiful than others, " says Michael Gazzaniga, president of the Cognitive Neuroscience Institute in America. "If we can boost our abilities to make up for the ones Mother Nature didn't give us, what is wrong with that?" After all, as the Nature authors point out: "Most readers would not consider that having a double shot of espresso or a soft drink containing caffeine would confer an unfair advantage at work. [So] does it matter if it is delivered as a pill or a drink?" Indeed, they argue that there are situations in which the use of drugs to improve concentration or planning "may be tolerated, if not encouraged", such as by "airtraffic controllers, surgeons and nurses who work long shifts, airport-security screeners, or by soldiers in active combat". However, they are quick to point out the f lipside. "Universities may have to decide whether to ban drug use altogether, or to tolerate it in some situations . . . whether to enable all-night study sessions or to boost alertness during lectures, " they say. Their biggest concern is for children. The long-term effects of many cognitive enhancers on the developing brains is still unknown. So what form should any regulation take? Should they only be available on prescription? "We believe it would be difficult to stop the spread in use of cognitive enhancers given a global market in pharmaceuticals with increasingly easy online access. They call on scientists, doctors and policymakers to "provide easy access to information about the advantages and dangers of using cognitive-enhancing drugs and set out clear guidelines for their future use." A softer approach is possible, they say, because at present, cognitive enhancers are "relatively safe" and yield "only moderate effects". But, with increasingly sophisticated and even genetically-tailored treatments, truly smart drugs with dangerous large effects on cognition will become feasible. "Fears have been raised of an overworked 24/7 society pushed to the limits of human endurance, or of direct and indirect coercion into taking such drugs, " they say. "If other colleagues at work, or children at your child's school, are taking cognitive-enhancing drugs, will you feel pressure to take them yourself?" For many, this is no longer a theoretical question. LOAD-DATE: January 4, 2008 LANGUAGE: ENGLISH GRAPHIC: CLEVER THINKING: Use of mind enhancing drugs is on the rise. PUBLICATION-TYPE: Newspaper JOURNAL-CODE: GH Copyright 2008 Newsquest Media Group All Rights Reserved 264 of 998 DOCUMENTS Internal Medicine News January 1, 2008 Postmarket Reports Spur New Modafinil Warnings BYLINE: Elizabeth Mechcatie, Senior Writer SECTION: Pg. 24 Vol. 41 No. 1 ISSN: 1097-8690 LENGTH: 628 words    Warnings about serious rashes-including Stevens-Johnson syndrome and hypersensitivity reactions-as well as psychiatric symptoms have been added to the label of modafinil, according to a MedWatch notice issued by the Food and Drug Administration.    Modafinil, described as a "wakefulness-promoting agent," is marketed as Provigil by Cephalon Inc., and is approved for improving wakefulness in adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome, and shift-work sleep disorder. It is not approved for any pediatric indications, the advisory emphasizes, although some reports have been in children.    The MedWatch notice and a "Dear Healthcare Professional" letter issued by Cephalon describe worldwide postmarketing reports of life-threatening rash, including toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms in adults and children. There have also been reports of angioedema and multiorgan hypersensitivity reactions.    The reporting rate-which is considered an underestimate, because postmarketing reports of adverse events tend to be underreported-of TEN and Stevens-Johnson syndrome (SJS) associated with modafinil use is higher than the background incidence rate, according to the letter. The background in the general population is estimated at 1-2 million cases per million person-years.    The potential for benign rashes-which have been associated with modafinil use-to develop into serious rashes cannot be reliably predicted, so "modafinil should ordinarily be discontinued at the first sign of rash, unless the rash is clearly not drug-related," the letter says. However, stopping treatment "may not prevent a rash from becoming life-threatening or permanently disabling or disfiguring."    Because of postmarketing reports of angioedema, the letter says that patients should be advised to stop treatment and "immediately report to their physician any signs of symptoms suggesting angioedema or anaphylaxis," which includes swelling of the face, eyes, lips, tongue, or larynx; difficulty breathing or swallowing; and hoarseness. There have also been postmarketing reports of multiorgan hypersensitivity reactions, including at least one fatal case, which have occurred "in close temporal association to the initiation of modafinil."    The letter also recommends that discontinuation of the drug should be considered in patients who develop psychiatric symptoms during treatment, because mania, anxiety, hallucinations, and suicidal ideation are among the psychiatric adverse reactions reported in people treated with modafinil. In addition, "caution should be exercised" when the drug is prescribed to patients with as history of psychosis, depression, or mania.    Cephalon had pursued approval of modafinil as a treatment for ADHD in children and adolescents, but in March 2006, the FDA's Psychopharmacologic Drugs Advisory Panel agreed that the drug was not safe for treating children and adolescents, largely because of concerns about its potential to cause SJS in this population. Last summer, Cephalon announced that it had received a "non-approvable" letter from the FDA for this indication and had stopped developing the drug.    The "Dear Healthcare Professional" letter states that in studies, the incidence of rash resulting in discontinuation of the drug in pediatric patients (younger than age 17 years) was 0.8% (13 of 1,585); these cases included one case of possible SJS and one case of what appeared to be a multiorgan hypersensitivity reaction.    Adverse reactions should be reported to the FDA's MedWatch program at 800-332-1088 or www.fda.gov/medwatch. More information is available at www.fda.gov/medwatch/safety/2007/safety07.htm#Provigil. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: IMNEWS Copyright 2008 Elsevier Inc., International Medical News Group All Rights Reserved 265 of 998 DOCUMENTS The Times (London) December 22, 2007, Saturday Can new pills boost brains? BYLINE: Mark henderson SECTION: FEATURES; Body & Soul; Pg. 4 LENGTH: 653 words Ritalin is well known as a treatment for attention deficit hyperactivity disorder, and modafinil is widely prescribed for narcolepsy. These drugs, however, also have a more controversial application. They are the first wave of "cognitive enhancers", which can not only treat brain conditions but improve healthy people's mental capabilities as well. Modafinil, for example, can improve alertness, accuracy and short-term memory. It is reportedly used by the US military to assist concentration, and it is widely used in academia. Barbara Sahakian and Sharon Morein-Zamir, of the University of Cambridge, write in this week's Nature that colleagues use it freely to counter jet lag or to enhance productivity. There is also anecdotal evidence that modafinil and Ritalin are popular with students, replacing coffee and ProPlus pills as essay-crisis aids. The idea of cognitive enhancement makes people uneasy. Some critics liken it to the use of drugs in sport and consider it a form of academic cheating. Most of these drugs are fairly new and there's only limited evidence that long-term use is safe. Another common objection is that "brain doping" amounts to buying intelligence, and could widen the gap between haves and have-nots. The better off already have academic advantages, and the benefits of cognitive enhancement could be limited to those who can afford them. The left-leaning think-tank Demos has suggested that universities back a ban with testing, to secure equal-opportunity brain chemistry. Neither argument, however, is entirely convincing. Chemical stimulation has long been a part of higher education: the difference between modafinil and espresso is one of degree. The doping analogy falls down because the drugs lack the known serious side-effects of steroids: Ritalin, for example, has been taken safely by millions of children. Cognitive enhancers also improve concentration and alertness only for a transient period: they do not influence underlying ability or diligence. A poor student will be no cleverer on Ritalin, just better equipped to pull an all-nighter. He'll not suddenly understand concepts he'd failed to grasp before. Intellect and hard work will still be rewarded. As for cost, while it is permitted for a child's parents to spend £ 20,000 a year on private school fees, it's hard to object to pills that cost no more than a Starbucks latte. There is some merit in the view that individual liberty trumps concern, and that adults should be allowed to decide for themselves what to put into their bodies. It is also unlikely that prohibition would work. Cognitive enhancers are now available very cheaply online and it would take international legislation to control supply. A British Medical Association report last month found that increasing use was "imminent and inevitable", and a government report has predicted they will become "as common as coffee". Experience with drugs such as cannabis and Ecstasy has shown that bans do not necessarily affect demand. Cognitive enhancers seem to have greater benefits and fewer risks, and some people are going to want them. Sahakian and Morein-Zamir, indeed, argue that a ban could be counterproductive as well as pointless. One of the biggest dangers of these drugs is interactions with other medications, and they make a sound case that it would be better for GPs to supervise access than to leave the market to the internet. That way, people will at least be reliably informed about safety evidence before they take a decision. It is welcome that society is starting to consider this issue. The debate, though, should start from the premise that cognitive enhancers are already with us and here to stay. Even if attempting to hold them back would be desirable, which is far from clear, it would probably be futile. It will be far more fruitful to think about how best to manage their implications. Mark Henderson is Science Editor of The Times LOAD-DATE: December 22, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2007 Times Newspapers Limited All Rights Reserved 266 of 998 DOCUMENTS Hindustan Times December 2, 2007 Sunday 11:36 AM EST Drugs for sleep disorder also helps ice addicts BYLINE: Report from Asian News International brought to you by HT Syndication. LENGTH: 377 words DATELINE: Sydney Sydney, Dec. 2 -- A research has revealed that the medication used for the treatment of sleep disorders could help ice addicts cut their drug use to half. The study, led by James Shearer from the National Drug and Alcohol Research Centre at the University of NSW, followed 80 heavy users of crystal methamphetamine over 10 weeks and found a daily dose of modafinil, marketed as Modavigil in Australia, significantly reduced their cravings for ice, saving each user about 500 dollars a month. Modafinil prevents nerve cells from re-absorbing dopamine once they release it into the brain but does not cause the dramatic highs and lows associated with most stimulants. It is not water-soluble and is destroyed at high temperatures so cannot be injected or smoked, reducing the chances of it being abused, and is not addictive. James said the users, who all either injected or smoked ice at least 20 days a month and spent about 100 dollars a day on the drug, were given one tablet of modafinil a day or a placebo. About 12 weeks after the trial, those who had been given modafinil were using ice about eight days in every 28, compared to the placebo group who were using an average of 13.5 days. After 22 weeks, those on modafinil were using 11 days a month, and the placebo group 16 days. "Six months after the trial, we still have better outcomes," the Sydney Morning Herald quoted Shearer, as saying. He added: "It is the first medication to show a demonstrable positive effect in heavy methamphetamine users and represents a major medical breakthrough in Australia. "Modafinil doesn't give them that euphoric feeling, but it does give them a bit of get up and go." He said that like methadone, it would not be used as a maintenance drug, but could be given to people in conjunction with extensive counselling and support. The use of crystal methamphetamine has decreased in recent months for the first time in a decade, which experts have attributed to the drug's negative effects. Ice use has been associated with a steady rise in psychosis cases and deaths in recent years. The study's findings were presented at the World Psychiatric Association Congress in Melbourne. Published by HT Syndication with permission from Asian News International. LOAD-DATE: December 2, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2007 HT Media Ltd. All Rights Reserved 267 of 998 DOCUMENTS ABC Premium News (Australia) December 1, 2007 Saturday 1:44 PM AEST Sleep medicine 'can help ice addicts quit' BYLINE: Michael Turtle LENGTH: 444 words Australian researchers say they have discovered a way to rehabilitate people addicted to the drug 'ice'. In what they call a world first, researchers from the National Drug and Alcohol Research Centre say they have discovered that Modafinil, a medication currently used to treat sleep disorders, can help ice addicts quit. The discovery of Modafinil's potential for fighting ice addiction comes after much media attention on what some experts say is an ice epidemic. The latest national figures show that as many as 70,000 people use ice - otherwise known as crystal methamphetamine hydrochloride. Researcher James Shearer explains how ice affects the brain. "What ice, or crystal, does is it actually hooks into your reward system in the brain, and the reward system is designed so that you can recognise positive stimuli, remember them, act on them," he said. "But by overdoing it, by chronic use, you end up with a depletion of these neurotransmitters." He says Modafinil is normally used to treat sleeping problems like narcolepsy or shift work sleep disorder, and acts on the same parts of the brain as ice does. "Modafinil actually works in those parts of the brain to kind of restore areas of those neurotransmitters," he said. "So that's what we think kind of reinforces the addiction in people, because they've got this neurotransmitter imbalance, as soon as they stop using ice, or crystal, they go into withdrawal. "So what we're hoping, by using Modafinil, is that they will be able to resist those kind of relapse situations." What this means is that Modafinil does not necessarily stop someone wanting to use ice, but will help people who want to stop using it. "As with all dependence - whether it's tobacco, alcohol, anything - you do need the person themselves to be quite committed to making changes, because otherwise these drugs don't work at all," he said. "So it's really a supportive drug for someone who's making an effort to quit." Mr Shearer says the finding is ground-breaking. "This drug has been tested in the [United] States with cocaine, with very good results," he said. "What we've found in this study is we've exactly replicated those results from the US, because cocaine, methamphetamine, they're all stimulants and they actually do work in the same way in the brain." "So we're all very excited and, frankly, relieved that we've actually found a drug which helps." The researchers now plan to do a larger study to confirm their results. If Modafinil begins to be used in the general community, it could be prescribed by doctors, rather than drug clinics. That's because, unlike something like methadone, it would not be classed as a drug of addiction. LOAD-DATE: December 1, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2007 Australian Broadcasting Corporation All Rights Reserved 268 of 998 DOCUMENTS ABC Transcripts (Australia) December 1, 2007 Saturday 8:15 AM AEST SHOW: AM 8:15 AM AEST ABC Sleep disorder medication may rehabilitate 'ice' addicts REPORTERS: Michael Turtle LENGTH: 490 words ELIZABETH JACKSON: Australian researchers say they've discovered a way to rehabilitate addicts of the drug 'ice'. In what they call a world-first, the scientists say they've discovered a medication, which already exists and is used to treat sleep disorders, can help addicts quit. Michael Turtle reports. MICHAEL TURTLE: There's been much said in the media in the last year or so about the increase in the use of crystal methamphetamine, or ice. The latest figures show there could up to 70,000 users in Australia, and some experts even say that the nation is in the grip of 'an ice epidemic'. But now researchers from the National Drug and Alcohol Research Centre believe they've found a medication that will help in battling the scourge. The drug is called Modafinil and is normally used to treat sleeping problems like narcolepsy or shift work sleep disorder. Researcher James Shearer explains how it works: JAMES SHEARER: What ice, or crystal, does is it actually hooks into your reward system in the brain, and the reward system is designed so that you can recognise positive stimuli, remember them, act on them. But by overdoing it, by chronic use, you end up with a depletion of these neurotransmitters. So this drug, Modafinil, actually works in those parts of the brain to kind of restore areas of those neurotransmitters. So that's what we think kind of reinforces the addiction in people, because they've got this neurotransmitter imbalance, as soon as they stop using ice, or crystal, they go into withdrawal. So what we're hoping, by using Modafinil, is that they will be able to resist those kind of relapse situations. MICHAEL TURTLE: So it doesn't necessarily stop someone wanting to use ice, but for people who want to stop using it, it will help them. JAMES SHEARER: Absolutely. Absolutely. As with all dependence, whether it's tobacco, alcohol, anything, you do need the person themselves to be quite committed to making changes, because otherwise these drugs don't work at all. So it's really a supportive drug for someone who's making an effort to quit. MICHAEL TURTLE: And is this quite ground-breaking? Have we seen this kind of treatment for ice before? JAMES SHEARER: Ah, this is ground-breaking in terms of ice. This drug has been tested in the States with cocaine, with very good results. What we've found in this study is we've exactly replicated those results from the US, because cocaine, methamphetamine, they're all stimulants and they actually do work in the same way in the brain. So we're all very excited and, frankly, relieved that we've actually found a drug which helps. MICHAEL TURTLE: The researchers now plan to do a larger study to confirm their results, and if Modafinil started to be used in the general community, it could be prescribed by doctors, rather than drug clinics. That's because, unlike something like methadone, it wouldn't be classed as a drug of addiction. ELIZABETH JACKSON: Michael Turtle reporting. LOAD-DATE: December 1, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Transcript Copyright 2007 Australian Broadcasting Corporation All Rights Reserved 269 of 998 DOCUMENTS Geelong Advertiser (Australia) December 1, 2007 Saturday Drug helps addicts break the ice habit SECTION: NEWS; Pg. 40 LENGTH: 200 words A DRUG that keeps narcoleptics awake and another that controls hyperactive kids have been found to help Australian ice addicts kick their dangerous habit. Fresh findings from two Australian drug trials have delivered new hope that much-needed medications to treat crystal methamphetamine addiction are on the horizon. One world-first study by Sydney researchers found that the drug modafinil, used to treat excessive sleepiness and fatigue, could help quash cravings in the heaviest ice users. Another medication, dexamphetamine, used widely to treat ADHD, was found by Adelaide scientists to help wean users off the stimulant. There is no treatment available for the 73,000 Australians addicted to methamphetamines, renowned for causing extreme violence and psychosis. The Sydney-based National Drug and Alcohol Research Centre presented the findings from its modafinil study at the World Psychiatry Association conference in Melbourne, with researchers labelling the effects ''dramatic''. More than 80 users took either modafinil or a dummy medication daily for 10 weeks. Those who received modafinil cut their methamphetamine use by more than half, significantly better than those who received the placebo. LOAD-DATE: December 3, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: GAT Copyright 2007 Nationwide News Pty Limited All Rights Reserved 270 of 998 DOCUMENTS Skin & Allergy News December 2007 Modafinil: Rash Warning Is Issued by FDA, Manufacturer BYLINE: Elizabeth Mechcatie, Senior Writer SECTION: Pg. 8 Vol. 38 No. 12 ISSN: 0037-6337 LENGTH: 604 words    Warnings about serious rashes-including Stevens-Johnson syndrome and hypersensitivity reactions-as well as psychiatric symptoms have been added to the label of modafinil, according to a MedWatch notice issued by the Food and Drug Administration.    Modafinil, described as a "wakefulness-promoting agent," is marketed as Provigil by Cephalon Inc., and was first approved as a treatment for narcolepsy in 1998.    It is approved for improving wakefulness in adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome, and shift-work sleep disorder. It is not approved for any pediatric indications, the advisory emphasizes, although some reports have been in children.    The MedWatch notice and a "Dear Healthcare Professional" letter issued by Cephalon describe worldwide postmarketing reports of life-threatening rash, including toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) in adults and children.    There have also been postmarketing reports of angioedema and multiorgan hypersensitivity reactions.    The reporting rate of TEN and Stevens-Johnson syndrome (SJS) associated with modafinil use is higher than the background incidence rate, according to the letter.    The background in the general population is estimated at 1-2 million cases per million person-years.    The potential for benign rashes-which have been associated with modafinil use-to develop into serious rashes cannot be reliably predicted, so "modafinil should ordinarily be discontinued at the first sign of rash, unless the rash is clearly not drug-related," the letter says.    However, stopping treatment "may not prevent a rash from becoming life-threatening or permanently disabling or disfiguring."    Because of postmarketing reports of angioedema, the letter says that patients should be advised to stop treatment and "immediately report to their physician any signs of symptoms suggesting angioedema or anaphylaxis," which includes swelling of the face, eyes, lips, tongue, or larynx; difficult breathing or swallowing; and hoarseness. There have also been postmarketing reports of multiorgan hypersensitivity reactions, including at least one fatal case, which have occurred "in close temporal association to the initiation of modafinil." Modafinil should be discontinued if such a rash is suspected.    The letter also recommends that discontinuation of the drug should be considered in patients who develop psychiatric symptoms during treatment, because mania, anxiety, hallucinations, and suicidal ideation are among the psychiatric adverse reactions reported in people treated with modafinil. In addition, "caution should be exercised" when the drug is prescribed to patients with a history of psychosis, depression, or mania.    Cephalon had pursued approval of modafinil as a treatment for attention-deficit/hyperactivity disorder in children and adolescents, but in March 2006, the FDA's Psychopharmacologic Drugs Advisory Panel agreed that the drug was not safe for treating children and adolescents, largely because of concerns about its potential to cause SJS in this population. Last summer, Cephalon announced that it had received a "non-approvable" letter from the FDA for this indication and had stopped developing the drug.    The "Dear Healthcare Professional" letter says that in studies, the incidence of rash resulting in discontinuation of the drug in pediatric patients (younger than age 17 years) was 0.8% (13 of 1,585).    More information is available at http://www.fda.gov/medwatch/safety/2007/safety07.htm#Provigil. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: SANEWS Copyright 2007 Elsevier Inc., International Medical News Group All Rights Reserved 271 of 998 DOCUMENTS Sydney Morning Herald (Australia) December 1, 2007 Saturday First Edition Sleep drug can halve ice addicts' cravings; STUDY BYLINE: Kate Benson Medical Reporter SECTION: NEWS AND FEATURES; Pg. 12 LENGTH: 345 words A MEDICATION used to treat sleep disorders has helped ice addicts cut their drug use in half, researchers say. The Sydney study followed 80 heavy users of crystal methamphetamine over 10 weeks and found a daily dose of modafinil, marketed as Modavigil in Australia, significantly reduced their cravings for ice, saving each user about $500 a month. Modafinil prevents nerve cells from re-absorbing dopamine once they release it into the brain but does not cause the dramatic highs and lows associated with most stimulants. It is not water-soluble and is destroyed at high temperatures so cannot be injected or smoked, reducing the chances of it being abused, and is not addictive. The study's author, James Shearer from the National Drug and Alcohol Research Centre at the University of NSW, said the users, who all either injected or smoked ice at least 20 days a month and spent about $100 a day on the drug, were given one tablet of modafinil a day or a placebo. About 12 weeks after the trial, those who had been given modafinil were using ice about eight days in every 28, compared to the placebo group who were using an average of 13.5 days. At 22 weeks, those on modafinil were using 11 days a month, and the placebo group 16 days. "Six months after the trial, we still have better outcomes," Mr Shearer said. "It is the first medication to show a demonstrable positive effect in heavy methamphetamine users and represents a major medical breakthrough in Australia. "Modafinil doesn't give them that euphoric feeling, but it does give them a bit of get up and go." It would not be used as a maintenance drug, like methadone, but could be given to people in conjunction with extensive counselling and support, he said. The use of crystal methamphetamine has dropped in recent months for the first time in a decade, which experts have attributed to the drug's negative effects. Ice use has been associated with a steady rise in psychosis cases and deaths in recent years. The study's findings were presented yesterday at the World Psychiatric Association Congress in Melbourne. LOAD-DATE: November 30, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2007 John Fairfax Publications Pty Ltd All Rights Reserved 272 of 998 DOCUMENTS Weekend Australian December 1, 2007 Saturday All-round Country Edition Drug 'aids addicts to quit ice' BYLINE: Adam Cresswell, Health editor SECTION: LOCAL; Pg. 3 LENGTH: 343 words USERS of methamphetamine could get a new treatment to help them quit the drug after a world-first Australian study showed a medicine already on the shelves helped addicts cut their use by more than 50 per cent. The drug modafinil, used to treat sleep disorders, has been shown to help treat cocaine addiction in the US. Now a federally funded Australian trial has shown it could be a new treatment for methamphetamine addiction, by helping users overcome their craving. Experts welcomed the findings, saying doctors had few options to help people hooked on methamphetamine, also known as ice. Researchers from the National Drug and Alcohol Research Centre recruited 80 methamphetamine users trying to stop their habit and divided them into two groups. All participants had used methamphetamine on an average of 20 days in the previous 28 days. One group received a daily dose of modafinil, while the other received a dummy pill. For the duration of the 10-week trial, neither patients nor treating doctors knew which patients were receiving the real pills. Those receiving modafinil cut their use of methamphetamine from the average of 20 days at the start of the trial to eight days. Those in the placebo group only cut their usage to an average of 14 days in the previous 28. No serious side-effects were reported. Researcher James Shearer, a PhD student at the centre, presented the results yesterday at the World Psychiatric Association congress in Melbourne. Mr Shearer said the drug was best thought of as similar to the anti-smoking drug Zyban, which helps to kill the cravings and withdrawal symptoms while a smoker is trying to quit. It was believed to work by boosting the activity of the frontal cortex, which helps users overcome the poor impulse control seen in ice addicts. ''You still need commitment to change a lot of things -- where you live, who you hang around with -- and it's only a short-term thing,'' Mr Shearer said. ''What we now need is national trials to conclude that the drug does work and should be on the Pharmaceutical Benefits Scheme.'' LOAD-DATE: November 30, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: AUS Copyright 2007 Nationwide News Pty Limited All Rights Reserved 273 of 998 DOCUMENTS Weekend Australian December 1, 2007 Saturday All-round First Edition Sleep drug 'helps addicts to give up ice' BYLINE: Adam Cresswell SECTION: LOCAL; Pg. 11 LENGTH: 251 words USERS of methamphetamine could get a new treatment to help them quit the drug after a world-first Australian study showed a medicine already on the shelves helped addicts cut their use by more than 50 per cent. The drug modafinil, used to treat sleep disorders, has been shown to help treat cocaine addiction in the US. Now a federally funded Australian trial has shown it could be a new treatment for methamphetamine addiction, by helping users overcome their craving. Experts welcomed the findings, saying doctors had few options to help people hooked on methamphetamine, also known as ice. Researchers from the National Drug and Alcohol Research Centre recruited 80 ice users trying to stop their habit and divided them into two groups. All participants had used the drug on an average of 20 days in the previous 28 days. One group received a daily dose of modafinil, while the other received a dummy pill. During the 10-week trial, neither patients nor doctors knew which patients were receiving the real pills. Those receiving modafinil cut their use of ice from the average of 20 days at the start of the trial to eight days. Those in the placebo group only cut their usage to an average of 14 days in the previous 28. No serious side effects were reported. Presenting the results at the World Psychiatric Association congress in Melbourne yesterday, researcher James Shearer, a PhD student at the centre, said the drug was like the anti-smoking drug Zyban, which helps kill cravings and withdrawal symptoms. LOAD-DATE: December 1, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: AUS Copyright 2007 Nationwide News Pty Limited All Rights Reserved 274 of 998 DOCUMENTS AAP Newsfeed November 30, 2007 Friday 12:22 PM AEST Fed: Sleepiness drug helps ice addicts break their habit: study BYLINE: Tamara McLean, Medical Writer SECTION: DOMESTIC NEWS LENGTH: 478 words DATELINE: MELBOURNE Nov 30   A drug that keeps narcoleptics awake and another that controls hyperactive kids have been found to help Australian ice addicts kick their dangerous habit, studies show.    Fresh findings from two Australian drug trials have delivered new hope that much-needed medications to treat crystal methamphetamine addiction are on the horizon.    One world-first study by Sydney researchers found that the drug modafinil, used to treat excessive sleepiness and fatigue, could help quash cravings in the heaviest ice users.    Another medication, dexamphetamine, used widely to treat ADHD in Australian children, was found by Adelaide scientists to help wean users off the stimulant.    Currently, there is no medical treatment available for the 73,000 Australians addicted to methamphetamines, renowned for causing extreme violence and psychosis. Treating physicians have been calling out for medications to relieve the addiction.    The Sydney-based National Drug and Alcohol Research Centre (NDARC) presented the latest findings from its modafinil study at the World Psychiatry Association (WPA) conference in Melbourne, with researchers labelling the effects "dramatic".    More than 80 dependent methamphetamine users took either modafinil or a dummy medication daily for 10 weeks. Those who received modafinil cut their methamphetamine use by more than half, significantly better than those who received the placebo.    "It has a brilliant effect on a third, a slight effect on another third and no effect at all on the last group," said researcher James Shearer, a PhD student at NDARC.    "That's very significant, given we've never seen results like this with ice."    The drug also appeared to be non-addictive and safe, with no serious side effects.    It works by restoring the levels of neurotransmitters or chemicals in the brain that may be depleted after heavy or long-term methamphetamine use, Mr Shearer said.    Users withdrawing from ice can take modafinil instead, giving them a non-amphetamine coffee-like high that still allows them to concentrate.    "Just getting up in the morning and trying to to do any of the normal things in life without ice was near impossible for these people, but the modafinil is really helping them," Mr Shearer said.    The team is currently seeking a larger clinic trial to verify their findings.    Preliminary results from the dexamphetamine trial were also reported to the congress today, with researcher Professor Jason White from the University of Adelaide saying they looked promising.    Dexamphetamine, which works as a methadone-like drug substitute, led to a decrease in methamphetamine use among 87 per cent of the addicts who took it. This compared to 70 per cent of those on a placebo.    However, the studies were not definitive, and drug approval processes could mean the treatment would not be available for several years. LOAD-DATE: November 30, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2007 Australian Associated Press Pty. Ltd. 275 of 998 DOCUMENTS Mental Health Update November 27, 2007 Tuesday 5:51 AM EST Modafinil for schizophrenia BYLINE: John Gale LENGTH: 234 words Nov. 27, 2007 (Mental Health Update delivered by Newstex) -- Schizophrenia is considered the most important cause of chronic psychiatric disability. In recent years the cognitive and motivational impairment seen in schizophrenia have been determined to be one of the main causes of the profound and persistent disability typically produced by the disorder. Although the psychotic symptoms of schizophrenia may improve following treatment a range of cognitive deficits will often persist and the disability resulting from them has recently been considered to have a greater impact on long-term functioning than delusions and hallucinations. Recently a drug called modafinil has emerged as a possible drug to improve cognition in schizophrenia. It was initially prescribed to reduce the fatigue and sedation induced by antipsychotic medication but a review of studies into the drug shows that it may lead to better executive functioning and attention performance in patients with schizophrenia. The drugs effectiveness is affected by the patients' current levels of cognitive functioning, genetic make-up and the other drugs that they are taking at the time allowing for future treatment to be targeted at those most likely to Morein-Zamir, Sharon, Turner, Danielle C. and Sahakian, Barbara J. - A review of the effects of modafinil on cognition in schizophrenia Schizophrenia Bulletin November 2007, 33(6), LOAD-DATE: November 27, 2007 LANGUAGE: ENGLISH NOTES: The views expressed on blogs distributed by Newstex and its re-distributors ("Blogs via Newstex") are solely the author's and not necessarily the views of Newstex or its re-distributors. Posts from such authors are provided "AS IS", with no warranties, and confer no rights. The material and information provided in Blogs via Newstex are for general information only and should not, in any respect, be relied on as professional advice. No content on such Blogs via Newstex is "read and approved" before it is posted. Accordingly, neither Newstex nor its re-distributors make any claims, promises or guarantees about the accuracy, completeness, or adequacy of the information contained therein or linked to from such blogs, nor take responsibility for any aspect of such blog content. All content on Blogs via Newstex shall be construed as author-based content and commentary. Accordingly, no warranties or other guarantees will be offered as to the quality of the opinions, commentary or anything else offered on such Blogs via Newstex. Reader's comments reflect their individual opinion and their publication within Blogs via Newstex shall not infer or connote an endorsement by Newstex or its re-distributors of such reader's comments or views. Newstex and its re-distributors expressly reserve the right to delete posts and comments at its and their sole discretion. PUBLICATION-TYPE: Web Blog Copyright 2007 Newstex LLC All Rights Reserved Newstex Web Blogs Copyright 2007 Mental Health Update 276 of 998 DOCUMENTS Targeted News Service November 22, 2007 Thursday 2:03 PM EST U.S. Patents Awarded to Inventors in Delaware (Nov. 22) BYLINE: Targeted News service Targeted News Service LENGTH: 207 words DATELINE: Alexandria, VA. ALEXANDRIA, Va., Nov. 22 -- The following federal patents were awarded to inventors in Delaware. *** Indiana, Ohio, Delaware Inventors Develop Modafinil Pharmaceutical Formulation ALEXANDRIA, Va., Nov. 22 -- Vincent Corvari of Carmel, Ind., George Grandolfi of Millford, Ohio, and Alpa Parikh of Hockessin, Del., have developed pharmaceutical formulations of modafinil. According to the U.S. Patent & Trademark Office: "The present invention is related to compositions of modafinil, including compositions of modafinil and one or more diluents, disintegrants, binders and lubricants, and the processes for their preparation thereof." The inventors were issued U.S. Patent No. 7,297,346 on Nov. 20. The patent has been assigned to Cephalon Inc., Frazer, Pa. The original application was filed on May 23, 2002, and is available at: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=% 2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=7,297,346.PN.&OS=PN/7,297,346&RS= PN/7,297,346. For more information about Targeted News Service's products, including its federal contract report, please contact: Myron Struck, Myron@targetednews.com, Editor, Targeted News Service LLC, Springfield, Va. (Managing Edi -537400 LOAD-DATE: November 22, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2007 Targeted News Service LLC. All Rights Reserved 277 of 998 DOCUMENTS Targeted News Service November 22, 2007 Thursday 2:03 PM EST U.S. Patents Awarded to Inventors in Indiana (Nov. 22) BYLINE: Targeted News service Targeted News Service LENGTH: 486 words DATELINE: Alexandria, VA. ALEXANDRIA, Va., Nov. 22 -- The following federal patents were awarded to inventors in Indiana. *** New York, Minnesota, Indiana, Iowa Inventor Develops Protein Material Treatment Method ALEXANDRIA, Va., Nov. 22 -- Tim Emerson of Churchville, N.Y., Christopher S. Penet of Henrietta, N.Y., Mary R. Higgins of Fridley, Minn., Madhu Kakade of Roseville, Minn., Jane Kitchar of Elkhart, Ind., and Bill L. Miller of Fort Dodge, Iowa, have developed a method of reducing the antigenicity of vegetable proteins. According to the U.S. Patent & Trademark Office, the invention relates to a "method of treating a proteinaceous material having a first concentration of beta-conglycinin, the method including combining the proteinaceous material with an enzyme to form a reaction mixture, the reaction mixture initially having a potential of Hydrogen (pH) of at least about 7.0 standard pH units, allowing the enzyme to hydrolyze beta-conglycinin present in the reaction mixture to form a proteinaceous intermediate, and inactivating the enzyme present in the reaction mixture after a reaction period to form a proteinaceous product, the proteinaceous product having a second concentration of beta-conglycinin, the second concentration of beta-conglycinin being at least 99 percent less than the first concentration of beta-conglycinin." The inventors were issued U.S. Patent No. 7,297,354 on Nov. 20. The patent has been assigned to Land O'Lakes Inc., Arden Hills, Minn., and Genencor International Inc., Palo Alto, Calif. The original application was filed on April 26, 2001, and is available at: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=% 2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=7,297,354.PN.&OS=PN/7,297,354&RS= PN/7,297,354. *** Indiana, Ohio, Delaware Inventors Develop Modafinil Pharmaceutical Formulation ALEXANDRIA, Va., Nov. 22 -- Vincent Corvari of Carmel, Ind., George Grandolfi of Millford, Ohio, and Alpa Parikh of Hockessin, Del., have developed pharmaceutical formulations of modafinil. According to the U.S. Patent & Trademark Office: "The present invention is related to compositions of modafinil, including compositions of modafinil and one or more diluents, disintegrants, binders and lubricants, and the processes for their preparation thereof." The inventors were issued U.S. Patent No. 7,297,346 on Nov. 20. The patent has been assigned to Cephalon Inc., Frazer, Pa. The original application was filed on May 23, 2002, and is available at: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=% 2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=7,297,346.PN.&OS=PN/7,297,346&RS= PN/7,297,346. For more information about Targeted News Service's products, including its federal contract report, please contact: Myron Struck, Myron@targetednews.com, Editor, Targeted News Service LLC, Springfield, Va. (Managing Edi -537407 LOAD-DATE: November 22, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2007 Targeted News Service LLC. All Rights Reserved 278 of 998 DOCUMENTS Targeted News Service November 22, 2007 Thursday 2:03 PM EST U.S. Patents Awarded to Inventors in Ohio (Nov. 22) BYLINE: Targeted News service Targeted News Service LENGTH: 1102 words DATELINE: Alexandria, VA. ALEXANDRIA, Va., Nov. 22 -- The following federal patents were awarded to inventors in Ohio. *** Ohio Inventor Develops Barrier Operator Controller ALEXANDRIA, Va., Nov. 22 -- Michael T. McMahon of Salem, Ohio, has developed a barrier operator controller. According to the U.S. Patent & Trademark Office: "A control unit for a moveable barrier, such as a garage door, includes a microcontroller connected to a motor speed detector, motor current sensor or a sensor for determining forces exerted on or by the barrier. A user interface includes user actuatable switches for setting a first maximum force value to be exerted on or by the barrier when moving in one direction and the microcontroller automatically sets the value of a second maximum force to be exerted on or by the barrier when moving in the opposite direction." An abstract of the invention, released by the Patent Office, said: "The second force value may be based on the force value set by the user or the second force value may be a preset value. Both force limits may be automatically set as a function of a maximum force exerted on said barrier during movement thereof, during a force learning operation." The inventor was issued U.S. Patent No. 7,298,107 on Nov. 20. The patent has been assigned to Overhead Door Corp., Lewisville, Texas. The original application was filed on Feb. 16, 2006, and is available at: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=% 2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=7,298,107.PN.&OS=PN/7,298,107&RS= PN/7,298,107. *** Michigan, California, Florida, Ohio Inventors Develop Model Toy Train Motor Arrangement ALEXANDRIA, Va., Nov. 22 -- Gary L. Moreau of Rochester, Mich., Martin Pierson of Howell, Mich., Neil P. Young of Redwood City, Calif., Robert Grubba of Ormond Beach, Fla., and Dennis J. Denen of Westerville, Ohio, have developed a model toy train motor arrangement. According to the U.S. Patent & Trademark Office: "A control and motor arrangement in accordance with the present invention includes a motor configured to generate a locomotive force for propelling the model train. The control and motor arragement further includes a command control interface configured to receive commands from a command control unit wherein the commands correspond to a desired speed. The control and motor arrangement still further includes a plurality of detectors configured to detect speed information of the motor, and a process control arrangement configured to receive the speed information from the sensors." An abstract of the invention, released by the Patent Office, said: "The process control arrangement is further configured and arranged to generate a plurality of motor control signals based on the speed information for controlling the speed of said motor. The control and motor arrangement yet still further includes a motor control arrangement configured to cause power to be applied to the motor at different times in response to the motor control signals." The inventors were issued U.S. Patent No. 7,298,103 on Nov. 20. The patent has been assigned to Lionel LLC, Chesterfield, Mich. The original application was filed on May 8, 2006, and is available at: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=% 2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=7,298,103.PN.&OS=PN/7,298,103&RS= PN/7,298,103. *** Ohio Inventors Develop Dehydrated Starch Ingredients Making Process ALEXANDRIA, Va., Nov. 22 -- David Cammiade Gruber and Paul Seiden, both of Cincinnati, Peter Yau Tak Lin of Liberty, Ohio, and Maria Dolores Martinez-Serna Villagran of Mason, Ohio, have developed dehydrated starch ingredients making emulsifier system. According to the U.S. Patent & Trademark Office: "Described is an improved emulsifier system suitable for use in making dehydrated starch ingredients. Also disclosed are a process for making the dehydrated ingredients using the improved emulsifier systems, doughs made using the dehydrated ingredients and the process for making those doughs, and food products containing the dehydrated ingredients." The inventors were issued U.S. Patent No. 7,297,358 on Nov. 20. The patent has been assigned to The Procter & Gamble Co., Cincinnati. The original application was filed on July 29, 2004, and is available at: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=% 2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=7,297,358.PN.&OS=PN/7,297,358&RS= PN/7,297,358. *** Indiana, Ohio, Delaware Inventors Develop Modafinil Pharmaceutical Formulation ALEXANDRIA, Va., Nov. 22 -- Vincent Corvari of Carmel, Ind., George Grandolfi of Millford, Ohio, and Alpa Parikh of Hockessin, Del., have developed pharmaceutical formulations of modafinil. According to the U.S. Patent & Trademark Office: "The present invention is related to compositions of modafinil, including compositions of modafinil and one or more diluents, disintegrants, binders and lubricants, and the processes for their preparation thereof." The inventors were issued U.S. Patent No. 7,297,346 on Nov. 20. The patent has been assigned to Cephalon Inc., Frazer, Pa. The original application was filed on May 23, 2002, and is available at: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=% 2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=7,297,346.PN.&OS=PN/7,297,346&RS= PN/7,297,346. *** Ohio Inventors Develop Boron Nitride Production Process ALEXANDRIA, Va., Nov. 22 -- Laurence Maniccia of Lyndhurst, Ohio, and Donald William Pultz Jr., of Parma, Ohio, have developed a hexagonal boron nitride compound production process. According to the U.S. Patent & Trademark Office, the invention relates to a "process for producing boron nitride using a boron containing ore as a starting material, by reacting naturally occurring ulexite with ammonia at high temperature, for a boron nitride with high impurity and at a high yield." The inventors were issued U.S. Patent No. 7,297,317 on Nov. 20. The patent has been assigned to Momentive Performance Materials Inc., Wilton, Conn. The original application was filed on Nov. 3, 2005, and is available at: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=% 2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=7,297,317.PN.&OS=PN/7,297,317&RS= PN/7,297,317. For more information about Targeted News Service's products, including its federal contract report, please contact: Myron Struck, Myron@targetednews.com, Editor, Targeted News Service LLC, Springfield, Va. (Managing Edi -537423 LOAD-DATE: November 22, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2007 Targeted News Service LLC. All Rights Reserved 279 of 998 DOCUMENTS US Fed News November 22, 2007 Thursday 12:47 AM EST Indiana, Ohio, Delaware Inventors Develop Modafinil Pharmaceutical Formulation BYLINE: US Fed News LENGTH: 170 words DATELINE: Alexandria, Va. ALEXANDRIA, Va., Nov. 22 -- Vincent Corvari of Carmel, Ind., George Grandolfi of Millford, Ohio, and Alpa Parikh of Hockessin, Del., have developed pharmaceutical formulations of modafinil. According to the U.S. Patent & Trademark Office: "The present invention is related to compositions of modafinil, including compositions of modafinil and one or more diluents, disintegrants, binders and lubricants, and the processes for their preparation thereof." The inventors were issued U.S. Patent No. 7,297,346 on Nov. 20. The patent has been assigned to Cephalon Inc., Frazer, Pa. The original application was filed on May 23, 2002, and is available at: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=% 2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=7,297,346.PN.&OS=PN/7,297,346&RS= PN/7,297,346. For more information about US Fed News federal patent awards please contact: Myron Struck, Managing Editor/US Bureau, US Fed News, Direct: 703/866-4708, Cell: 703/304-1897, Myron@targetednews.com LOAD-DATE: November 22, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2007 HT Media Ltd. All Rights Reserved 280 of 998 DOCUMENTS The Guardian (London) - Final Edition November 8, 2007 Thursday G2: Ways to make you think better: Students and exhausted workers have been abusing stimulants for decades. But these days, if you're keen to feel sharper, and work for longer, the drugs available are more effective than they once were - and less likely to make you feel awful afterwards. No wonder then that the abuse of pills such as Ritalin and modafinil is becoming a major problem. Katharine Hibbert reports on the rise of cognitive-enhancing drugs - and doctors' fears over their long-term safety BYLINE: Katharine Hibbert SECTION: GUARDIAN FEATURES PAGES; Pg. 7 LENGTH: 2095 words Mark is a good student. Intelligent and diligent, he won a place to read modern languages at one of Britain's top 10 universities. But in the run-up to his finals this summer, with a towering pile of revision still to go, the 23-year-old decided he wasn't going to be good enough. So he went on the internet, found an online pharmacy based in Turkey, and bought a pack of modafinil. It's a prescription drug given to narcoleptics, but it has also been shown to boost alertness and mental agility in healthy users. After a week of taking a tablet a day, sleeping only four hours a night, then, thanks to the drug, waking up refreshed, Mark took his exams. He got a first. Would he have done so well without pharmaceutical help? "Unlikely," he says. Mark is not the only one. The British Medical Association believes that a growing number of healthy people in this country are illicitly using brain-boosting drugs that should really only be taken on prescription. More specifically, they're taking modafinil and Ritalin, a drug licensed for use in those suffering from attention deficit hyperactivity disorder (ADHD). Some people may find a way to obtain the drugs from a doctor, but if not, they are available from websites based abroad. The going rate for a dose is around £3. Although the scale of the problem is as yet undefined in this country, there is evidence that self-dosing with brain-boosting drugs is already rife in the United States. There's thought to be a particular problem among students (some of whom have nicknamed Ritalin "Vitamin R"): in a survey of 1,025 students at a north-eastern US university, published in the Journal of American College Health last year, one in six of those who responded admitted taking prescription drugs illicitly, mainly to improve concentration and alertness. But even beyond the world of student panic, abuse of Ritalin (also known as "kiddie coke") is widespread. Meanwhile many millions of people who have problems with tiredness - truckers, for example, and night workers - are using modafinil. It's even been found in the systems of top American athletes during dope testing. The BMA is so concerned about the use of such drugs on this side of the Atlantic that its medical ethics committee is today publishing a discussion paper on the ethics of cognitive-enhancement. The paper predicts that increasing use of Ritalin and modafinil in Britain is "both imminent and inevitable". One of the experts who pro duced the report, Barbara Sahakian, professor of neuropsychology at Cambridge University, knows at first-hand how widely used the drugs already are. "I have been offered modafinil on several occasions when I've been at conferences, without asking for it," she says. "My fellow academics have taken it to counteract jetlag and tiredness, and I've been offered it when I've complained about my own jet lag, or having been allocated a slot to talk late in the day. I haven't taken it - I work in the lab where we have many of these substances, so it would be unethical for me to be taking things off the shelves. But the use of these drugs is clearly quite widespread within the profession." Such anecdotal evidence isn't hard to uncover; these are the sort of drugs that students talk about nowadays. Anna, 24, now a junior doctor, says that her use of prescription drugs to boost her ability to work was unexceptional while she was studying medicine at a Scottish university. "We'd have these revision parties. It was usually about three of us, we'd get wired on Ritalin, and I'd do my anatomy revision, another would work on her economics coursework, and the other would do a history of art essay. We'd sit there working like mad, really racing through it, totally focused, turning out good quality work for hours and hours. "I ended up taking Ritalin in every exam during the first semester at medical school - I was just so snowed under that I couldn't cope with the work otherwise, and I was positive I was going to fail. I remember in the exam that I was pulling in knowledge from when I was at school. It all seemed to come into my head much better than it would normally - it might just have been psychosomatic, but it felt like it helped. And I passed every exam." Dosing up on stimulants to improve focus and ward off tiredness is nothing new. Caffeine, amphetamines and other, harder drugs have long been used by people seeking ways to make their brains work better, for longer. The difference with modern drugs such as Ritalin - which is actually an amphetamine, but far more subtle than old-fashioned "speed" - is that they have been developed to minimise both unpleasant side-effects and the risk of addiction. Ritalin, the trade name in the UK for the drug methylphenidate, was invented in 1954 and first prescribed to ADHD sufferers in the 1960s, but its use rocketed during the 90s. In the US, doctors write 3m prescriptions for the drug every month; here doctors average more than 30,000 a month. Although Ritalin is medically a stimulant, it calms those who suffer from ADHD, making them more able to concentrate on the task in hand, and has similar effects on healthy users (although it can also cause insomnia, headaches and heart palpitations.) The fact that it's currently so widely prescribed to even very young children makes many adults think that it must be perfectly safe to take. Modafinil, meanwhile, has been prescribed in the UK since 1997, and has similar effects, but it also works to stave off tiredness without the slight euphoric high and cardiovascular effects brought on by Ritalin, which can be dangerous for those with weak hearts. Neither drug is considered addictive at the doses normally prescribed - although it is possible to develop a psychological dependence. Sahakian and a team of researchers at Cambridge tested modafinil on healthy male undergraduates in 2003. Those who took a single 200mg dose were found to use information more efficiently within two hours of taking it. They were better at mental planning tests, completed puzzles more accurately, could remember longer strings of digits and recognise pictures more quickly. Long-term memory was not enhanced, but the increased ability to concentrate for longer periods of time would, the researchers say, allow them to learn more. Modafinil has also been tested by both the British and American armed forces, and could one day offer a substitute for the caffeine and amphetamine "go pills" the US army and air force have long relied on for night-time operations. But the new BMA paper emphasises that the long-term side-effects of using such drugs are unknown: they may turn out to be harmful. Such risks may be worthwhile for those suffering from the conditions the drugs were created to treat, but perhaps not for a healthy user. The report highlights speculation among academics that there could be particular dangers for children and younger people who take the drugs while their brains are developing, and that people who use cognitive-enhancing pharmaceuticals in their youth may become more susceptible to premature cognitive decline as they age. "We simply do not know what the long-term effect of the use of such drugs in healthy populations will be," the report concludes. Whether or not the drugs should be so widely prescribed, especially to primary school children, is a matter of some controversy. But it seems clear that healthy young adults are taking a gamble when they dabble with them. This may not be enough to put everyone off. Modafinil's apparent harmlessness persuaded John, who is studying for a neuroscience PhD in London, to try it. "When I was thinking about taking modafinil, I read the scientific studies," the 29-year-old says. "I've never even taken cannabis, let alone any harder drugs, but I thought modafinil might benefit me. Sometimes I find it hard to concentrate, some days I'm just tired out and I need to work. A friend who's a doctor wrote me a prescription - he uses it occasionally himself. I've also bought it off the internet. For me, it's something to have in the medicine cupboard in case you're totally exhausted and just need to get through the day. I only use it maybe once or twice a month - it's just a nice backup. It doesn't feel like much, it just stops you from feeling sleepy, takes away that mid-afternoon drop-off . You certainly wouldn't take it for enjoyment, for its own sake. I don't notice any side-effects - sometimes my mouth goes a bit dry, but that's all." The idea of competing with pharmaceutically enhanced peers at work or university will strike many as deeply unfair. "It may not be a fair thing that I took modafinil," Mark says, "but so many students have Ritalin and other drugs, some who have been prescribed it for more or less spurious reasons, or others who can just get hold of it one way or another. Loads of students I knew were using it to stay up and write essays. And at that particular time, this particular drug seemed quite helpful to me, so I didn't feel too bad about taking it." And the playing field isn't exactly level anyway, since many students will be legitimately prescribed drugs by doctors even if their peers might not consider them ill. "Prescribing Ritalin for ADHD brings a grey area," Sahakian says. "It's a spectrum disorder, and while at one end it can be deeply debilitating, many people are diagnosed for much more minor symptoms. Studies in America have shown a huge variation in diagnosis rates - in some areas up to one in five children have it prescribed to them. The line between enhancement and treatment is a subjective decision, and if students have found someone who will prescribe where other doctors might not, then they are already going into exams on drugs, where other students, with similar symptoms, are not. The pressure to compete is already boosting prescribed use of these drugs - we hear about parents putting pressure on doctors to prescribe Ritalin because they think that everyone else's children are taking it. "And maybe people who have the money will be able to afford cognitive-enhancing drugs that aren't prescribed - so people who are already limited in finances and background will be even more disadvantaged. But then that's already the case, as they can afford better education, better food, more extra-curricular lessons." Trevor Robbins, professor of neuroscience at Cambridge University, who has carried out extensive research on drugs for cognitive enhancement and on drug abuse, is surprisingly sanguine about the use of these drugs by healthy adults. "We already enhance our performance in all sorts of ways," he says. "Some of us wear contact lenses, some of us drink coffee. Some may be horrified that normal people would take drugs to improve their performance, but if you called it a food or a drink, they wouldn't bat an eyelid - people take fish oil because it may make their brains work better, but drugs have a stigma to them. "I don't really see any argument against self-improvement in itself, except in a competitive situation - in exams, for example. Then it's analogous with doping in competitive sport. But what can you do? Even if you do drug tests in the exam hall, people might have used modafinil to improve their learning on a course in November, for instance, then taken the exam in July. How are you going to test it by then?" Both Robbins and Sahakian believe that the use of the drugs is set to grow, no matter what regulation is put in place. The BMA report concurs, acknowledging that even if the drugs were banned in Britain, it would take international laws to prevent them from being sold over the internet. And right now there are more mind-sharpening medicines in development, and those who want to enhance their mental performance may soon be able to choose, legally or illegally, from a wider range of drugs, each operating on different parts of the brain. The Alzheimer's drug Donepezil, for example, has been shown to delay loss of mental ability in patients, and improve memory in those without dementia. Early clinical trials, meanwhile, suggest that a new and so far unlicensed class of drugs, ampakines, may enhance learning capacity and memory in healthy users, as well as increasing attention span and alertness. Drugs may not negate the need for talent, creativity and self-discipline in achieving success. But even if the ethics and the uncertainties about long-term risks are hard to swallow, more and more people may soon find themselves tempted by the chance to be sharper, smarter and more alert if it's on offer in tablet form. LOAD-DATE: November 8, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2007 Guardian Newspapers Limited All Rights Reserved 281 of 998 DOCUMENTS Clinical Neurology News November 2007 SJS, Rash Warnings Added to Modafinil Label BYLINE: Elizabeth Mechcatie, Senior Writer SECTION: Pg. 4 Vol. 3 No. 11 ISSN: 1553-3212 LENGTH: 652 words    Adverse reactions should be reported to the FDA's MedWatch program at 800-332-1088 or www.fda.gov/medwatch. More information is available at www.fda.gov/medwatch/safety/2007/safety07.htm#Provigil.    Warnings about Stevens-Johnson syndrome, hypersensitivity reactions, and psychiatric symptoms have been added to the label of modafinil, according to a MedWatch notice issued by the Food and Drug Administration on Oct. 24.    Modafinil, a "wakefulness-promoting agent," is marketed as Provigil by Cephalon Inc., and was first approved as a treatment for narcolepsy in 1998. It is approved for improving wakefulness in adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome, and shift-work sleep disorder. It is not approved for any pediatric indications, though some reports have been in children.    The MedWatch notice and a "Dear Healthcare Professional" letter issued by Cephalon describe worldwide postmarketing reports of life-threatening rash, including toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) in adults and children. There have also been postmarketing reports of angioedema and multiorgan hypersensitivity reactions.    The reporting rate-considered an underestimate, because postmarketing reports of adverse events tend to be underreported-of TEN and Stevens-Johnson syndrome (SJS) associated with modafinil is higher than the background incidence rate, according to the letter. The background in the general population is estimated at 1-2 million cases per million person-years.    The potential for benign rashes-which have been associated with modafinil use-to develop into serious rashes cannot be reliably predicted, so "modafinil should ordinarily be discontinued at the first sign of rash, unless the rash is clearly not drug-related," the letter says. However, stopping treatment "may not prevent a rash from becoming life-threatening or permanently disabling or disfiguring."    Because of postmarketing reports of angioedema, the letter says that patients should be advised to stop treatment and "immediately report to their physician any signs of symptoms suggesting angioedema or anaphylaxis," which includes swelling of the face, eyes, lips, tongue, or larynx; difficult breathing or swallowing; and hoarseness. There have also been postmarketing reports of multiorgan hypersensitivity reactions, including at least one fatal case, which have occurred "in close temporal association to the initiation of modafinil." Modafinil should be discontinued if such a rash is suspected.    The letter also recommends that discontinuation of the drug should be considered in patients who develop psychiatric symptoms during treatment, because mania, anxiety, hallucinations, and suicidal ideation are among the psychiatric adverse reactions reported in people treated with modafinil. In addition, "caution should be exercised" when the drug is prescribed to patients with as history of psychosis, depression, or mania.    Cephalon had pursued approval of modafinil as a treatment for attention-deficit/hyperactivity disorder in children and adolescents, but in March 2006, the FDA's Psychopharmacologic Drugs Advisory Panel agreed that the drug was not safe for treating children and adolescents, largely because of concerns about its potential to cause SJS in this population. Last summer, Cephalon announced that it had received a "non-approvable" letter from the FDA for this indication and had stopped developing the drug.    The "Dear Healthcare Professional" letter says in studies, the incidence of rash resulting in discontinuation of the drug in pediatric patients (younger than 17 years) was 0.8% (13 of 1,585); these included one case of possible SJS and one case of a possible multiorgan hypersensitivity reaction. There were no such cases among 380 pediatric patients on placebo. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: CNNEWS Copyright 2007 Elsevier Inc., International Medical News Group All Rights Reserved 282 of 998 DOCUMENTS The International Herald Tribune October 18, 2007 Thursday Rider nears victory in bid to stay awake; CYCLING BYLINE: Samuel Abt - The New York Times Media Group SECTION: SPORT; Pg. 19 LENGTH: 602 words DATELINE: PARIS Franck Bouyer sounds raring to go, up and at 'em, as bright-eyed and bushy-tailed as a fellow with sleeping sickness can be. After three years of legal struggle to regain his place as a bicycle racer, Bouyer says the happy ending is finally in sight. He has succeeded, he feels, in sending the overlords of the sport a wake-up call. ''Yes,'' he said in a phone interview from his home near Cholet in western France, ''things are looking good. I'm trying not to get too excited about my chances since I've had so many setbacks before, but this time it really looks good. ''This time, if all goes well, they'll have to do the right thing by me.'' Unless, that is, somebody is asleep at the switch. Often, that has been Bouyer. The 33-year-old Frenchman has narcolepsy, a disorder marked by recurring and unpredictable episodes of sleep during normal waking hours and disturbed sleep at night. He was diagnosed with the genetic disease, which is believed to afflict one person in 200,000, late in 2003 and since then his life has been, as he says without irony, a nightmare. It's not just that he tosses and turns while trying to grab some shut-eye. When the sun is up, he sometimes dozes off on training rides and finds himself suddenly on the ground. ''One time, I found myself in the courtyard of a farm, woken up by a barking dog without knowing how I got there,'' he has said. This has not happened in a race, where the result could be a mass crash. Bouyer can master his disorder by taking a drug called modafinil. But, in addition to keeping him awake and alert, modafinil is classified by the International Cycling Union, which governs the sport, as an illegal performance-enhancing drug. The World Anti-Doping Agency disagrees in Bouyer's case and ruled in 2005 that he could take the drug while competing. That decision, a reversal of the agency's ruling the same year, followed one of many lawsuits. For a brief period late in 2005 and early last year, Bouyer returned to racing for the Bouygues T[#x17d]l[#x17d]com team from France. Then the cycling union appealed the World Anti-Doping Agency's decision to the Court of Arbitration for Sport, and Bouyer lost. ''I have a sickness, you know,'' Bouyer explained last year. ''I'm not trying to cheat, I'm trying to compete.'' This year, he turned to a French court to obtain what is called a Therapeutic Use Exemption for modafinil. Last month, the court upheld him. ''Finally somebody agrees with me and considers me ill,'' he told the sports newspaper L'[#x192]quipe. On the phone last week, he elaborated: ''The case goes now to a doctor named by the court. He's an expert. If he says I have a right to use modafinil, I should be racing next year. ''I'm so hopeful that I've already resumed training. Whew, it's hard. Such a long time since I've been in a race or even training. There wasn't much point in training while I was going from one courtroom to another. ''Now I think all this may finally be over. Time to start getting my legs ready.'' The Bouygues team, which has supported him throughout the legal process, has said that it will welcome him back. Although Bouyer has never been a star, he has won such races as Paris-Camembert, the Tour of the Vend[#x17d]e and the Tour of the Limousin since he turned professional in 1994. ''I understand that I don't have too many years left as a racer,'' he said. ''But that's how I'd like to finish my career, as a racer, not a spectator. ''Once again, I'm waiting for a ruling. So many doctors, so many courts. ''This time, maybe somebody will say, 'He's sick. He needs his medicine. There's nothing wrong with that. Sick people have rights too.' '' LOAD-DATE: October 31, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2007 International Herald Tribune All Rights Reserved 283 of 998 DOCUMENTS Pharma Company Insight Pharmaceuticals September 21, 2007 Cephalon completes Provigil label updates LENGTH: 177 words Cephalon has finalised and shared with healthcare professionals revisions to the label for Provigil ( modafinil ) Tablets [C-IV], its wake-promoting agent. As announced by the company in both March and June, these changes were necessary to make the Provigil label consistent with the Nuvigil ( armodafinil ) Tablets [C-IV] label that was approved and made available by the FDA in June. Nuvigil is the single isomer formulation of modafinil, the active ingredient contained in Provigil. Provigil and Nuvigil are indicated to improve wakefulness in adults with excessive sleepiness associated with obstructive sleep apnoea/hypopnoea syndrome (OSAHS), shift work sleep disorder and narcolepsy. In OSAHS, Provigil and Nuvigil are indicated as adjuncts to standard treatments for the underlying obstruction. Cephalon's ongoing development programme is evaluating the use of Nuvigil as a treatment for serious psychiatric and neurological medical conditions. Currently, the company plans a commercial launch of the product once additional clinical data have been amassed. LOAD-DATE: September 21, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2007 ESPICOM Business Intelligence Ltd. All Rights Reserved 284 of 998 DOCUMENTS Daily International Pharma Alert September 18, 2007 Tuesday Cephalon Completes Provigil Label Updates SECTION: Vol. 4 No. 183 LENGTH: 114 words Cephalon has finalized revisions to the label for Provigil tablets, its product to improve wakefulness in adults with obstructive sleep apnea/hypopnea syndrome, shift work sleep disorder and narcolepsy. Cephalon said these changes were necessary to make the Provigil (modafinil) label consistent with the Nuvigil (armodafinil) label approved by the FDA in June. Nuvigil is the single isomer formulation of modafinil. Cephalon's ongoing development program is evaluating Nuvigil as a treatment for serious psychiatric and neurological medical conditions. The company said it plans a commercial launch of Nuvigil once additional clinical data has been amassed. Release date: Sept. 18, 2007 LOAD-DATE: September 19, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2007 Washington Business Information, Inc. All Rights Reserved 285 of 998 DOCUMENTS Reuters Health Medical News August 23, 2007 Thursday 9:00 PM EST Modafinil seen beneficial in bipolar disorder SECTION: DRUG & DEVICE DEVELOPMENT LENGTH: 497 words DATELINE: NEW YORK Modafinil improves depressive symptoms in patients with bipolar disorder that responds inadequately to a mood stabilizer, according to a report in the August issue of the American Journal of Psychiatry. Modafinil is currently approved in the U.S. for improving wakefulness in patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea or hypopnea syndrome, and shift-work sleep disorder, the authors explain, but it may also be effective for attention deficit hyperactivity disorder (ADHD), cocaine dependence, and unipolar depression. Dr. Mark A. Frye from the Mayo Clinic, Rochester, Minnesota and associates investigated the efficacy and safety of adjunctive modafinil versus placebo for 6 weeks in the treatment of 85 patients with bipolar depression. They had had an inadequate response on a mood stabilizer with or without concomitant antidepressant therapy The endpoint scores on the Inventory of Depressive Symptoms (IDS), four-item fatigue-and-energy subset of the IDS, and Clinical Global Impression-Bipolar Disorder depression severity item were significantly improved in the modafinil group compared with the placebo group, the investigators found. Concomitant antidepressant therapy did not contribute to the difference between groups in these scores, the report indicates. Significantly more patients in the modafinil group (43.9%) than in the placebo group (22.7%) achieved at least a 50% improvement in their IDS score, and similar differential response rates were seen for the other two measures. These improvements were evident at every visit from week 2 through week 6, except for week 3, the investigators say. "Although an antidepressant effect was observed for modafinil," the researchers note, "no reduction in sleepiness, as measured by the Epworth Sleepiness Scale, or in fatigue, as measured by the Fatigue Severity Scale, was observed." There were no differences between the groups in treatment-emergent hypomania or mania or in hospitalizations for mania. "Our results in this 6-week trial suggest that adjunctive modafinil at doses of 100-200 mg a day may improve symptoms of bipolar depression without mood destabilization," the authors conclude. "It will be important in our 4-month open-trial continuation phase of this study to assess ongoing antidepressant response and stability." "It is biologically plausible that modafinil might be useful in some cases of bipolar depression, and the present results in 85 patients support this possibility," writes Dr. R. H. Belmaker from Ben-Gurion University of the Negev, Beer-Sheba, Israel in a related editorial. "We should avoid assuming that a statistical benefit of one treatment for bipolar depression as a diagnostic entity is relevant for every patient with this heterogeneous condition," cautions Dr. Belmaker. "The patients in the present study were all taking mood stabilizers. Starting a mood stabilizer would be the first choice for any patient not being so treated." LOAD-DATE: March 4, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2007 Reuters Health All Rights Reserved 286 of 998 DOCUMENTS Straight From the Doc August 8, 2007 Wednesday 12:30 AM EST Wake-up Pill Modafinil May Help Bipolar Disorder Patients LENGTH: 220 words Aug. 8, 2007 (Straight From the Doc delivered by Newstex) -- Modafinil is a drug approved by the US FDA for the treatment of patients suffering from excessive sleepiness associated with narcolepsy, obstructive sleep apnea and shift work sleep > Now, this "wake-up pill" has been found to control the depressive symptoms associated with bipolar disorder - a condition characterized by an alternating pattern of emotional highs (mania) and lows (depression),which (according to the National Institute of Mental Health) is suffered by some 5.7 million adults in the United > Appearing in the August 2007 issue of the American Journal of Psychiatry, according to the study's author, Mark Frye, M.D., director of the Mayo Clinic Mood Disorders Clinic and Research > At least 44 percent of the participants in the study reported improved symptoms, a noteworthy improvement for a disorder in which new treatments are > There are very few treatments for the depressive phase of bipolar disorder and as a result there is an urgent need to evaluate potential > Mood stabilizers in general are better at treating mania than depression, but the depressive phase of the illness is far more common. We really need continued research in this > Modafinil is manufactured by Cephalon Inc. and is sold under the brand name Provigil.> > Mayo Clinic> LOAD-DATE: August 8, 2007 LANGUAGE: ENGLISH NOTES: The views expressed on blogs distributed by Newstex and its re-distributors ("Blogs via Newstex") are solely the author's and not necessarily the views of Newstex or its re-distributors. Posts from such authors are provided "AS IS", with no warranties, and confer no rights. The material and information provided in Blogs via Newstex are for general information only and should not, in any respect, be relied on as professional advice. No content on such Blogs via Newstex is "read and approved" before it is posted. Accordingly, neither Newstex nor its re-distributors make any claims, promises or guarantees about the accuracy, completeness, or adequacy of the information contained therein or linked to from such blogs, nor take responsibility for any aspect of such blog content. All content on Blogs via Newstex shall be construed as author-based content and commentary. Accordingly, no warranties or other guarantees will be offered as to the quality of the opinions, commentary or anything else offered on such Blogs via Newstex. Reader's comments reflect their individual opinion and their publication within Blogs via Newstex shall not infer or connote an endorsement by Newstex or its re-distributors of such reader's comments or views. Newstex and its re-distributors expressly reserve the right to delete posts and comments at its and their sole discretion. PUBLICATION-TYPE: Web Blog Copyright 2007 Newstex LLC All Rights Reserved Newstex Web Blogs Copyright 2007 Straight From the Doc 287 of 998 DOCUMENTS Food and Drug Adminstration Documents and Publications August 7, 2007 Summaries of Medical and Clinical Pharmacology Reviews of Pediatric Studies; Availability SECTION: FOOD AND DRUG ADMINISTRATION - REGULATORY DOCUMENTS LENGTH: 581 words SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of summaries of medical and clinical pharmacology reviews of pediatric studies submitted in supplements for ACTIQ (fentanyl), ALDARA (imiquimod), AMBIEN (zolpidem), COREG (carvedilol), PROVIGIL (modafinil), and ZYPREXA (olanzapine). These summaries are being made available consistent with the Best Pharmaceuticals for Children Act (the BPCA). For all pediatric supplements submitted under the BPCA, the BPCA requires FDA to make available to the public a summary of the medical and clinical pharmacology reviews of the pediatric studies conducted for the supplement. ADDRESSES: Submit written requests for single copies of the summaries to the Division of Drug Information (HFD-240), Center for Drug Evaluation and Research, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857. Please specify by product name which summary or summaries you are requesting. Send one self-addressed adhesive label to assist that office in processing your requests. See the SUPPLEMENTARY INFORMATION section for electronic access to the summaries. FOR FURTHER INFORMATION CONTACT: Grace Carmouze, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 6460, Silver Spring, MD 20993-0002, 301-796-0700, e-mail: grace.carmouze@fda.hhs.gov SUPPLEMENTARY INFORMATION: FDA is announcing the availability of summaries of medical and clinical pharmacology reviews of pediatric studies conducted for ACTIQ (fentanyl), ALDARA (imiquimod), AMBIEN (zolpidem), COREG (carvedilol), PROVIGIL (modafinil), and ZYPREXA (olanzapine). The summaries are being made available consistent with section 9 of the BPCA (Public Law 107-109). Enacted on January 4, 2002, the BPCA reauthorizes, with certain important changes, the pediatric exclusivity program described in section 505A of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 355a). Section 505A of the act permits certain applications to obtain 6 months of marketing exclusivity if, in accordance with the requirements of the statute, the sponsor submits requested information relating to the use of the drug in the pediatric population. One of the provisions the BPCA added to the pediatric exclusivity program pertains to the dissemination of pediatric information. Specifically, for all pediatric supplements submitted under the BPCA, the BPCA requires FDA to make available to the public a summary of the medical and clinical pharmacology reviews of pediatric studies conducted for the supplement (21 U.S.C. 355a(m)(1)). The summaries are to be made available not later than 180 days after the report on the pediatric study is submitted to FDA (21 U.S.C. 355a(m)(1)). Consistent with this provision of the BPCA, FDA has posted on the Internet at http://www.fda.gov/cder/pediatric/index.htm summaries of medical and clinical pharmacology reviews of pediatric studies submitted in supplements for ACTIQ (fentanyl), ALDARA (imiquimod), AMBIEN (zolpidem), COREG (carvedilol), PROVIGIL (modafinil), and ZYPREXA (olanzapine). Copies are also available by mail (see ADDRESSES). II. Electronic Access Persons with access to the Internet may obtain the document at http://www.fda.gov/cder/pediatric/index.htm. Dated: July 30, 2007. Randall W. Lutter, Deputy Commissioner for Policy. [FR Doc. E7-15234 Filed 8-6-07; 8:45 am] BILLING CODE 4160-01-S Notice. Citation: "72 FR 44161" Federal Register Page Number: "44161" "Notices" LOAD-DATE: August 7, 2007 LANGUAGE: ENGLISH Copyright 2007 Federal Information and News Dispatch, Inc. 288 of 998 DOCUMENTS CNS Drug News Pharmaceuticals August 3, 2007 Modafinil shows potential for BPD LENGTH: 247 words A preliminary study of 85 patients with bipolar disorder (BPD) has indicated that modafinil , a drug used to treat patients with sleep disorders, might also control the depressive symptoms associated with BPD. Modafinil is approved by the FDA to treat patients who suffer from excessive sleepiness associated with narcolepsy, obstructive sleep apnoea and shift work sleep disorder, and is marketed as Provigil by Cephalon . During the depressive phase of BPD, the symptoms include excessive sleepiness and fatigue, therefore researchers wondered if modafinil could address these symptoms in patients with this disorder. Half of the patients in the randomised, double-blind, placebo-controlled study, which was conducted at five sites and published in the August issue of the American Journal of Psychiatry (2007;164:1242-1249), were given modafinil 100-200mg/day, while the other half were given placebo over a six-week period. While the trial was small, 44 per cent of those receiving modafinil reported feeling better, while 39 per cent said their symptoms were in remission after six weeks. This compares to 23 and 18 per cent, respectively, in the control group. Modafinil was not associated with any greater risk of the manic and depressive mood swings associated with BPD. How exactly modafinil works to promote wakefulness or improve mood in BPD is not completely understood. Indeed, it appears to have an entirely different mechanism of action compared to other psychostimulants. LOAD-DATE: August 3, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2007 ESPICOM Business Intelligence Ltd. All Rights Reserved 289 of 998 DOCUMENTS M2 EquityBites July 23, 2007 Caraco Pharmaceutical Laboratories Ltd receives tentative FDA approval for Generic Provigil LENGTH: 150 words M2 EQUITYBITES-23 July 2007-Caraco Pharmaceutical Laboratories Ltd receives tentative FDA approval for Generic Provigil ©2007 M2 COMMUNICATIONS LTD http://www.m2.com Caraco Pharmaceutical Laboratories Ltd (Amex: CPD), which develops, manufactures, markets and distributes generic and private-label pharmaceuticals, reported on 20 July that the company has received tentative approval for its Abbreviated New Drug Application (ANDA) for Modafinil Tablets (modafinil), 100mg and 200mg from the US Food and Drug Administration (FDA). Modafinil is indicated to improve wakefulness in patients with excessive sleepiness associated with narcolepsy. The new product is the bioequivalent to Provigil, a registered trademark of Cephalon Inc. Provigil tablets had US sales of approximately USD753m for the 12-month period ended 31 March 2007, according to IMS Data. (Comments on this story may be sent to admin@m2.com) LOAD-DATE: July 23, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2007 M2 Communications Ltd All rights reserved 290 of 998 DOCUMENTS Knobias.com This content is provided to LexisNexis by Comtex News Network, Inc. July 20, 2007 Friday 2:37 PM EST CPD: FDA Grants Tentative Approval for Generic Provigil(R) LENGTH: 373 words DATELINE: Ridgeland, MS By Fain Hughes, fhughes@knobias.com Caraco Pharmaceutical Laboratories, Ltd. (CPD) announced that the FDA has granted tentative approval for the Company's Abbreviated New Drug Application (ANDA) for Modafinil Tablets (modafinil), 100mg and 200mg. Modafinil is indicated to improve wakefulness in patients with excessive sleepiness associated with narcolepsy. This new product is the bioequivalent to Provigil(R), a registered trademark of Cephalon, Inc. (CEPH). Provigil(R) tablets had U.S. sales of approximately $753 million for the 12-month period ended March 31, 2007, according to IMS Data. KNOBIAS DISCLAIMER: All statements made in this article were made by the Company and do not in any way reflect the opinions of Knobias. Knobias is not a registered broker-dealer, nor investment advisor, and does not endorse or recommend any securities mentioned. This story is provided for informational purposes only and is not intended for trading purposes. Knobias shall not be liable for any actions taken in reliance of any information provided herein. Republication or redistribution of Knobias content is expressly prohibited without prior written consent of Knobias.com, LLC. ABOUT KNOBIAS: Knobias is a premier financial information provider of trading and investing data covering all U.S. equities for investors and security professionals. Knobias is best described by its three major components: Real-time desktop applications providing quotes, charts, level 2, analysis etc.; Knobias RAiDAR providing thousands of real-time news stories, alerts and documents daily; Knobias fundamentals providing a comprehensive database of fundamental research information. If your company wishes to participate in the EventX newswire, please contact Knobias: http://www.knobias.com Knobias.com, LLC 601-978-3399 601-978-3675 info@knobias.com www.knobias.com/cmtx As of Monday, 07-16-2007 23:59, the latest Comtex SmarTrend® Alert, an automated pattern recognition system, indicated a DOWNTREND on 05-19-2006 for CPD @ $11.48. For more information on SmarTrend, contact your market data provider or go to www.mysmartrend.com SmarTrend is a registered trademark of Comtex News Network, Inc. Copyright © 2004-2007 Comtex News Network, Inc. All rights reserved. LOAD-DATE: July 21, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Web Publication Copyright 2007 Comtex News Network, Inc. All Rights Reserved Copyright 2007 Knobias.com, LLC, All rights reserved. 291 of 998 DOCUMENTS Theflyonthewall.com This content is provided to LexisNexis by Comtex News Network, Inc. July 20, 2007 Friday 2:35 PM EST CPD, CEPH: Hot Stocks LENGTH: 166 words 14:34 EDT Caraco Pharm-CPD announces tenative approval for generic Provigil - Caraco announced that the FDA has granted tentative approval for the company's Abbreviated New Drug Application (ANDA) for Modafinil Tablets, 100mg and 200mg. Modafinil is indicated to improve wakefulness in patients with excessive sleepiness associated with narcolepsy. This new product is the bioequivalent to Provigil, a registered trademark of Cephalon (CEPH). As of Monday, 07-16-2007 23:59, the latest Comtex SmarTrend® Alert, an automated pattern recognition system, indicated an UPTREND on 07-12-2007 for CEPH @ $82.86. As of Monday, 07-16-2007 23:59, the latest Comtex SmarTrend Alert, an automated pattern recognition system, indicated a DOWNTREND on 05-19-2006 for CPD @ $11.48. For more information on SmarTrend, contact your market data provider or go to www.mysmartrend.com SmarTrend is a registered trademark of Comtex News Network, Inc. Copyright © 2004-2007 Comtex News Network, Inc. All rights reserved. LOAD-DATE: July 21, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Web Publication Copyright 2007 Comtex News Network, Inc. All Rights Reserved Copyright 2007 TheFlyOnTheWall.com 292 of 998 DOCUMENTS UPI July 20, 2007 Friday 4:04 PM EST Caraco close to OK on generic Provigil LENGTH: 144 words DATELINE: DETROIT, July 20 Caraco Pharmaceutical Laboratories said Friday it has been granted tentative U.S. approval to market a generic version of Cephalon's Provigil. The company said the Food and Drug Administration has granted tentative approval to its modafinil tablets in 100-mg and 200-mg strengths, indicated to improve wakefulness in patients with excessive sleepiness associated with narcolepsy. Caraco said Provigil tablets had U.S. sales of roughly $753 million for the 12-month period ending March 31, based on IMS data. "We are extremely pleased to receive this tentative approval," said Daniel Movens, Caraco's CEO. "Modafinil was filed with a paragraph IV certification that we do not infringe and or that the Cephalon patent is invalid. We were not sued by Cephalon. We looked forward to marketing this product subsequent to the expiration of the patent and exclusivity period." LOAD-DATE: July 21, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2007 U.P.I. All Rights Reserved 293 of 998 DOCUMENTS US Fed News July 18, 2007 Wednesday 7:15 AM EST Missouri Inventors Develop Benzhydrylthioacetamide Preparation Process BYLINE: US Fed News LENGTH: 234 words DATELINE: Alexandria, Va. ALEXANDRIA, Va., July 18 -- Sidney Liang of Olivette, Mo., has developed a process for preparing benzhydrylthioacetamide. According to the U.S. Patent & Trademark Office: "The reaction employing the haloacetamide is conducted in a solvent comprising water and an organic solvent such as dimethylformamide having dissolved therein a basic salt such as potassium carbonate. The resulting benzhydrylthioacetamide can be oxidized to provide the pharmaceutical modafinil." An abstract of the invention, released by the Patent Office, said: "The reaction employing the haloacetamide is conducted in a solvent comprising water and an organic solvent such as dimethylformamide having dissolved therein a basic salt such as potassium carbonate. The resulting benzhydrylthioacetamide can be oxidized to provide the pharmaceutical modafinil." The inventor was issued U.S. Patent No. 7,244,865 on July 17. The patent has been assigned to Mallinckrodt Inc, Hazelwood, Mo. The original application was filed on Feb. 23, 2004, and is available at: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=% 2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=7,244,865.PN.&OS=PN/7,244,865&RS= PN/7,244,865. For more information about US Fed News federal patent awards please contact: Myron Struck, Managing Editor/US Bureau, US Fed News, Direct: 703/866-4708, Cell: 703/304-1897, Myron@targetednews.com LOAD-DATE: July 18, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2007 HT Media Ltd. All Rights Reserved 294 of 998 DOCUMENTS The Sunday Times (London) July 15, 2007 Tired professors take 'smart' pills to perk up lectures BYLINE: Will Iredale SECTION: HOME NEWS; News; Pg. 7 LENGTH: 456 words UNIVERSITY academics are using a "smart" prescription drug that enhances memory and boosts concentration to give them the edge over their rivals when giving presentations. Studies into the effects of Modafinil, an American drug, have shown it can improve mental ability without the side effects of stimulants such as amphetamines or caffeine. Modafinil was created to help sufferers from sleep disorders. It is also stocked by the American army for use by exhausted soldiers. Those academics who use the drug often do so because they fly round the world giving lectures. They take Modafinil to perk themselves up after long flights so that they can make their presentations despite jetlag. Philip Harvey, professor of psychiatry and behavioural sciences at Emory University school of medicine in Atlanta, said he had recently taken a Modafinil tablet before flying to Britain to give a presentation the afternoon he landed. "Ratings I have received for those presentations when I have used Modafinil have been the same as at other times (when not jetlagged)," said Harvey. "It makes you seem less tired and helps you perform the same as usual under less than optimal conditions." Barbara Sahakian, professor of neuropsychology at Cambridge University, who has researched Modafinil, said academics she knew had started using the drug after hearing about it through their work. "I flew over to a conference in Florida and one of my colleagues offered me some Modafinil. I found at least four colleagues took it and that was without me even asking them. One was at Oxford, two were from The Hague and one was in Washington," said Sahakian. Researchers at Cambridge University who examined the effects of Modafinil found that it dramatically improved memory function in healthy people who were not sleep deprived. Danielle Turner, from the department of psychiatry at Cambridge, tested 60 healthy young males on their ability to use touch-sensitive computer screens after they had received either a placebo or a Modafinil tablet. She found the volunteers given Modafinil performed significantly better and showed less impulsive responding and an increased tendency to reflect on the tasks they were given. Modafinil can be bought over the internet or as a prescription drug in Britain to treat sleep disorders such as narcolepsy. Although it can have mild side effects, such as headaches, it is not addictive. In April Foresight, a government think tank, said "cognitive enhancers" such as Modafinil could be "as common as coffee" within a couple of decades to help a person think faster and sleep more efficiently. The Department of Health has asked The Academy of Medical Sciences to assess the impact of such substances and a report is due in November. LOAD-DATE: July 15, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2007 Times Newspapers Limited All Rights Reserved 295 of 998 DOCUMENTS Ob/Gyn. News July 1, 2007 Modafinil May Help Patients With Chemo Brain BYLINE: Kerri Wachter, Senior Writer SECTION: Pg. 4 Vol. 42 No. 13 ISSN: 0029-7437 LENGTH: 649 words    CHICAGO - The narcolepsy drug modafinil (Provigil) appears to improve attention and memory in breast cancer patients with chemo brain, a reduction in cognitive function that has been associated with chemotherapy, according to data presented at the annual meeting of the American Society of Clinical Oncology.    In a secondary analysis, Sadhna Kohli, Ph.D., of the University of Rochester (N.Y.), and her colleagues assessed the effect of modafinil on memory and attention in 68 women with breast cancer who had completed chemotherapy. The study's primary end point was fatigue. The researchers hypothesized that improvements in fatigue would be associated with improvements in cognition as well. "Our results are the first to suggest that modafinil should be further investigated as a new therapy for treating cognitive dysfunction after breast cancer therapy," said Dr. Kohli.    Persistent cognitive impairment is a recognized side effect of chemotherapy for cancer. The condition is often referred to as "chemo brain" or "chemo fog." Dr. Kohli previously reported that 82% of cancer patients who underwent chemotherapy experienced problems with memory and concentration.    The study began with 82 women who had scores of at least two on question No. 3 of the Brief Inventory of Fatigue (0-10 rating of worst fatigue in the past 24 hours) and had been off chemotherapy for an average of 22 months. They received 200 mg modafinil once daily for 4 weeks in the open-label portion of the trial. A total of 76 women completed this portion of the trial. Following the open-label phase, 68 women were randomized to receive either 200 mg modafinil or placebo daily.    Tests of memory and attention, selected from the Cognitive Drug Research computerized cognitive assessment, were performed at baseline and after completing the open-label and randomized phases. The validity, test-retest reliability, and sensitivity of this assessment tool had been demonstrated in several populations, including those with normal aging, depression, and drug-induced cognitive changes.    In particular, the researchers looked at five memory/attention components: quality of episodic memory, speed of memory, continuity of attention, quality of working memory, and power of attention.    There was a statistically significant improvement in the quality of episodic memory (immediate word recall, word recognition accuracy, and picture recognition accuracy) and speed of memory (two memory tasks and two recognition tasks) from baseline to week 4 (the open-label phase).    At 4-8 weeks (the randomized phase), patients on modafinil had a larger improvement in speed of picture recognition (a subsummary measure of memory speed) than those on placebo. Likewise, patients on modafinil had a greater improvement in immediate word recall (a subsummary measure of quality of episodic memory).    Although there was no statistically significant difference in the improvement of continuity of attention between baseline and week 4 (when all women were on modafinil), women who continued on the drug did show a statistically significant improvement at week 8, compared with week 4. "Taking modafinil for a longer period does improve attention skills," said Dr. Kohli. In addition to being faster, patients were also more accurate at retrieving information from memory. Improvement in the quality of episodic memory indicates that patients on modafinil were better able to store, retain, and retrieve both verbal and pictorial information.    Modafinil is a central nervous system stimulant that is indicated to improve wakefulness in patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome, and shift-work sleep disorder. The drug has been shown to reduce fatigue and improve declining mental performance in military personnel performing continuous cognitive work. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: OBNEWS Copyright 2007 Elsevier Inc., International Medical News Group All Rights Reserved 296 of 998 DOCUMENTS The Daily Telegraph (LONDON) June 23, 2007 Saturday Students using prescription drug to boost performance in exams BYLINE: Laura Clout SECTION: NEWS; Pg. 10 LENGTH: 420 words STUDENTS are using a controversial prescription drug that can keep them awake for days and boost their short-term memory to improve their exam performance, experts claimed last night. Modafinil pills, known on the drugs scene as "zombies'', are among a new breed of cognitive enhancers, or "smart drugs''. Widely used in America and easily available on the internet, they appear to be satisfying a growing demand for chemical mental enhancement among students when revising for important exams. It was reported this year that students at Oxford University were rejecting the traditional choices, caffeine and ginseng, in favour of the anti-hyperactivity drug Ritalin. Drug trials suggest that Modafinil leads to an increase in energy and alertness, boosts short-term memory and enables users to go for long periods without sleep. Its makers say there are no side-effects, but experts are worried about the potential for the drug to be abused. In the United States, where Modafinil is used by students, clubbers and office workers, there is anecdotal evidence that high doses of the drug cause anxiety and headaches. Paul Cooper, the director of education at Leicester University, has called for a debate on whether such drugs, which are banned for athletes, should be permitted for students in exams. He said last night: "Should we regard these drugs as a pharmaceutical version of the pocket calculator - something that students now rely on in exams as a matter of course? This is a debate that needs to happen.'' Barbara Sahakian, professor of clinical neuropsychology at Cambridge University, agreed that a debate was needed about how smart drugs should be treated given their benefits. She said: "We've done studies on Modafinil. It's very effective and it doesn't have the same side-effects as Ritalin. I've been at meetings where I've been offered Modafinil by colleagues, to combat jet lag. "This is one of the first drugs where it doesn't seem to have abuse potential. It seems to be a good enhancing agent with minimal side-effects.'' But she added: "The question is, what do we do? Should we treat it like coffee?'' If the answer is yes, the next question facing universities may be whether they should encourage students to take drugs. Foresight, the Government think-tank, has said such drugs could be "as common as coffee'' within a couple of decades. Such is the concern that the Department of Health has asked the Academy of Medical Sciences to assess their potential impact in a report due to be published in November. LOAD-DATE: June 23, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2007 Telegraph Group Limited All Rights Reserved 297 of 998 DOCUMENTS The Times (London) June 23, 2007, Saturday Cheating students turn to 'smart drug' for edge in exams BYLINE: Alexandra Frean Patrick Foster SECTION: HOME NEWS; Pg. 16 LENGTH: 546 words Students say they are turning to a powerful prescription drug that is stocked by the Army to keep combat troops alert. Modafinil, used to treat sleep disorders such as narcolepsy, appears to be overtaking the anti-hyperactivity medicine Ritalin as the "smart drug" of choice on university campuses. Drug trials suggest that modafinil, which can be bought on the internet, is highly effective at enhancing short-term memory and enabling users to stay up for extended periods. But experts say overuse can produce adverse side-effects. Some are also beginning to question why a performance-enhancing drug that is banned for athletes in the Olympics should be allowed for students in exams. Paul Cooper, director of education at Leicester University, said that, although universities had been aware for some time that students were using drugs such as Ritalin and modafinil to get them through their exams, there had been no proper consideration of whether this constituted cheating. "As a society we need to ask whether we are happy about people who have no impairments using these drugs to enhance their exam performance -we don't allow it in sport, so why at university? Should we regard these drugs as a pharmaceutical version of the pocket calculator -something that students now rely on in exams as a matter of course? This is a debate that needs to happen." Barbara Sahakian, Professor of Clinical Neuropsychology at Cambridge University, agreed that it was difficult to know where to draw the line. "We've done studies on modafinil. It's very effective and it doesn't have the same side-effects as Ritalin. I've been at meetings where I've been offered modafinil by colleagues to combat jet lag," she said. "This is one of the first drugs where it doesn't seem to have abuse potential. It seems to be a good enhancing agent with minimal side-effects. The question is what do we do? Should we treat it like coffee?" If the answer is yes, the next question facing universities may be this: should students be encouraged to take such drugs? Students have used drugs to boost their study performance in the past. Caffeine and ginseng are traditional favourites. But recently the use of more powerful, restricted drugs, particularly Ritalin, has spread from campuses in the US. At present the debate within British universities remains focused on the health risks faced by students taking prescription drugs. But students appear not to share these concerns. An undergraduate at Oxford told The Times that he was selling modafinil tablets to other students. "I bought the tablets on a Canadian website but they were produced in India," he said. "I paid less than £ 1 per tablet and sold them on for £ 8 to £ 12 a hit. I made over £ 3,000 in less than two months. It got even more popular as finals approached." He said that he would get up at 5am, take a tablet and then go back to sleep for an hour. "I'd get up and feel completely refreshed, and I could work all the way through until going to bed at 1am the next morning." A spokesman for Oxford University said that any student aware of drug dealing should report it to the police. Veronica King, head of welfare at the National Union of Students, said that such dealing may be a sign of the increasing pressures placed on today's students. LOAD-DATE: June 23, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2007 Times Newspapers Limited All Rights Reserved 298 of 998 DOCUMENTS The Times (London) June 23, 2007, Saturday It might be useful for judges and soldiers -but there are drawbacks BYLINE: Dr Thomas Stuttaford SECTION: HOME NEWS; Pg. 16 LENGTH: 521 words Modafinil first came to the public notice when it was suggested that this was the ideal pill to ensure that judges stayed awake in the court room and that it might have the additional advantage that it might make their already-keen brains even sharper. Reports about the clinical use of modafinil first appeared in the journal Neurology in 1997; the following year an even larger study was published in the Annals of Neurology about an American trial of the drug. Following these initial research papers there has been a host of other papers describing its use in different neurological conditions. It is now the drug of choice in treating narcolepsy, which can cause an overwhelming need to go to sleep, often at inconvenient moments. Modafinil is also prescribed to counteract the tiredness associated with shift working, and in those who suffer from sleepiness or lack of energy as the result of obstructive sleep apnoea (loud snoring and restless sleep). The Army, which during the Second World War used amphetamines to keep soldiers awake, is said to have stocks of modafinil as it is safer than amphetamines and is not thought to be addictive. However, psychological dependence can develop and it has many potential side-effects. It should not be taken by those who have cardiovascular problems, liver or kidney disease. Within the past two or three years it has been tried as a drug that might sharpen up the intellects of people who have suffered strokes, and in general it does seem to have the ability to improve short-term memory. As with any useful drug there is the possibility of abuse and misuse. Some students take modafinil so they can work all hours of the day and night. They don't realise that the brain, like any other organ, needs periods of rest in between activity if it is to give its best performance. If someone continuously takes a stimulant day after day to cut down on sleep, they are likely to become sleep deprived. They will then become tense, edgy, irritable, aggressive and even confused and paranoid. Not the ideal mindset to have before sitting an exam. There is a well-known danger that athletics contests can degenerate into a competition between pharmacologists rather than sportsmen. It would be even more socially destructive if the difference between a first and a second at a university was determined by the skill of the student doctors' and their understanding of pharmacology rather than the inherent ability of the student. The drugs Modafinil Licensed in 1997, it is used to treat narcolepsy and other sleep disorders. Helps users to stay awake when needed but still sleep at night. Is not a cure but reduces sleepiness Sold under the name Provigil; modafinil is the active ingredient Less likely than Ritalin to cause jitteriness; side-effects can include headaches Ritalin Licensed in 1997, it is used for attention-deficit hyperactivity disorder. Children with ADHD tend to be restless and find it difficult to concentrate Its active ingredient is methylphenidate hydrochloride Side-effects can include headaches, loss of appetite and jitteriness Sources: Cephalon/provigil.com; Novartis LOAD-DATE: June 23, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2007 Times Newspapers Limited All Rights Reserved 299 of 998 DOCUMENTS PR Newswire US June 18, 2007 Monday 10:55 AM GMT Cephalon Receives FDA Approval of NUVIGIL(TM) for the Treatment of Excessive Sleepiness Associated with Three Disorders LENGTH: 1082 words DATELINE: FRAZER, Pa. June 18 FRAZER, Pa., June 18 /PRNewswire-FirstCall/ -- Cephalon, Inc. (NASDAQ:CEPH) today announced that it has received approval from the U.S. Food and Drug Administration to market NUVIGIL(TM) (armodafinil) Tablets [C- IV], a non-amphetamine wake-promoting agent for the treatment of excessive sleepiness associated with obstructive sleep apnea/hypopnea syndrome (OSAHS), narcolepsy, and shift work sleep disorder (SWSD). In OSAHS, NUVIGIL is indicated as an adjunct to standard treatment(s) for the underlying obstruction. NUVIGIL is the single-isomer formulation of modafinil, the active pharmaceutical ingredient contained in PROVIGIL(R) (modafinil) Tablets [C-IV], which was approved by FDA in 1998 to improve wakefulness. "FDA approval of NUVIGIL is a major accomplishment and the result of collaborative efforts with the scientific and regulatory communities," said Dr. Lesley Russell, Executive Vice President, Worldwide Medical and Regulatory Operations. "We are excited about the future of NUVIGIL and we have initiated additional clinical work to explore its potential in a wide range of medical disorders." Cephalon's clinical program will evaluate the use of NUVIGIL as a treatment for serious medical conditions such as bipolar depression, cognition associated with schizophrenia, excessive sleepiness in medical conditions such as Parkinson's disease, and fatigue in patients who are being treated for cancer. The company currently plans a commercial launch of NUVIGIL once additional clinical data has been amassed. "The approval of NUVIGIL allows us to preserve our current leadership position in the area of wakefulness," said Frank Baldino, Jr., Ph.D., Chairman and CEO, Cephalon. "More importantly, we now have a longer-term opportunity to further characterize the utility of this compound beyond wakefulness." NUVIGIL is protected by a U.S. patent expiring in 2023. The agency has approved final labeling for NUVIGIL, including a bolded warning, which is consistent with the draft labeling received by the company in March 2007. Full prescribing information will be available on the FDA website or on the company's website at: http://www.cephalon.com/newsroom/assets/Nuvigil_Prescribing_Information.pdf . As expected, the agency also has indicated that it will request similar language in the label for PROVIGIL. About NUVIGIL The active pharmaceutical ingredient in NUVIGIL, armodafinil, is the longer-lived r-enantiomer of modafinil, the active ingredient in PROVIGIL. The approval of NUVIGIL is based on positive results of four double-blind, randomized, placebo-controlled studies in patients with excessive sleepiness associated with either narcolepsy, SWSD or OSAHS. In these studies, NUVIGIL was generally well tolerated. The most common side effects were mild to moderate in intensity and included nausea, headaches, dizziness, diarrhea, decreased appetite and upset stomach. About Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products in four core therapeutic areas: central nervous system, pain, oncology and addiction. Cephalon has delivered a seven-year compound annual growth rate (CAGR) greater than 75% and 2006 revenue of $1.760 billion. A member of the Fortune 1000, Cephalon currently employs approximately 3,000 people in the United States and Europe. U.S. sites include the company's headquarters in Frazer, Pennsylvania, and offices, laboratories or manufacturing facilities in West Chester, Pennsylvania, Salt Lake City, Utah, and suburban Minneapolis, Minnesota. Cephalon's European headquarters are located in Maisons-Alfort, France. The company's proprietary products in the United States include: PROVIGIL, FENTORA(R) (fentanyl buccal tablet) [C-II], TRISENOX(R) (arsenic trioxide) injection, VIVITROL(R) (naltrexone for extended-release injectable suspension), GABITRIL(R) (tiagabine hydrochloride), and ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II]. The Company also markets numerous products internationally. Full prescribing information on its U.S. products is available at http://www.cephalon.com/ or by calling 1-800-896-5855. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs; development of potential pharmaceutical products, including any additional clinical programs with respect to NUVIGIL; interpretation of clinical results, particularly with respect to the NUVIGIL clinical trials; manufacturing development and capabilities; market prospects for its products, including the timing of the commercial launch of NUVIGIL, the clinical utility of NUVIGIL and the longer-term opportunities with NUVIGIL beyond its current indication; sales and earnings guidance; and other statements regarding matters that are not historical facts, including the protection afforded by any patents covering NUVIGIL. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. CONTACT: Media: Jenifer Antonacci, +1-610-738-6674, jantonacci@cephalon.com , or Investors: Robert (Chip) Merritt, +1-610-738-6376, cmerritt@cephalon.com , both of Cephalon, Inc. Web site: http://www.cephalon.com/ Company News On-Call: http://www.prnewswire.com/comp/134563.html SOURCE Cephalon, Inc. URL: http://www.prnewswire.com LOAD-DATE: June 19, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2007 PR Newswire Association LLC. All Rights Reserved. 300 of 998 DOCUMENTS US Fed News June 12, 2007 Tuesday 4:42 AM EST Indiana, Ohio, Delaware Inventors Develop Modafinil Pharmaceutical Formulations BYLINE: US Fed News LENGTH: 157 words DATELINE: Alexandria, Va. ALEXANDRIA, Va., June 12 -- Vincent Corvari of Carmel, Ind., George Grandolfi of Milford, Ohio, and Alpa Parikh of Hockessin, Del., have developed compositions of modafinil, including compositions of modafinil and one or more diluents, disintegrants, binders and lubricants, and the processes for their preparation thereof, the U.S. Patent & Trademark Office announced. The inventors were issued U.S. Patent No. 7,229,644 on June 12. The patent has been assigned to Cephalon Inc., Frazer, Pa. The original application was filed on Sept. 13, 2002, and is available at: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=% 2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=7,229,644.PN.&OS=PN/7,229,644&RS= PN/7,229,644. For more information about US Fed News federal patent awards please contact: Myron Struck, Managing Editor/US Bureau, US Fed News, Direct: 703/866-4708, Cell: 703/304-1897, Myron@targetednews.com LOAD-DATE: June 12, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2007 HT Media Ltd. All Rights Reserved 301 of 998 DOCUMENTS CTV Television, Inc. June 3, 2007 Sunday SHOW: CTV NEWS 23:00:00 ET Latest cancer research and treatments ANCHORS: SANDIE RINALDO LENGTH: 396 words SANDIE RINALDO: Some of the world's leading cancer experts are in Chicago this weekend to discuss the latest research and treatments, and today they're talking about a little pill that's showing big promise. It's used to stimulate brain activity in people with neurological disorders, but researchers found it's also very effective in easing some of the debilitating side-effects of chemotherapy. CTV's Denelle Balfour has the details. DENELLE BALFOUR (Reporter): Diagnosed with breast cancer six years ago, Brenda Oathout faced her disease with courage and resolve to survive. But it was the side-effects of the treatment that nearly destroyed her will to go on. BRENDA OATHOUT (Cancer Survivor): It was hard for me to be a mother and a wife and to take care of my home. BALFOUR: She suffered from chemo brain or chemo fog, a long misunderstood and untreated side-effect of chemotherapy in some patients. OATHOUT: You forget phone numbers. You forget how to get to places. It's just, you draw a blank. You just simply draw a blank. It's scary. BALFOUR: Now there could be help in a drug described by some as a genius pill because it's often sought out by sleep deprived students and athletes. It's called Modafinil, most often used to treat narcolepsy. SADHNA KOHLI (University of Rochester Medical Centre): And what we found was that Modafinil did improve fatigue and memory and did improve memory and attention skills. BALFOUR: In a first of its kind study, New York researchers, funded by the drug maker, tested the effects of Modafinil on 68 women being treated for breast cancer. Oathout was one of them. OATHOUT: It was instantaneous. The very first thing I noticed was the fatigue was gone, and then I noticed the struggle wasn't there. BALFOUR: All of the women took Modafinil for the first four weeks of the trial. For the next month, half of the women were given a placebo, but only the women who continued to take Modafinil reported less fatigue and better concentration. DR. BARBARA COLLINS (Ottawa Hospital): What this study is I think doing is giving some hope that perhaps there is a treatment for this, and also validation I think of patients' complaints. BALFOUR: It's hoped this study will lead to an approach in the medical community that is not only focused on beating the cancer, but also improving quality of life during treatment. Denelle Balfour, CTV News, Toronto. LOAD-DATE: June 4, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Transcript Copyright 2007 CTV Televisions, Inc. All Rights Reserved 302 of 998 DOCUMENTS Internal Medicine News May 15, 2007 FDA Cites Provigil Maker for Unapproved 'Fatigue' Promotion BYLINE: Elizabeth Mechcatie SECTION: Pg. 6 Vol. 40 No. 10 ISSN: 1097-8690 LENGTH: 269 words    The Food and Drug Administration has sent a warning letter to the manufacturer of modafinil about promoting the drug for treating fatigue associated with some neurologic and psychiatric disorders for which the drug is not approved.    Promoting a drug for an indication that is not approved by the FDA is a violation of the Federal Food, Drug, and Cosmetic Act.    Modafinil, marketed as Provigil by Cephalon, is approved for improving wakefulness in people with excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome (OSAHS), and shift-work sleep disorder. It is also approved for people with OSAHS as an adjunct to standard treatment for the underlying obstruction.    But a warning letter sent by the FDA to Cephalon said that as part of a presentation made on behalf of the company at a meeting of the Maryland Department of Health and Hygiene's Pharmacy and Therapeutics Committee in August 2006, a handout was provided on the use of modafinil in the medical and psychiatric population.    The handout was "false and misleading," because it "states or suggests that Provigil is safe and effective in the treatment of various disorders associated with fatigue, sleepiness, or inattentiveness, when in fact, Provigil is not indicated for fatigue at all and is indicated only for specific groups of patients with excessive sleepiness," according to the FDA letter.    A spokesperson for Cephalon said that the company takes its regulatory responsibility seriously and has "worked diligently to develop procedures and policies to ensure that our products are lawfully promoted." LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: IMNEWS Copyright 2007 Elsevier Inc., International Medical News Group All Rights Reserved 303 of 998 DOCUMENTS The Times (London) May 14, 2007, Monday Smart drugs for straight As BYLINE: Peta Bee SECTION: FEATURES; Times2; Pg. 8 LENGTH: 1820 words Boosting your brain power by taking a pill could become a reality in the next few years - but such drugs raise serious ethical and medical issues. PETA BEE investigates It is probably fair to say that Bjorn Stenger was not at the back of the queue when brains were being handed out. In fact, many might think there was little room for improvement, given that he had graduated with a PhD in engineering from Cambridge University. Within an hour of taking a drug called Modafinil, though, Stenger appeared to become cleverer. Taking part in a study at the university, Stenger, 33, took the drug, commonly used to treat sleep disorders such as narcolepsy, and then performed some computerised tests. Results showed improvements in his short-term memory, attention span and reaction time. "I definitely felt a change," he says. "It was a bit like the feeling you get after drinking strong coffee. I was somewhat more alert, but not as jittery as after I have drunk coffee. I became very focused on those tests." Caffeine, guarana and other stimulants have long been used to ward off tiredness or give an instant lift when needed. But their boost to the brain, by firing the entire nervous system, is short-lived. Modafinil, though, is one of a new breed of "smart" drugs that offer targeted, more powerful mental sharpening. They are already widely used in America -studies have indicated that the black market for such drugs is rife, particularly among university students -and there are indications that the demand for chemical mental enhancement is about to take off in the UK. Modafinil is easily purchased on the internet -I bought a packet of the green tablets for £ 64. Such is the concern that the Government has commissioned research to review the safety of brain-boosting pills. A report by the Academy of Medical Sciences (AMS), commissioned by the Department of Health, is due to be published and presented to the Government by November. Dr Danielle Turner, a researcher in the department of experimental psychology at Cambridge University who is working on the AMS review, says there is growing evidence that certain drugs do help the brain work better. "So far, we do not know enough about the full range of drugs that can affect thinking, but in the case of Modafinil the side-effects appear to be benign," Turner says. "It seems to improve short-term memory, the ability to plan and process information, and helps a person to be less impulsive and more reflective about their decision-making, which lends itself to greater accuracy." In a 2003 study with Barbara Sahakian, a professor of clinical neuropsychology at Cambridge, Turner found that healthy, male Cambridge students such as Stenger who took a standard 200mg dose of Modafinil were found to use information more effectively and efficiently. When confronted with conflicting stimuli, the people who had taken Modafinil moved from one task to the next more smoothly and adjusted swiftly without getting stressed or anxious. Sahakian suggested that Modafinil "may be the first real smart drug" and that "a lot of people will probably take it. I suspect they do already." Last year it was revealed that Modafinil has been tested by British Armed Forces and was reportedly stockpiled by the Ministry of Defence before the Iraq War, although it was never given to combat personnel. But Modafinil does not stand alone in its ability to sharpen the mind. A drug prescribed for Alzheimer's disease -donepezil -has been shown to delay loss of mental ability in patients and, more recently, to boost performance in tests of cognitive skill. In one trial, published in the journal Neurology, pilots who took donepezil for a month performed better in flight simulator tests than pilots who had taken a placebo. Another drug, propanolol, seems to erase the negative emotions associated with bad memories so that people who have taken it reel off disturbing stories as if they were reading a food label. Ritalin, best known as a treatment for attention-deficit hyperactivity disorder, improves concentration and the ability to plan, perhaps appealing to adults who want an edge in mental multitasking. Studies have also shown that the drug boosts spatial working memory and the ability to remember graphs and diagrams, and anecdotal evidence suggests that it improves concentration levels. A study of 2,200 American students published in the journal Pharmacotherapy in 2004 found that 66 of them admitted using Ritalin as a study aid in the previous 12 months. Chat rooms on US-based websites such as the Student Doctor Network frequently discuss the purported merits of taking Ritalin and other drugs to boost mental output in preparation for exams. Research at the University of Michigan shows that 8 per cent of undergraduates report having illegally used prescription drugs most commonly to improve alertness and attention. In many cases, scientists have stumbled across cognition-enhancing effects of drugs while researching their applications for serious neurological conditions. Stroke patients who took small doses of amphetamines an hour before therapy were found to perform better in simple motor skills (the tying of shoelaces and using cutlery, for example) and scientists confirmed that the drugs seem to promote "neuroplasticity" or the strengthening of brain connections. That led some, including Dr Anjan Chatterjee, a neurologist at the University of Pennsylvania, to question whether amphetamines might help healthy adults to learn skills more easily. Other potential smart drugs, each operating on different parts of the brain, are in development (see box) and, provided they pass safety and effectiveness tests, are likely to become available in the next few years. One is a new class of drugs called ampakines that have already proved to be effective memory-boosters in early trials. In marketing terms, the potential for such drugs has never been greater. By 2012, about 41 per cent of the UK population (23.8 million people) will be over 50, an age at which memory and mental acuity demonstrate a significant decline. For the baby boomer generation, the anxiety of watching their parents slip into dementia means that the prospect of delaying their own mental decline is likely to become as enticing as the possibility of preserving a youthful appearance. Like Botox (originally developed for eye muscle problems), each of the drugs identified as having cognition-boosting effects also has genuine medical applications. Yet, potentially, they could follow the same marketing pattern as the drug that has become better known as a wrinkle eraser. Dr Chatterjee goes so far as to suggest that the trend for what he terms "cosmetic neurology" will one day mean not only sharpening intelligence but enhancement of other dictates of the brain -attention span, memory and reflexes. Writing in the journal Neurology three years ago, he said the day when healthy individuals pop a pill before an exam or a golf lesson "is coming, and we need to know it's coming". It presents an overwhelming ethical dilemma, he wrote, namely that "if the purpose of medicine is to improve the quality of life of individuals who happen to be sick, then should medical knowledge also be used to enhance the life quality of those who happen to be healthy?" That is, should drugs with known cognitive benefits be restricted for use only by those with illnesses such as Alzheimer's. The emergence of brain-boosting drugs raises serious ethical questions. Drugs such as Modafinil can cost as much as £ 4 a dose on the black market: will the rich simply get smarter and the poor be destined never to catch up? In an interview with the Los Angeles Times, Professor James McGaugh, a neurobiology professor at the University of California, suggested that it is inevitable that pushy parents will one day give mind-enhancing pills to their children. "If there is a drug that is safe and effective and not too expensive for enhancing memory in normal adults, why not normal children?" he proposed. "After all, they're going to school and what's more important than the education of the young? And what would be more important than giving them a little chemical edge?" But will those who don't take them at work or school be at a disadvantage, and will the taking of drugs to boost performance become, in essence, a form of cheating and be deemed as unethical as doping in sport? There are concerns, too, about the long-term effects of healthy people using such drugs. All drugs have side-effects, says Turner. In cases where people require them for medical reasons, they are often prepared to overlook those side effects if the medication improves their condition. But, she says, "it would be devastating to learn that a dazzling youth of successful cognitive enhancement meant a middle-age of premature memory loss and cognitive decline". Perhaps most worrying is the way that these drugs might change who we are. To be human is to be in possession of a personality with a unique blend of traits; some scientists argue that changing one mental function might have an effect on others. To tinker with the mind, then, might result in better memory, focus and attention in particular tests, but limit ability to shift attention and interpret anything new or different. In short, cognitive enhancers might enable us to know everything, but to lose our sense of individuality and opinion and to understand nothing. BRAIN-BOOSTERS: WHAT'S ON THE HORIZON? Ampakines: research has indicated that this group of memory-modulating drugs, developed for the treatment of Alzheimer's disease, has cognitive enhancing effects. Donepezil: a cholinesterase inhibitor developed for the treatment of dementia that has also been shown to boost the brain function of healthy people. It increases the concentration of a neurotransmitter called acetylcholine, boosting the power of certain electrical transmissions between brain cells. Modafinil: developed to treat the sleeping disorder narcolepsy, it has been shown in clinical trials to boost the cognitive performance of healthy young people and of helicopter pilots deprived of sleep. Ritalin: a stimulant with a medical use as a treatment for attention deficit hyperactivity disorder (ADHD) in children. It's easily obtained on the internet or black market (it is dubbed "vitamin R") and studies reveal widespread use among American students looking to improve concentration and alertness. Propranolol: a beta-blocker shown in tests to neutralise emotionally-distressing memories. A study in the journal Biological Psychiatry showed that patients in A&E departments who were given the drug had a lower incidence of post-traumatic stress symptoms. Mem compounds: three separate compounds are under development by the US company Memory Pharmaceuticals Corporation as possible treatments for Alzheimer's disease. Animal studies suggest that they can help to restore memory. LOAD-DATE: May 14, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2007 Times Newspapers Limited All Rights Reserved 304 of 998 DOCUMENTS Clinical Psychiatry News May 2007 Provigil Maker Cited After Promotion Of Unapproved 'Fatigue' Indication BYLINE: Elizabeth Mechcatie, Senior Writer SECTION: Pg. 3 Vol. 35 No. 5 ISSN: 0270-6644 LENGTH: 354 words    The Food and Drug Administration has sent a warning letter to the manufacturer of modafinil about promoting the drug for the treatment of fatigue associated with some neurologic and psychiatric disorders for which it is not approved.    Promoting a drug for an indication not approved by the FDA is a violation of the Federal Food, Drug and Cosmetic Act.    Modafinil, marketed as Provigil by Cephalon, is approved for improving wakefulness in people with excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome (OSAHS), and shift work sleep disorder (SWSD). It is also approved for people with OSAHS as an adjunct to standard treatment for the underlying obstruction.    But a warning letter sent by the FDA to Cephalon, dated Feb. 27, said that as part of a presentation made on behalf of the company at a meeting of the Maryland Department of Health and Hygiene's Pharmacy and Therapeutics Committee in August 2006, a handout was provided on the use of modafinil in the medical and psychiatric population. The handout was "false and misleading," because it "states or suggests that Provigil is safe and effective in the treatment of various disorders associated with fatigue, sleepiness, or inattentiveness, when in fact, Provigil is not indicated for fatigue at all and is indicated only for specific groups of patients with excessive sleepiness," according to the FDA letter.    The promotional piece included the statement that modafinil "has utility" in treating the following neurologic and psychiatric disorders associated with fatigue, sleeplessness or inattentiveness: multiple sclerosis-related fatigue; Parkinson's disease-related fatigue; chronic fatigue syndrome, fibromyalgia and chronic pain conditions; attention-deficit disorder; and depression.    As requested by the FDA, Cephalon submitted a response to the letter by March 12, according to a company spokesperson, who said that the company takes its regulatory responsibility seriously and that the company has "worked diligently to develop procedures and policies to ensure that our products are lawfully promoted." LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: CPNEWS Copyright 2007 Elsevier Inc., International Medical News Group All Rights Reserved 305 of 998 DOCUMENTS Clinical Neurology News May 2007 News From The FDA Provigil Maker Cited for False 'Fatigue' Promotion BYLINE: Elizabeth Mechcatie, Senior Writer SECTION: Pg. 8 Vol. 3 No. 5 ISSN: 1553-3212 LENGTH: 337 words    The Food and Drug Administration has sent a warning letter to the manufacturer of modafinil about promoting the drug for the treatment of fatigue associated with some neurologic and psychiatric disorders for which the drug is not approved.    Modafinil, marketed as Provigil by Cephalon, is approved for improving wakefulness in people with excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome (OSAHS), and shift work sleep disorder (SWSD). It is also approved for people with OSAHS as an adjunct to standard treatment for the underlying obstruction.    But a warning letter sent by the FDA to Cephalon, dated Feb. 27, said that as part of a presentation made on behalf of the company at a meeting of the Maryland Department of Health and Hygiene's Pharmacy and Therapeutics Committee in August 2006, a handout was provided on the use of modafinil in the medical and psychiatric population.    The handout was "false and misleading," because it "states or suggests that Provigil is safe and effective in the treatment of various disorders associated with fatigue, sleepiness, or inattentiveness, when in fact, Provigil is not indicated for fatigue at all and is indicated only for specific groups of patients with excessive sleepiness," according to the letter.    The promotional piece included the statement that modafinil "has utility" in treating the following neurologic and psychiatric disorders associated with fatigue, sleeplessness or inattentiveness: multiple sclerosis-related fatigue; Parkinson's disease-related fatigue; chronic fatigue syndrome, fibromyalgia and chronic pain conditions; attention deficit disorder; and depression.    As requested by the Food and Drug Administration, Cephalon submitted a response to the letter, according to a company spokesperson, who said that the company takes its regulatory responsibility seriously and that the company has "worked diligently to develop procedures and policies to ensure that our products are lawfully promoted." LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: CNNEWS Copyright 2007 Elsevier Inc., International Medical News Group All Rights Reserved 306 of 998 DOCUMENTS Hindustan Times April 29, 2007 Sunday 12:19 PM EST Jury is out on wakefulness drug BYLINE: Hindustan Times LENGTH: 354 words DATELINE: NEW DELHI, India NEW DELHI, India, April 29 -- MEDICAL EXPERTS are saying highly stressed individuals in India - call center workers, corporate honchos and even students - have lately been using Modalert or Modafinil to cut down on sleeping time and enhancing alertness. Before you think it is yet another high inducing 'upper' like Amphetamine or Speed, here is what the drug actually is. Last week, Britain's Department of Health asked the Academy of Medical Sciences to assess Modafinil as a cognition-enhancing drug. In India, the medicine has been around for three years. It is given to narcoleptics, people with a neurological disorder marked by uncontrollable attacks of daytime sleep. A prescription drug, Modalert is manufactured by Sun Pharma and sold at Rs 60 for a strip of 10. Psychiatrist Dr Samir Parikh says, "we do not know the long term effects" of the "relatively new drug". "I have to work for long hours. I heard about Modalert from a friend and tried it. I was awake for 26 hours at a stretch, " says 29-year-old web designer, Raman Shah, who works in a publishing outsourcing firm. Dr Rajesh Sagar, associate professor, psychiatry, AIIMS, says he frequently gets patients who demand the drug. "We turn them away, as this drug may have serious side effects in the long run." He also says Modalert is often used by medical students at AIIMS for extended study sessions. "Recently, a patient wanted me to prescribe Modalert: he claimed he had to work long hours, he wanted to cut down on his sleep, yet stay alert," says Dr Anoop Misra, Head of the Diabetics and Metabolism, Fortis Hospital. While doctors in India are suspicious about the trend, the Department of Clinical Neurosciences in Cambridge University has examined the effects of Modafinil on healthy volunteers, and the results have been "dramatic". "With Modafinil they [the volunteers] seemed to think a bit longer and they were more accurate," Dr Danielle Turner, who headed the study, told the BBC. So, will Modalert be the new wonder drug? Don't try it out till the debate is settled. The Hindustan Times is provided through HT Syndication, New Delhi. LOAD-DATE: April 30, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2007 HT Media Ltd. All Rights Reserved 307 of 998 DOCUMENTS Hindustan Times April 28, 2007 Saturday 12:28 PM EST Disaster pill for staying awake BYLINE: Hindustan Times LENGTH: 353 words DATELINE: NEW DELHI, India NEW DELHI, India, April 28 -- MODAFINIL, A medicine prescribed for a rare sleep disorder, is being lapped up by students, call centre workers, corporate honchos - in fact, anyone leading a high stress 24/7 lifestyle - to help them stay alert, and not feel sleepy for as long as 36 hours. The medicine has been around in India for a little over three years and is normally given to people who suffer from narcolepsy, a neurological disorder marked by uncontrollable attacks of daytime sleep. In India, Modalert is manufactured by Sun Pharma and is sold for Rs 60 for a strip of 10. Last month, a white-collar corporate worker approached Dr Anoop Misra, head of the diabetics and metabolism, Fortis Hospital, requesting him for a prescription for Modalert. "He claimed he had to work long hours, he wanted to cut down on his sleep, yet stay alert", says Dr Misra. "Narcolepsy is a rare disease and one must understand Modafinil is a not a replacement for sleep." Dr Rajesh Sagar, associate professor, psychiatry, AIIMS, says that he regularly gets patients who demand the drug. "We turn away these people, as this drug may have serious side effects in the long run. It is not meant for healthy individuals". "We issue regular warnings to students about the harm of sleep deprivation", he says. "I have to work for long hours. I heard about Modalert from a friend and tried it. I was awake for 26 hours at a stretch", says 29-year-old web designer, Raman Shah (name changed). One reason for the rampant abuse of the drug are conflicting research findings. While clinical practitioners warn about the harmful effects of Modafilin, researchers are exploring its positive effects on human cognition. Last week, the BBC reported that researchers at the Department of Clinical Neurosciences in Cambridge University had examined the effects of Modafinil on healthy volunteers. The results were dramatic. "With Modafinil they [the volunteers] seemed to think a bit longer and they were more accurate," said Dr Danielle Turner, who headed the study, to the BBC. The Hindustan Times is provided through HT Syndication, New Delhi. LOAD-DATE: April 29, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2007 HT Media Ltd. All Rights Reserved 308 of 998 DOCUMENTS Hindustan Times April 28, 2007 Saturday 12:08 PM EST Jury is out on wakefulness drug BYLINE: Hindustan Times LENGTH: 354 words DATELINE: NEW DELHI, India NEW DELHI, India, April 28 -- MEDICAL EXPERTS are saying highly stressed individuals in India - call center workers, corporate honchos and even students - have lately been using Modalert or Modafinil to cut down on sleeping time and enhancing alertness. Before you think it is yet another high inducing 'upper' like Amphetamine or Speed, here is what the drug actually is. Last week, Britain's Department of Health asked the Academy of Medical Sciences to assess Modafinil as a cognition-enhancing drug. In India, the medicine has been around for three years. It is given to narcoleptics, people with a neurological disorder marked by uncontrollable attacks of daytime sleep. A prescription drug, Modalert is manufactured by Sun Pharma and sold at Rs 60 for a strip of 10. Psychiatrist Dr Samir Parikh says, "we do not know the long term effects" of the "relatively new drug". "I have to work for long hours. I heard about Modalert from a friend and tried it. I was awake for 26 hours at a stretch, " says 29-year-old web designer, Raman Shah, who works in a publishing outsourcing firm. Dr Rajesh Sagar, associate professor, psychiatry, AIIMS, says he frequently gets patients who demand the drug. "We turn them away, as this drug may have serious side effects in the long run." He also says Modalert is often used by medical students at AIIMS for extended study sessions. "Recently, a patient wanted me to prescribe Modalert: he claimed he had to work long hours, he wanted to cut down on his sleep, yet stay alert," says Dr Anoop Misra, Head of the Diabetics and Metabolism, Fortis Hospital. While doctors in India are suspicious about the trend, the Department of Clinical Neurosciences in Cambridge University has examined the effects of Modafinil on healthy volunteers, and the results have been "dramatic". "With Modafinil they [the volunteers] seemed to think a bit longer and they were more accurate," Dr Danielle Turner, who headed the study, told the BBC. So, will Modalert be the new wonder drug? Don't try it out till the debate is settled. The Hindustan Times is provided through HT Syndication, New Delhi. LOAD-DATE: April 29, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2007 HT Media Ltd. All Rights Reserved 309 of 998 DOCUMENTS Sydney Morning Herald (Australia) April 28, 2007 Saturday First Edition Perchance to dream; The office BYLINE: Lissa Christopher SECTION: MY CAREER; Pg. 2 LENGTH: 550 words Drugs to keep you awake would be a nightmare, writes Lissa Christopher. Last night I was awake for hours worrying about Allan Moss, the managing director of Macquarie Bank. I couldn't remember if his salary package last year was $20 million or $21 million. Either way, I thought, as the clock showed 3:07am in sickening green, why is he still working at all? Surely any balanced person who earned that much money in one year would work for precisely one year and then quit to do a whole lot of shopping and lying around looking smug. Are you all right, Allan? Why do you stay? And could you spare us $50 until payday? By 4am I had moved on to fretting about Richard Fairbank from Capital One Financial, who is the highest paid chief executive in the United States. In 2005, he earned US$249.42 million ($299 million), according to Forbes magazine. And, like Moss, he's still working. (He also calls himself Rich rather than Richard, which does strange things to my gag reflex.) If I earned that kind of money, there's no way I'd still be working. Frankly, I'd consider hiring someone to blink for me. Yet Fairbank has been head of COF for 11 years and on he plugs. It's another one of life's little mysteries. Thanks to all that stewing over executive salaries in the hour of the wolf, I now have a sleep debt that would rival your average Sydney mortgage. I have heard, however, that sleepiness - indeed, sleep itself - may soon be a thing of the past. A "wakefulness promoting agent" called Modafinil has been available on prescription in the UK for some time. It's meant for people with sleep-inducing conditions, such as narcolepsy. It's not a nasty amphetamine and it improves cognitive performance as well as reducing the need for sleep. It has scientists excited. New Scientist says everyone may soon be able to take Modafinil-like medications which could alleviate the need for sleep altogether. And I can just imagine what Australian Workplace Agreements will look like when that happens. I don't want to give up sleep. I'm really good at it. And dreaming gives me an exciting second life. I have been chased by a herd of marauding 10-litre buckets and had a fight with a tiny orange witch who wanted to hurt me with anchovies. And, just like you, I've had a few Kamasutra-esqe encounters with work colleagues with whom, when I'm awake, I can hardly bear to share an office complex. Anyway, apparently some perfectly healthy innovative types have bought Modafinil illegally via the internet and are using it to give them the edge at work, says London's Daily Telegraph. The British health department has commissioned a report into what might happen if everyone starts doing the same thing. "In a world that is increasingly non-stop and competitive," the report says, "the use of such substances may move from the fringe to the norm, with cognition enhancers used as coffee is today." The ethics of using cognitive enhancers in the workplace and elsewhere, it says, will take years to resolve. In the meantime, office workers could come to resemble elite athletes in one of those sports where everyone takes performance-enhancing drugs but no one admits it. To apply for a job, you will need to send in your resume and a urine sample. No one will sleep. The orange witch and her anchovies will be lonely. LOAD-DATE: July 17, 2007 LANGUAGE: ENGLISH GRAPHIC: CARTOON: By aweldon PUBLICATION-TYPE: Newspaper Copyright 2007 John Fairfax Publications Pty Ltd All Rights Reserved 310 of 998 DOCUMENTS The Associated Press April 25, 2007 Wednesday 5:59 PM GMT License of doctor in BALCO steroids scandal suspended SECTION: SPORTS NEWS LENGTH: 234 words DATELINE: SAN FRANCISCO The former medical director of the clinic involved in a sports doping scandal has been suspended from practicing medicine after investigators found he prescribed a stimulant to a sprinter without examining her. Dr. Brian Halevie-Goldman, a psychiatrist who was medical director for the Bay Area Laboratory Co-Operative that provided steroids to top athletes, was suspended for 90 days by the state medical board. Halevie-Goldman also was placed on five years' probation and ordered to undergo a psychiatric evaluation for allegedly providing the drug modafinil to the athlete at the request of BALCO founder Victor Conte, who served four months in federal prison for dealing steroids. Goldman told the board Conte provided him with false information about the sprinter's medical condition in order to obtain drugs for her. The doctor had no immediate comment when contacted Wednesday by The Associated Press. The medical board's accusation said the athlete, identified only as K.W., tested positive for modafinil at an international track meet in August 2003 and accepted a two-year suspension for admitting to its use in 2004. Kelli White, a BALCO client who tested positive for modafinil after winning gold medals in the 100- and 200-meter races at the world championships in Paris in August 2003, was stripped of those medals and suspended for two years after admitting in 2004 to using the banned stimulant. LOAD-DATE: April 26, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2007 Associated Press All Rights Reserved 311 of 998 DOCUMENTS THE SAN FRANCISCO CHRONICLE (California) April 25, 2007 Wednesday FINAL Edition THE BALCO CASE; Doctor who provided stimulant is suspended; State Medical Board calls sprinter's case 'gross negligence' BYLINE: Lance Williams, Mark Fainaru-Wada, Chronicle Staff Writers SECTION: BAY AREA; Pg. B3 LENGTH: 708 words The former medical director of BALCO, the Burlingame laboratory at the center of the sports steroids scandal, has been suspended from practicing medicine for 90 days because he provided prescription stimulants to a champion sprinter without ever examining her. The state Medical Board also put Dr. Brian Halevie-Goldman on five years' probation, ordered him to undergo a psychiatric evaluation and imposed other restrictions on his medical practice, saying he was guilty of "gross negligence" for misconduct in a high-profile sports doping case in 2003. In its decision, the board said Goldman had provided the powerful stimulant modafinil for the sprinter it identified only by the initials KW simply because he was asked to do so by BALCO founder Victor Conte, who later pleaded guilty to providing banned drugs to elite athletes. When KW failed a doping test after a track meet, Goldman faked a medical history and diagnosis in an effort to help her avoid punishment for using banned drugs before the race, the board said. Though the Medical Board withheld identification of the sprinter, the case involves elite sprinter Kelli White of Union City, a BALCO client who tested positive for modafinil after winning two gold medals at the World Championships in Paris in 2003. White later confessed to using banned drugs and was suspended from competition for two years. Saying she wanted to help clean up sports, White has testified at several athletes' disciplinary hearings conducted by the U.S. Anti-Doping Agency. Documents show Goldman told the Medical Board he had been "set up" by Conte, complaining that the BALCO founder had provided him with false information about the sprinter's medical condition in order to obtain drugs for her. Goldman didn't respond to a phone message Tuesday. Goldman is a psychiatrist who has worked at Fairfield's Amen Clinic. In 1984, he began moonlighting as medical director at Conte's Bay Area Laboratory Co-Operative in Burlingame. At some point Goldman stopped working there, but BALCO continued to list him on state documents as the lab's medical director, and he and Conte stayed in touch. In January 2003, according to the Medical Board, Conte asked Goldman to give him modafinil for White and, without ever talking with White, Goldman gave Conte samples of modafinil for her. At the time, Conte was providing the banned stimulant to several sprinters to help them run faster, according to court records. In August 2003, White won both the 100- and 200-meter races at the Paris world championships. Two days later, authorities announced that she had tested positive for modafinil. With Goldman's help, White tried to fight the charges. Goldman wrote a letter falsely claiming that White had a family history of narcolepsy and that he had given her the drug to treat the ailment, the Medical Board said. Goldman also wrote a letter to the International Association of Athletics Federations arguing that modafinil could not enhance athletic performance. Goldman was paid $5,000 for the letters, the Medical Board said. White later acknowledged that she had never suffered from narcolepsy, saying Goldman's diagnosis was part of a false alibi concocted by Conte. White said Conte and her coach, Remi Korchemny, had provided her many other banned drugs, including the undetectable steroid known as "the clear." Conte served four months in federal prison on his guilty plea in the BALCO steroids conspiracy case. Korchemny, who also pleaded guilty to steroid dealing, was put on probation. When Goldman was interviewed by the Medical Board, he acknowledged that he had first examined White on Oct. 1, 2003, weeks after she was suspended for using modafinil. At first, Goldman told investigators that he had consulted with White by phone before providing her with the drug, but he later admitted that he couldn't remember talking to her, the Medical Board said. In its April 16 decision, the board said Goldman "needs to gain insight into what caused him to participate in such unethical and dishonest conduct." In addition to the psychiatric examination, the board ordered him to take a course in medical ethics. Goldman also must hire a physician to monitor his medical practice and make regular reports to the medical board. LOAD-DATE: April 25, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2007 San Francisco Chronicle All Rights Reserved 312 of 998 DOCUMENTS Associated Press Worldstream April 25, 2007 Wednesday 6:17 PM GMT License of doctor in BALCO steroids scandal suspended SECTION: SPORTS NEWS LENGTH: 234 words DATELINE: SAN FRANCISCO The former medical director of the clinic involved in a sports doping scandal has been suspended from practicing medicine after investigators found he prescribed a stimulant to a sprinter without examining her. Dr. Brian Halevie-Goldman, a psychiatrist who was medical director for the Bay Area Laboratory Co-Operative that provided steroids to top athletes, was suspended for 90 days by the state medical board. Halevie-Goldman also was placed on five years' probation and ordered to undergo a psychiatric evaluation for allegedly providing the drug modafinil to the athlete at the request of BALCO founder Victor Conte, who served four months in federal prison for dealing steroids. Goldman told the board Conte provided him with false information about the sprinter's medical condition in order to obtain drugs for her. The doctor had no immediate comment when contacted Wednesday by The Associated Press. The medical board's accusation said the athlete, identified only as K.W., tested positive for modafinil at an international track meet in August 2003 and accepted a two-year suspension for admitting to its use in 2004. Kelli White, a BALCO client who tested positive for modafinil after winning gold medals in the 100- and 200-meter races at the world championships in Paris in August 2003, was stripped of those medals and suspended for two years after admitting in 2004 to using the banned stimulant. LOAD-DATE: April 26, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2007 Associated Press All Rights Reserved 313 of 998 DOCUMENTS The Associated Press State & Local Wire April 25, 2007 Wednesday 5:59 PM GMT License of doctor in BALCO steroids scandal suspended SECTION: SPORTS NEWS LENGTH: 234 words DATELINE: SAN FRANCISCO The former medical director of the clinic involved in a sports doping scandal has been suspended from practicing medicine after investigators found he prescribed a stimulant to a sprinter without examining her. Dr. Brian Halevie-Goldman, a psychiatrist who was medical director for the Bay Area Laboratory Co-Operative that provided steroids to top athletes, was suspended for 90 days by the state medical board. Halevie-Goldman also was placed on five years' probation and ordered to undergo a psychiatric evaluation for allegedly providing the drug modafinil to the athlete at the request of BALCO founder Victor Conte, who served four months in federal prison for dealing steroids. Goldman told the board Conte provided him with false information about the sprinter's medical condition in order to obtain drugs for her. The doctor had no immediate comment when contacted Wednesday by The Associated Press. The medical board's accusation said the athlete, identified only as K.W., tested positive for modafinil at an international track meet in August 2003 and accepted a two-year suspension for admitting to its use in 2004. Kelli White, a BALCO client who tested positive for modafinil after winning gold medals in the 100- and 200-meter races at the world championships in Paris in August 2003, was stripped of those medals and suspended for two years after admitting in 2004 to using the banned stimulant. LOAD-DATE: April 26, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2007 Associated Press All Rights Reserved 314 of 998 DOCUMENTS Daily Mail (London) April 18, 2007 Wednesday Fears over drugs that can boost your brain BYLINE: JENNY HOPE SECTION: ED 1ST; Pg. 17 LENGTH: 674 words NEW drugs that can boost brainpower could be given to children by pushy parents, it was claimed yesterday. There are also fears that high- flying professionals might take the 'cognition enhancers' to gain a competitive edge at work. The warnings came as Government backed researchers examine the potential of the drugs which previous research has shown to improve memory, concentration and learning ability. Critics say users can put themselves at risk of sleep deprivation and suffer damage to their brain and central nervous systems. In the U.S., cognition drugs are taken by people such as long-distance truckers, students and taxi drivers because it 'turns off' the need to sleep while allowing them to remain mentally alert for days. One of the drugs modafinil is licensed in the UK only to treat narcolepsy, a rare condition in which sufferers fall asleep without warning. It emerged last year that the UK military has tested modafinil and reportedly stockpiled thousands of pills ahead of the Iraq war. It has, however, never been given to combat troops. The drug has been banned by the International Olympic Committee, along with another stimulant, ephedrine, which has also been tested by the Ministry of Defence. Sales have risen by 39 per cent since modafinil was launched in 2004. The Academy of Medical Sciences is heading an independent official review of all medical substances that come under the banner of cognition enhancers. Professor John Bell, the academy's president, said: 'Our knowledge of how the brain works, how genes influence its behaviour and how it is influenced by chemicals, is developing at such a pace that we could be nearing a new era of drug use where we have medicines that can enhance our performance as well as improve our health.' But reaction from public workshops held by the academy across the country brought forth fears that students and workers might misuse the drugs. One respondent wondered whether she would be putting her children at a disadvantage if she did not give them access to such drugs. Another expressed concern that workers would have to take the drugs to keep up with colleagues. The review, commissioned by the Department of Health, follows research carried out by the Government's Foresight programme on brain science, addiction and drugs. It looked at the potential development of cognitive enhancers over the next 20 years and concluded they could become as 'common as coffee'. Professor Leslie Iversen, a member of the review team, told a London seminar it was vital to gauge public reaction. He said: 'We need to know the answer to the question Should cognition enhancers become available? 'We need evidence-based clarification of the effects of illegal and legal drugs and we can't exclude legal drugs from causing harm.' Research carried out at Cambridge University in 2002 found that healthy volunteers taking modafinil scored higher on computer games designed to test their mental functions than those given a placebo. Amphetamine-style drugs have been used in the past in an attempt to improve some aspects of performance when subjects are tired. But they can cause impairments in other functions and may be addictive. The review team will send a report to the Government in November. j.hope@dailymail.co.uk WIDESPREAD sale of ' cognition enhancers' could change the face of work and study, according to experts. For decades caffeine and vitamins have been the mainstays of students needing to stave off sleep to improve their performance in revision and exams. But the next generation of drugs could herald an era of 'mental cosmetics' that promises to enhance the brain power of millions. Prescription drugs used for Alzheimer's and sleep disorders have been tested on healthy volunteers with startling results. They were able to memorise more words than normal, concentrate better and work tirelessly for longer. But the potential abuse of these products has raised ethical and health concerns. Should children face dope tests before taking exams and should the sale of the drugs be restricted? LOAD-DATE: April 18, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Papers Copyright 2007 Associated Newspapers Ltd. All Rights Reserved 315 of 998 DOCUMENTS ABC Transcripts (Australia) April 17, 2007 Tuesday 12:54 PM AEST SHOW: The World Today 12:54 PM AEST ABC Smart drugs under examination REPORTERS: Rafael Epstein LENGTH: 480 words EMMA ALBERICI: They're calling it the thinking person's Viagra; a group of drugs that some scientists say could make you smarter. The British government is assessing the impact of these substances, as Europe Correspondent, Rafael Epstein reports. RAFAEL EPSTEIN: Britain's Department of Health has asked the Academy of Medical Sciences here to have a look at the so-called "cognition enhancing" drugs, some of which are already available in the US and Australia. Modafinil was created to help people who can't stop themselves falling asleep. It's now used by many to work and play longer and harder with less sleep. At Cambridge University Dr Danielle Turner gave the drug to 60 volunteers. DANIELLE TURNER: After one day, about two hours after they had the dose, they were better at remembering strings of numbers, they were better at planning, they were less impulsive, they were better at inhibiting impulsive actions that they were making. They remembered longer strings of numbers, their short term memory was improved, and that might help you if you were for example a receptionist or something, where somebody tells you, you know, this is my phone number, can you actually write, down the phone number without... RAFAEL EPSTEIN: And say your boss gives you four things, four tasks very quickly, perhaps you could remember that better? DANIELLE TURNER: Yes, exactly. RAFAEL EPSTEIN: The idea of looking for what other people might call lifestyle drugs, do you have any of those concerns about looking at these sorts of effects. DANIELLE TURNER: There are so many different viewpoints. Do you think it's a good idea that we enhance ourselves and should we make it compulsory for everyone to take whatever they've got, in the same way that people need to take vaccinations or have to learn to read, so could cognitive enhancers go that way? Or do we want to ban them which is what the sporting world has done, so the sporting world has banned modafinil, that in fact... I've just applied for funding to look at comparing modafinil and caffeine, because in some ways, I don't think modafinil is a wonder drug, it doesn't make you Einstein or anything, it just improves your performance a little bit. RAFAEL EPSTEIN: Are you saying that you just think it's like a lot of good coffee or is it something more than that? DANIELLE TURNER: Well, that's what we don't know and, you know, is it just because it's a pharmaceutical drug that they're concerned about it. We don't know yet what the long term effects are, we don't really have a good idea of what happens if you take it every day for several years. RAFAEL EPSTEIN: Drugs like this work by boosting the activity of glutamate, a key neurotransmitter that makes it easier to learn and encode memory. The drugs could change the rules about what it takes to create a memory, and how strong those memories can be. EMMA ALBERICI: Rafael Epstein. LOAD-DATE: April 17, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Transcript Copyright 2007 Australian Broadcasting Corporation All Rights Reserved 316 of 998 DOCUMENTS BioWorld Insight April 9, 2007 Cephalon Opinion Spectrum Wide After Latest On Nuvigil LENGTH: 1177 words West Coast Editor The FDA's blessing of Cephalon Inc.'s sleepiness drug Nuvigil came right on time, but brought a demand for boldface label warnings about skin rash - and didn't do much to soothe investors chafing over a government investigation of the firm's marketing practices. A single-isomer formulation of modafinil, Nuvigil improves wakefulness in particularly groggy narcoleptics, as well as those with shift-work sleep disorder and obstructive sleep apnea/hypopnea syndrome. The FDA got Cephalon' new drug application for Nuvigil in March 2005, and sent back the first approvable letter a year ago. In the latest letter, the agency does not ask for new trials, but wants a standard safety update on Nuvigil from research conducted since June, and wants to see the introductory promotional materials. Earlier this year, Cephalon got a warning letter from the FDA about efforts to push Provigil (modafinil), the company's approved narcolepsy drug. Regulators said the one-shot marketing message created new intended uses and did not provided information about risks. Another shadow on Nuvigil is the history of Sparlon, a different formulation of modafinil intended for attention-deficit/hyperactivity disorder, declared not approvable by the FDA and dropped by Cephalon last summer. Sparlon was associated with a single suspected case of a rare but serious skin rash called Stevens-Johnson syndrome, and the FDA's Psychopharmacologic Drugs Advisory Committee had voted unanimously that the drug is effective for its intended use but also recommended that the company put together more safety data in children and adolescents. Some speculated that Sparlon, yet another potential ADHD drug, might have been turned down partly because the agency was fed up with the proliferation of therapies for the condition and the high rate of prescriptions written by doctors. Still, the rash possibility was enough to make the FDA insist that Cephalon smack the label warning not only on Nuvigil, but add it to the Provigil label as well. Most suspicion of regulatory disfavor for ADHD drugs was dispelled by later FDA actions, such as the approval in February of Vyvanse from Shire plc and New River Pharmaceuticals Inc., who planned to push to switch prescribers from Adderall XR, Shire's ADHD capsule. Shire is buying New River for $2.6 billion in cash. Separately for Cephalon, there's the probe demanded by Rep. Henry Waxman (D-Calif.), chairman of the House Committee on Oversight and Government Reform (a panel that keeps tabs on pharmaceutical marketing practices) into the way Cephalon markets the narcotics Actiq and Fentora, which are approved for cancer breakthrough pain and often prescribed off label. Another for Cephalon involves competitors with generic versions of Provigil. The firm's deals with generic drug makers caused Apotex Corp. to file a lawsuit against Cephalon last June, alleging that the settlements - which keep cheaper versions of Provigil off the market until 2012 - create a monopoly, in a situation that also drew the interest of the Federal Trade Commission. In the legal action, Apotex named Cephalon and the licensees involved: Barr Laboratories Inc., Mylan Laboratories Inc., Teva Pharmaceutical Industries Ltd., and Ranbaxy Laboratories Ltd. Cephalon's plan is to shift Provigil patients to Nuvigil in 2009, ahead of the launch of the generics. Russell McAllister, analyst with Merriman Curhan Ford & Co., put the matter plainly in a research report: "Although full approval of Nuvigil would moderate Provigil risk exposure, we continue to see two distinct sources of risk for Cephalon - aggressive marketing and related off-label usage of both Actiq/Fentora and Provigil/Nuvigil," and Cephalon's settlements with the generic filers. McAllister maintained his "sell" rating on Cephalon shares this month. At the other end of the spectrum, though, analysts at Robert W. Baird & Co. stayed with an "outperform" rating and predicted approval of Nuvigil in late June, only three months later than previously expected. Analyst David Windley with Jefferies & Co. upgraded the stock from "hold" to "buy," and hiked his price target to $88 from $69. Analysts at UBS, who had initiated coverage of Cephalon in late March with a "buy" rating (target price: $85), reiterated their opinion after the Nuvigil news. JMP Securities held to their "strong buy," with a target price of $80. Banc of America Securities, later in the week, started coverage of Cephalon with a "neutral" opinion and $75 price target. Megan Murphy at Lazard Capital Markets deemed the stock worth holding. The situation could worsen if the boldface warning finds its way onto Nuvigil's promotional materials as well as the label, but if it were limited to the label, "we wouldn't expect anyone to know about it other than the FDA and Wall Street," Murphy wrote in a research report. Clinical proof that Nuvigil boasts broader utility than Provigil would provide "higher confidence that this franchise can continue to grow and expand after eight years rather than merely be sustained," Murphy wrote, and another question is whether Nuvigil can hold ground against the generic Provigil, "be it two years after Nuvigil launches or perhaps much earlier." She pointed to Nuvigil study data offered at a scientific meeting in 2006 that showed the secondary endpoints of attention and speed of memory were not better than placebo, and quality of episodic memory was met in the 150 mg study but not in the larger 150 mg and 250 mg study. "They haven't expanded the [Provigil] label, and separate from that is whether the sales force expansion has played out in the scrip growth," Murphy told BioWorld Financial Watch. Cephalon added 500 reps to the sales force last June and, three months ago, another 250, but the prescriptions have not jumped appreciably, and growth is settling into the 10 percent to 12 percent range. The question becomes whether Provigil users can be converted to Nuvigil - and, ultimately, how much the sleep franchise can grow, especially with the advent of Provigil generics, which might well reach the market sooner than 2012, Murphy believes. She compared Cephalon's Provigil to the likes of Endo Pharmaceuticals Inc.'s Lidoderm, a 5 percent lidocaine topical patch for the treatment of post-herpetic neuralgia. Endo investors are nervous about a Lidoderm generic threat, and the stock is trading lower even before one has been disclosed - even though Endo has a more robust pipeline than Cephalon. She also pointed to Forest Laboratories Inc., whose blockbuster antidepressant Lexopro (escitalopram oxalate) also faces trouble similar to Cephalon's, albeit not until around the time Cephalon expects Provigil's competition to arrive, if the settlements hold. Last summer, a court determined that Forest's patent covering escitalopram is valid and enforceable and is infringed by a proposed generic IVAX Pharmaceuticals Inc. and Teva Pharmaceuticals Industries Ltd. The judge found in favor of Forest and partner H. Lundbeck A/S. LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2007 AHC Media LLC All Rights Reserved 317 of 998 DOCUMENTS Global Insight April 4, 2007 FDA Issues Second Approvable Letter for Cephalon's Nuvigil BYLINE: Milena Izmirlieva SECTION: In Brief LENGTH: 320 words U.S. drug-maker Cephalon announced it has received a second approvable letter from the FDA for its investigational drug Nuvigil (armodafinil) Tablets [C-IV] for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome (OSAHS) and shift work sleep disorder (SWSD). The company is not required to conduct additional clinical trials but will have to provide a standard safety update on trials conducted since its last update submission in June 2006. In addition, Cephalon will have to supply the FDA with its launch promotional materials for the drug. Nuvigil is a single-isomer formulation of modafinil; the active ingredient contained in Cephalon's drug Provigil, which is marketed for the same indications. Significance: The issuing of a second approvable letter is actually good news for Cephalon. It puts an end to the period of uncertainty following the FDA's first approvable letter, particularly with respect to the labelling of the drug. Nuvigil will carry a bolded warning section detailing the risk of a skin rash and hypersensitivity in patients taking modafinil and amodafinil reactions seen with the drug's predecessor Provigil but the language of the warning is expected to be rather mild. There is now finally a timeline for the approval of Nuvigil: Cephalon will file its response to the FDA within 30 days and FDA approval is expected within 60 days thereafter. The Nuvigil approval delay could have been a problem for Cephalon if Provigil had lost its patent protection in the meantime, but the threat of this was effectively postponed (see United States: 12 December 2005: ). Upon its launch, Nuvigil will cannibalise sales of Cephalon's own Provigil, but this is a risk well worth taking considering that the successful launch of Nuvigil will ensure that Cephalon retains exclusive access to part of the modafinil market until 2023 via the successor drug. LOAD-DATE: April 4, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Web Publication Copyright 2007 World Markets Research Limited All Rights Reserved 318 of 998 DOCUMENTS Pharma Marketletter April 3, 2007 Tuesday Cephalon's Nuvigil gets tentative OK from FDA LENGTH: 245 words US drugmaker Cephalon has received an approvable letter, together with draft labeling from the Food and Drug Administration for its New Drug Application for Nuvigil (armodafinil) tablets for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea (OSAHS) and shift-work sleep disorder (SWSD). The draft labeling includes a proposed bolded warning section that characterizes the potential occurrence of skin rash and hypersensitivity in patients taking modafinil and armodafinil and Cephalon's first-generation wakefulness drug Provigil (modafinil). Among other things, the agency has requested that the company provides a standard safety update from clinical trials conducted since the last update in June 2006, and introductory promotional materials to be used for the product. The company's response will be submitted within 30 days and will be considered a Class I response; the agency is expected to complete its review within 60 days thereafter and has not requested any additional studies prior to final approval of Nuvigil. Nuvigil is a single-isomer formulation of modafinil, the active pharmaceutical ingredient contained in Provigil which is FDA-approved for the treatment of excessive sleepiness associated with narcolepsy, OSAHS and SWSD. The Nuvigil NDA is based on positive results of four double-blind, randomized, placebo-controlled studies in patients with excessive sleepiness associated with any of the three indications. LOAD-DATE: April 3, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2007 Marketletter Publications Ltd. All Rights Reserved 319 of 998 DOCUMENTS CNS Drug News Pharmaceuticals April 2, 2007 Cephalon provides update on Nuvigil NDA LENGTH: 371 words Cephalon has received an approvable letter, together with draft labelling, from the FDA for its NDA for Nuvigil ( armodafinil ) Tablets [C-IV], for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnoea/hypopnoea syndrome (OSAHS) and shift work sleep disorder (SWSD). The draft labelling includes a proposed bolded warning section that characterises the potential occurrence of skin rash and hypersensitivity in patients taking modafinil and armodafinil. As expected, the Agency also indicated that it will request similar language in the label for Provigil ( modafinil ) Tablets [C-IV]. Among other things, the Agency requested that Cephalon provide a standard safety update from clinical trials conducted since the last update in June 2006, and introductory promotional materials to be used for the product. The company's response will be submitted within 30 days and considered a Class I response; the FDA, which has not requested any additional studies prior to final approval of Nuvigil, is expected to complete its review within 60 days thereafter. Editor's note: Nuvigil is a single-isomer formulation of modafinil, the active pharmaceutical ingredient contained in Provigil, which is FDA-approved for the treatment of excessive sleepiness associated with narcolepsy, OSAHS and SWSD. The Nuvigil NDA is based on positive results of four double-blind, randomised, placebo-controlled studies in patients with excessive sleepiness associated with either narcolepsy, SWSD or OSAHS. In these studies, the product was generally well tolerated, with the most common side effects being mild-to-moderate in intensity and including nausea, headaches, dizziness, diarrhoea, decreased appetite and upset stomach. The company submitted its NDA for Nuvigil, which is protected by a US patent expiring in 2023 that claims the Form 1 polymorph of armodafinil, to the FDA in March 2005 and received an initial approvable letter in April 2006. Furthermore, Cephalon also plans to conduct clinical trials evaluating the use of Nuvigil as a treatment for bipolar depression, cognition associated with schizophrenia, and excessive sleepiness and fatigue in conditions such as Parkinson's disease and cancer. LOAD-DATE: April 2, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2007 ESPICOM Business Intelligence Ltd. All Rights Reserved 320 of 998 DOCUMENTS Clinical Psychiatry News April 2007 Try Inhibiting Serotonin to Return Executive Functioning BYLINE: Damian Mcnamara, Miami Bureau SECTION: Pg. 34 Vol. 35 No. 4 ISSN: 0270-6644 LENGTH: 686 words    ORLANDO - Alterations in brain circuitry and chemistry mediated through the dorsolateral prefrontal cortex can cause executive dysfunction in multiple disorders, according to a presentation at a psychopharmacology congress sponsored by the Neuroscience Education Institute.    "Executive dysfunction is there. It hits you in the face if you are dealing with schizophrenia," said Dr. Thomas L. Schwartz. "But in depression you may have to look for it. I was always looking for that in the background-insomnia, fatigue, and executive dysfunction-the key residual symptoms of depression treatment."    Decreased metabolism in the dorsal and medial prefrontal cortex and the anterior cingulate are neurobiologic factors that might contribute to executive dysfunction in depression, Dr. Schwartz said. A decrease in N-acetyl aspartate, a marker or neuronal function, also may play a role. "It's another way to look at the brain, and in depressed folks you can show the brain is not doing what it is supposed to," said Dr. Schwartz, director of the depression and anxiety disorders research program at the State University of New York, Syracuse.    Executive dysfunction is associated with noradrenergic, dopaminergic, and histaminergic projections to the dorsolateral prefrontal cortex. One tactic to get more norepinephrine to flow in that circuitry is to manipulate the serotonin levels, Dr. Schwartz said.    "Too much serotonin can be a bad thing in the frontal lobes. If you inhibit the inhibitor you can get more norepinephrine up there and help return executive functioning," he added.    Pharmacologic agents that might increase norepinephrine, dopamine, and/or histamine and help improve executive function include drugs such as bupropion, atomoxetine (Straterra), and modafinil (Provigil), and drug classes such as stimulants and atypical antipsychotics, Dr. Schwartz said.    "Use of atomoxetine for executive dysfunction in depression makes biological sense and circuitry sense," he said. "But there are no controlled studies [of atomoxetine] in executive dysfunction in depression."    Executive dysfunction also is associated with sleep disorders. "Your brain wants you to have a homeostatic amount of sleep. If you get sleep deprived, no matter what the cause, you function poorly and make errors in omission and commission," Dr. Schwartz said. Again, "there is poor metabolism in the prefrontal cortex."    Addition of a sleep aid can have positive effects on next-day functioning. Stimulants, modafinil, or armodafinil can improve attention and concentration during the day, Dr. Schwartz said. "If you can keep people more awake during the day, and they avoid napping, they may not need a sleeping pill at night."    Insomnia is comorbid with depression in around 85% of people (J. Clin. Psychiatry 2004;65:27-32). "That is a lot of people," Dr. Schwartz said. Some antidepressant medications can have a direct effect on sleep, he added. For example, bupropion increases REM sleep and sleep latency, but reduces sleep continuity. Trazodone decreases REM sleep time and may cause daytime sedation. In contrast, nefazodone increases REM sleep time and is associated with minimal daytime sedation.    Sleep aids are a treatment option. Examples include zolpidem (Ambien), eszopiclone (Lunesta), and zaleplon (Sonata). "I don't think one is better than the other, so choose based on half-life," Dr. Schwartz suggested. Sonata has the shorter half life; Ambien is in the middle; Lunesta has the longest. "Which one can you take at 3 a.m, if you need to work at 9 in the morning? Sonata."    Modafinil is another pharmacologic option in patients with executive dysfunction and other adverse effects of impaired sleep. "This will not save every one of your patients but you can try it," Dr. Schwartz said. "It's the only product that raises histamine that I know of, and histamine going up to the cortex is good for executive function."    Dr. Schwartz said, "Modafinil is a funny drug-doses above 300 mg backfire in certain populations. Lower doses may be better for treatment of executive dysfunction." LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: CPNEWS Copyright 2007 Elsevier Inc., International Medical News Group All Rights Reserved 321 of 998 DOCUMENTS PR Newswire US March 30, 2007 Friday 8:51 PM GMT Cephalon Provides Update Related to NUVIGIL(TM) New Drug Application LENGTH: 1090 words DATELINE: FRAZER, Pa. March 30 FRAZER, Pa., March 30 /PRNewswire-FirstCall/ -- Cephalon, Inc. (NASDAQ:CEPH) today announced that it has received an approvable letter, together with draft labeling, from the U.S. Food and Drug Administration (FDA) for its new drug application (NDA) for NUVIGIL(TM) (armodafinil) Tablets [C-IV] for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome (OSAHS) and shift work sleep disorder (SWSD). The draft labeling includes a proposed bolded warning section that characterizes the potential occurrence of skin rash and hypersensitivity in patients taking modafinil and armodafinil. As expected, the agency also has indicated that it will request similar language in the label for PROVIGIL(R) (modafinil) Tablets [C-IV]. The proposed labeling is subject to final approval by the FDA. "We have worked diligently with the FDA over the past six months on this issue, and they have now informed us that their review is complete. We are very pleased that the proposed warning language appropriately describes the product's safety profile," said Dr. Lesley Russell, Executive Vice President, Worldwide Medical and Regulatory Operations. Among other things, the agency has requested that the company provide a standard safety update from clinical trials conducted since the last update in June 2006, and introductory promotional materials to be used for the product. The company's response will be submitted within 30 days and will be considered a Class I response; the agency is expected to complete its review within 60 days thereafter. The agency has not requested any additional studies prior to final approval of NUVIGIL. "While we fully appreciate that this regulatory review has been difficult and lengthy for stockholders and others interested in the outcome, we are convinced that in this unusual situation where multiple products may be affected, the final result will prove to be worth the investment of time and effort," said Frank Baldino Jr., Ph.D., Chairman and CEO of Cephalon. About NUVIGIL NUVIGIL is a single-isomer formulation of modafinil, the active pharmaceutical ingredient contained in PROVIGIL which is FDA-approved for the treatment of excessive sleepiness associated with narcolepsy, OSAHS and SWSD. The NUVIGIL NDA is based on positive results of four double-blind, randomized, placebo-controlled studies in patients with excessive sleepiness associated with either narcolepsy, SWSD or OSAHS. In these studies, NUVIGIL was generally well tolerated. The most common side effects were mild to moderate in intensity and included nausea, headaches, dizziness, diarrhea, decreased appetite and upset stomach. The company submitted its NDA for NUVIGIL to FDA in March 2005 and received an initial approvable letter in April 2006. Cephalon also plans to conduct clinical trials evaluating the use of NUVIGIL as a treatment for serious medical conditions such as bipolar depression, cognition associated with schizophrenia, and excessive sleepiness and fatigue in conditions such as Parkinson's disease and cancer. NUVIGIL is protected by a U.S. patent expiring in 2023 that claims the Form 1 polymorph of armodafinil. About Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products in four core therapeutic areas: central nervous system, pain, oncology and addiction. Cephalon currently employs approximately 3,000 people in the United States and Europe. Cephalon's U.S. headquarters are located in Frazer, Pennsylvania, with offices, laboratories and manufacturing facilities in West Chester, Pennsylvania, Salt Lake City, Utah, and suburban Minneapolis, Minnesota. Cephalon's European headquarters are located in Maisons-Alfort, France. The company currently markets six proprietary products in the United States: PROVIGIL, FENTORA(R) (fentanyl buccal tablet) [C-II], ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II], GABITRIL(R) (tiagabine hydrochloride), TRISENOX(R) (arsenic trioxide) injection, and VIVITROL(R) (naltrexone for extended-release injectable suspension). Full prescribing information on its U.S. products is available at http://www.cephalon.com/ or by calling 1-800-896-5855. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs; development of potential pharmaceutical products, including future clinical development plans for NUVIGIL; interpretation of clinical results, particularly with respect to the NUVIGIL Phase 3 trials; prospects for regulatory approval of NUVIGIL, including the likelihood of receiving final approval from FDA and the characterization of serious skin rash, among other things, in the final approved labeling for NUVIGIL; manufacturing development and capabilities; market prospects for its products; sales and earnings guidance; and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. CONTACT: Media: Jenifer Antonacci, +1-610-738-6674, jantonac@cephalon.com ; Investors: Robert (Chip) Merritt, +1-610-738-6376, cmerritt@cephalon.com , both of Cephalon, Inc. Web site: http://www.cephalon.com/ Company News On-Call: http://www.prnewswire.com/comp/134563.html SOURCE Cephalon, Inc. URL: http://www.prnewswire.com LOAD-DATE: March 31, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2007 PR Newswire Association LLC. All Rights Reserved. 322 of 998 DOCUMENTS US Fed News March 12, 2007 Monday 2:44 AM EST Indian Inventors Develop 2-[(Diphenylmethyl) Thio] Acetamide Preparation Process BYLINE: US Fed News LENGTH: 261 words DATELINE: Alexandria, Va. ALEXANDRIA, Va., March 12 -- Surendra B. Bhatt, Jiten R. Patel, Dinesh Panchasara, Hetal R. Shah, Keshav Deo and Vinod Kumar Kansal, all from Vadodara, India, have developed a process for the preparation of 2-[(diphenylmethyl) thio] acetamide. According to the U.S. Patent & Trademark Office, the invention relates to a "process for the preparation of 2-[(diphenylmethyl)thioacetamide, an intermediate for the preparation of Modafinil which is a central nervous system stimulant and used for the treatment of narcolepsia." An abstract of the invention, released by the Patent Office, said: "The process comprises reacting 2-[(diphenylmethyl)thio]acetic acid with alcohols, in presence of catalytic amount of inorganic acid or organic acid at reflux temperature of alcohol to obtain corresponding ester which is reacted with ammonia to give 2-[(diphenylmethyl)thio]acetamide. If desired 2-[(diphenylmethyl)thioacetamide thus produced is reacted with hydrogen peroxide to produce Modafinil." The inventors were issued U.S. Patent No. 7,186,860 on March 6. The patent has been assigned to Alembic Ltd., Gujarat, India. The original application was filed on Jan. 30, 2004, and is available at: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=% 2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=7,186,860.PN.&OS=PN/7,186,860&RS= PN/7,186,860. For more information about US Fed News federal patent awards please contact: Myron Struck, Managing Editor/US Bureau, US Fed News, Direct: 703/866-4708, Cell: 703/304-1897, Myron@targetednews.com. LOAD-DATE: March 13, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2007 HT Media Ltd. All Rights Reserved 323 of 998 DOCUMENTS Australian Doctor March 9, 2007 BYLINE: By Gabrielle Babbington LENGTH: 257 words PATIENTS with wet age-related macular degeneration are closer to having affordable sight-saving treatment. At their latest meeting, the Australian Drug Evaluation Committee approved ranibizumab (Lucentis) intravitreal injection for registration. A spokeswoman for the drug's manufacturer Novartis said the decision paved the way for pursuing PBS listing of the drug. Ranibizumab had been shown to improve sight in patients with wet age-related macular degeneration - the leading cause of blindness in the elderly, she said. The move to increase access to the drug would not necessarily increase its availability because there were already 85 authorised prescribers registered with the Therapeutic Goods Administration, which probably included all of Australia's retinal specialists and a few ophthalmologists, she said. The current supply arrangement still stood, whereby Novartis provided the drug on physician request at an initial patient cost of $6000 for three treatments and gratis thereafter, she said. ADEC has also extended the indications for the wakefulness-promoting drug modafinil (Modavigil). The tablets were approved for patients with obstructive sleep apnoea who have persisting excessive sleepiness, despite interventions such as lifestyle measures and continuous positive airway pressure (CPAP). Modafinil was also approved to treat moderate-to-severe chronic shiftwork sleep disorder. Associate Professor Ron Grunstein, head of the sleep research group at the Woolcock Institute in Sydney, said Modafinil was not a substitute for sleep. LOAD-DATE: March 8, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Magazine JOURNAL-CODE: AD Copyright 2007 Reed Business Information Ltd. All Rights Reserved 324 of 998 DOCUMENTS University Wire March 8, 2007 Thursday U. Kentucky study follows up on drug to aid smoking withdrawal BYLINE: By Erica Mitchell, Kentucky Kernel; SOURCE: U. Kentucky LENGTH: 471 words DATELINE: LEXINGTON, Ky. Galen Winthrow has a love-hate relationship with smoking. "Smoking is a harsh mistress," said the philosophy and political science sophomore. "One second she is the cure-all drug but when she leaves your system, the anxiety, the stress, the shakes start." Winthrow would like to quit but more factors than nicotine play a role. "I'd love to quit, but withdrawal can be excruciating," Winthrow said. "If you have papers, tests, a job or anything else you need to do, it can drive you insane." But a new pill may help ease the side effects of giving up cigarettes. UK is looking for participants for a follow-up study on modafinil, a drug that may help alleviate nicotine cravings, concentration problems, hunger and weight gain -- all symptoms that make giving up nicotine difficult for smokers, said Dr. Catherine Martin. Martin, the principle investigator in the study being conducted by the Psychiatry Research Center, said the drug was originally used to treat excessive sleepiness associated with narcolepsy, obstructive sleep apnea-hypopnea syndrome and shift work sleep disorder. "Modafinil is a promising medication for helping with addiction," Martin said. "It may help with nicotine withdrawal symptoms and it may help with some predisposing symptoms that contribute to people starting and continuing to smoke." Participants in the trial will be randomly assigned to receive either modafinil or a placebo. Investigators will monitor participants for changes in behavior for 13 days out of a 20-week period. The study is a double-blind placebo controlled trial, where neither the participants nor the investigators know who receives the actual drug, which is designed to reduce bias and self-deception. The Department of Psychiatry has already tested modafinil on smokers in two human laboratory studies. Afterward, researchers concluded that modafinil and nicotine are safe to use together. The studies also showed smokers had decreased cravings, hunger and improved concentration on days when they took modafinil, Martin said. The new study is a larger clinical follow up to the previous one. Smoking increases the risk of lung cancer, heart disease and chronic obstructive pulmonary disease (emphysema) among other things. About 28.7 percent of adults in Kentucky smoke and more than 8,000 people in Kentucky die of tobacco-related illnesses each year, according to the Kentucky Cabinet for Health and Family Services. But the health benefits of quitting don't make it any easier for many. "Stopping smoking is one of the most difficult challenges smokers face," Martin said. "We think modafinil may help smokers stop smoking." Daily smokers between the ages of 18 and 45, in good health and interested in participating in the study can call (859) 257-9341 or (859) 230-3220 for more information. (C) 2007 Kentucky Kernel via U-WIRE LOAD-DATE: March 8, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2007 Kentucky Kernel via U-Wire 325 of 998 DOCUMENTS University Wire March 7, 2007 Wednesday U. Kentucky study follows up on drug to aid smoking withdrawal BYLINE: By Erica Mitchell, Kentucky Kernel; SOURCE: U. Kentucky LENGTH: 450 words DATELINE: LEXINGTON, Ky. Galen Winthrow has a love-hate relationship with smoking. "Smoking is a harsh mistress," said the philosophy and political science sophomore at the University of Kentucky. "One second she is the cure-all drug, but when she leaves your system, the anxiety, the stress, the shakes start." Winthrow would like to quit, but more factors than nicotine play a role. "I'd love to quit, but withdrawal can be excruciating," Winthrow said. "If you have papers, tests, a job or anything else you need to do, it can drive you insane." But a new pill may help ease the side effects of giving up cigarettes. The University is looking for participants for a follow-up study on modafinil, a drug that may help alleviate nicotine cravings, concentration problems, hunger and weight gain -- all symptoms that make giving up nicotine difficult for smokers, said Dr. Catherine Martin. Martin, the principle investigator in the study being conducted by the Psychiatry Research Center, said the drug was originally used to treat excessive sleepiness associated with narcolepsy, obstructive sleep apnea-hypopnea syndrome and shift work sleep disorder. "Modafinil is a promising medication for helping with addiction," Martin said. "It may help with nicotine withdrawal symptoms and it may help with some predisposing symptoms that contribute to people starting and continuing to smoke." Participants in the trial will be randomly assigned to receive either modafinil or a placebo. Investigators will monitor participants for changes in behavior for 13 days out of a 20-week period. The study is a double-blind placebo controlled trial, where neither the participants nor the investigators know who receives the actual drug, which is designed to reduce bias and self-deception. The Department of Psychiatry has already tested modafinil on smokers in two human laboratory studies. Afterward, researchers concluded that modafinil and nicotine are safe to use together. The studies also showed smokers had decreased cravings, hunger and improved concentration on days when they took modafinil, Martin said. The new study is a larger clinical follow up to the previous one. Smoking increases the risk of lung cancer, heart disease and chronic obstructive pulmonary disease (emphysema) among other things. About 28.7 percent of adults in Kentucky smoke and more than 8,000 people in Kentucky die of tobacco related illnesses each year, according to the Kentucky Cabinet for Health and Family Services. But the health benefits of quitting don't make it any easier for many. "Stopping smoking is one of the most difficult challenges smokers face," Martin said. "We think modafinil may help smokers stop smoking." (C) 2007 Kentucky Kernel via U-WIRE LOAD-DATE: March 7, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2007 Kentucky Kernel via U-Wire 326 of 998 DOCUMENTS Charleston Gazette (West Virginia) March 4, 2007, Sunday Competitor paid off Mylan, suit alleges BYLINE: Paul J. Nyden SECTION: NEWS; Pg. P1B LENGTH: 1014 words pjnyden@wvgazette.com A lawsuit charges that Mylan Laboratories Inc. was one of four generic-drug companies paid off by a brand-name drug company to delay marketing cheaper versions of a sleep-disorder pill. The Prescription Action Litigation Project, a consumer coalition, filed the suit against Cephalon Inc., maker of Provigil, which treats sleep disorders. The suit, filed in federal court in October, alleges Frazier, Pa.-based Cephalon paid $136 million to Mylan and three other generic pharmaceutical companies so they would hold off on marketing generic Provigil until 2011 or 2012. Generic drugs, the suit states, typically cost 30 percent less than brand drugs with a single generic competitor. Generic drugs cost between 50 percent and 80 percent less when there are multiple generic competitors on the market. Mylan is based in Canonsburg, Pa., and was founded in White Sulphur Springs. Its biggest production facility is in Morgantown. The three other generic companies accused in the suit are: Barr Laboratories of Pomona, N.Y.; Ranbaxy Laboratories, based in New Dehli, India, with offices in Princeton, N.J.; and Teva Pharmaceutical Industries, based in Petach Tikva, Israel, with offices in North Wales, Pa. Cephalon and those four companies are all defendants in the lawsuit. The plaintiffs include: Vista Healthplan Inc., a Florida health-benefits provider; the Pennsylvania Turnpike Commission, which pays medical benefits for more than 2,000 employees; and the Pennsylvania Employees Benefit Trust Fund, which provides health coverage to more than 270,000 beneficiaries. The U.S. Food and Drug Administration originally approved Provigil in December 1998, giving Cephalon exclusive marketing rights for five years. Then, in December 2002, a year before those marketing rights expired, each of the four generic drug makers filed applications with the FDA to market modafinil , the generic name of Provigil. Modafinil counters narcolepsy, a rare sleep disorder making it difficult for people to get up in the morning and stay awake during the day. Provigil is also prescribed to treat fatigue, depression, sleepiness and attention-deficit disorders. The lawsuit focuses on "Cephalon's illegal conduct" that allegedly increased the costs for modafinil by discouraging competitors from "marketing generic versions of Provigil." Provigil sales increased from $417 million in 2004 to $588 million in 2005, according to a related lawsuit by Apotex Inc., a drug manufacturer based in Weston, Ontario. Prices for prescription drugs have recently been rising at rates between 14 percent and 18 percent a year, the lawsuit states. The pharmaceutical industry, the lawsuit adds, "is one of the most profitable industries in the United States. The U.S. market accounts for more than 40 percent of the world's prescription pharmaceutical revenues." Both suits are pending in the U.S. District Court for the Eastern District of Pennsylvania in Philadelphia. The Prescription Action Litigation Project, based in Boston, is a coalition of more than 125 organizations in 36 states and Washington, D.C., including consumer, senior, health care, labor and women's health groups. The West Virginia Citizen Action Group is a member. The suit is one of 26 class actions Prescription Action has filed seeking to lower prices of pharmaceutical drugs. Settlements in four suits have allowed consumers to collect money they were overcharged. Telephone calls to Mylan's offices on Thursday and Friday were not returned. The lawsuit alleges the goal of "Cephalon's scheme was to prevent, delay and/or minimize the success of the entry of generic modafinil competitors which would have sold ... at prices significantly below [Cephalon's] prices for Provigil." Alex Sugerman-Brozan, Prescription Action's director, said the lawsuit's allegations are "very timely" because of new federal legislation. Last week, the Senate Judiciary Committee unanimously approved a bill called the Preserve Access to Affordable Generics Act, sending it to the full Senate for its consideration. The bill's supporters include: Sens. Herb Kohl and Russ Feingold, both D-Wis.; Charles Grassley, R-Iowa; Patrick Leahy, D-Vermont; Ted Kennedy, D-Mass.; and Charles Schumer, D-N.Y. "That bill would ban lawsuit settlement agreements that keep generics from being available to people," Sugerman-Brozan said during a telephone interview from his offices in Boston on Friday. "Pharmaceutical companies usually have 10 or 12 years without any competition for a new drug. But other drug companies can challenge the uniqueness of a patent and say they should be able to market a generic alternative. "The original manufacturer can then sue [generic drug companies] for patent infringement. Typically, the brand-name company then gets a 30-month extension of its patent. For a blockbuster drug that earns billions of dollars, that is a lot of extra sales. "So brand-name companies are often willing to settle lawsuits with generic companies by paying them. 'We will give you millions if you delay the entry of your drug into the marketplace.'" Sugerman-Brozan said the practice of paying competitors to delay selling generics, under "reverse payment settlements," is becoming more common. "When companies conspire to keep drugs away from citizens who need them to maintain their health, they should be called on the carpet," said Gary Zuckett, director of the West Virginia Citizen Action Group. "There is supposed to be a free market. If drug companies conspire to keep prices artificially high, that is unfair to the individual consumer." Such action affects West Virginia in that it pays for prescription drugs for Public Employee Insurance Agency beneficiaries and for Medicare and Medicaid patients, Zuckett said. "This hurts everybody. ... Drug prices should not be fixed behind closed doors." Sugerman-Brozan said: "Pharmaceutical companies make products vital to people's health and well-being. Their products can be lifesaving. They should not put medications beyond people's reach." To contact staff writer Paul J. Nyden, use e-mail or call 348-5164. LOAD-DATE: March 5, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2007 Charleston Newspapers 327 of 998 DOCUMENTS US States News February 28, 2007 Wednesday 5:59 AM EST STUDY TO FURTHER INVESTIGATE MODAFINIL AS SMOKING CESSATION AID BYLINE: US States News LENGTH: 213 words DATELINE: LEXINGTON, Ky. The University of Kentucky issued the following news release: Most cigarette smokers trying to quit often fail because of nicotine cravings, increased appetite and weight gain, and problems with inattention. Researchers at the University of Kentucky have studied the difficulties associated with trying to quit smoking. In a laboratory setting, smokers underwent multiple measures of performance on tasks and feelings after not smoking for 24 hours. All smokers received modafinil and a placebo on different laboratory days. Researchers discovered that smokers had decreased cravings, hunger, and improved attention span on days when they took modafinil as compared to laboratory days when they received only a placebo. Because increases in cigarette cravings and hunger and the associated weight gain are major factors in smokers relapsing, this study suggests that modafinil may help smokers quit. A new study at the University of Kentucky will further investigate modafinil as a smoking cessation aid. If you are a daily smoker between the ages of 18 and 45, in generally good health, and would like to stop smoking, you might qualify to be part of this research study. For more information, please call (859) 257-9341 or (859) 230-3220. Contact: Melanie Jackson, 859/323-6363. LOAD-DATE: June 11, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2007 HT Media Ltd. All Rights Reserved 328 of 998 DOCUMENTS The Sunday Times (London) December 17, 2006 MoD tests drugs for 'supertroops' BYLINE: Jonathan Leake SECTION: HOME NEWS; News; Pg. 7 LENGTH: 338 words THE Ministry of Defence has been testing controversial drugs aimed at making military personnel stronger, faster-thinking and quicker at recovering from fatigue, writes Jonathan Leake. The drugs -some banned from Olympic sports -range from modafinil, which raises the IQ, to creatine, used by bodybuilders. Defence scientists have also been experimenting with prescription sedatives like temazepam and diazepam, aimed at helping soldiers get vital sleep between bouts of combat. And they have looked at pemoline, a drug designed to help children concentrate. Details of the experiments emerged after a researcher from Qinetiq, one of the contractors doing the testing, was asked to give evidence to MPs. "There is a lot of research funded by the MoD into substances like modafinil, ephedrine, those types of things," Anna Casey told a select committee investigating drug misuse in sport. "It does not mean such substances are being used (operationally) but it does mean they are keeping an open mind." The research is linked to a £ 20m MoD programme to find novel ways to improve the performance of soldiers. Besides Qinetiq, the money is being given to six universities -Nottingham, Loughborough, Birmingham, Cardiff, Glasgow and Cranfield School of Management - and a dozen firms that specialise in boosting human performance. This weekend the MoD released a list of the substances it has been researching, including dichloroacetate and ubiquinone, thought to reduce fatigue and aid recovery, and ephedrine, a stimulant. A US military study has shown combat stress can hit soldiers' performance. After a week of combat exercises they performed worse than if they were drunk or sedated. But there are risks. The practice of offering US aircrew amphetamines was criticised after two F-16 pilots bombed a Canadian unit in Afghanistan in 2002, killing four soldiers. Colonel Bob Stewart, who served in Bosnia in the early 1990s, said such drugs could assist troops. "When you have to stay awake for a long time they could be a great help." LOAD-DATE: December 17, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2006 Times Newspapers Limited All Rights Reserved 329 of 998 DOCUMENTS University Wire December 14, 2006 Thursday Modafinil may be as bad as amphetamine relatives BYLINE: By Ben Dedman, The Guilfordian; SOURCE: Guilford College SECTION: COLUMN LENGTH: 723 words DATELINE: GREENSBORO, N.C. According to a 2005 survey published by America's Office of National Drug Control Policy, 13.8 percent of Americans older than 12, or 33.7 million people, had tried cocaine at some point in their life. Of these, 8.8% of college students have tried it in their lives and 5.7% have tried it in the last year. However, as pressure levels rise with the upcoming exam week, cocaine is certainly not the most prominent, or even the most dangerous drug in student circles. Many students are ready to "taste the rainbow" in an attempt to stay awake and alert, eating a kaleidoscope of yellow, blue, white, and yellow pills as if they were Skittles. Amphetamines, including Ritalin, Adderall, Conserta, and Focalin, are much easier for most college students to find than cocaine, and the negative stigmas attached to cocaine often don't carry over. This creates an increased likelihood to abuse the pills, leading to harmful side effects and addiction. But, with the increased availability of a relatively new "superdrug," amphetamines may not be the biggest danger. Modafinil, also known as Provigil, was released by the drug company Cephalon in 1998 to treat narcolepsy, a sleep disorder, and was re-released as generics by competing companies earlier this year, making it cheaper and perhaps even more accessible. Though it is not an amphetamine, Modafinil has many similar effects. A single dose can sustain wakefulness and alertness for up to forty-eight hours and, unlike amphetamines, when you finally go to sleep you can become fully rested in only six hours, not the eight usually required to catch up. And, perhaps most appealing to college students, if taken just before bed, eight hours of restful sleep can be crammed into half the time. Modafinil is supposedly non-addictive and, according to the National Institute on Drug Abuse, it can even help to kick a cocaine addiction. According to the study, "More than twice as many Modafinil patients as placebo patients (33 percent compared with 13 percent) were able to attain abstinence [from cocaine] for 3 weeks or more." Militaries, including those in France, the United Kingdom, and the United States have researched the drug, perhaps looking to replace amphetamines they have used in the past. According to one study of helicopter pilots, three doses, 600 mg total, might be able keep pilots alert over a span of 88 hours with only eight hours of sleep. In the past, the U.S. military has used amphetamines to keep pilots alert on long missions. According to ABC news, on April 17, 2002 American pilots complaining of fatigue before a mission were advised to take amphetamines before a mission in Afghanistan. During the mission, the American pilots bombed Canadian infantry participating in a live-fire training exercise, killing four Canadian soldiers and wounding eight. Modafinil could potentially offer a way to stop many of the negative effects of amphetamines, while substantially increasing the benefits. But, the pill should still not be taken lightly because and if even more stigmas are removed from Modafinil the results could be disastrous. According to an estimate in Adrugrecall.com, at least 40 million Americans have been prescribed amphetamines since 1996. Modafinil is less likely to be prescribed, making it less accessible to students either legally or illegally, but as is the case with most drugs, if there is a will to find it then there is a way. Amphetamines are more popular than candy to college students - even health food fanatics won't even think before knocking a couple back. And now, with the stigma of addiction and the juiced-up buzz gone, Modafinil has the potential to become even more popular. Maybe, instead of drowning your drowsiness with pills, you should reconsider those classic remedies, caffeine and a Snickers bar, as safer remedies on those long nights of studying. David Poltz, writing for Slate.com, experimented with Modafinil to help him crunch for a deadline. Writing about his first day on the drug, Poltz said, "Today I am my own Superman, dosed on 100 milligrams of Modafinil." Though he loved the drug's short term effects, an unexpected addiction kicks in and he later says, "I end my experiment after two days. I am acting like a lunatic." That's just what we all need - even more lunatics at Guilford. (C) 2006 The Guilfordian via U-WIRE LOAD-DATE: December 14, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2006 The Guilfordian via U-Wire 330 of 998 DOCUMENTS FDAnews Drug Pipeline Alert December 11, 2006 Monday CEPHALON WORKING WITH FDA TO FINALIZE NUVIGIL LABELING SECTION: Vol. 3 No. 492 LENGTH: 191 words Cephalon has provided an update on the status of its new drug application (NDA) for Nuvigil (armodafinil). The company announced that the FDA said it is continuing to evaluate the single case of serious rash reported in a clinical study of Sparlon (modafinil). The agency has requested additional information to help place this isolated case in the context of the safety profile of modafinil. The FDA has not requested any additional information related to Nuvigil and is working with the company to finalize the product's label. Nuvigil is a single-isomer formulation of modafinil. The Nuvigil NDA is based on positive results of four double-blind, randomized, placebo-controlled studies in patients with excessive sleepiness. In these studies, Nuvigil was generally well-tolerated. In May the company announced that it had received an approvable letter from the FDA for the NDA requesting approval of Nuvigil for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome and shift work sleep disorder. FDA approval of Nuvigil is contingent upon finalizing the product label. Release date: Dec. 11, 2006 LOAD-DATE: December 8, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2006 Washington Business Information, Inc. All Rights Reserved 331 of 998 DOCUMENTS CNS Drug News Pharmaceuticals December 8, 2006 Cephalon provides update on final Nuvigil labelling LENGTH: 338 words The Division of Neurology Products of the FDA has informed Cephalon that it is continuing to evaluate the single case of serious rash reported in a clinical study of Sparlon ( modafinil ) Tablets [C-IV]. The Division has requested additional information to help place this isolated case in the context of the safety profile for modafinil, but has not requested any additional information related to Nuvigil (armodafinil) Tablets, and is working with the company to finalise the product's label. Cephalon has held discussions with the FDA concerning this case. The company is in the process of collecting the requested information and expects to make the submission to the Agency within the next few weeks. However, the submission may be considered a major amendment and result in an extension of the 31st December PDUFA date. In May, Cephalon reported that it had received an approvable letter from the FDA for the NDA requesting approval of Nuvigil for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome (OSA/HS) and shift work sleep disorder (SWSD). FDA approval of Nuvigil is contingent upon finalising the product label. Nuvigil is a single-isomer formulation of modafinil, the active pharmaceutical ingredient contained in Provigil . It is protected by a composition of matter patent that will expire on 18th December 2023 and covers a novel polymorphic form of armodafinil. The Nuvigil NDA is based on positive results of four double-blind, randomised, placebo-controlled studies in patients with excessive sleepiness associated with either narcolepsy, SWSD or OSA/HS. In these studies, Nuvigil was generally well tolerated, with a safety profile consistent with that observed in studies of Provigil. The most common adverse effects observed included headache, nausea, dizziness, insomnia and anxiety. In 2007, the company expects to initiate new clinical programmes with Nuvigil in fatigue and cognition, with the longer-term objective of expanding the product's label. LOAD-DATE: December 8, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2006 ESPICOM Business Intelligence Ltd. All Rights Reserved 332 of 998 DOCUMENTS Global Insight December 8, 2006 Cephalon Says that FDA Decision on Approving Nuvigil May Be Delayed BYLINE: Dr Jonathan Goodall SECTION: In Brief LENGTH: 354 words The U.S. FDA has requested additional information on Sparlon (modafinil), as part of its ongoing assessment of Cephalon s experimental attention deficit disorder drug, the company announced yesterday. This is to help the agency place a single case of serious rash observed in the clinical programme for this drug in the context of the safety profile of the modafinil molecule, the company explained. The FDA has not requested any additional information on the marketing application for Nuvigil (armodafinil), which is Cephalon s follow-up to its flagship narcolepsy treatment Provigil. However, the company acknowledged that because the active ingredient in Nuvigil is closely related to modafinil, the submission of this additional material may be considered a major amendment to Nuvigil's application. As a result, the company warned that this request may delay the FDA's action on Nuvigil beyond its current 31 December PDUFA date (see United States: 10 August 2006: ). Significance: In May, Cephalon received an FDA approvable letter regarding its new drug application (NDA) for Nuvigil as a treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome and shift work sleep disorder. Final approval for the drug is contingent on the company finalising the product labelling. With respect to this, Cephalon officials remain upbeat about the potential delay that the additional information request may impose on Nuvigil's approval. Robert Grupp, a spokesperson for Cephalon, told Bloomberg that the company was "delighted that the agency is taking time to ask about that single case", adding that it would allow safety information to be reflected in the label. In part, this relaxed approach may be down to the company's confidence that, at the lower doses used in Nuvigil compared to Sparlon, modafinil and its related molecules have a proven safety track record. The company s confidence might also come from the fact that the risk that generic competition poses to Nuvigil's predecessor, Provigil, has considerably eased over the last year (see United States: 12 December 2005:). LOAD-DATE: December 8, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Web Publication Copyright 2006 World Markets Research Limited All Rights Reserved 333 of 998 DOCUMENTS M2 Presswire December 7, 2006 WorldTradeStocks.com: Cephalon Says FDA Continues To Evaluate Rash Case Of Sparlon Study; Nuvigil Pending For Label Finalization [NASDAQ:CEPH] LENGTH: 1013 words M2 PRESSWIRE-DECEMBER 7, 2006-WorldTradeStocks.com: Cephalon Says FDA Continues To Evaluate Rash Case Of Sparlon Study; Nuvigil Pending For Label Finalization [NASDAQ:CEPH] ©1994-2006 M2 COMMUNICATIONS LTD NEW YORK, WORLDTRADESTOCKS.COM -On Thursday, Cephalon, Inc. (NASDAQ:CEPH), a pharmaceutical company, revealed that the Division of Neurology Products of the U.S. Food and Drug Administration continues to evaluate a case of serious rash reported in a Sparlon - modafinil tablets clinical study. The FDA had also asked for additional information on Sparlon relative to its safety profile established over a period of time. The Frazer, Pennsylvania based company said the U.S. Food and Drug Administration is working with the company to finalize the label for Nuvigil - armodafinil. Nuvigil is indicated in the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome and shift work sleep disorder. Cephalon said the FDA's approvable letter relating to Nuvigil is contingent upon finalizing the product label. The company clarified the 2007 sales and earnings guidance announced earlier would remain in effect, notwithstanding any delay in the PDUFA date that may result from this submission. The company expects to initiate in 2007 new clinical programs with Nuvigil related to fatigue and cognition, with the longer-term objective of expanding Nuvigil's label. [NASDAQ:CEPH] Dr. Lesley Russell, Executive Vice President, Worldwide Medical and Regulatory Operations, Cephalon, said, "We are pleased that the agency continues to work with us and outside experts in trying to better understand this case in the context of modafinil's generally benign side effect profile. Although this submission may be considered a major amendment and result in an extension of the December 31, 2006 PDUFA date, we see this as an important opportunity to ensure that the final label for NUVIGIL reflects the actual medical condition of this child." Cephalon said it was in the process of accumulating information on Sparlon as requested by the FDA and was likely to make forward the same within the next few weeks. About Cephalon, Inc Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products in four core therapeutic areas: central nervous system, pain, oncology and addiction. Cephalon currently employs approximately 3,000 people in the United States and Europe. U.S. sites include the company's headquarters in Frazer, Pa., and offices, laboratories or manufacturing facilities in West Chester, Pa., Salt Lake City, and suburban Minneapolis. Cephalon's European headquarters are located in Maisons-Alfort, France. The company currently markets six proprietary products in the United States: PROVIGIL(R) (modafinil) Tablets [C-IV], FENTORA(TM) (fentanyl buccal tablet) [C-II], ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II], GABITRIL(R) (tiagabine hydrochloride), TRISENOX(R) (arsenic trioxide) injection, and VIVITROL(R) (naltrexone for extended-release injectable suspension). Full prescribing information on its U.S. products is available at http://www.cephalon.com or by calling 1-800-896-5855. About WorldTradestocks.com WorldTradestocks.com an infomation research company , provides stock market information , breaking wall street news for day traders, nasdaq information and breaking stock news. http://www.worldtradestocks.com does not recommend stocks and is for informational purposes only. We recommend that visitors using World Trade Stocks consult with their financial advisors or financial brokers before investing. DISCLAIMER:worldtradestocks.com shall not be liable for any errors or delays in the content,or for any action taken in reliance thereon nor shall any of our third party infomation shall be held liable for any actions taken thereon.. 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Consult with your financial advisor before investing This release contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E the Securities Exchange Act of 1934, as amended and such forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. "Forward-looking statements" describe future expectations, plans, results, or strategies and are generally preceded by words such as "may", "future", "plan" or "planned", "will" or "should", "expected," "anticipates", "draft", "eventually" or "projected". You are cautioned that such statements are subject to a multitude of risks and uncertainties that could cause future circumstances, events, or results to differ materially from those projected in the forward-looking statements, including the risks that actual results may differ materially from those projected in the forward-looking statements as a result of various factors, and other risks identified in a companies' annual report on Form 10-K or 10-KSB and other filings made by such company with the Securities and Exchange Commission. CONTACT: J Rubiano, Infomation Specialist e-mail: info@worldtradestocks.com (M2 Communications Ltd disclaims all liability for information provided within M2 PressWIRE. Data supplied by named party/parties. Further information on M2 PressWIRE can be obtained at http://www.presswire.net on the world wide web. Inquiries to info@m2.com). LOAD-DATE: December 7, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: NEWSWIRE Copyright 2006 M2 Communications Ltd All rights reserved 334 of 998 DOCUMENTS Pharma Marketletter December 7, 2006 Thursday Cephalon updates on final Nuvigil labeling LENGTH: 229 words Cephalon says that the Division of Neurology Products of the US Food and Drug Administration has informed the company that it is continuing to evaluate the single case of serious rash reported in a child taking part in a Sparlon ( modafinil) tablets [C-IV] clinical study. The Division has requested additional information to help place this isolated case in the context of the safety profile for modafinil that has been established over more than a decade of commercial use. It has not requested any additional information related to Nuvigil (armodafinil) tablets and is working with the company to finalize the product's label. Lesley Russell, Cephalon's executive vice president, worldwide medical and regulatory operations, said: "although this submission may be considered a major amendment and result in an extension of the December 31, 2006, PDUFA [Prescription Drug User Fee Act] date, we see this as an important opportunity to ensure that the final label for Nuvigil reflects the actual medical condition of this child." On May 1, the company said it had received an approvable letter from the FDA for the New Drug Application requesting approval of Nuvigil for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome and shift work sleep disorder. FDA approval of the drug is contingent on finalizing the product label. LOAD-DATE: December 7, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2006 Marketletter Publications Ltd. All Rights Reserved 335 of 998 DOCUMENTS PR Newswire US December 7, 2006 Thursday 1:00 PM GMT Cephalon Provides Update Related to Final NUVIGIL(TM) Labeling LENGTH: 1060 words DATELINE: FRAZER, Pa. Dec. 7 FRAZER, Pa., Dec. 7 /PRNewswire-FirstCall/ -- Cephalon, Inc. (NASDAQ:CEPH) announced today that the Division of Neurology Products of the U.S. Food and Drug Administration (FDA) has informed the company that it is continuing to evaluate the single case of serious rash reported in a SPARLON(TM) (modafinil) Tablets [C-IV] clinical study. The division has requested additional information to help place this isolated case in the context of the safety profile for modafinil that has been established over more than a decade of commercial use. The division has not requested any additional information related to NUVIGIL (armodafinil) Tablets and is working with the company to finalize the product's label. "We are pleased that the agency continues to work with us and outside experts in trying to better understand this case in the context of modafinil's generally benign side effect profile," said Dr. Lesley Russell, Executive Vice President, Worldwide Medical and Regulatory Operations. "Although this submission may be considered a major amendment and result in an extension of the December 31, 2006 PDUFA date, we see this as an important opportunity to ensure that the final label for NUVIGIL reflects the actual medical condition of this child." As the company disclosed in its November 2, 2006 earnings conference call, it has had discussions with the FDA concerning this case. The company is in the process of collecting the requested information and expects to make the submission to the FDA within the next few weeks. On May 1, 2006, the company announced that it had received an approvable letter from the FDA for the NDA requesting approval of NUVIGIL for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome (OSA/HS) and shift work sleep disorder (SWSD). FDA approval of NUVIGIL is contingent upon finalizing the product label. The company's previously issued 2007 sales and earnings guidance will remain in effect, notwithstanding any delay in the PDUFA date that may result from this submission. As previously disclosed, the company expects to initiate in 2007 new clinical programs with NUVIGIL in fatigue and cognition, with the longer-term objective of expanding NUVIGIL's label. About NUVIGIL NUVIGIL is a single-isomer formulation of modafinil, the active pharmaceutical ingredient contained in PROVIGIL. The NUVIGIL NDA is based on positive results of four double-blind, randomized, placebo-controlled studies in patients with excessive sleepiness associated with either narcolepsy, SWSD or OSA/HS. In these studies, NUVIGIL was generally well tolerated, with a safety profile consistent with that observed in studies of PROVIGIL. The most common adverse effects observed included headache, nausea, dizziness, insomnia and anxiety. NUVIGIL is protected by a composition of matter patent that will expire on December 18, 2023 and covers a novel polymorphic form of armodafinil, the active pharmaceutical ingredient in NUVIGIL. Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products in four core therapeutic areas: central nervous system, pain, oncology and addiction. Cephalon currently employs approximately 3,000 people in the United States and Europe. U.S. sites include the company's headquarters in Frazer, Pa., and offices, laboratories or manufacturing facilities in West Chester, Pa., Salt Lake City, and suburban Minneapolis. Cephalon's European headquarters are located in Maisons-Alfort, France. The company currently markets six proprietary products in the United States: PROVIGIL(R) (modafinil) Tablets [C-IV], FENTORA(TM) (fentanyl buccal tablet) [C-II], ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II], GABITRIL(R) (tiagabine hydrochloride), TRISENOX(R) (arsenic trioxide) injection, and VIVITROL(R) (naltrexone for extended-release injectable suspension). Full prescribing information on its U.S. products is available at http://www.cephalon.com/ or by calling 1-800-896-5855. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs; development of potential pharmaceutical products; interpretation of clinical results; prospects for regulatory approval, including the timing of the submission of additional data to FDA, the possibility of a delay in the NUVIGIL PDUFA action date and the likelihood that the final label for NUVIGIL reflects the actual medical condition of the single case of serious rash seen in the SPARLON clinical trials; manufacturing development and capabilities; market prospects for its products; sales and earnings guidance; and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. CONTACT: Media: Robert W. Grupp, +1-610-738-6402, rgrupp@cephalon.com , or Investors: Robert (Chip) Merritt, +1-610-738-6376, cmerritt@cephalon.com , both of Cephalon, Inc. Web site: http://www.cephalon.com/ Company News On-Call: http://www.prnewswire.com/comp/134563.html SOURCE Cephalon, Inc. URL: http://www.prnewswire.com LOAD-DATE: December 8, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 PR Newswire Association LLC. All Rights Reserved. 336 of 998 DOCUMENTS Reuters Health Medical News November 16, 2006 Thursday 9:00 PM EST Modafinil counteracts adverse effects of sleep deprivation SECTION: CLINICAL LENGTH: 296 words DATELINE: NEW YORK (Reuters Health) The non amphetamine, wake-promoting drug, modafinil counters the adverse effects of sleep deprivation on working memory, researchers report in the November 1st issue of Sleep. In a randomized, double-blind study, Dr. Robert Joseph Thomas, of Beth Israel Deaconess Medical Center, Boston, and Dr. Kenneth K. Kwong of Massachusetts General Hospital, Charlestown examined the effect of modafinil on working memory and brain activation in the executive network following overnight sleep deprivation. Functional magnetic resonance imaging was used to assess the functional neurobiology of executive function in eight sleep-deprived medication-free men (ages 21 to 35 years) treated with 200 mg of modafinil or placebo. They underwent a verbal working-memory task with 3 levels of difficulty. Subjects in the sleep-deprived condition, had approximately 28 hours of continuous wakefulness, and in the rested condition, had 8 hours of scheduled sleep opportunity. The team assessed brain activation patterns and regional signal intensity based on the blood-oxygen level-dependent signal. Modafinil effectively countered the ill effects of sleep deprivation on working memory, but only when the task difficulty was moderate, according to the researchers. "Effects when sleep deprived are clearly task load dependent," Dr. Thomas said in an interview with Reuters Health. "When the task is easy, it offers no benefit." However, "the moderate levels of task difficulty, typical of what we face in real-life conditions, seem best enhanced neurobiologically." The most obvious use of the agent, he continued, would be in "those on extended duty hours due to unexpected circumstances." Moreover, he concluded that the results "support military use, where sleep deprivation is rampant in combat." LOAD-DATE: March 4, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 Reuters Health All Rights Reserved 337 of 998 DOCUMENTS US Fed News November 9, 2006 Thursday 3:51 AM EST French Inventors Develop Crystalline Forms Production Method BYLINE: US Fed News LENGTH: 221 words DATELINE: Alexandria, Va. ALEXANDRIA, Va., Nov. 9 -- Olivier Neckebrock of Ponteau Combault, France, and Pierre Leproust of Creteil, France, have developed a method for the production of crystalline forms and crystalline forms of optical enantiomers of modafinil. According to the U.S. Patent & Trademark Office: "The invention relates to a process for the preparation of crystalline forms of the optical enantiomers of modafinil, comprising stages comprising: dissolving one of the optical enantiomers of modafinil in a solvent other than ethanol, crystallising the modafinil enantiomer, recovering the crystalline form of the modafinil enantiomer so obtained. The invention also relates to a process for the preparation of the optical enantiomers of modafinil." The inventors were issued U.S. Patent No. 7,132,570 on Nov. 7. The patent has been assigned to Cephalon France, Maisons-Alfort Cedex, France. The original application was filed on Dec. 18, 2003, and is available at: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=% 2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=7,132,570.PN.&OS=PN/7,132,570&RS= PN/7,132,570. For more information about US Fed News federal patent awards please contact: Myron Struck, Managing Editor/US Bureau, US Fed News, Direct: 703/866-4708, Cell: 703/304-1897, Myron@targetednews.com. LOAD-DATE: November 9, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 HT Media Ltd. All Rights Reserved 338 of 998 DOCUMENTS Hindustan Times November 2, 2006 Thursday 2:02 PM EST Exercise is still the best fatigue buster BYLINE: Report from the Asian News International brought to you by the Hindustan Times LENGTH: 301 words DATELINE: Washington Washington, Nov 2 -- The time has come to flush all those energy drinks down the loo, for a new study by researchers at the University of Georgia has found that nothing is as effective as boosting energy levels, and reducing fatigue, as regular exercise. As a part of the study, professor Patrick O'Connor, co-director of the UGA exercise psychology laboratory, kinesiology professor Rod Dishman and lead author Tim Puetz analyzed 70 randomized, controlled trials that enrolled a total of 6,807 subjects. The researchers quantified the magnitude of the effect of exercise and found that it was stronger than the treatment of fatigued people with drugs such as the narcolepsy drug modafinil. They found that exercise increased energy and reduced fatigue by 0.37 standard deviations when compared to control groups, whereas participants in a previous study taking modafinil had an improvement of 0.23 standard deviations. "A lot of times when people are fatigued the last thing they want to do is exercise. But if you're physically inactive and fatigued, being just a bit more active will help," said O'Connor. Tim Puetz added that though energy drinks were becoming increasingly popular among people, the study showed that the best way to up energy levels and beat fatigue was to exercise. "We live in a society where people are always looking for the next sports drink, energy bar or cup of coffee that will give them the extra edge to get through the day. But it may be that lacing up your tennis shoes and getting out and doing some physical activity every morning can provide that spark of energy that people are looking for," Puetz said. The study is published in the November issue of the journal Psychological Bulletin. Published by HT Media Ltd. with permission from Asian News International. LOAD-DATE: November 2, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 HT Media Ltd. All Rights Reserved 339 of 998 DOCUMENTS The Toronto Star October 29, 2006 Sunday ON THE ALERTEyes wide open BYLINE: Andrew Chung, Toronto Star SECTION: NEWS; Pg. A11 LENGTH: 858 words "Could I have a non-fat cappuccino with modafinil to go?" It's quite possible that a few years from now, that will be the wake-up mantra for millions of people around the world. Modafinil, distributed in Canada as Alertec, is a chemical first made in France in the 1970s for treating narcolepsy. But in the past few years, it has been used more and more to combat daytime sleepiness among shift workers. Doctors say it is safe, and that it can "turn off" the urge to sleep. "Maybe there will be a soft drink with Alertec in it," says Dr. James MacFarlane, director of the sleep laboratory at Toronto's Hospital for Sick Children. "It may be just that safe." Our stimulant of choice right now, of course, is caffeine, which is safe if taken in moderate amounts. But it can raise blood pressure and induce the jitters. Modafinil, meanwhile, is attracting more and more attention in various quarters. In some large U.S. cities, it's giving a boost to the party circuit. And the British, U.S. and French militaries have been testing it for use as a drug safer than amphetamines to keep infantries alert. The surging interest in modafinil is part of the growing focus on sleep and wakefulness in medical and pharmaceutical circles as we strive to further manipulate our circadian rhythms. It's just one of a flurry of drugs in production or development that are heralding a brave new world where we will finally be able to take complete control of sleep and wakefulness."I think people want their personal biology to be more like a square wave these days," says MacFarlane. But it's not a future MacFarlane sees positively. "If you try to make it that way, you eventually pay the price." On modafinil, one of a growing class of so-called "wakefulness promoters," people could theoretically stay awake for days. And while it is considered to be very very safe and effective, MacFarlane cautions: "You're not reducing the need for sleep, you're just improving performance during 'wake.' So, basically, you're taking a stimulant, you're taking cocaine, even though it's not cocaine. It does not in any way reduce your sleep requirement." Using these drugs as lifestyle aids is a symptom of our increasingly fast-paced and overworked society. North America's growing numbers of shift workers, for example, often have trouble adjusting their sleep patterns, so they reach for chemical solutions. In the absence of a medical or psychiatric illness, their sleep/wake problems arise from their jobs, leaving physicians loath to prescribe drugs like modafinil. At the same time, though, many doctors understand the need."At first I thought it's not such a good idea," says sleep expert and neurologist Dr. Brian Murray at the Sunnybrook Health Sciences Centre. "But on the other hand it's probably better than crashing your car. So that's why I think maybe we, or I, need to have a more open mind to this." Other such substances currently under study include modafinil's chemical cousin armodafinil, as well as a group of drugs called ampakines, which boost glutamate, the brain's excitatory neurotransmitter. Sleep aids have also vastly improved from the highly addictive barbituates of the 1950s, and the benzodiazepines that started coming on strong in the '70s. Though many new medications still target the brain's GABA system, part of the circuitry that puts people to sleep - and come with hangover effects - the newest drugs mimic the effect of melatonin, a naturally occurring hormone that's present in the blood at night and promotes sleep. (Though many of the newest drugs - such as the popular Ambien and Lunestra - are available in the U.S., few have made their way to Canada.) Canada's military is currently studying melatonin, available in health food stores, and photo therapy to figure out the best combination, and when to give it, to reduce jet lag and shift-work problems in soldiers sent out to battlefield or on warships, often in far-off places like Afghanistan. Any serious military these days is 24/7. "They have equipment for owning the night, and to exploit that capability they have to be vigilant around the clock," says Michel Paul, defence scientist at the Defence Research and Development Canada facility in Toronto. The Canadian military currently gives no special wakefulness agents to personnel, other than coffee. Paul stresses if the military expresses a desire for drugs to maintain alertness, modafinil, and not amphetamines, would be the route to take. Other research underway includes drugs to increase the amount of time a person spends in the most restorative phase of sleep, called slow wave. In the future, people might be able to get a better-quality sleep in less time. Will sleep ever become obsolete? That seems to be the goal of some research. But few think it will ever happen. Murray points out the positive effects sleep has on the immune system. "It's doubtful modafinil would cover up those effects. So there's no replacement at this point for natural sleep." Amid a tide of new chemical helpers, doctors today still recommend one particular remedy for restoring the body and staying awake the next day: eight hours of sleep. LOAD-DATE: October 30, 2006 LANGUAGE: ENGLISH GRAPHIC: Sleep research has led to a host of new drugs, including such "wakefulness promoters" as Alertec. DOCUMENT-TYPE: COLUMN PUBLICATION-TYPE: NEWSPAPER Copyright 2006 Toronto Star Newspapers, Ltd. 340 of 998 DOCUMENTS The Sun Herald (Sydney, Australia) October 15, 2006 Sunday First Edition 'Ice' drug trial bid to help users kick habit BYLINE: LOUISE HALL HEALTH REPORTER SECTION: NEWS; Pg. 35 LENGTH: 317 words ADDICTS of the dangerous party drug "ice" are taking part in a world-first trial in Sydney that could help users kick their destructive habit. Researchers are testing whether a drug normally used to treat the excessive sleep disorder narcolepsy can wean addicts off the illegal methamphetamine described as a "scourge on Australian society". The National Drug and Alcohol Research Centre (NDARC) is conducting a clinical trial of Modafinil, a non-habit forming stimulant medication. Forty users are taking part in the 10-week trial. Unlike heroin, there is no easily available drug to get addicts off "meth" or deal with the violent and psychotic tendencies it induces. Ice, the crystalline form of methamphetamine, is a powerfully addictive synthetic drug that works by quickly boosting levels of dopamine, the brain chemical responsible for movement, emotion, motivation and feelings of pleasure. But long-term abuse can impede the body's ability to produce dopamine and cause paranoic and violent rages, as well as depression and sleeplessness. There has been a rapid rise in methamphetamine use in recent years. NDARC figures suggest there are about 37,000 regular amphetamine users in NSW aged between 15 and 49 and 28,000 are dependant on the drug. Ice has been recognised by the Federal Government as the "nation's worst drug problem". Parliamentary secretary for health Christopher Pyne, who is responsible for drug policy, told a newspaper last week that ice was causing more community problems than heroin. "Ice is a scourge on Australian society," he said. Modafinil (marketed as Modavigil in Australia) has shown great promise in treating cocaine users in US trials. It reduces cravings and restores proper dopamine function. James Shearer, from NDARC, said this was one of the first trials to extend modafinil to methamphetamine users. The NRARC wants 50 more recruits. Call James Shearer on 0414 385 149. LOAD-DATE: June 20, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2006 John Fairfax Publications Pty Ltd All Rights Reserved 341 of 998 DOCUMENTS MediaNet Press Release Wire October 4, 2006 Wednesday 7:07 AM AEST Media Release 4 October 2006 LENGTH: 322 words              Treatment trials for amphetamine dependence   Mental health problems, dependence, polydrug use and unsafe sex and injecting practices are all associated with amphetamine use.  While there are a number of medications available to treat problems such as anxiety or depression, there are no specific pharmacotherapies to optimally treat amphetamine withdrawal and relapse.   Turning Point Alcohol and Drug Centre is working to improve the health and well-being of people with amphetamine dependence by examining withdrawal and treatment options.  A clinical trial of modafinil with a small group of amphetamine users is currently being facilitated by Turning Point and Western Hospital.  Modafinil, a "wakefulness drug" possesses some stimulant properties without euphoric effects and has shown preliminary potential for treating cocaine dependence.   Professor Ernest Drucker, a US-based leading authority on drug addiction, AIDS and human rights, has been invited by Turning Point to provide insight on amphetamines and other stimulants.   "There is cause for optimism about the use of substitution stimulant drugs to treat amphetamine dependency," says Dr Drucker.  "Over twenty published reports going back to the 1980s show that orally administered drugs with longer-term effects such as modafinil have considerable promise."   Dr Drucker will speak on the subject of "Responding to the global epidemic of amphetamines" at Turning Point's annual oration later today.  The Honourable Daniel Andrews, Parliamentary Secretary for Health will also launch the 2005-2006 Turning Point Annual Report.   The oration is being held on Wednesday 4th October at 5.30pm in The Age Theatre, Lower Ground Level, Melbourne Museum, Carlton Gardens, Carlton.   For more information, please contact:   Professor Ernest Drucker   M: 0427 597 612   Professor Nick Crofts   T: 8413 8400   M: 0417 363 449   SOURCE:  Turning Point Alcohol and Drug Centre LOAD-DATE: October 4, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 Australian Associated Press Pty. Ltd. 342 of 998 DOCUMENTS Pharmacy News (Australia) September 14, 2006 LENGTH: 293 words ADHD drug snag It had been touted as a safer alternative to the amphetamine-like stimulants prescribed to millions of hyperactive children and young adults. Now concerns about a potentially fatal side effect have crushed plans to market modafinil as a treatment for attention deficit hyperactivity disorder (ADHD). Modafinil, which boosts wakefulness and focus, is approved for adults with excessive sleepiness. A proposal to market it for treating ADHD hit a snag in March when one of 933 children taking part in a clinical trial developed a life-threatening skin condition. The manufacturer, Cephalon, tried to convince the US Food and Drug Administration that the child's rash was not a reaction to the drug. But it has now abandoned its ADHD plans after the FDA refused to approve modafinil without further extensive safety studies. Pill pushing Fancy a free trial of an impotence drug? How about a free course of sleeping pills? USconsumer groups are worried about the way pharmaceutical companies give away coupons offering discounts on their prescription drugs or free trials. "The incentive for you to buy it is irrelevant to whether that's the best medication for you or not," said Susan Sherry, of the health pressure group Community Catalyst, which has joined 22 other groups calling on the FDA to ban the practice. The companies have responded that coupons help to lower health care costs and increase access. "We believe this programme benefits patients," said a spokeswoman for Sanofi-Aventis, which offers a free seven-day trial of its insomnia pill Ambien. Patients still need to get a prescription from their doctor. "We're taking a look to see if FDA action is needed,' said an agency spokeswoman. Stories are from the 19 August issue of New Scientist. LOAD-DATE: September 11, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Magazine JOURNAL-CODE: PN Copyright 2006 Reed Business Information Ltd. All Rights Reserved 343 of 998 DOCUMENTS The Associated Press September 8, 2006 Friday 9:29 PM GMT Doctor in BALCO steroids scandal could lose license BYLINE: By MARCUS WOHLSEN, Associated Press Writer SECTION: DOMESTIC NEWS LENGTH: 288 words DATELINE: SAN FRANCISCO The former medical director of the clinic involved in a sports doping scandal could lose his license for allegedly prescribing a stimulant to a track and field athlete without examining her. The state medical board is seeking to revoke or suspend the license of psychiatrist Brian Halevie-Goldman, who was medical director for the Bay Area Laboratory Co-Operative that provided steroids to top athletes. Halevie-Goldman was accused of gross negligence for allegedly providing the drug modafinil to the athlete at the request of BALCO founder Victor Conte, who served four months in federal prison for dealing steroids. The doctor, who now specializes in childhood autism at two San Francisco Bay area clinics, did not immediately return calls Friday seeking comment. The athlete in the case was identified by her initials, K.W., to protect her privacy. The medical board's accusation, filed in May, said K.W. tested positive for modafinil at an international track meet in August 2003 and accepted a two-year suspension for admitting to its use in 2004. Kelli White, a BALCO client who tested positive for modafinil after winning gold medals in the 100- and 200-meter races at the world championships in Paris in August 2003, was stripped of those medals and suspended for two years after admitting in 2004 to using the banned stimulant. The medical board said investigators examined medical charts kept by Halevie-Goldman that showed he diagnosed K.W. with narcolepsy in January 2003 without examining her, basing his analysis solely on a description of symptoms provided by Conte. Modafinil is used to treat narcolepsy, a sleep disorder. The medical board has scheduled a hearing on the allegations Nov. 13, said spokeswoman Candis Cohen. LOAD-DATE: September 9, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 Associated Press All Rights Reserved 344 of 998 DOCUMENTS The Associated Press State & Local Wire September 8, 2006 Friday 9:29 PM GMT Doctor in BALCO steroids scandal could lose license BYLINE: By MARCUS WOHLSEN, Associated Press Writer SECTION: SPORTS NEWS LENGTH: 288 words DATELINE: SAN FRANCISCO The former medical director of the clinic involved in a sports doping scandal could lose his license for allegedly prescribing a stimulant to a track and field athlete without examining her. The state medical board is seeking to revoke or suspend the license of psychiatrist Brian Halevie-Goldman, who was medical director for the Bay Area Laboratory Co-Operative that provided steroids to top athletes. Halevie-Goldman was accused of gross negligence for allegedly providing the drug modafinil to the athlete at the request of BALCO founder Victor Conte, who served four months in federal prison for dealing steroids. The doctor, who now specializes in childhood autism at two San Francisco Bay area clinics, did not immediately return calls Friday seeking comment. The athlete in the case was identified by her initials, K.W., to protect her privacy. The medical board's accusation, filed in May, said K.W. tested positive for modafinil at an international track meet in August 2003 and accepted a two-year suspension for admitting to its use in 2004. Kelli White, a BALCO client who tested positive for modafinil after winning gold medals in the 100- and 200-meter races at the world championships in Paris in August 2003, was stripped of those medals and suspended for two years after admitting in 2004 to using the banned stimulant. The medical board said investigators examined medical charts kept by Halevie-Goldman that showed he diagnosed K.W. with narcolepsy in January 2003 without examining her, basing his analysis solely on a description of symptoms provided by Conte. Modafinil is used to treat narcolepsy, a sleep disorder. The medical board has scheduled a hearing on the allegations Nov. 13, said spokeswoman Candis Cohen. LOAD-DATE: September 9, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 Associated Press All Rights Reserved 345 of 998 DOCUMENTS The Associated Press State & Local Wire September 8, 2006 Friday 8:47 PM GMT Doctor in BALCO steroids scandal could lose license BYLINE: By MARCUS WOHLSEN, Associated Press Writer SECTION: STATE AND REGIONAL LENGTH: 529 words DATELINE: SAN FRANCISCO The former medical director of the clinic at the center of a massive sports-doping scandal could lose his license for allegedly prescribing a stimulant to a track-and-field athlete without examining her. The state medical board is seeking to revoke or suspend the medical license of Fairfield psychiatrist Dr. Brian Halevie-Goldman, who was medical director for the Bay Area Laboratory Co-operative that peddled steroids to top athletes. Halevie-Goldman was accused of gross negligence for allegedly providing the drug modafinil to the unnamed athlete at the request of BALCO founder Victor Conte, who served four months in federal prison for dealing steroids. The doctor, who now specializes in childhood autism at two San Francisco Bay area clinics, did not immediately return calls Friday seeking comment. The athlete in the case was identified by her initials, K.W., to protect her privacy. The report indicates the initials could be those of elite sprinter Kelli White, a BALCO client who tested positive for modafinil after winning gold medals in the 100- and 200-meter races at the World Championships in Paris in August 2003. White was stripped of her gold medals and suspended for two years after admitting in 2004 to using the banned stimulant. The medical board's accusation, filed in May, said K.W. tested positive for modafinil at an international track meet in August 2003 and accepted a two-year suspension for admitting to its use in 2004. White provided information to the U.S. Anti-Doping Agency on Conte and her former coach Remi Korchemny. The medical board said investigators examined medical charts kept by Halevie-Goldman that showed he diagnosed K.W. with narcolepsy in January 2003 without examining her, basing his analysis solely on a description of symptoms provided by Conte. In June 2003, the charts indicate Halevie-Goldman gave K.W. prescriptions for the painkiller Motrin, the sedative Ambien and two medications to treat a rash, though he had never seen or examined her, the medical board said. After K.W. tested positive for modafinil in August 2003, Halevie-Goldman sent a letter to her agents saying he had dispensed modafinil samples to treat her narcolepsy, though he had never met her as a patient, according to the board's accusation. Halevie-Goldman's records show he examined K.W. in October 2003, after she tested positive for the stimulant, the medical board said. He later wrote a memo blaming Conte, the athlete and her mother for deceiving him about K.W.'s condition. The medical board has scheduled a hearing on the allegations Nov. 13, said spokeswoman Candis Cohen. BALCO peddled performance-enhancing drugs designed to avoid detection by the USADA and professional sporting leagues, including Major League Baseball and the National Football League. The names of several prominent athletes have surfaced in the federal probe, including other track stars and baseball players, such as Giants slugger Barry Bonds. The BALCO probe brought guilty pleas in U.S. District Court from Conte, Bonds' trainer Greg Anderson, BALCO vice president James Valente, Korchemny and Patrick Arnold, the chemist who designed a previously undetectable steroid. LOAD-DATE: September 9, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 Associated Press All Rights Reserved 346 of 998 DOCUMENTS The Associated Press State & Local Wire September 8, 2006 Friday 8:46 PM GMT Doctor in BALCO steroids scandal could lose license BYLINE: By MARCUS WOHLSEN, Associated Press Writer SECTION: SPORTS NEWS LENGTH: 529 words DATELINE: SAN FRANCISCO The former medical director of the clinic at the center of a massive sports-doping scandal could lose his license for allegedly prescribing a stimulant to a track-and-field athlete without examining her. The state medical board is seeking to revoke or suspend the medical license of Fairfield psychiatrist Dr. Brian Halevie-Goldman, who was medical director for the Bay Area Laboratory Co-operative that peddled steroids to top athletes. Halevie-Goldman was accused of gross negligence for allegedly providing the drug modafinil to the unnamed athlete at the request of BALCO founder Victor Conte, who served four months in federal prison for dealing steroids. The doctor, who now specializes in childhood autism at two San Francisco Bay area clinics, did not immediately return calls Friday seeking comment. The athlete in the case was identified by her initials, K.W., to protect her privacy. The report indicates the initials could be those of elite sprinter Kelli White, a BALCO client who tested positive for modafinil after winning gold medals in the 100- and 200-meter races at the World Championships in Paris in August 2003. White was stripped of her gold medals and suspended for two years after admitting in 2004 to using the banned stimulant. The medical board's accusation, filed in May, said K.W. tested positive for modafinil at an international track meet in August 2003 and accepted a two-year suspension for admitting to its use in 2004. White provided information to the U.S. Anti-Doping Agency on Conte and her former coach Remi Korchemny. The medical board said investigators examined medical charts kept by Halevie-Goldman that showed he diagnosed K.W. with narcolepsy in January 2003 without examining her, basing his analysis solely on a description of symptoms provided by Conte. In June 2003, the charts indicate Halevie-Goldman gave K.W. prescriptions for the painkiller Motrin, the sedative Ambien and two medications to treat a rash, though he had never seen or examined her, the medical board said. After K.W. tested positive for modafinil in August 2003, Halevie-Goldman sent a letter to her agents saying he had dispensed modafinil samples to treat her narcolepsy, though he had never met her as a patient, according to the board's accusation. Halevie-Goldman's records show he examined K.W. in October 2003, after she tested positive for the stimulant, the medical board said. He later wrote a memo blaming Conte, the athlete and her mother for deceiving him about K.W.'s condition. The medical board has scheduled a hearing on the allegations Nov. 13, said spokeswoman Candis Cohen. BALCO peddled performance-enhancing drugs designed to avoid detection by the USADA and professional sporting leagues, including Major League Baseball and the National Football League. The names of several prominent athletes have surfaced in the federal probe, including other track stars and baseball players, such as Giants slugger Barry Bonds. The BALCO probe brought guilty pleas in U.S. District Court from Conte, Bonds' trainer Greg Anderson, BALCO vice president James Valente, Korchemny and Patrick Arnold, the chemist who designed a previously undetectable steroid. LOAD-DATE: September 9, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 Associated Press All Rights Reserved 347 of 998 DOCUMENTS THE SAN FRANCISCO CHRONICLE (California) September 8, 2006 Friday FINAL Edition THE BALCO CASE; Doctor who gave sprinter stimulant may lose license BYLINE: Lance Williams, Mark Fainaru-Wada, Chronicle Staff Writers SECTION: BAY AREA; Pg. B2 LENGTH: 831 words The former medical director at BALCO, the laboratory implicated in an international sports-doping scandal, has been accused of gross negligence for allegedly giving the prescription stimulant modafinil to a champion sprinter without ever examining her. In a pending accusation, the state Medical Board said it was seeking to revoke or suspend the medical license of Dr. Brian Halevie-Goldman for allegedly providing the drug to the athlete simply because he was asked to do so by BALCO founder and confessed steroid dealer Victor Conte. When the athlete tested positive for the stimulant at a track meet, Goldman concocted a medical history and diagnosis in an effort to excuse the doping offense, the Medical Board charged. Goldman blamed Conte for deceiving him about the athlete's medical condition, according to the Medical Board. The doctor did not respond to telephone messages and a letter faxed to his office requesting comment. The Medical Board identified the athlete by the initials KW. But the allegations in the filing obviously refer to elite sprinter Kelli White, a BALCO client who tested positive for modafinil after winning gold medals in the 100- and 200-meter races at the World Championships in Paris in 2003. White, of Union City, later admitted using several banned drugs and was suspended from competition for two years. Saying she wanted to help clean up sports, she gave interviews about her drug use and testified at disciplinary hearings conducted by the U.S. Anti-Doping Agency. Goldman is a psychiatrist who has worked at Fairfield's Amen Clinic and at Diablo Behavioral Healthcare Center in Danville. In 1984, he began moonlighting as medical director at Conte's Bay Area Laboratory Co-Operative in Burlingame. At some point Goldman stopped working there, but BALCO continued to list him on state documents as the lab's medical director, and he and Conte stayed in touch. In January 2003, according to the Medical Board, Conte contacted Goldman, seeking modafinil for White. According to the Medical Board, Conte told Goldman that White was suffering from fatigue and sleeplessness. Goldman recommended evaluating her for the sleep disorder narcolepsy. But instead of examining White, Goldman gave Conte samples of modafinil, an anti-narcolepsy drug. At the time, Conte was providing the banned stimulant to several sprinters to help them run faster, according to court records. In June 2003, even though Goldman still hadn't examined White, the Medical Board said he began prescribing other drugs for her: two medicines to treat a skin rash; the painkiller Motrin; and the sedative Ambien. In August 2003, White became the first American woman ever to win both the 100- and 200-meter races at the World Championships. Two days later, authorities announced she had tested positive for modafinil. At first, with Goldman's help, White fought the charges. Goldman gave White a letter falsely claiming that she had a family history of narcolepsy and that he had provided her with the drug to treat the ailment, the Medical Board said. Goldman also wrote a letter to the International Association of Athletics Federations arguing that modafinil could not enhance athletic performance. Goldman was paid $5,000 for the letters, the Medical Board said. In a 2004 interview with The Chronicle and other newspapers, White acknowledged she had never suffered from narcolepsy, saying Goldman's diagnosis was part of a false story devised by Conte to excuse her use of drugs. White said Conte and her coach, Remi Korchemny, also had provided her many other banned drugs, including the undetectable steroid known as "the clear." Conte served four months in federal prison on his guilty plea in the BALCO steroids conspiracy case. Korchemny, who also pleaded guilty to steroid dealing, was put on probation. When Goldman was interviewed by the Medical Board, he admitted he had only examined White once -- on Oct. 1, 2003, weeks after she was suspended for using modafinil. At first, Goldman told investigators that he had consulted with White by phone before providing her with the drug, but he later admitted he couldn't remember talking to her, the Medical Board said. Federal authorities investigating BALCO were told of another instance where Goldman allegedly prescribed a drug for an athlete at Conte's request. Former world champion sprinter Tim Montgomery told authorities that in 2001 he got the women's fertility drug Clomid via a phony prescription written by Goldman, The Chronicle has reported. Montgomery said Conte advised him to use Clomid, which is sometimes used to mask steroids in drug tests. Montgomery said Conte called Goldman, who by his account wrote a prescription for Montgomery using a false name so it would not be traceable. Goldman disputed Montgomery's allegations, telling The Chronicle in 2004, "Everything is a lie." The Medical Board's accusation was filed against Goldman in May, said board spokeswoman Candis Cohen. A hearing has been set for Nov. 13. LOAD-DATE: September 8, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2006 San Francisco Chronicle All Rights Reserved 348 of 998 DOCUMENTS Associated Press Worldstream September 8, 2006 Friday 9:56 PM GMT Doctor in BALCO steroids scandal could lose license BYLINE: By MARCUS WOHLSEN, Associated Press Writer SECTION: SPORTS NEWS LENGTH: 293 words DATELINE: SAN FRANCISCO The former medical director of the clinic involved in a U.S. sports doping scandal could lose his license for allegedly prescribing a stimulant to a track and field athlete without examining her. The California state medical board is seeking to revoke or suspend the license of psychiatrist Brian Halevie-Goldman, who was medical director for the Bay Area Laboratory Co-Operative that provided steroids to top American athletes. Halevie-Goldman was accused of gross negligence for allegedly providing the drug modafinil to the athlete at the request of BALCO founder Victor Conte, who served four months in federal prison for dealing steroids. The doctor, who now specializes in childhood autism at two San Francisco Bay area clinics, did not immediately return calls on Friday seeking comment. The athlete in the case was identified by her initials, K.W., to protect her privacy. The medical board's accusation, filed in May, said K.W. tested positive for modafinil at an international track meet in August 2003 and accepted a two-year suspension for admitting to its use in 2004. Kelli White, a BALCO client who tested positive for modafinil after winning gold medals in the 100- and 200-meter races at the world championships in Paris in August 2003, was stripped of those medals and suspended for two years after admitting in 2004 to using the banned stimulant. The medical board said investigators examined medical charts kept by Halevie-Goldman that showed he diagnosed K.W. with narcolepsy in January 2003 without examining her, basing his analysis solely on a description of symptoms provided by Conte. Modafinil is used to treat narcolepsy, a sleep disorder. The medical board has scheduled a hearing on the allegations on Nov. 13, said spokeswoman Candis Cohen. LOAD-DATE: September 9, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 Associated Press All Rights Reserved 349 of 998 DOCUMENTS Associated Press Online September 8, 2006 Friday 9:35 PM GMT Doc in Steroids Scandal May Lose License BYLINE: By MARCUS WOHLSEN, Associated Press Writer SECTION: SPORTS NEWS LENGTH: 288 words DATELINE: SAN FRANCISCO The former medical director of the clinic involved in a sports doping scandal could lose his license for allegedly prescribing a stimulant to a track and field athlete without examining her. The state medical board is seeking to revoke or suspend the license of psychiatrist Brian Halevie-Goldman, who was medical director for the Bay Area Laboratory Co-Operative that provided steroids to top athletes. Halevie-Goldman was accused of gross negligence for allegedly providing the drug modafinil to the athlete at the request of BALCO founder Victor Conte, who served four months in federal prison for dealing steroids. The doctor, who now specializes in childhood autism at two San Francisco Bay area clinics, did not immediately return calls Friday seeking comment. The athlete in the case was identified by her initials, K.W., to protect her privacy. The medical board's accusation, filed in May, said K.W. tested positive for modafinil at an international track meet in August 2003 and accepted a two-year suspension for admitting to its use in 2004. Kelli White, a BALCO client who tested positive for modafinil after winning gold medals in the 100- and 200-meter races at the world championships in Paris in August 2003, was stripped of those medals and suspended for two years after admitting in 2004 to using the banned stimulant. The medical board said investigators examined medical charts kept by Halevie-Goldman that showed he diagnosed K.W. with narcolepsy in January 2003 without examining her, basing his analysis solely on a description of symptoms provided by Conte. Modafinil is used to treat narcolepsy, a sleep disorder. The medical board has scheduled a hearing on the allegations Nov. 13, said spokeswoman Candis Cohen. LOAD-DATE: September 9, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 Associated Press All Rights Reserved 350 of 998 DOCUMENTS Clinical Psychiatry News September 2006 FDA Cites Stevens-Johnson in Modafinil's ADHD Rejection BYLINE: Elizabeth Mechcatie SECTION: Pg. 7 Vol. 34 No. 9 ISSN: 0270-6644 LENGTH: 390 words    Modafinil, first approved for narcolepsy almost a decade ago, will not be among the Food and Drug Administration-approved options for treating attention-deficit hyperactivity disorder in children and adolescents.    In response to the FDA's decision not to approve the drug for this indication, the manufacturer, Cephalon Inc., has announced that it will stop development of the drug for this indication.    The company said in early August that the FDA had issued a nonapprovable letter for the drug for treating children and adolescents with ADHD. Had it been approved for this use, Cephalon would have marketed it under the trade name Sparlon.    The FDA does not typically comment on nonapprovable decisions.    Modafinil, described as a "wakefulness-promoting agent" in its label, was approved in 1998 for improving wakefulness in narcolepsy, and in 2004 to improve wakefulness in patients with excessive sleepiness associated with obstructive sleep apnea/hypopnea syndrome and shift work sleep disorder.    At a meeting in March, convened by the FDA to review the safety of modafinil for the ADHD indication, the FDA's Psychopharmacologic Drugs Advisory Panel noted in a 12 to 1 vote that modafinil was not safe for treating children and adolescents. The panel agreed the drug was effective but was mainly concerned about its potential to cause Stevens-Johnson syndrome (SJS) in this population.    In a group of 933 children and adolescents treated with modafinil in trials, there were 12 cases that could have been definite erythema multiforme (EM) or SJS, early prodromal EM or SJS, or were suggestive of EM or SJS, according to an FDA reviewer at the meeting.    One case was considered most likely to be SJS, for a risk of about 1 in 1,000. Although there were no reports of SJS among 36,000 children prescribed the drug off-label between 2002 and 2005, there was concern that some cases could occur with wider use of the drug, and the panel recommended that the company conduct a 3,000 patient study to further clarify the risk.    In the Cephalon release, Chairman and Chief Executive Officer Frank Baldino Jr., Ph.D., said the company was "surprised that the agency disagreed with the opinions of our experts, which were based on photographic and other evidence concerning a single suspected case of Stevens Johnson syndrome." LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: CPNEWS Copyright 2006 Elsevier Inc., International Medical News Group All Rights Reserved 351 of 998 DOCUMENTS Pediatric News September 2006 Modafinil to Treat ADHD Is Rejected by the FDA BYLINE: Elizabeth Mechcatie, Senior Writer SECTION: Pg. 11 Vol. 40 No. 9 ISSN: 0031-398X LENGTH: 387 words    Modafinil, first approved for narcolepsy almost a decade ago, will not be among the Food and Drug Administration-approved options for treating attention-deficit hyperactivity disorder in children and adolescents.    In response to the FDA's decision not to approve the drug for this indication, the manufacturer, Cephalon Inc., has announced that it will stop development of the drug for this indication.    On August 9, the company announced that the FDA had issued a nonapprovable letter for the drug for treating children and adolescents with ADHD. If it had been approved for this use, Cephalon would have marketed it under the trade name Sparlon.    The FDA does not typically comment on nonapprovable decisions.    Modafinil, described as a "wakefulness-promoting agent" in its label, was approved in 1998 for improving wakefulness in narcolepsy, and in 2004 to improve wakefulness in patients with excessive sleepiness associated with obstructive sleep apnea/hypopnea syndrome and shift work sleep disorder.    At a meeting in March, convened by the FDA to review the safety of modafinil for the ADHD indication, the FDA's Psychopharmacologic Drugs Advisory Panel noted in a 12 to 1 vote that modafinil was not safe for treating children and adolescents. The panel agreed the drug was effective but was mainly concerned about its poential to cause Stevens-Johnson syndrome (SJS) in this population.    In a group of 933 children and adolescents treated with modafinil in trials, there were 12 cases that could have been definite erythema multiforme (EM) or SJS, early prodromal EM or SJS, or were suggestive of EM or SJS, according to an FDA reviewer at the meeting. One case was considered most likely to be SJS, for a risk of about 1 in 1,000. Although there were no reports of SJS among 36,000 children prescribed the drug off-label between 2002 and 2005, there was concern that some cases could occur with wider use of the drug, and the panel recommended that the company conduct a 3,000-patient study to further clarify the risk.    In the Cephalon release, chairman and CEO Frank Baldino Jr., Ph.D., said the company was "surprised that the agency disagreed with the opinions of our experts, which were based on photographic and other evidence concerning a single suspected case of Stevens Johnson syndrome." LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: PDNEWS Copyright 2006 Elsevier Inc., International Medical News Group All Rights Reserved 352 of 998 DOCUMENTS WALL STREET JOURNAL ABSTRACTS August 31, 2006 Thursday BARR PHARMACEUTICALS INC SECTION: Section D; Column 3; Pg. 7 LENGTH: 43 words Barr Pharmaceuticals Inc says the FTC has asked it to submit information regarding a settlement agreement for the sleep-disorder drug Modafinil; the FTC is investigating whether Barr and others violated federal trade laws by restricting the sale of Modafinil (S) LOAD-DATE: September 1, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Abstract JOURNAL-CODE: WSJ Copyright 2006 The New York Times Company All Rights Reserved Information Bank Abstracts 353 of 998 DOCUMENTS New Scientist August 19, 2006 ADHD drug snag BYLINE: Staff SECTION: NEWS; Upfront; Pg. 7 LENGTH: 187 words IT HAD been touted as a safer alternative to the amphetamine-like stimulants prescribed to millions of hyperactive children and young adults. Now concerns about a potentially fatal side effect have crushed plans to market modafinil as a treatment for attention deficit hyperactivity disorder (ADHD). Modafinil, which boosts wakefulness and focus, is approved for adults with excessive sleepiness. A proposal to market it for treating ADHD hit a snag in March when one of 933 children taking part in a clinical trial developed a life-threatening skin condition (New Scientist , 1 April, p 8). Manufacturer Cephalon of Frazer, Pennsylvania, tried to convince the Food and Drug Administration that the child's rash was not a reaction to the drug. It has now abandoned its ADHD plans after the FDA refused to approve modafinil without further extensive safety studies. "It's really unfortunate," says James Swanson, a psychologist at the University of California, Irvine, who was involved in Cephalon's ADHD trials. He still believes modafinil is safer than other stimulants, which may cause hallucinations in a minority of children. LOAD-DATE: August 19, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Magazine Copyright 2006 Reed Business Information, UK, a division of Reed Elsevier Inc. All Rights Reserved 354 of 998 DOCUMENTS Pharma Marketletter August 17, 2006 Thursday Stock Commentary - New York - week to Aug 14, 2006 LENGTH: 377 words NEW YORK: equities finished the reporting period to August 14 in negative territory, with the Dow Jones falling 1.1%, in a week that was impacted by escalating oil prices on the back of alleged terrorist activities in the UK. Drug and biotechnology stocks were also mostly weaker, with 15 of those tracked rising, 26 falling. Better-than-expected second-quarter adjusted earnings helped Watson move up a little more than 11% during the reported week, with generics accounting for over 80% of the revenue (see page 6). Though the generic industry is showing some weak fundamentals generally, David Maris of Banc of America feels Watson shares still could see a nice rise. He has set a $26 target for the stock, and puts the same figure on Andrx (down 0.6%), which said its merger with Watson is still progressing on target, with antitrust concerns being addressed. But Andrx' earnings figures were not as positive, with it pointing to fees to try to clear up some issues with the Food and Drug Administration. Concerns are mounting for Cephalon, whose stock fell 16.3%. The news that it would give up development of Sparlon (modafinil) for attention-deficit hyperactivity disorder (see page 20) led several brokers to downgrade the shares to sell, and some investors sold off the stock. The safety issues for Sparlon raised worries about Provigil ( modafinil) and Nuvigil (r-modafinil). S & P's Equity Research Services downgraded Cephalon to hold from buy, on concerns over Nuvigil and Jefferies & Co, with a hold rating, said it would reserve $8.6 million as of June 30 for unused Sparlon inventory. Optimists now feel that the firm can concentrate on marketing Nuvigil, leveraging its existing sales force and its doctor contacts to switch patients to the newer product before modafinil comes off patent in 2011. A 12.3% drop in ImClone signaled investor unhappiness with the company's decision to stay independent (see page 2). While the firm pointed to strong sales of Erbitux (cetuximab), the cancer drug could soon face competition from an Amgen product. Investor Carl Icahn, the firm's largest shareholder aside from Bristol-Myers Squibb, has not yet decided whether to join ImClone's board, and investors are not convinced he could solve the company's problems. LOAD-DATE: August 18, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2006 Marketletter Publications Ltd. All Rights Reserved 355 of 998 DOCUMENTS Datamonitor CommentWire August 11, 2006 Cephalon: Sparlon rejection could prove a blessing in disguise; Cephalon has received non-approvable letter from the FDA regarding the use of Sparlon in ADHD. LENGTH: 287 words HIGHLIGHT: Cephalon has received a non-approvable letter from the FDA for its application to market Sparlon (modafinil) for the treatment of ADHD in children and adolescents. Although the rejection is a blow for Cephalon, the company is now free to concentrate its marketing efforts on modafinil's follow-up drug Nuvigil in sleep disorders, which Modafinil is currently marketed under the name Provigil for the treatment of narcolepsy and idiopathic hypersomnia, and generated sales of $513 million in 2005. The attempt to expand the drug's indication into ADHD was part of Cephalon's strategy to minimize the effect of generic competition to modafinil on revenues. The FDA's rejection of Sparlon is due to concerns regarding the possible induction of Stevens-Johnson syndrome, a hypersensitivity complex affecting the skin and mucous membranes. While Cephalon expressed its disappointment at the FDA ruling in a statement, the regulator's decision should not come as a surprise to either Cephalon's management or the investment community as an FDA scientific advisory panel voted not to recommend approval of the drug in March. Perhaps tellingly, in light of this recommendation, the company reduced its 2006 sales guidance by $100 million to between $1.45 billion and $1.50 billion. Although the non-approvable letter is a clearly a blow to Cephalon, this sales guidance suggests that Cephalon may have actually overestimated the earnings potential for Sparlon. In May 2005, Datamonitor estimated that, if approved, Sparlon would generate annual sales revenue of $3 million in 2006, reaching $100 million in 2008 and peaking at between $210 million and $230 million between 2010 and 2015. The regulatory setback could also act as a blessing in disguise for Cephalon, as the company can now focus its efforts on its modafinil follow-on drug, Nuvigil (r-modafinil). Cephalon should be able to leverage the experience of its existing sales force and relationships with sleep specialists to ensure a smooth switch to the new product before modafinil comes off patent in 2011. LOAD-DATE: August 16, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: NEWSWIRE JOURNAL-CODE: DTMCWF Copyright 2006 Datamonitor All rights reserved 356 of 998 DOCUMENTS Pharma Marketletter August 11, 2006 Friday FDA rejects Cephalon's Sparlon for ADHD LENGTH: 242 words US drugmaker Cephalon has received a letter from the Food and Drug Administration rejecting its supplemental New Drug Application Sparlon ( modafinil) tablets, a prop rietary dosage form for this drug for the treatment of atten tion- deficit/hyperactivity disorder in children and adolesc ents. In light of the FDA's "not approvable" letter, the firm says it will not develop Sparlon further. On the day of the news, August 10, the firm's share price fell 11% to $28.86. Frank Baldino, the company's chief executive, noted his surprise that the agency had disagreed with the opinions of Cepha lon's experts, which were based on photographic and other evidence concerning a single suspected case of Stevens Johnson syndrome, but he stressed that the decision has no impact on the company's previously-iss ued sales and earnings guidance or on its expectations for strong earnings in 2007. Late last year, the company received an approvable letter from the FDA to market the agent, which is a proprietary dosage form of modafinil, the active ingredient of the narcolepsy drug Provigilne, requesting additional information, but Cephalon still hoped to launch the drug early this year (Marketletter October 31, 2005). The company has decided to fully reserve the $8.6 million of net Sparlon inventory on its balance sheet but stressed that its previously-reported adjusted income per common share for the three and six months ended June 30, 2006, remains unchanged. LOAD-DATE: August 12, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2006 Marketletter Publications Ltd. All Rights Reserved 357 of 998 DOCUMENTS Global Insight August 10, 2006 FDA Rejects Cephalon's Hyperactivity Drug Sparlon BYLINE: Dr Jonathan Goodall LENGTH: 874 words U.S. drug-maker Cephalon has received a not approvable letter from the U.S. FDA for its supplemental new drug application (sNDA) for Sparlon (modafinil); an experimental drug for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children. Global Insight Perspective Significance U.S.-based drug-maker Cephalon has received a not approvable letter from the U.S. regulatory authority, regarding its sNDA for experimental ADHD treatment Sparlon. Implications This is a major setback for the company, since Sparlon was expected to prove an important franchise extension for its flagship product Provigil, which is close to facing generic challenges. Outlook Another major concern for Cephalon and its investors is that this decision could affect approval for the follow-on to Provigil; Nuvigil. However, observers generally feel that any potential link between Nuvigil and the severe skin rash Stevens-Johnson Syndrome (SJS) can be managed through more stringent labelling of Nuvigil. The central nervous system (CNS) research specialist Cephalon confirmed yesterday that it had received a letter from the U.S. FDA stating that its sNDA for Sparlon (modafinil) is not approvable. As a result, Cephalon announced that it will not pursue further development of the drug, which is a proprietary higher-dosage form of its flagship narcolepsy drug, Provigil (modafinil). This decision was not entirely unexpected. Sparlon received the thumbs-down from the agency s paediatric advisory panel on 23 March, over concerns that the sNDA submission did not contain sufficient information about whether the drug could cause the severe and potentially fatal skin rash, Stevens-Johnson Syndrome (SJS). The panel s decision caused the FDA to issue an approvable letter for the drug back in April of this year. A theoretical risk linking modafinil to SJS was discovered during post-marketing surveillance for Provigil. Although the rate of SJS occurrence was about the same as that which would be observed in the general population, the FDA s panel decided that, without further data, the risk of approving Sparlon was unacceptable. Reuters reports that as recently as last month, Cephalon s management appeared optimistic about Sparlon s chances of gaining approval, on the basis of new safety data that it provided to the agency. However, it appears that the FDA remained unconvinced about the safety of the drug. In a press release, Cephalon s Chairman and Chief Executive Officer, Frank Baldino, stated that Cephalon is extremely disappointed and surprised that the FDA disagreed with the opinion of its] experts, which was based on photographic and other evidence concerning a single suspected case of Stevens Johnson Syndrome . Outlook and Implications The decision to reject Sparlon deals a significant blow to Cephalon, which has now lost what was once thought by many to be an extremely promising product candidate. Many observers thought the approval of Sparlon would be fairly straightforward, due to it sharing the same active pharmaceutical ingredient as Provigil. Cephalon s flagship drug has gained widespread market acceptance in the treatment of excessive daytime sleepiness, and generated US$177.0 million in sales in the second quarter of 2006. Sparlon was considered an important line franchise extension for Provigil. It had been widely anticipated to gain market share in the ADHD treatment market, on account of the fact that it was not considered a stimulant (although its exact action mechanism was not well characterised). However, Cephalon s inability to demonstrate to the FDA s satisfaction that Sparlon was not associated with SJS seems to have caused its demise. This is despite the company s announcement in April that it had submitted additional information to the FDA, which it believed indicated that the skin rash observed in clinical trials was not SJS. As the FDA s decision was expected, Cephalon has already factored in the loss of Sparlon into its full-year financial projections. According to Cephalon, this decision will not impact previously-issued sales and earnings guidance, nor its expectations of strong earnings in 2007. Nevertheless, this rejection of Sparlon does pose a certain risk to Cephalon s optimistic future forecasts. Specifically, there is concern that this rejection may influence the FDA s decision over Cephalon s follow-up to Provigil, Nuvigil (armodafinil), which is currently under review by the agency. Nuvigil is a single isomer formulation of modafinil, designed to improve wakefulness in patients suffering from excessive sleepiness associated with narcolepsy, shift-work sleep disorder and obstructive sleep apnea/hypopnea syndrome. However, many observers believe that that Sparlon s rejection will not unduly affect the approval of Nuvigil, even if it is believed there is a theoretical link between modafinil and SJS. They note that if similar concerns persist with Nuvigil, they will probably be addressed through more stringent labelling of the product. Related Articles United States: 14 July 2006: United States: 25 April 2006: United States: 24 March 2006: United States: 2 February 2006: LOAD-DATE: August 10, 2006 LANGUAGE: ENGLISH Copyright 2006 World Markets Research Limited; All Rights Reserved 358 of 998 DOCUMENTS The Philadelphia Inquirer August 10, 2006 Thursday Cephalon shares plunge on discontinuation of Sparlon BYLINE: Linda Loyd, INQUIRER STAFF WRITER LENGTH: 211 words Shares of Cephalon Inc. plunged today after the company said it was abandoning development of Sparlon, a treatment for attention deficit hyperactivity disorder, because the Food and Drug Administration rejected the drug. Shares of the Frazer company were down 13.2 percent, or $8.45, to $55.50 in late-morning trading on the Nasdaq. Cephalon announced late Wednesday after the stock markets closed that it received a "non-approvable" letter from the FDA for Sparlon to treat ADHD in children. The company said it would not pursue further development of the drug, adding that regulators were particularly concerned that the drug had triggered a suspected case of Stevens-Johnson syndrome, a potentially fatal skin rash. Sparlon contains the same main ingredient, modafinil, that is in Cephalon's biggest-selling drug, Provigil, for sleep disorders. Cephalon said that its discontinuation of Sparlon would have no impact on previously issued financial guidance for 2007. Cephalon is developing another formulation of modafinil in a new drug, called Nuvigil. The FDA's rejection of Sparlon could cast doubt on the future of Nuvigil, which may have to carry additional warning labels, some analysts said. Contact staff writer Linda Loyd at 215-854-2831 or lloyd@phillynews.com. LOAD-DATE: August 10, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2006 Philadelphia Newspapers, LLC All Rights Reserved 359 of 998 DOCUMENTS Theflyonthewall.com This content is provided to LexisNexis by Comtex News Network, Inc. August 10, 2006 Thursday 7:15 AM Eastern Time CEPH: Hot Stocks LENGTH: 164 words 19:45 EDT Cephalon-CEPH says FDA says Sparlon is not approvable, will not pursue development - CEPH announced Wednesday day that it has received a letter from the U.S. Food and Drug Administrationstating that the company's supplemental new drug application (sNDA) for SPARLON (modafinil) Tablets [C-IV], a proprietary dosage form of modafinil for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents, is not approvable. In consideration of the FDA's decision, the company has determined that it will not pursue further development of Sparlon. As of Sunday, 08-06-2006 23:59, the latest Comtex SmarTrend(SM) Alert, an automated pattern recognition system, indicated an UPTREND on 06-30-2006 for CEPH @ $59.83. For more information on Comtex SmarTrend® Alert, contact your market data provider or go to CSTADirect.com SmarTrend is a registered trademark of Comtex News Network, Inc. Copyright © 2004-2006 Comtex News Network, Inc. All rights reserved. LOAD-DATE: August 11, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Web Publication Copyright 2006 Comtex News Network, Inc. All Rights Reserved Copyright 2006 TheFlyOnTheWall.com 360 of 998 DOCUMENTS US Fed News August 10, 2006 Thursday 12:03 AM EST Pennsylvania, Massachusetts Inventors Develop Modafinil BYLINE: US Fed News LENGTH: 202 words DATELINE: Alexandria, Va. ALEXANDRIA, Va., Aug. 10 -- Matthew S. Miller of Newtown, Pa., and Thomas E. Scammell of Wellesley, Ma., have developed compositions including modafinil for treatment of attention deficit hyperactivity disorder and multiple sclerosis fatigue. According to the U.S. Patent & Trademark Office: "Modafinil is effective in improving symptoms of attention deficit hyperactivity disorder and symptoms of multiple sclerosis fatigue. The administration of modafinil is also shown to activate the tuberomamillary neurons of the posterior hypothalamus, and thus exhibits activity in an area of the brain associated with normal wakefulness functions." The inventors were issued U.S. Patent No. 7,087,647 on Aug. 8. The patent has been assigned to Cephalon Inc., Frazer, Pa. The original application was filed on Oct. 30, 2002, and is available at: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=% 2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=7,087,647.PN.&OS=PN/7,087,647&RS= PN/7,087,647. For more information about US Fed News federal patent awards please contact: Myron Struck, Managing Editor/US Bureau, US Fed News, Direct: 703/866-4708, Cell: 703/304-1897, Myron@targetednews.com. LOAD-DATE: August 15, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 HT Media Ltd. All Rights Reserved 361 of 998 DOCUMENTS PR Newswire US August 9, 2006 Wednesday 9:01 PM GMT Cephalon Receives Non-Approvable Letter on SPARLON(TM); Company Will Not Pursue Further Development of the Product LENGTH: 873 words DATELINE: FRAZER, Pa. Aug. 9 FRAZER, Pa., Aug. 9 /PRNewswire-FirstCall/ -- Cephalon, Inc. (NASDAQ:CEPH) announced today that it has received a letter from the U.S. Food and Drug Administration (FDA) stating that the company's supplemental new drug application (sNDA) for SPARLON(TM) (modafinil) Tablets [C-IV], a proprietary dosage form of modafinil for the treatment of attention- deficit/hyperactivity disorder (ADHD) in children and adolescents, is not approvable. In consideration of the FDA's decision, the company has determined that it will not pursue further development of SPARLON. "Obviously, we are extremely disappointed and surprised that the agency disagreed with the opinions of our experts, which were based on photographic and other evidence concerning a single suspected case of Stevens Johnson syndrome," said Frank Baldino, Jr., Ph.D., Chairman and CEO. This decision by the FDA has no impact on the company's previously issued sales and earnings guidance or on its expectations for strong earnings in 2007. Second Quarter 2006 Financial Results The company's August 3, 2006 press release announcing its unaudited financial results for the three- and six-month periods ended June 30, 2006 did not reflect the impact of FDA's decision today on the SPARLON sNDA. The company has now determined to fully reserve the $8.6 million of net SPARLON inventory on its balance sheet as of June 30, 2006. The Company's previously reported adjusted income per common share for the three and six months ended June 30, 2006 does not change. The company expects to file its Form 10-Q for the quarterly period ended June 30, 2006 no later than August 14, 2006, which will reflect the impact of this event on the financial statements and related disclosures. Conference Call Scheduled Cephalon's management will discuss SPARLON in a conference call with investors beginning at 5:30 p.m. EDT today, Wednesday, August 9, 2006. To participate in the conference call, dial +1-888-856-9426 and refer to conference code 4413648. About Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products in four core therapeutic areas: central nervous system, pain, oncology and addiction. Cephalon currently employs approximately 3,000 people in the United States and Europe. U.S. sites include the company's headquarters in Frazer, Pennsylvania, and offices, laboratories or manufacturing facilities in West Chester, Pennsylvania, Salt Lake City, Utah, and suburban Minneapolis, Minnesota. Cephalon's European headquarters are located in Maisons-Alfort, France. The company currently markets five proprietary products in the United States: PROVIGIL(R) (modafinil) Tablets [C-IV], GABITRIL(R) (tiagabine hydrochloride), ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II], TRISENOX(R) (arsenic trioxide) injection, VIVITROL(TM) (naltrexone for extended-release injectable suspension) and numerous products internationally. Full prescribing information on its U.S. products is available at http://www.cephalon.com/ or by calling 1-800-896-5855. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs, development of potential pharmaceutical products, interpretation of clinical results, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, sales and earnings guidance, including the impact of the FDA's action on the SPARLON sNDA on sales and earnings guidance for 2006 and the outlook for strong earnings growth in 2007; and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. CONTACT: media, Robert Grupp, +1-610-738-6402, or rgrupp@cephalon.com , or investors, Robert (Chip) Merritt, +1-610-738-6376, or cmerritt@cephalon.com , both of Cephalon, Inc. Web site: http://www.cephalon.com/ Company News On-Call: http://www.prnewswire.com/comp/134563.html SOURCE Cephalon, Inc. URL: http://www.prnewswire.com LOAD-DATE: August 10, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 PR Newswire Association LLC. All Rights Reserved. 362 of 998 DOCUMENTS Theflyonthewall.com This content is provided to LexisNexis by Comtex News Network, Inc. August 9, 2006 Wednesday 7:45 PM Eastern Time CEPH: Hot Stocks LENGTH: 165 words 19:45 EDT Cephalon-CEPH says FDA says Sparlon is not approvable, will not pursue development - CEPH announced Wednesday day that it has received a letter from the U.S. Food and Drug Administrationstating that the company's supplemental new drug application (sNDA) for SPARLON (modafinil) Tablets [C-IV], a proprietary dosage form of modafinil for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents, is not approvable. In consideration of the FDA's decision, the company has determined that it will not pursue further development of Sparlon. As of Saturday, 08-05-2006 23:59, the latest Comtex SmarTrend(SM) Alert, an automated pattern recognition system, indicated an UPTREND on 06-30-2006 for CEPH @ $59.83. For more information on Comtex SmarTrend® Alert, contact your market data provider or go to CSTADirect.com SmarTrend is a registered trademark of Comtex News Network, Inc. Copyright © 2004-2006 Comtex News Network, Inc. All rights reserved. LOAD-DATE: August 10, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Web Publication Copyright 2006 Comtex News Network, Inc. All Rights Reserved Copyright 2006 TheFlyOnTheWall.com 363 of 998 DOCUMENTS Theflyonthewall.com This content is provided to LexisNexis by Comtex News Network, Inc. August 9, 2006 Wednesday 7:45 PM Eastern Time CEPH: Hot Stocks LENGTH: 165 words 19:45 EDT Cephalon-CEPH says FDA says Sparlon is not approvable, will not pursue development - CEPH announced Wednesday day that it has received a letter from the U.S. Food and Drug Administrationstating that the company's supplemental new drug application (sNDA) for SPARLON (modafinil) Tablets [C-IV], a proprietary dosage form of modafinil for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents, is not approvable. In consideration of the FDA's decision, the company has determined that it will not pursue further development of Sparlon. As of Saturday, 08-05-2006 23:59, the latest Comtex SmarTrend(SM) Alert, an automated pattern recognition system, indicated an UPTREND on 06-30-2006 for CEPH @ $59.83. For more information on Comtex SmarTrend® Alert, contact your market data provider or go to CSTADirect.com SmarTrend is a registered trademark of Comtex News Network, Inc. Copyright © 2004-2006 Comtex News Network, Inc. All rights reserved. LOAD-DATE: August 10, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Web Publication Copyright 2006 Comtex News Network, Inc. All Rights Reserved Copyright 2006 TheFlyOnTheWall.com 364 of 998 DOCUMENTS Clinical Neurology News July 2006 Sleep Medication Improves Cognition, Mood in Brain Tumor Patients BYLINE: Fran Lowry, Orlando Bureau SECTION: Pg. 6 Vol. 2 No. 7 ISSN: 1553-3212 LENGTH: 417 words    ATLANTA - Modafinil, a medication commonly used to treat sleep disorders, improves cognitive function, fatigue, and depression in adult brain tumor patients, according to results of a pilot study presented at the American Society of Clinical Oncology.    "Patients with brain cancer develop neurobehavioral dysfunction and fatigue that seriously compromise their quality of life. Modafinil has been used to treat the fatigue associated with multiple sclerosis, Parkinson's disease, stroke, and HIV infection, and we decided to see if it would be of help in this medically fragile patient population," said Thomas A. Kaleita, Ph.D., of the department of psychiatry at the University of California, Los Angeles.    In comparison with baseline measures, self-reported test scores in cognitive abilities, mood, and fatigue improved by an average of 21%, 35%, and 47%, respectively, after 8 weeks of modafinil therapy. All improvements were statistically significant, with P values less than .0001, Dr. Kaleita reported.    The study included 30 patients aged 21-65 years old with primary malignant and nonmalignant tumors. Eighteen patients had high-grade gliomas, 10 had low-grade gliomas, 1 had meningioma, and 1 had CNS lymphoma. All patients were treated with neurosurgical resection and radiotherapy, and some patients also received chemotherapy.    After treatment patients were randomized, in a double-blind fashion, to 200 mg or 400 mg of modafinil per day for 3 weeks. After a 1-week washout period, the study was extended for an 8-week open-label phase, in which patients were given modafinil at what was deemed to be their optimal dose, which ranged from 50 mg to 600 mg per day, Dr. Kaleita explained.    There was a lack of response in three patients, which Dr. Kaleita attributed to the size of the tumor or psychological factors. The drug was "generally well tolerated," he added; no serious adverse events were reported.    The most common side effects were headache in 42% of patients (which was "not surprising in this patient population," Dr. Kaleita noted), insomnia, dizziness, and nausea. These generally resolved after the dose of modafinil was adjusted.    "We find these preliminary results from this small study very encouraging, because they show that it is possible to improve the quality of life in people with brain cancer. Our next step is to determine long-term outcomes and verify that modafinil does not create a tolerance or loses its efficacy over time," said Dr. Kaleita. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: CNNEWS Copyright 2006 Elsevier Inc., International Medical News Group All Rights Reserved 365 of 998 DOCUMENTS The Leader-Post (Regina, Saskatchewan) June 29, 2006 Thursday Final Edition Scientists working on sleep/wake equation BYLINE: Ed Willett, Special to The Leader-Post SECTION: ARTS & LIFE; Science; Pg. A6 LENGTH: 686 words Do you have trouble falling asleep? Do you have trouble waking up? By one estimate, 75 per cent of adults have some kind of sleep problem every week, so it's not surprising some people use artificial means to both get to sleep and to wake up. According to a 1998 study from the Henry Ford Health Sciences Research Institute in Detroit, 13 per cent of adult Americans had used alcohol to get to sleep in the previous year, and 18 per cent had used sleeping pills. On the flip side, plenty of people try to keep themselves awake after a sleepless night by the use of stimulants such as caffeine or nicotine. Sometimes they're the same people, trapped in a "stimulant-sedative loop." It would be wonderful if we could do away with pharmaceutical sleep aids or stimulants altogether--but that seems unlikely. Instead, as a recent article in New Scientist magazine makes clear, scientists are working hard to come up with less damaging and more effective wake-you-up and put-you-to-sleep pills. Most sleeping pills currently on the market work (as does alcohol) by making neurons in the brain more sensitive to a neurotransmitter called GABA, what New Scientist called "the brain's all-purpose dimmer switch." However, the resulting sleep is short on the most restful "slow-wave" stage of sleep. A new drug called gaboxadol, on the other hand, which could be on the market next year, is a "slow-wave sleep promoter." There's at least one other in the works. The hope is these drugs can make a relatively short period of sleep more restful by filling it up with slow-wave sleep: they're power-nap pills, as it were. There are several other new approaches in the works for sleeping pills. One from Japan called Rozerem, which appeared last year, mimics the effect of the hormone melatonin, which promotes sleep. Meanwhile, on the more stimulating side of the sleep/wake equation, there's even more action, not least because the military has a strong interest in keeping personnel awake and alert. One stimulant that's been on the market for about seven years now is modafinil. It's marketed for the treatment of sleep disorders such as narcolepsy, but it has also become popular as a "lifestyle" drug because it can keep you awake without apparent side effects. (It's called a "eugeroic," which means "good arousal" in Greek.) Modafinil's effects are so subtle most people aren't even aware of them -- they just don't think about being tired. People taking it for medical reasons just take enough to get through the day. The U.S. military has experimented with sequential doses, and found it works for about 48 hours. After that, sleep is required -- but rather than needing 16 hours of sleep after staying awake for 48, modafinil users catch up just fine with about eight. Another drug in development, currently called CX717, successfully kept 11 rhesus monkeys at Wake Forest University in Winstom-Salem, North Carolina, awake for 36 hours -- after which they actually performed better on short-term memory and general alertness test than undrugged monkeys did after normal sleep! A test on humans showed that the drug could reverse the cognitive decline that you'd normally expect after 24 hours of sleep deprivation. CX717 is an ampakine, a type of drug that increases brain activity by enhancing the action of glutamate, the brain's main excitatory neurotransmitter. Within a decade or two, we may be able to structure our sleep/wake cycle to suit our lifestyles: staying awake when we need to, sleeping when it suits us. We might be able to, say, stay awake for 22 hours and get all the rest we need in just two. There may be long-term effects to messing with the natural sleep-cycle, even with these new, safer drugs, that we don't know about yet. But in a world where people are already buying modafinil from online pharmacies just so they can party longer on weekends, it seems inevitable that the age-old cycle of 16 hours awake, eight hours asleep is about to become a dusty old relic, stored permanently beneath the bed of history. - Willett is a Regina freelance writer. E-mail comments or questions to edward@edwardwillett.com. LOAD-DATE: June 29, 2006 LANGUAGE: ENGLISH DOCUMENT-TYPE: Column PUBLICATION-TYPE: Newspaper Copyright 2006 The Leader-Post, a division of Canwest MediaWorks Publication Inc. All Rights Reserved 366 of 998 DOCUMENTS Cancer Drug News Pharmaceuticals June 15, 2006 Modasomil improves neurobehavioural dysfunction and fatigue in adult patients with brain tumours LENGTH: 403 words According to data presented at the 42nd Annual Meeting of the American Society for Clinical Oncology (ASCO), held from 2nd to 6th June in Atlanta, GA, a University of California , Los Angeles, study has found that Cephalon 's drug, Modasomil ( modafinil ), which is generally used to treat sleep disorders, can enhance the quality of life in patients with brain cancer by improving cognitive functions, mood and fatigue levels, with a low incidence of negative side effects. The 30 patients in the study had a variety of brain tumour types, and most were categorised as having severe attention, memory and fatigue problems. All of the patients had received some combination of neurosurgery, radiation therapy and chemotherapy treatments, and several were receiving chemotherapy whilst participating in the study. The first part of the study was double-blind and patients were randomised between two different dosage levels of the drug for three weeks. After a one-week period in which patients did not receive the drug at all, there was an eight-week open-label phase in which all patients received modafinil at what was determined to be each patients optimal dose, which varied between 50 and 600mg/day. Patients were evaluated at specified times with various measures, including standardised tests of concentration and attention, fatigue self-ratings and a structured interview. In addition, patients received comprehensive neurological examinations at specified times as well as brain MRIs, which were performed before, during and after completion of this therapeutic trial. Comparing patient scores before they started taking modafinil to their scores after they had been on it for two to three months, the majority of subjects exhibited clinically meaningful improvements in all areas. Test scores in cognitive abilities improved by an average of 21 per cent, mood improved by 35 per cent and fatigue improved by 47 per cent. The site of the tumour or psychological factors were believed to be responsible for a lack of response to the drug in three patients. Modafinil was generally well tolerated and there were no serious adverse events. The most common side effects were headache (42 per cent), insomnia (26 per cent), dizziness (23 per cent) and nausea (13 per cent). These side effects were considered mild-to-moderate in severity and typically resolved after adjustments in dose and scheduling of medication. LOAD-DATE: June 15, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2006 ESPICOM Business Intelligence Ltd. All Rights Reserved 367 of 998 DOCUMENTS Jiji Press Ticker Service June 13, 2006 Tuesday 6:32 PM JST Takeda to Sell Cephalon's Wake-Promoting Agent in U.S. LENGTH: 183 words DATELINE: Osaka, June 13 Japan's Takeda Pharmaceutical Co. said Tuesday that Takeda Pharmaceutical North America Inc., a U.S. unit, and U.S. drug maker Cephalon Inc. will jointly promote Cephalon's Provigil, a wake-promoting agent, in the United States. In July, 500 Takeda sales representatives will begin promoting Provigil, or modafinil, to primary care physicians and other appropriate health care professionals in the United States. The copromotion agreement will run for three years with an annual option to renew. Cephalon, based in Frazer, Pennsylvania, will pay the Takeda unit based in Lincolnshire, Illinois, a royalty based on certain sales criteria for the product. Modafinil is the first and only medication in a new class of wake-promoting agents believed to work selectively through the brain's sleep/wake centers to activate the cortex of the brain, Cephalon said. The medication has been approved in more than 20 countries and is available under several brand names including Provigil. In 2004, the U.S. Food and Drug Administration approved Provigil for improving wakefulness in patients with excessive sleepiness. LOAD-DATE: June 13, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 Jiji Press Ltd. All Rights Reserved 368 of 998 DOCUMENTS UPI June 7, 2006 Wednesday 4:16 PM EST Analysis: Sleep drug has brain-tumor use BYLINE: ED SUSMAN LENGTH: 611 words DATELINE: ATLANTA, June 7 A drug often prescribed to help people overcome drowsiness caused by shift work or other conditions appears to improve depression, fatigue and difficulty in maintaining attention to the activities of daily living that often accompanies people battling brain cancer. While most cancers that arise in the brain are incurable and are difficult to treat, recent advances with precise surgery, new drugs and devices that actually can be placed in the brain to combat the disease have lengthened survival considerably for people with these diseases. At this week's American Society of Clinical Oncology meeting, researchers described how they markedly improved quality of life of patients by administering modafinil -- sold as Cephalon's Provigil -- a drug primarily used to treat patients with narcolepsy -- a condition in which people suddenly fall asleep at inappropriate times, and the lethargy that accompanies people who work odd hours. "We were able to see clinically meaningful outcomes in this trial," said Thomas Kaleita, assistant professor of psychiatry at the University of California, Los Angeles. In his trial of 30 individuals -- 19 men and 11 women -- statistically significant improvement was seen in tests of mental acuity, in measurements of depression and in tests of fatigue. "The improvements that were seen in this trial were huge," said Jeff Sloan, a researcher in oncology at the Mayo Clinic Comprehensive Cancer Center in Rochester, Minn. Sloan, who commented on the study at the ASCO meeting, said that the effect of the treatments were likely to make meaningful differences in the lives of the patients. The study was among hundreds presented to the 25,000 health care professionals attending the sessions in Atlanta. "This is very encouraging study," Suzan Streichenwein, a psychiatrist based in West Palm Beach, Fla., told United Press International. "Oncologists are concerned about quantity of life but equally important is the quality of life." She said that often, these patients are so sluggish due to their medications and disease, they can barely move around. In the study, Kaleita administered several psychological tests to the patients. The patients took between 50 milligrams of modafinil and 600 mg a day. He said he saw across-the-board improvement. Cognitive abilities increased 21 percent, mood improved by 35 percent, fatigue improved by 47 percent and depression improved 43 percent. All the changes from the start of the trial through 12 weeks of the study proved to be highly statistically significant. For example, in one test of fatigue levels, patients were asked to measure their fatigue on a 0 to 10 scale with 10 representing extreme fatigue. They averaged a score of "4" -- or moderate fatigue -- when they began the test. After 10 weeks of modafinil, their average fatigue scores dropped by 3 points, indicating a 75 decline in fatigue, and after 12 weeks, there was an 83 percent decline in scores. Sloan said those fatigue scores really represent more than a doubling in how well a patient feels, recognizing that this improvement occurred even while the patient was struggling with brain cancer. "The improvements with this drug are important," said Streichenwein, but she cautioned that some dosages of modafinil used in the study are above that normally prescribed for depression, and added that the drug is expensive. Sloan said the studies show there is a complex, complicated system involved in brain cancer and that fatigue plays a major role in a patient's well being. "This study shows there is hope for people with brain cancer, and that there are interventions that can improve quality of life," Kaleita said. LOAD-DATE: June 8, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 U.P.I. All Rights Reserved 369 of 998 DOCUMENTS The Herald (Glasgow) June 6, 2006 I WISH ... You make a wish. We find the people who could make it happen; THIS WEEK: I wish I could live without sleep BYLINE: James Morgan SECTION: TUESDAY; Pg. 11 LENGTH: 290 words Sleeping is a pleasure. I want more not less. That's only because you're tired. What if you could party all night and wake up the next morning feeling alert and refreshed? A new drug being developed will make two hours' sleep feel like a full night's rest. After a late night in the office, or on the town, you pop the pill before bedtime and wake up two hours later feeling fully recovered. Two hours? Come on, Even Margaret Thatcher needed four. Wake up. There are already thousands of high-fliers in the US who use a new stimulant - modafinil - to get by on four hours a night. Modafinil users report up to 48 hours of continuous wakefulness without any ill effects, and, afterwards, only need eight hours to sleep the tiredness off. Officially prescribed only for "medical" sleepiness, it is fast becoming a lifestyle drug. Sales reached GBP330m in 2005. Now its creators, Cephalon, are working on a successor, armodafinil, which would halve that to just two hours a night. Both drugs are known as "eugeroics", meaning "good arousal" in Greek. Basically, they block the actions of the neurotransmitters dopamine and noradrenaline. Isn't it dangerous to disobey our body's natural circadian rhythms? Many of us already do, by relying on generic stimulants such as caffeine and sleeping pills. So why not, say some sleep experts, develop more precise drugs? There are no side effects yet reported for modafinil, and the race is on to develop even more powerful sleep-control drugs. The US military is funding development of another stimulant, CX717, which could keep soldiers awake for 72 hours. Then there's gaboxadol, a pill that delivers the ultimate power nap by stimulating deep, healing "long-wave" sleep over shallow short-wave slumber. LOAD-DATE: June 6, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: NEWSPAPER JOURNAL-CODE: GHERLD Copyright 2006 Newsquest Media Group All rights reserved 370 of 998 DOCUMENTS The Sunday Times (London) June 4, 2006 No 10 scientist urges brain pills for all BYLINE: David Cracknell and Steven Swinford SECTION: HOME NEWS; News; Pg. 3 LENGTH: 578 words SMART drugs to make people think faster, improve their memory and reduce tiredness will be commonplace within 20 years, according to the government's chief scientific adviser. Sir David King told ministers at a presentation in Downing Street that a new generation of "recreational psychoactive substances" could be given to healthy people to enhance their lives. He said that brain enhancing chemicals could also "revolutionise" treatment for mental disorders and create new treatments to fight drug addiction. King's report adds to calls from scientists for the removal of restrictions on "cognitive enhancers" which have been dubbed "cosmetic neurology" or "nip and tuck" for the mind. It also cements King's reputation as an increasingly influential figure in the government -a civil servant who is unafraid to speak his mind on topics ranging from climate change to drought and drugs. Ritalin and Modafinil, the first generation of mind enhancing drugs, were originally intended to treat disorders but have since been adopted by people from across the social spectrum because of their ability to enhance performance. Ritalin was originally intended as a treatment for children and adults with hyperactivity problems, but has since been adopted by students to help them to concentrate. A study in America last year revealed that 20% of healthy American college students use Ritalin before exams. Modafinil is generally prescribed for the treatment of narcolepsy, a condition which causes people suddenly to fall asleep. It is now becoming popular for its ability to help people to think clearly and make decisions when tired. Scientists are keen to see restrictions removed on more drugs to make them available without prescription. Dr Andrea Malizia, a consultant senior lecturer in the Department of Psychopharmacology at Bristol University, is calling for Donepezil, an Alzheimer's treatment, to be more available. Donepezil has a "remarkable impact" on a wide range of functions, including memory, concentration and the ability to learn. "The potential for these drugs is enormous. People already buy vitamins and take caffeine to improve mental functions but these drugs will offer a whole new dimension," said Malizia. "Studies have shown that people who take these drugs are able to memorise more words than they normally could -and increase their general brainpower. "We have used them to treat mental disease with great effect, but there is obviously the market for healthy people to take them just to get smarter." Other scientists remain concerned about smart drugs. Dr Paul Howard-Jones, neuroscience and education network co-ordinator at Bristol University, said that the drugs needed to be carefully regulated. "The (smart) pills are likely to be available to the general public in a few years. But we do not know how they will be regulated -it may be that they are only sold on prescription, or it may be that they are sold on supermarket shelves like vitamin pills," he said. "There could be restrictions placed on their sale, but that might mean people buy them illegally. I would call on people to start discussing their impact before they start causing tremendous problems in society." This concern was also raised by King during his cabinet briefing. "Should we change regulatory structures to enable new procedures in non-medical psychoactive substances?" he said. "Are 'cognitive enhancers' a great market for social opportunity or destabilising and divisive?" LOAD-DATE: June 4, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2006 Times Newspapers Limited All Rights Reserved 371 of 998 DOCUMENTS Clinical Psychiatry News June 2006 Panel Cites Potential for Severe Rash; Stalls Modafinil for Children BYLINE: Alicia Ault, Associate Editor, Practice Trends SECTION: Pg. 7 Vol. 34 No. 6 ISSN: 0270-6644 LENGTH: 798 words    GAITHERSBURG, MD. - A Food and Drug Administration advisory committee said modafinil is not safe for treating ADHD in children and adolescents by a 12-1 vote, although committee members unanimously agreed the drug was effective for that indication.    At a meeting of the FDA's Psychopharmacologic Drugs Advisory Committee, the panel members were mainly concerned about modafinil's potential to cause Stevens-Johnson syndrome (SJS). The severe rash, which is often attributable to a hypersensitivity reaction to a drug, can be fatal in up to 5% of cases, according to Dr. Michael E. Bigby of the dermatology department at Harvard Medical School, Boston, and consultant to the panel.    In a group of 933 children and adolescents exposed to the drug during trials, there were 12 cases that could have been definite erythema multiforme (EM) or SJS, early prodromal EM or SJS, or suggestive of prodromal EM or SJS-a rate of 1.29%, said Dr. Glenn B. Mannheim, a medical reviewer in the FDA's division of psychiatry products.    The panel's discussion focused on one case that seemed most likely to be SJS-indicating a 1 in 1,000 risk. But they weren't certain that was the true risk.    Dr. Bigby and Dr. Mannheim said more cases could occur once modafinil (Provigil) is more widely used--even though there have been no reports of SJS in the 36,000 children who were prescribed the drug off label in 2002-2005.    Given the trial data and the assumption that modafinil could capture 10% of the market for children under age 19, there could be 500-3,250 cases of EM or SJS, and 25-488 deaths, Dr. Mannheim said.    The dichotomy between postmarketing experience and the trial data prompted the FDA to seek its advisers' input, said Dr. Robert J. Temple, director of the FDA's office of medical policy.    The FDA usually follows the advice of its panels.    The FDA has received six reports of serious skin reactions in adults, said Dr. Mannheim.    "I'd like to see an opportunity for the company to come back with additional data. That will give us additional assurance that this case was a fluke," said panel chair Dr. Wayne K. Goodman, chair of the department of psychiatry at the University of Florida, Gainesville.    The committee said modafinil's manufacturer, Cephalon Inc., should conduct a 3,000-patient, open-label study to further clarify the risk of SJS.    After the meeting, Dr. Thomas Laughren, director of the FDA's division of psychiatry products, told reporters that if a case turns up in such a study, "then they have a problem."    It was not clear why children had higher rates of skin-related adverse events than adults, but Dr. Mannheim noted that lab tests indicated that they had a 7-16 times higher area under the curve ratio of modafinil sulfone, a metabolite. The levels could not be explained by higher milligram-per-kilogram dosing, he said.    In two of the three phase III studies, children were given a flexible dose with weekly titration (170 mg, 255 mg, 340 mg, or 425 mg). In the third study they were given a fixed dose, with those under 30 kg receiving 340 mg daily, and those over 30 kg receiving 425 mg daily.    The primary outcome was the total score on the school ADHD rating scale. In all three trials, children taking modafinil had a more significant drop in scores than those taking placebo. The total score for modafinil recipients was close to the normative score for a 10-year-old male, according to a statement made by Cephalon.    Panelists did not dispute the drug's efficacy, although many said it would not be a first-line choice.    Lesley Russell, Cephalon's senior vice president of worldwide clinical research, said modafinil offers clinicians an alternative, especially when children don't respond to other marketed drugs.    But Dr. Temple said that even though it's plausible that modafinil might work in nonresponsive children, the company had not proved that. "The mere fact that people given a second drug respond after failing to respond to the first tells you nothing at all."    According to a company statement, modafinil may be less addictive and less apt to be diverted because it does not offer a "high" to recreational users. Jeffrey L. Vaught, executive vice president of research and development at Cephalon, said the drug is not water soluble and is not stable at high heat, which makes it difficult to crush for injection or smoke. Studies show that modafinil does not activate reward centers, and that it does not cause release of dopamine in vitro or in vivo.    The Drug Enforcement Administration has deemed modafinil a schedule IV drug; other stimulants used to treat ADHD, such as Ritalin, are schedule II.    Despite potential advantages, the panel did not want modafinil to be marketed for children yet. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: CPNEWS Copyright 2006 Elsevier Inc., International Medical News Group All Rights Reserved 372 of 998 DOCUMENTS Hindustan Times May 30, 2006 Tuesday 11:23 AM EST Amphetamine salts most effective for treating ADHD BYLINE: Hindustan Times LENGTH: 264 words DATELINE: Washington Washington, May 30 -- Stimulant medications, such as mixed amphetamine salts (MAS) and methylphenidates are significantly more effective than nonstimulant ADHD medications or novel stimulants, such as modafinil, in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). This conclusion is based on a meta-analysis of 29 controlled-treatment studies representing the past 25 years of research involving nearly 4,500 children with ADHD presented recently at the 2006 American Psychiatric Association meeting in Toronto, Canada. Among stimulant medications classes, long-acting mixed amphetamine salts (MAS XR) and immediate-release mixed amphetamine salts showed a similar level of efficacy to short- or long-acting methylphenidates. The effectiveness of short- and long-acting stimulants did not differ from one another. "The larger effect sizes we calculated for stimulant ADHD medications, compared to nonstimulants or the novel stimulant modafinil, leads us to conclude that amphetamine and methylphenidate based stimulant medications are more effective in treating symptoms of ADHD," said Stephen V. Faraone, Ph.D., lead researcher and director of child and adolescent psychiatry at SUNY Upstate Medical University. The researchers compared study outcomes using effect sizes, a commonly used, standard statistical measure to determine the magnitude of a particular effect resulting from an intervention, such as a drug used on a population, irrespective of the population size. Published by HT Media Ltd. with permission from Asian News International. LOAD-DATE: June 1, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 HT Media Ltd. All Rights Reserved 373 of 998 DOCUMENTS UPI May 30, 2006 Tuesday 5:36 PM EST Stimulant drugs most effective for ADHD LENGTH: 276 words DATELINE: WASHINGTON, May 30 Stimulants are better than non-stimulants or novel stimulants for children with attention-deficit/hyperactivity disorder. That's the finding of a new study recently released at the 2006 meeting of the American Psychiatric Association in Toronto. Stephen Faraone and colleagues at SUNY Upstate Medical University conducted a meta-analysis of 29 double-blind, placebo-controlled studies on the effectiveness of ADHD medication in children who were treated during the last 25 years. The studies enrolled nearly 4,500 subjects. The team found that stimulant medications -- such as mixed amphetamine salts and methylphenidates -- treated the symptoms of ADHD much more effectively than either non-stimulants or novel stimulants. Fifteen medications were tested and 17 measures of ADHD symptoms were reviewed, including hyperactivity, inattentiveness, impulsiveness and oppositional behavior. The non-stimulant/novel stimulant drugs involved were atomoxetine, bupropion, modafinil and desipramine. The analysis used effect sizes, a standard statistical measure, to determine each drug's usefulness. Effect sizes are usually categorized as small (0.2), medium (0.5) and large (0.8). After adjusting for the influence of individual study designs, the effect size was calculated based on total ADHD scores. Long- and short-acting stimulant medications had the largest effect size (0.83 and 0.9, respectively), followed by non-stimulants/modafinil-based stimulants (E = 0.62). Statistically significant differences in effect size occurred between non-stimulants/modafinil-based stimulants and both short-acting stimulants (p = 0.002) and long-acting stimulants (0.004). LOAD-DATE: May 31, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 U.P.I. All Rights Reserved 374 of 998 DOCUMENTS CNS Drug News Pharmaceuticals May 26, 2006 Mixed amphetamine salts may be most effective in treating ADHD in youths LENGTH: 444 words Stimulant medications, such as mixed amphetamine salts and methylphenidate s are significantly more effective than non-stimulant attention deficit hyperactivity disorder (ADHD) medications or novel stimulants, such as modafinil , in the treatment of children with the disorder. This conclusion is based on a meta-analysis that was presented at the Annual Meeting of the American Psychiatric Association, held from 20th to 25th May, in Toronto, Canada. For the analysis, Dr Stephen V Faraone, lead researcher and director of child and adolescent psychiatry at SUNY Upstate Medical University, and his colleagues used data from 29 treatment studies of 4,465 children with ADHD, with an average age of ten years, published during or after 1980. Designs for all of the studies were randomised and double-blind, with placebo controls that lasted for two or more weeks in populations diagnosed with ADHD, as defined using criteria from the DSM-IIIR or DSM-IV. This study was supported by Shire , whose product, Adderall XR (mixed amphetamine salts), is indicated for the treatment of ADHD. The analysis included 15 drugs using 17 different outcome measures of ADHD symptoms, including hyperactive, inattentive, impulsive or oppositional behaviour. The most commonly-identified treatments included both methylphenidate and amphetamine compounds. Non-stimulant drugs included in the analysis were Eli Lilly 's Strattera ( atomoxetine ), bupropion , modafinil and desipramine . Among stimulant medication classes, long-acting mixed amphetamine salts and immediate-release mixed amphetamine salts showed a similar level of efficacy to short- or long-acting methylphenidates. The effectiveness of short- and long-acting stimulants did not differ from one another. The researchers compared study outcomes using effect sizes. After adjusting for the influence of individual study design features, effect size was calculated based on Total ADHD scores. Long- and short-acting stimulant medications showed the largest effect size among all medications (E=0.83 and 0.9, respectively), followed by non-stimulant or modafinil-based stimulants medications (E=0.62). Statistically significant differences in effect size occurred in comparisons between non-stimulant/modafinil-based stimulant medications and long-acting (p=0.004), as well as short-acting, stimulants (p=0.002). According to Faraone, the larger effect sizes that the researchers calculated for stimulant ADHD medications, compared to non-stimulants or the novel stimulant, modafinil, leads them to conclude that amphetamine and methylphenidate-based stimulant medications are more effective in treating symptoms of ADHD. LOAD-DATE: May 26, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2006 ESPICOM Business Intelligence Ltd. All Rights Reserved 375 of 998 DOCUMENTS CNS Drug News Pharmaceuticals May 26, 2006 Mixed amphetamine salts may be most effective in treating ADHD in youths LENGTH: 444 words Stimulant medications, such as mixed amphetamine salts and methylphenidate s are significantly more effective than non-stimulant attention deficit hyperactivity disorder (ADHD) medications or novel stimulants, such as modafinil , in the treatment of children with the disorder. This conclusion is based on a meta-analysis that was presented at the Annual Meeting of the American Psychiatric Association, held from 20th to 25th May, in Toronto, Canada. For the analysis, Dr Stephen V Faraone, lead researcher and director of child and adolescent psychiatry at SUNY Upstate Medical University, and his colleagues used data from 29 treatment studies of 4,465 children with ADHD, with an average age of ten years, published during or after 1980. Designs for all of the studies were randomised and double-blind, with placebo controls that lasted for two or more weeks in populations diagnosed with ADHD, as defined using criteria from the DSM-IIIR or DSM-IV. This study was supported by Shire , whose product, Adderall XR (mixed amphetamine salts), is indicated for the treatment of ADHD. The analysis included 15 drugs using 17 different outcome measures of ADHD symptoms, including hyperactive, inattentive, impulsive or oppositional behaviour. The most commonly-identified treatments included both methylphenidate and amphetamine compounds. Non-stimulant drugs included in the analysis were Eli Lilly 's Strattera ( atomoxetine ), bupropion , modafinil and desipramine . Among stimulant medication classes, long-acting mixed amphetamine salts and immediate-release mixed amphetamine salts showed a similar level of efficacy to short- or long-acting methylphenidates. The effectiveness of short- and long-acting stimulants did not differ from one another. The researchers compared study outcomes using effect sizes. After adjusting for the influence of individual study design features, effect size was calculated based on Total ADHD scores. Long- and short-acting stimulant medications showed the largest effect size among all medications (E=0.83 and 0.9, respectively), followed by non-stimulant or modafinil-based stimulants medications (E=0.62). Statistically significant differences in effect size occurred in comparisons between non-stimulant/modafinil-based stimulant medications and long-acting (p=0.004), as well as short-acting, stimulants (p=0.002). According to Faraone, the larger effect sizes that the researchers calculated for stimulant ADHD medications, compared to non-stimulants or the novel stimulant, modafinil, leads them to conclude that amphetamine and methylphenidate-based stimulant medications are more effective in treating symptoms of ADHD. LOAD-DATE: May 29, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2006 ESPICOM Business Intelligence Ltd. All Rights Reserved 376 of 998 DOCUMENTS PR Newswire US May 24, 2006 Wednesday 4:00 PM GMT Mixed Amphetamine Salts Most Effective in the Treatment of ADHD in Youths Reports the SUNY Upstate Medical Center; Analysis of data from nearly 4,500 children presented at the 2006 American Psychiatric Association Meeting LENGTH: 1123 words DATELINE: TORONTO May 24 TORONTO, May 24 /PRNewswire/ -- Stimulant medications, such as mixed amphetamine salts (MAS) and methylphenidates are significantly more effective than nonstimulant ADHD medications or novel stimulants, such as modafinil, in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). This conclusion is based on a meta-analysis of 29 controlled-treatment studies representing the past 25 years of research involving nearly 4,500 children with ADHD presented today at the 2006 American Psychiatric Association meeting in Toronto, Canada. Among stimulant medications classes, long-acting mixed amphetamine salts (MAS XR) and immediate-release mixed amphetamine salts showed a similar level of efficacy to short- or long-acting methylphenidates. The effectiveness of short- and long-acting stimulants did not differ from one another. "The larger effect sizes we calculated for stimulant ADHD medications, compared to nonstimulants or the novel stimulant modafinil, leads us to conclude that amphetamine and methylphenidate based stimulant medications are more effective in treating symptoms of ADHD," said Stephen V. Faraone, Ph.D., lead researcher and director of child and adolescent psychiatry at SUNY Upstate Medical University. "Our results should help physicians who have had to rely on qualitative comparisons among published trials, along with their own clinical experience, to draw conclusions about an ADHD medication's relative efficacy because of largely absent direct head-to-head drug comparisons." The researchers compared study outcomes using effect sizes, a commonly used, standard statistical measure to determine the magnitude of a particular effect resulting from an intervention, such as a drug used on a population, irrespective of the population size. Effect sizes are generally categorized as small (0.2), medium (0.5) and large (0.8). Standardized mean averages, or effect sizes, for dependent measures in each study were computed by taking the mean of the active drug group minus the mean of the placebo group and dividing the result by the pooled standard deviation of the groups. After adjusting for the influence of individual study design features, the researchers calculated effect size based on Total ADHD scores. Long-acting and short-acting stimulant medications showed the largest effect size among all medications (E = 0.83 and E = 0.9 respectively), followed by nonstimulant or modafinil based stimulants medications (E = 0.62). Statistically significant differences in effect size occurred in comparisons between nonstimulant/ modafinil based stimulant medications and long-acting (p = 0.004) as well as short-acting stimulants (p = 0.002). For the analysis, Faraone and his colleagues used data from 29 double-blind, placebo-controlled treatment studies of 4,465 children with ADHD, with an average age 10 years, published during or after 1980. Designs for all of the studies were randomized, double-blind with placebo controls that lasted for two or more weeks in populations diagnosed with ADHD as defined using criteria from the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition or Fourth Edition (DSM). The analysis included 15 drugs using 17 different outcome measures of ADHD symptoms, including hyperactive, inattentive, impulsive or oppositional behavior. The most commonly identified treatments included both methylphenidate and amphetamine compounds. Nonstimulant drugs included in the analysis were atomoxetine, bupropion, modafinil and desipramine.   Shire US Inc. supported the study.    About ADHD ADHD is a neurological brain disorder that manifests as a persistent pattern of inattention and/or hyperactivity-impulsivity that is more frequent and severe than typically observed in individuals at a comparable age and maturity level. Because everyone shows signs of these behaviors at times, the behaviors must appear early in life (before age 7 years) and continue for at least six months, according to the ADHD diagnosis criteria as defined in DSM-IV-TR(R). Up to 65 percent of children with ADHD may still exhibit symptoms into adulthood. In fact, approximately eight million American adults currently struggle with the inattention, impulsivity and hyperactivity symptoms of ADHD. Without an effective treatment program, the symptoms of ADHD may lead to potentially serious consequences. A survey has shown that when compared to adults without ADHD symptoms, adults with untreated ADHD were more than twice as likely to have been arrested, 47 percent more likely to have received more than one speeding ticket in the last year, twice as likely to have been divorced and twice as likely to have held six or more jobs in the past decade. Further, evidence suggests that many adults with untreated ADHD may be at risk for other problems, including poor performance in the workplace and poor self-image. Although there is no cure for ADHD, physicians and advocates are finding ways to help people with the condition learn to adapt to their school, home, social and work settings. ADHD usually can be successfully managed with behavioral therapy, structured coping techniques and medication. Psychostimulant medications are thought to stimulate areas of the brain that control attention, impulses, and self-regulation of behavior, remain among the most successful treatments for people with ADHD. Up to 70 percent of children with ADHD respond positively to psychostimulants. Medication should be considered part of an overall multi-modal treatment plan for ADHD. For further information on ADHD please visit http://www.adhdsupport.com/ , http://www.chadd.org/ or http://www.nmha.org/ . About SUNY Upstate Medical University SUNY Upstate Medical University, located in Syracuse, N.Y., is a comprehensive academic medical center featuring an aggressive program of biomedical research with world experts in the areas of ADHD, neural coding, heart arrhythmias, enzyme structure and function and human retro viruses. In addition to its research program, the university features the colleges of Graduate Studies, Health Profession, Medicine and Nursing, and a teaching hospital, University Hospital that sees more than 130,000 patient visits annually. Poster # NR 652: Comparing the Efficacy of Medications for ADHD Using Meta-Analysis. Stephen V. Faraone, Ph.D. CONTACT: Darryl Geddes of SUNY Upstate Medical Center, +1-315-464-4828; or Priya Namjoshi, +1-212-601-8337, +1-609-213-8987 on-site, or Marion Glick, +1-212-601-8273 or on site: +1-917-301-4206, both of Porter Novelli for Shire Web site: http://www.adhdsupport.com/ http://www.chadd.org/ http://www.nmha.org/ SOURCE SUNY Upstate Medical Center URL: http://www.prnewswire.com LOAD-DATE: May 25, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 PR Newswire Association LLC. All Rights Reserved. 377 of 998 DOCUMENTS The Age (Melbourne, Australia) May 9, 2006 Tuesday First Edition Anti-sleep drug use on the rise; Fears pill may fuel '24-hour lifestyle' BYLINE: MELISSA FYFE HEALTH EDITOR SECTION: NEWS; Pg. 7 LENGTH: 495 words AUSTRALIAN doctors are increasingly prescribing an anti-sleep pill that has become a lifestyle drug in Britain and the US. Modafinil, a stimulant designed to treat sufferers of narcolepsy - the uncontrolled desire for sleep - has been available in Australia since 2002. But anecdotal reports suggest doctors are increasingly prescribing it to people who simply want to stay awake for longer. In the US, the drug is now prescribed for shift workers. Figures from Medicare Australia show doctors are writing more prescriptions for modafinil, also known as Modavigil. There were 289 prescriptions written last year and 224 in the year to date. No figures are available for earlier years. The drug's distributor in Australia, CSL Limited, said it had heard occasional reports of doctors prescribing the drug "off label" (for purposes other than its intended use). "We don't want to see a situation where an employer is suggesting people use the drug so they can spend longer on the job," said spokeswoman Rachel David. "It is not appropriate in Australia . . . It could easily be used as a drug of dependence." She said CSL would monitor sales of the pill to ensure it did not become a lifestyle drug. Under Federal Government regulations, only specialist sleep doctors can prescribe the drug. The comments come as Monash University prepares to analyse data from a new study on the effects of modafinil on mood, driving and intellectual performance. Little is known about the drug - even how it works to promote wakefulness - and the Monash study hopes to clarify the drug's psychological effects, especially if it becomes popular, which most observers tip it will. "If you have a drug that has all the good effects of things such as amphetamines and coffee, but with not as many side effects, quite a lot of people are going to want to get a hold of it," said Clint Gurtman, who is conducting the study at Monash. "With drug tests now for driving, people will want to steer away from illicit drugs. Why wouldn't you go out and get a script for this sort of thing?" The drug, which has been used in France for more than a decade, allows people to survive on less sleep, but without the agitation or euphoria caused by amphetamine-based drugs. However, side effects include headaches and the possibility that it could trigger a psychotic episode in people with bipolar disorder (manic depression). The drug peaks after about three hours and is effective for 13 hours. Mr Gurtman queried whether it was right to introduce a drug to counter fatigue. "What are the implications if we are going to become a 24-hour society? If we say people don't need sleep, what are going to be the negative consequences of that?" he asked. His supervisor, Associate Professor Jenny Redman, said there was a huge market in drugs that could promote wakefulness. Mr Gurtman said groups who could be interested in modafinil included truck and taxi drivers, doctors, computer programmers, nightclubbers and shift workers. LOAD-DATE: June 18, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2006 The Age Company Limited All Rights Reserved 378 of 998 DOCUMENTS The Philadelphia Inquirer May 2, 2006 Tuesday Business news in brief SECTION: BRIEFS; Pg. D03 LENGTH: 1271 words IN THE REGION Phila. airport near top in passenger-traffic growth Philadelphia International Airport led North America in 2005 in passenger-traffic growth, and was outpaced among the world's 30 busiest airports only by Beijing, a trade group said. A record 31.5 million passengers, 10.5 percent more than in 2004, got on or off flights at Philadelphia, making it the 15th-busiest U.S. airport and the 27th-busiest in the world, according to statistics released by the Airports Council International - North America. Beijing's traffic increased 17.5 percent last year compared with 2004, the council said. Earlier, the airports group said that Philadelphia was the ninth-busiest airport in the United States and the world last year in takeoffs and landings, with a record 565,666 aircraft operations.- Tom Belden Region's unemployment rate fell in March to 4.4% The unemployment rate in the Philadelphia area fell two-tenths of a percentage point, to 4.4 percent in March, the Pennsylvania Department of Labor and Industry said. For the month, the number of unemployed people declined 4,300, to 131,400. Meanwhile, employment rose 10,000 to 2,822,700. In March last year, the local jobless rate was 4.8 percent. The local area consists of Philadelphia, Bucks, Delaware, Montgomery and Chester Counties in Pennsylvania; Burlington, Camden, Gloucester and Salem Counties in New Jersey; New Castle County in Delaware; and Cecil County in Maryland. In Philadelphia, the March jobless rate was 6.4 percent, unchanged from February but down from 7.0 percent in March 2005.- Paul Schweizer Cephalon gets initial OK for drug to treat sleepiness Cephalon Inc. said U.S. regulators granted conditional approval to the Frazer company to sell Nuvigil tablets to treat excessive sleepiness caused by certain sleep disorders. The Food and Drug Administration withheld final approval until Nuvigil's product label is made final, Cephalon said after the stock markets closed. Modafinil, the active ingredient in Nuvigil, can cause skin rashes. The FDA said, in an "approvable" letter for Nuvigil, that until regulators decide the outcome of another experimental Cephalon drug, Sparlon, which contains modafinil to treat attention deficit hyperactivity disorder in children, the FDA will wait to make final Nuvigil's product label. The company's best-selling sleep-disorder medicine, Provigil, contains modafinil and bears a label warning of possible serious skin rashes.- Linda Loyd Verticalnet to appeal Nasdaq's delisting notification Verticalnet Inc. said it would appeal a delisting notification it received last week from Nasdaq. The stock exchange told Verticalnet it was subject to delisting from the Nasdaq Capital Market this Friday because Verticalnet shares had not maintained the minimum $1 bid price required by Nasdaq rules. Verticalnet said it expected its appeal to prevent delisting until it received a hearing from Nasdaq's listing-qualifications panel. Among the proposals listed in Verticalnet's proxy statement for its May 19 shareholder meeting is a request to perform a reverse stock split. That would, in effect, raise the company's share price while reducing the number of outstanding shares. Verticalnet's shares closed yesterday at 37 cents, down 3 cents.- Akweli Parker Rohm & Haas looking to make some acquisitions Rohm & Haas Co. chief executive officer Raj L. Gupta said the company was looking for acquisitions for the first time in several years. The Philadelphia specialty-chemicals company could spend $400 million to $500 million a year on companies that will boost its specialty-chemicals and electronics businesses, Gupta said.- Bob Fernandez Teva wins U.S. court ruling on generic Zocor Teva Pharmaceutical Industries Ltd. said a U.S. court ruled in its favor, sending the issue of exclusive marketing rights to make a generic form of Zocor, the blockbuster cholesterol-lowering drug, back to federal regulators to reconsider. The Food and Drug Administration had rejected a bid by Teva's Ivax unit and Ranbaxy Laboratories Ltd. to receive a six-month period of marketing exclusivity to sell Zocor when the drug's main patent expired in June. Israel-based Teva has its U.S. headquarters in North Wales, Montgomery County. A six-month period of marketing exclusivity is key to generic companies, which can charge higher prices before other generic competitors can sell their own generic versions of a brand-name drug. Merck has an agreement with Dr. Reddy's Laboratories Ltd. to sell an "authorized" generic version of Zocor when the Zocor patent expires. Teva's shares closed up $1.61, to $42.11, on the Nasdaq. Merck shares were down 18 cents at $34.18 on the New York Stock Exchange.- Linda Loyd Cardiokine raises $50 million for clinical drug trials Cardiokine Inc., a Philadelphia specialty-pharmaceutical company, announced it had raised $50 million in venture financing to begin Phase 3 clinical trials for its lead drug candidate, Lixivaptan. The financing brings to $87 million the total amount raised from private-equity investors by Cardiokine, which is developing treatments for congestive heart failure and has licensed Lixivaptan from Wyeth. Cardiokine's latest financing was led by Advent Venture Partners and Fidelity Biosciences, joined by Teachers' Private Capital.- Linda Loyd Comcast makes deal with IGN Entertainment Comcast Corp., Philadelphia, said it had signed an agreement with IGN Entertainment to launch "Game Invasion," a package of high-speed Internet service and gaming content. Customers who subscribe to Comcast's 8-megabit Internet service, which costs $52.95 monthly, will get IGN premium gaming content at no extra cost. IGN premium, whose Internet content includes TeamXbox and FilePlanet, normally costs $120 yearly. Comcast also said it had completed the purchase of Susquehanna Communications, the cable-television and broadband-services division of Susquehanna Pfaltzgraff. Comcast paid about $540 million in cash, or $440 million after taking into account certain tax benefits, for about 301,000 basic- and digital-cable customers and 86,000 high-speed-Internet customers. Comcast previously owned about 30 percent of Susquehanna Communications. - Miriam Hill Business group wins contract to provide training The MidAtlantic Employers' Association, a membership organization representing about 700 midsize companies in the area, landed an $80,000 contract to provide human-resource training and organizational development for the Philadelphia Workforce Development Corp. The Valley Forge association will develop workbooks and provide facilitator guides for PWDC's employee-training programs.- Jane M. Von Bergen ELSEWHERE Ford resumes work after fixing transmission problems Ford Motor Co. resumed production at seven plants yesterday after fixing a problem it discovered in its engine transmissions, Ford spokeswoman Anne Marie Gattari said. Ford halted production at the plants late Thursday and continued the shutdown all day Friday, idling about 15,000 workers.- AP T-bill rates reach highest levels in more than five years Interest rates on short-term Treasury bills rose in yesterday's auction to the highest levels in more than five years. The Treasury Department auctioned $15 billion in three-month bills at a discount rate of 4.685 percent, up from 4.635 percent last week. An additional $14 billion in six-month bills was auctioned at a discount rate of 4.780 percent, up from 4.735 percent last week. The discount rates reflect that the bills sell for less than face value. For a $10,000 bill, the three-month price was $9,881.57 while a six-month bill sold for $9,758.34.- AP LOAD-DATE: May 2, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2006 Philadelphia Newspapers, LLC All Rights Reserved 379 of 998 DOCUMENTS Internal Medicine News May 1, 2006 Panel: Modafinil Not Safe for ADHD in Teens BYLINE: Alicia Ault, Associate Editor, Practice Trends SECTION: Pgs. 36-37 Vol. 39 No. 9 ISSN: 1097-8690 LENGTH: 793 words    GAITHERSBURG, MD. - A Food and Drug Administration advisory committee declared that modafinil is not safe for treating ADHD in children and adolescents by a 12-1 vote, although committee members unanimously agreed the drug was effective for that indication.    At a meeting of the FDA's Psychopharmacologic Drugs Advisory Committee, the panel members were mainly concerned about modafinil's potential to cause Stevens-Johnson syndrome (SJS). The severe rash, which is often due to a hypersensitivity reaction to a drug, can be fatal in up to 5% of cases, according to Dr. Michael E. Bigby of the dermatology department at Harvard Medical School, Boston, and consultant to the panel.    Among 933 children and adolescents exposed to the drug during trials, there were 12 cases that could have been definite erythema multiforme (EM) or SJS, early prodromal EM or SJS, or suggestive of prodromal EM or SJS-a rate of 1.29%, said Dr. Glenn B. Mannheim, a medical reviewer in the FDA's division of psychiatry products.    The panel's discussion focused on one case that seemed most likely to be SJS-indicating a 1 in 1,000 risk. But they were not certain that was the true risk.    Dr. Bigby and Dr. Mannheim said that more cases could occur once modafinil (Provigil) is more widely used-even though there have been no reports of SJS in the 36,000 children who were prescribed the drug off-label in 2002-2005.    Given the trial data and the assumption that modafinil could capture 10% of the market for children under age 19 (based on other stimulants' sales), there could be 500-3,250 cases of EM or SJS, and 25-488 deaths, said Dr. Mannheim.    The dichotomy between the postmarketing experience and the trial data prompted the FDA to seek its advisers' input, said Dr. Robert J. Temple, director of the FDA's office of medical policy.    The FDA usually follows the advice of its panels.    The FDA has received six reports of serious skin reactions in adults, said Dr. Mannheim.    "I'd like to see an opportunity for the company to come back with additional data. That will give us additional assurance that this case was a fluke," said panel chair Dr. Wayne K. Goodman, chair of the department of psychiatry at the University of Florida, Gainesville.    The committee said modafinil's manufacturer, Cephalon Inc., should conduct a 3,000-patient, open-label study to further clarify the risk of SJS.    After the meeting, Dr. Thomas Laughren, director of the FDA's division of psychiatry products, told reporters that if a case turns up in such a study, "then they have a problem."    It was not clear why children had higher rates of skin-related adverse events than adults, but Dr. Mannheim noted that lab tests indicated that they had a 7-16 times higher area under the curve ratio of modafinil sulfone, a metabolite. The levels could not be explained by higher milligram-per-kilogram dosing, he said.    In two of the three phase III studies, children were given a flexible dose with weekly titration (170 mg, 255 mg, 340 mg, or 425 mg). In the third study they were given a fixed dose, with those under 30 kg receiving 340 mg daily, and those over 30 kg receiving 425 mg daily. The primary outcome was the total score on the school ADHD rating scale. In all three trials, children taking modafinil had a more significant drop in scores than those taking placebo. The total score for modafinil recipients-just over 20-was close to the normative score for a 10-year-old male, according to a Cephalon statement.    Panelists did not dispute the drug's efficacy, although many said it would not be a first-line choice.    Lesley Russell, Cephalon's senior vice president of worldwide clinical research, said modafinil offers clinicians an alternative, especially when children don't respond to other marketed drugs.    But Dr. Temple said that even though it's plausible that modafinil might work in nonresponsive children, the company had not proved that.    "The mere fact that people given a second drug respond after failing to respond to the first tells you nothing at all," he said.    According to a company statement, modafinil may be less addictive and less apt to be diverted because it does not offer a "high" to recreational users. Jeffrey L. Vaught, executive vice president of research and development at Cephalon, said the drug is not water soluble and is not stable at high heat, which makes it difficult to crush for injection or smoking. Studies have shown that modafinil does not activate reward centers in the brain, and that it does not cause release of dopamine in vitro or in vivo.    The Drug Enforcement Administration has deemed modafinil a schedule IV drug; other stimulants used to treat ADHD, such as Ritalin, are schedule II. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: IMNEWS Copyright 2006 Elsevier Inc., International Medical News Group All Rights Reserved 380 of 998 DOCUMENTS PR Newswire US May 1, 2006 Monday 8:45 PM GMT Cephalon Receives Approvable Letter for NUVIGIL(TM) (armodafinil) LENGTH: 1024 words DATELINE: FRAZER, Pa. May 1 FRAZER, Pa., May 1 /PRNewswire-FirstCall/ -- Cephalon, Inc. (NASDAQ:CEPH) announced today that it has received an approvable letter from the U.S. Food and Drug Administration (FDA) for NUVIGIL(TM) (armodafinil) Tablets. The company submitted a new drug application (NDA) on March 31, 2005, seeking to market NUVIGIL for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome (OSA/HS) and shift work sleep disorder (SWSD). FDA approval of NUVIGIL is contingent upon finalizing the product label. "We are working closely with the FDA to move this application to an approval and expand our offering of wake-promotion choices for patients," said Dr. Paul Blake, Executive Vice President, Worldwide Medical and Regulatory Operations. "Based on the clinical trials, NUVIGIL demonstrated a long duration of effect throughout the waking hours and we are excited at the potential to offer broader options to meet the needs of patients and physicians seeking treatment for excessive sleepiness." Armodafinil is a single-isomer formulation of modafinil, the active pharmaceutical ingredient contained in PROVIGIL(R) (modafinil) Tablets [C-IV]. Cephalon submitted data from four double-blind, randomized, placebo-controlled studies of NUVIGIL in patients with excessive sleepiness associated with either narcolepsy, OSA/HS or SWSD to FDA for evaluation as part of the NDA. In these studies, NUVIGIL was generally well tolerated, with a safety profile consistent with that observed in studies of PROVIGIL. The most common adverse effects observed included headache, nausea, dizziness, insomnia and anxiety. As previously announced, the company submitted additional information to the FDA related to a possible case of Stevens Johnson Syndrome associated with its SPARLON(TM) (modafinil) application. In its NUVIGIL approvable letter, the FDA indicated that the outcome of its review of this new information will be addressed directly in the label for NUVIGIL. About Excessive Sleepiness (Hypersomnolence) Excessive sleepiness, medically known as hypersomnolence, is the primary symptom -- and often the most debilitating feature -- experienced by the millions of Americans who suffer from narcolepsy, OSA/HS, and SWSD. Despite this fact, it is estimated that 50 to 90 percent of the time, health care professionals fail to recognize that these patients are suffering from excessive sleepiness. The defining characteristic of excessive sleepiness is a consistent inability to stay awake and alert enough to safely and successfully accomplish tasks of daily living. Persons experiencing excessive sleepiness who seek medical attention typically complain of fatigue, tiredness, lapses of attention, lack of energy, low motivation, difficulty concentrating, disrupted sleep, snoring or difficulties at work. Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products in four core therapeutic areas: central nervous system, pain, oncology and addiction. Cephalon currently employs approximately 3,000 people in the United States and Europe. U.S. sites include the company's headquarters in Frazer, Pennsylvania, and offices, laboratories or manufacturing facilities in West Chester, Pennsylvania, Salt Lake City, Utah, and suburban Minneapolis, Minnesota. Cephalon's European headquarters are located in Maisons-Alfort, France. Cephalon currently markets four proprietary products in the United States: PROVIGIL, GABITRIL(R) (tiagabine hydrochloride), ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II], and TRISENOX(R) (arsenic trioxide) injection. In addition, VIVITROL(TM) (naltrexone for extended-release suspension) was recently approved in the United States and is expected to be available in June 2006. Cephalon also markets numerous products internationally. Full prescribing information for Cephalon products in the United States is available at http://www.cephalon.com/ or by calling 1-800-896-5855. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs; development of potential pharmaceutical products, interpretation of clinical results, including the results of the clinical trials of NUVIGIL; prospects for regulatory approval, including for final FDA approval of NUVIGIL; manufacturing development and capabilities; market prospects for its products; sales and earnings guidance; and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. CONTACT: Media: Sheryl Williams, +1-610-738-6493, swilliam@cephalon.com , or Investors: Robert (Chip) Merritt, +1-610-738-6376, cmerritt@cephalon.com , both of Cephalon, Inc. Web site: http://www.cephalon.com/ Company News On-Call: http://www.prnewswire.com/comp/134563.html SOURCE Cephalon, Inc. URL: http://www.prnewswire.com LOAD-DATE: May 2, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 PR Newswire Association LLC. All Rights Reserved. 381 of 998 DOCUMENTS PSYCHIATRIC TIMES May 1, 2006 FDA Committees Examine Concerns About Psychiatric Drugs Used by Children BYLINE: Stephen Barlas SECTION: WASHINGTON REPORT; Pg. 25 LENGTH: 1786 words HIGHLIGHT: Concerns about the appropriate use of psychiatric medications in children continue to be the subject of discussion by regulatory agencies. In late 2004, the issues were possible suicidal ideation and suicide attempts as side effects of selective serotonin reuptake inhibitors (SSRIs) and other antidepressants. This past February, concerns arose about potential cardiovascular effects of drugs used to manage attention-deficit/hyperactivity disorder (ADHD). At the same time, questions remain about the effectiveness of SSRIs for depression in children. The FDA's Pediatric Advisory Committee met on March 22, a month after the Drug Safety and Risk Management Advisory Committee first raised questions about possible cardiovascular adverse effects caused by stimulants used to treat children with ADHD. The Drug Safety Committee had voted 8 to 7 in February to recommend that the FDA require drug companies selling stimulants to put a black-box warning on the professional labeling, a measure the agency had required in 2004 for labels of antidepressants. The Pediatric Committee looked at a report from the FDA staff on adverse event reports possibly related to 4 drugs, 1 of which was a dextroamphetamine/amphetamine combination product (Adderall). In continuation of a previous committee discussion of adverse events for the class of methylphenidate products used to treat ADHD, the committee discussed neuropsychiatric adverse events possibly related to other approved ADHD medications. The committee received an update on efforts to better understand cardiovascular adverse events possibly related to ADHD medications. The FDA's Psychopharmacologic Drugs Advisory Committee met the following day to examine the safety and efficacy of modafinil (Provigil) for ADHD in children. Cephalon already markets modafinil as a wake-enhancing drug for patients with sleep problems. The issue of possible cardiovascular effects and psychiatric adverse events came up during this meeting too. Sheryl Williams, a spokeswoman for Cephalon, said that modafinil has a different chemical structure from that of the stimulants targeted by the drug safety committee. "There have never been any sudden cardiac events associated with our product, even in patients with obstructive sleep apnea who may have underlying cardiac problems." Antidepressant effectiveness, treatment duration Not only is the safety of psychiatric drugs taken by children a growing issue so is their effectiveness. In a recent article in Biological Psychiatry, researchers from the psychiatry department at The Johns Hopkins University Medical School and Daniel Pine, MD, the head of pediatric mood and anxiety research at the intramural program at the National Institute of Mental Health (NIMH), discuss clinical trial data for SSRIs tested on children and adolescents. The article states that there is "reasonably strong evidence for efficacy of fluoxetine [Prozac]" and that "the efficacy of the remaining SSRIs is modest at best." The article's conclusion on fluoxetine is based on 4 clinical trials, including 1 (which showed no benefit) that was tossed out because of the small size of the sample (40 adolescents). In the other 3 trials, the spread between the positive effect of fluoxetine and that of a placebo was never more than 26 percentage points. In 2 cases, the difference was 12 and 14 percentage points. The number of children in the 3 trials was 96, 219, and 439, and none of the patients participated for more than 12 weeks. Three-month or shorter clinical trials with fewer than 500 participants are typical of the evidence pharmaceutical companies submit to the FDA to prove efficacy and an acceptable adverse- effects profile for already-approved drugs and existing chemical entities that are seeking labels for new indications or new methods of administration. Some drug companies "roll over" some of the participants in those trials into open label trials, mostly to see how well patients tolerate the drug over slightly longer periods (but never longer than 1 to 2 years and sometimes as little as 6 months). In interviews with Psychiatric Times, Pine, whose formal title is chief of developmental studies, mood and anxiety disorders program, NIMH, and Thomas Laughren, MD, director, division of psychiatry products at the FDA, stated that a 30 percentage point spread between drug and placebo was strong evidence of efficacy. But both expressed some reservations about results from 12-week clinical trials and emphasized that current efficacy and safety data on SSRIs leave much to be desired. Pine, for example, noted that SSRI data in children are much stronger for anxiety than for depression. "That is a point that people haven't picked up on," he said. When asked why the spreads for SSRI antidepressants are so narrow, Pine added, "That is the $64,000 question." Laughren said it is more difficult to conduct reliable clinical trials with antidepressants. "That is because we don't understand most psychiatric disorders at a biological level," he explained. "All we have is the phenomenology of the disease. It is not like some types of heart disease or cancer where you understand the disease at the pathological level and have a better chance of distinguishing between different subgroups of patients who might respond differently to one drug or another." Laughren compared the shakier SSRI efficacy data with those for ADHD drugs, which include methylphenidate (Concerta, Ritalin) and amphetamines (Adderall XR). He said it isn't unusual to see an ADHD drug trial in which 80% of those taking the active drug improve while only 20% of those taking placebo improve. "There is fairly robust evidence for this class of drugs," Laughren stated. "You see a more predictable drug effect and less of a placebo effect." Nevertheless, Laughren admitted, "There is only a limited amount you can learn from a short-term clinical trial which lasts only a few weeks. You need longer-term trials to learn about longer-term risks and also benefits." In the case of Cephalon's application for an ADHD label for modafinil, the company did 3 clinical trials, each lasting 9 weeks, in which 400 children aged 9 to 16 years were given progressively titrated doses of modafinil. The drug was considered effective because the 300 children who were given a placebo showed a mean 8-point improvement on the ADHD rating scale used in the study, while those who took modafinil showed a mean improvement of 16 points. But even for methylphenidate, which has been around since the 1950s, there have been few clinical studies extending for a year or more and involving large populations. There have not been enough dose-response tests, much less brain-imaging testing, which looks at the effect of stimulants or antidepressants on the brain development of children 10 or 20 years after the fact. Gerardo Torres, vice president, Central Nervous System Therapeutic Area at Shire, maker of Adderall, which has been on the market since 1996, explained, "We have not systematically looked at [that]. We have postmarketing surveillance. If we picked up anything, we would begin to address it." Pine called the lack of brain-imaging testing "a very legitimate question." Laughren explained that there are impediments in some instances to longer, more detailed clinical trials with children. For example, a parent of a severely depressed child might be very hesitant to enroll him or her in a long-term randomized trial in which there was the possibility the child would be receiving a placebo. In addition, Laughren pointed out, the FDA has to weigh the benefits of holding up a new medication-even if efficacy data are unimpressive-against the costs of depriving those in need of relief from a debilitating condition. Nonetheless, the FDA has pushed for some additional testing. Last October, Laughren asked the Psychopharmacologic Drugs Advisory Committee whether the FDA ought to require relapse prevention trials for antidepressants as a condition of approval. These trials monitor successfully treated children after antidepressants are discontinued to see whether the children experience a relapse; the goal is to determine the optimal period for which a depressed child should be taking an SSRI, a question that few clinical trials in children have examined. "How long do you need to use this drug? That is what we think really needs to be explored," explained Laughren. "But everybody on the advisory committee said 'no,' it would be too burdensome to companies to require this prior to initial approval." He added that, for adults at least, companies do usually conduct such trials within a few years of initial approval of the drug. While the members of the advisory committee are mostly academics, 8 of the 11 members had relationships with drug companies whose products could have been affected by decisions the advisory committee made that day. Before the meeting started, Karen M. Templeton-Somers, PhD, acting executive secretary, read off a list of those members and their relationships. She noted that the advisory committee's chairperson, Wayne Goodman, MD, works for 2 employers (the University of Florida College of Medicine and the McKnight Brain Institute at the University of Florida) that have 4 separate contracts-2 with firms funded at less than $100,000 per year and 2 others with separate drug firms funded at between $100,001 and $300,000 per year. Goodman pointed out that those relationships pertained to contracts held by other investigators in his department with a company developing a drug that would be a competitor to selegiline (Emsam), the first transdermal patch medication used for treating major depression. The committee voted to recommend Emsam's approval on the second day of that October meeting, and the FDA approved the drug on February 28, 2006. Emsam was developed by Somerset Pharmaceuticals, Inc. In December 2004, Bristol-Myers Squibb and Somerset entered into an agreement that provides Bristol-Myers Squibb with distribution rights to market Emsam. Goodman did not address whether he himself has contracts with companies like Wyeth, for example, that oppose an FDA requirement on relapse prevention trials for new psychiatric drugs for children. But he pointed out that he did vote in favor of a suicidality black-box warning for antidepressants when that issue came up in the advisory committee in 2004. He noted that this probably didn't sit all that well with drug companies with whom he may have contracts. "I'm so clean I am sterile," he said. Laughren stated that the FDA is still thinking about "how to change things because of all the controversy," which, he added, has dampened the interest of industry in studying children." He explained that he knows of 1 situation in which a company had positive clinical trial results with a drug tested for a psychiatric condition in children but was unwilling to submit an application for approval for fear of running into a public buzz saw. Goodman added, "There is no question we need to do long-term clinical trials with kids and psychiatric drugs." He said the companies, the FDA, and the NIMH should pool their money and establish those trials. http://www.psychiatrictimes.com/ Copyright © 2006 CMP Media LLC. All rights reserved. LOAD-DATE: June 2, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Magazine JOURNAL-CODE: PTM Copyright 2006 CMP Media LLC All Rights Reserved 382 of 998 DOCUMENTS Skin & Allergy News May 2006 FDA Panel: Modafinil Not Safe for ADHD in Children BYLINE: Alicia Ault, Associate Editor, Practice Trends SECTION: Pg. 5 Vol. 37 No. 5 ISSN: 0037-6337 LENGTH: 852 words    GAITHERSBURG, MD. - A Food and Drug Administration advisory committee said modafinil is not safe for treating ADHD in children and adolescents by a 12-1 vote, although committee members unanimously agreed the drug was effective for that indication.    At a meeting of the FDA's Psychopharmacologic Drugs Advisory Committee, the panel members were mainly concerned about modafinil's potential to cause Stevens-Johnson syndrome (SJS). The severe rash, which is often due to a hypersensitivity reaction to a drug, can be fatal in up to 5% of cases, according to Dr. Michael E. Bigby of the dermatology department at Harvard Medical School, Boston, and consultant to the panel.    In a group of 933 children and adolescents exposed to the drug in trials, there were 12 cases that could have been definite erythema multiforme (EM) or SJS, early prodromal EM or SJS, or suggestive of prodromal EM or SJS-a rate of 1.29%, said Dr. Glenn B. Mannheim, a medical reviewer in the FDA's division of psychiatry products.    The panel's discussion focused on one case that seemed most likely to be SJS-indicating a 1 in 1,000 risk. But they weren't certain that was the true risk.    Dr. Bigby and Dr. Mannheim said more cases could occur once modafinil (Provigil) is more widely used, even though there have been no reports of SJS in the 36,000 children who were prescribed the drug off-label in 2002-2005.    Given the trial data and the assumption that modafinil could capture 10% of the market for children under age 19 (based on other stimulants' sales), there could be 500-3,250 cases of EM or SJS, and 25-488 deaths, said Dr. Mannheim.    The dichotomy between the postmarketing experience and the trial data prompted the FDA to seek its advisers' input, said Dr. Robert J. Temple, director of the FDA's office of medical policy.    The FDA usually follows the recommendations of its advisory panels.    The FDA has received six reports of serious skin reactions in adults, said Dr. Mannheim.    "I'd like to see an opportunity for the company to come back with additional data. That will give us additional assurance that this case was a fluke," said panel chair Dr. Wayne K. Goodman, chair of the department of psychiatry at the University of Florida, Gainesville.    The committee said modafinil's manufacturer, Cephalon Inc., should conduct a 3,000-patient, open-label study to further clarify the risk of SJS.    After the meeting, Dr. Thomas Laughren, director of the FDA's division of psychiatry products, told reporters that if a case turns up in such a study, "then they have a problem."    It was not clear why children had higher rates of skin-related adverse events than adults, but Dr. Mannheim noted that lab tests indicated that they had a 7-16 times higher area under the curve ratio of modafinil sulfone, a metabolite. The levels could not be explained by higher milligram-per-kilogram dosing, he said.    In two of the three phase III studies, children were given a flexible dose with weekly titration (170 mg, 255 mg, 340 mg, or 425 mg). In the third study they were given a fixed dose, with those under 30 kg receiving 340 mg daily, and those over 30 kg receiving 425 mg daily.    The primary outcome was the total score on the school ADHD rating scale. In all three trials, children taking modafinil had a more significant drop in scores than those taking placebo. The total score for modafinil recipients-just over 20-was close to normal for a 10-year-old male, according to a Cephalon statement.    Panelists did not dispute the drug's efficacy, although many said it would not be a first-line choice.    Lesley Russell, Cephalon's senior vice president of worldwide clinical research, said modafinil offers clinicians an alternative, especially when children don't respond to other marketed drugs.    But Dr. Temple said that even though it's plausible that modafinil might work in nonresponsive children, the company had not proved that. "The mere fact that people given a second drug respond after failing to respond to the first tells you nothing at all."    According to a company statement, modafinil may be less addictive and less apt to be diverted because it does not offer a "high" to recreational users. Jeffrey L. Vaught, executive vice president of research and development at Cephalon, said the drug is not water soluble and is not stable at high heat, which makes it difficult to crush for injection or smoking. Studies have shown that modafinil does not activate reward centers in the brain, and that it does not cause release of dopamine in vitro or in vivo.    Despite potential advantages, the panel did not want modafinil to be marketed for children yet.    "I think we did err on the side of consumer protection," said Dr. Goodman.    In a statement after the meeting, Dr. Paul Blake, Cephalon's executive vice president of worldwide medical and regulatory operations, said, "We are obviously disappointed with the recommendation of the advisory committee. We will continue our discussions with the FDA to determine the next steps in the review of this drug application." LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: SANEWS Copyright 2006 Elsevier Inc., International Medical News Group All Rights Reserved 383 of 998 DOCUMENTS St. Petersburg Times (Florida) April 25, 2006 Tuesday 0 South Pinellas Edition Narcolepsy pill may blunt cocaine craving SECTION: NATIONAL; Pg. 6A LENGTH: 554 words DATELINE: WASHINGTON The hottest topic in cocaine addiction is another drug: a medicine already sold to wake up narcoleptics. Hundreds of cocaine users are testing whether that legal pill, called modafinil, could help them kick the addiction, and there's early evidence that it may. In addition to easing cocaine's notorious cravings, modafinil also might counter the damage that cocaine wreaks on users' brain circuits - damage that in turn fuels the cycle of addiction. That prospect has the National Institutes of Health spending $10.8-million researching modafinil as a potential cocaine treatment. Results from the first of three key clinical trials could arrive by year's end. Scientists are cautious. But for Dr. Nora Volkow, director of the National Institute on Drug Abuse, the narcolepsy medicine tops the list of potential therapies. It may help restore proper function of a crucial brain chemical, dopamine, that addiction hijacks. And in describing why he's hopeful, one leading researcher recounts the man who accused his drug dealer of selling bad coke before realizing modafinil had kept him from getting high - and several other modafinil testers who told of flushing cocaine down the toilet. "I've been treating cocaine-addicted patients for something like 25 years, more, and I've never heard of anybody throwing away cocaine," says Dr. Charles Dackis of the University of Pennsylvania, who led a pilot study that suggested modafinil more than doubled addicts' chances of going cocaine-free for at least three weeks. That study enrolled just 62 people, but the results were significant enough for the NIH to fund research enrolling about 650 cocaine users to see if modafinil really does work. The main side effect so far: insomnia, not surprising as modafinil is sold today to help narcolepsy patients fend off that neurologic disease's sudden sleep attacks. Close relationships slow the effects of Alzheimer's Patients with Alzheimer's disease who have rich social networks lose mental ability more slowly and function better than those without such networks, a large study found. Maintaining close relationships with friends and relatives, being able to call on others for help and meeting people regularly reduced the impact of Alzheimer's, the study found. The disease appeared to cause as much damage to the brains of patients who had many social ties, but it did not have the same effect on behavior and functioning. The study suggests that disease processes only partly explain how quickly patients decline, said David A. Bennett, an Alzheimer's expert at Rush University Medical Center in Chicago: "Some people can tolerate a lot of pathology without losing their thinking ability, and others can have only a little pathology and lose a lot." The difference apparently lies in people's reserves - their ability to tolerate stress and damage. "The extent of social networks, or something related to social networks, provides some type of reserve which reduces the deleterious effect of Alzheimer's disease pathology on cognitive abilities in old age," Bennett and a team of researchers wrote online this month in the journal Lancet Neurology. Bennett said that while the study could not say whether seeking out more social ties could reduce the effects of dementia, "being socially engaged is good for you for a whole host of reasons." LOAD-DATE: April 25, 2006 LANGUAGE: ENGLISH DOCUMENT-TYPE: DIGEST PUBLICATION-TYPE: Newspaper Copyright 2006 Times Publishing Company All Rights Reserved 384 of 998 DOCUMENTS Wilkes Barre Times Leader (Pennsylvania) April 25, 2006 Tuesday In brief SECTION: A; Pg. 4 LENGTH: 509 words Iran might exit nuclear treaty Iranian President Mahmoud Ahmadinejad said Monday he is thinking about withdrawing from the nuclear nonproliferation treaty if the United Nations atomic agency tries to prevent his country from enriching uranium. At a rare news conference in Tehran, Ahmadinejad also predicted the U.N. Security Council will not impose sanctions on Iran, which is facing a deadline Friday to halt enrichment. WASHINGTON Drug might combat cocaine The hottest topic in cocaine addiction is another drug - a medicine already sold to wake up narcoleptics. Hundreds of cocaine users are testing whether that legal pill, called modafinil, could help them beat the addiction, and there's early evidence it might. In addition to blunting cocaine's notorious cravings, modafinil also might counter the damage that cocaine wreaks on users' brain circuits - damage that in turn fuels the cycle of addiction. Cocaine is highly addictive: About 16 percent of people who try it become hooked, often rapidly. In 2003, the latest data, the government estimated that more than 1.5 million Americans were dependent on or abusing cocaine, and more reported recently experimenting with it. KATMANDU, Nepal Beleaguered king relenting Nepal's embattled king appeared to defuse weeks of mass protests that have pushed this Himalayan country near the brink of anarchy, reinstating the lower house of parliament on Monday as his opponents had demanded. With few choices left and hoping to avoid a bloody showdown between demonstrators and his security forces, Gyanendra's announcement cleared the way for the creation of a new constitution that could leave him largely powerless, or even eliminate the monarchy. Gyanendra also expressed his sympathies for the 14 demonstrators killed by his security forces in nearly three weeks of protests. Nepal's three largest opposition. INDIANAPOLIS Workers face sex charges Nine former employees of a county juvenile detention center were charged Monday with using their positions of authority to have sex with teenage girls. The nine workers were accused of having sex with six girls who were 13 to 15 years old at the time. Marion County prosecutor Carl Brizzi said one girl was raped by one of the defendants. The five others agreed to have sex with one or more of the men, but in Indiana the age of sexual consent is 16. Brizzi said the defendants sent the victims love letters and even a teddy bear bearing the words "I love you." PORTLAND, Maine Sex offender case widens A man suspected of killing two people on the state's online sex offender registry appears to have visited the homes of other sex offenders during a five-hour gap between the killings, police said Monday. Detectives have gathered evidence suggesting Stephen Marshall drove to homes belonging to registered sex offenders on Easter morning, said Detective Brian Strout, a state police investigator in Bangor. The information about Marshall's travels was based on global positioning software contained on his laptop, The Canadian Press reported. From Times Leader wire services LOAD-DATE: April 25, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2006 Wilkes Barre Times Leader All Rights Reserved 385 of 998 DOCUMENTS Associated Press Online April 25, 2006 Tuesday 12:30 AM GMT Narcolepsy Drug Eyed for Cocaine Users BYLINE: By LAURAN NEERGAARD, AP Medical Writer SECTION: WASHINGTON DATELINE LENGTH: 824 words DATELINE: WASHINGTON The hottest topic in cocaine addiction is another drug a medicine already sold to wake up narcoleptics. Hundreds of cocaine users are testing whether that legal pill, called modafinil, could help them kick the addiction, and there's early evidence that it may. In addition to blunting cocaine's notorious cravings, modafinil might also counter the damage that cocaine wreaks on users' brain circuits damage that in turn fuels the cycle of addiction. The prospect of that double-whammy has the National Institutes of Health spending $10.8 million researching modafinil as a potential cocaine treatment. Results from the first of three key clinical trials could arrive by year's end. Scientists are cautious: In a hunt spanning two decades, no one has found a medication to help treat cocaine addiction, and there's no guarantee that modafinil will pan out. But for Dr. Nora Volkow, director of NIH's National Institute on Drug Abuse, the narcolepsy medicine tops the list of promising potential therapies. It may help restore proper function of a crucial brain chemical, dopamine, that addiction hijacks. And in describing why he's hopeful, one leading researcher recounts the man who accused his drug dealer of selling bad coke before realizing modafinil had kept him from getting high and several other modafinil testers who told of flushing cocaine down the toilet. "I've been treating cocaine-addicted patients for something like 25 years, more, and I've never heard of anybody throwing away cocaine," says Dr. Charles Dackis of the University of Pennsylvania, who led a pilot study that suggested modafinil more than doubled addicts' chances of going cocaine-free for at least three weeks. That study enrolled just 62 people, but the results were significant enough for NIH to fund new research at Pennsylvania, the University of Texas in Houston, Boston University and other sites enrolling about 650 cocaine users to see if modafinil really does work. The main side effect so far: insomnia, not surprising as modafinil is sold today to help narcolepsy patients fend off that neurologic disease's sudden sleep attacks. Addiction specialists gave it a look because even though modafinil isn't a classic stimulant, it triggered something in the brain to also improve patients' mood, energy levels and ability to concentrate effects that might counter cocaine withdrawal. Then came the surprises: Cocaine intensely stimulates the brain's pleasure centers, producing not just a "buzz" or a "rush," but outright euphoria. In a small safety study to ensure that modafinil didn't make cocaine worse, some users found the once-a-day pill blocked that high. "We didn't expect that at all," Dackis says. Potentially more important, he says, modafinil seems to increase activity in the prefrontal cortex, the brain's decision-making command center and the spot that allows reasoning to override impulse or emotion. Cocaine reduces activity in that key brain region, making it even harder for would-be quitters to ignore cravings and resist another hit. Modafinil also increases the ability to think strategically, a means of weighing variables and risks to make decisions, says Frank Vocci, NIDA's pharmacotherapy chief. "The effects on cognitive processes are very subtle, and very interesting," Vocci says and that's the reason that of half a dozen medications being studied as potential cocaine treatments, the government's biggest emphasis is on modafinil. Cocaine is highly addictive: About 16 percent of people who try it become hooked, often rapidly. In 2003, the latest data, the government estimated that more than 1.5 million Americans were dependent on or abusing cocaine, and more reported recently experimenting with it. Addictions in general rewire the brain, says Volkow, the NIDA director. Drugs cause a feel-good rush by increasing amounts of the brain chemical dopamine. The brain reacts by tamping down regular dopamine production, making users feel lousy between hits and setting up the cycle of addiction. At the same time, the dopamine surge also creates memory circuits that eventually establish so-called "cue-induced cravings": If an addict passes the crack house or sees friends he did drugs with, his brain literally sends a strong impulse to use again. "One of the strategies of course, in terms of treatment ... is how can we help recover the function of the dopamine system, so the person that's addicted can become sensitive to natural stimuli," Volkow explains. Modafinil seems to affect chemicals that in turn regulate dopamine production, a different pathway than cocaine takes in altering normal dopamine, and thus one that might counter it, adds Dackis. "You can't assume this is going to work," he cautions. But if it pans out, a drug that could help cognition instead of just numb cravings would be "a big benefit in treatment." EDITOR'S NOTE Lauran Neergaard covers health and medical issues for The Associated Press in Washington. LOAD-DATE: April 25, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 Associated Press All Rights Reserved 386 of 998 DOCUMENTS The Associated Press April 24, 2006 Monday 7:51 PM GMT HEALTHBEAT: Could narcolepsy wake-up drug fight cocaine addiction? BYLINE: By LAURAN NEERGAARD, AP Medical Writer SECTION: WASHINGTON DATELINE LENGTH: 824 words DATELINE: WASHINGTON The hottest topic in cocaine addiction is another drug a medicine already sold to wake up narcoleptics. Hundreds of cocaine users are testing whether that legal pill, called modafinil, could help them kick the addiction, and there's early evidence that it may. In addition to blunting cocaine's notorious cravings, modafinil might also counter the damage that cocaine wreaks on users' brain circuits damage that in turn fuels the cycle of addiction. The prospect of that double-whammy has the National Institutes of Health spending $10.8 million researching modafinil as a potential cocaine treatment. Results from the first of three key clinical trials could arrive by year's end. Scientists are cautious: In a hunt spanning two decades, no one has found a medication to help treat cocaine addiction, and there's no guarantee that modafinil will pan out. But for Dr. Nora Volkow, director of NIH's National Institute on Drug Abuse, the narcolepsy medicine tops the list of promising potential therapies. It may help restore proper function of a crucial brain chemical, dopamine, that addiction hijacks. And in describing why he's hopeful, one leading researcher recounts the man who accused his drug dealer of selling bad coke before realizing modafinil had kept him from getting high and several other modafinil testers who told of flushing cocaine down the toilet. "I've been treating cocaine-addicted patients for something like 25 years, more, and I've never heard of anybody throwing away cocaine," says Dr. Charles Dackis of the University of Pennsylvania, who led a pilot study that suggested modafinil more than doubled addicts' chances of going cocaine-free for at least three weeks. That study enrolled just 62 people, but the results were significant enough for NIH to fund new research at Pennsylvania, the University of Texas in Houston, Boston University and other sites enrolling about 650 cocaine users to see if modafinil really does work. The main side effect so far: insomnia, not surprising as modafinil is sold today to help narcolepsy patients fend off that neurologic disease's sudden sleep attacks. Addiction specialists gave it a look because even though modafinil isn't a classic stimulant, it triggered something in the brain to also improve patients' mood, energy levels and ability to concentrate effects that might counter cocaine withdrawal. Then came the surprises: Cocaine intensely stimulates the brain's pleasure centers, producing not just a "buzz" or a "rush," but outright euphoria. In a small safety study to ensure that modafinil didn't make cocaine worse, some users found the once-a-day pill blocked that high. "We didn't expect that at all," Dackis says. Potentially more important, he says, modafinil seems to increase activity in the prefrontal cortex, the brain's decision-making command center and the spot that allows reasoning to override impulse or emotion. Cocaine reduces activity in that key brain region, making it even harder for would-be quitters to ignore cravings and resist another hit. Modafinil also increases the ability to think strategically, a means of weighing variables and risks to make decisions, says Frank Vocci, NIDA's pharmacotherapy chief. "The effects on cognitive processes are very subtle, and very interesting," Vocci says and that's the reason that of half a dozen medications being studied as potential cocaine treatments, the government's biggest emphasis is on modafinil. Cocaine is highly addictive: About 16 percent of people who try it become hooked, often rapidly. In 2003, the latest data, the government estimated that more than 1.5 million Americans were dependent on or abusing cocaine, and more reported recently experimenting with it. Addictions in general rewire the brain, says Volkow, the NIDA director. Drugs cause a feel-good rush by increasing amounts of the brain chemical dopamine. The brain reacts by tamping down regular dopamine production, making users feel lousy between hits and setting up the cycle of addiction. At the same time, the dopamine surge also creates memory circuits that eventually establish so-called "cue-induced cravings": If an addict passes the crack house or sees friends he did drugs with, his brain literally sends a strong impulse to use again. "One of the strategies of course, in terms of treatment ... is how can we help recover the function of the dopamine system, so the person that's addicted can become sensitive to natural stimuli," Volkow explains. Modafinil seems to affect chemicals that in turn regulate dopamine production, a different pathway than cocaine takes in altering normal dopamine, and thus one that might counter it, adds Dackis. "You can't assume this is going to work," he cautions. But if it pans out, a drug that could help cognition instead of just numb cravings would be "a big benefit in treatment." EDITOR'S NOTE Lauran Neergaard covers health and medical issues for The Associated Press in Washington. LOAD-DATE: April 25, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 Associated Press All Rights Reserved 387 of 998 DOCUMENTS Associated Press Worldstream April 24, 2006 Monday 7:54 PM GMT Could narcolepsy wake-up drug fight cocaine addiction? BYLINE: By LAURAN NEERGAARD, AP Medical Writer SECTION: INTERNATIONAL NEWS LENGTH: 829 words DATELINE: WASHINGTON The hottest topic in cocaine addiction is another drug, a medicine already sold to wake up narcoleptics. Hundreds of cocaine users are testing whether that legal pill, called modafinil, could help them kick the addiction, and there is intriguing early evidence that it might. In addition to blunting cocaine's notorious cravings, modafinil might also counter the damage that cocaine wreaks on users' brain circuits damage that in turn fuels the cycle of addiction. The prospect of that double-whammy has the National Institutes of Health spending $10.8 million (euro8.75 million) researching modafinil as a potential cocaine treatment. Results from the first of three crucial clinical trials could arrive by year's end. Scientists are cautious: In a hunt spanning two decades, no one has found a medication to help treat cocaine addiction, and there is no guarantee that modafinil will pan out. But for Dr. Nora Volkow, director of NIH's National Institute on Drug Abuse, the narcolepsy medicine tops the list of promising potential therapies. It may help restore proper function of a crucial brain chemical, dopamine, that addiction hijacks. And in describing why he is hopeful, one leading researcher recalls the man who accused his drug dealer of selling bad coke before realizing that modafinil had kept him from getting high and several other modafinil testers who told of flushing cocaine down the toilet. "I've been treating cocaine-addicted patients for something like 25 years, more, and I've never heard of anybody throwing away cocaine," says Dr. Charles Dackis of the University of Pennsylvania, who led a pilot study that suggested modafinil more than doubled addicts' chances of going cocaine-free for at least three weeks. That study enrolled just 62 people, but the results were significant enough for NIH to pay for new research at Pennsylvania, the University of Texas in Houston, Boston University and other sites enrolling about 650 cocaine users to see if modafinil works. The main side effect so far: insomnia, not surprising as modafinil is sold today to help narcolepsy patients fend off that neurologic disease's sudden sleep attacks. Addiction specialists gave it a look because even though modafinil is not a classic stimulant, it triggered something in the brain that also improves patients' moods, energy levels and ability to concentrate. Those effects might counter cocaine withdrawal. Then came the surprises: Cocaine intensely stimulates the brain's pleasure centers, producing not just a "buzz" or a "rush," but outright euphoria. In a small safety study to ensure that modafinil did not make cocaine worse, some users found the once-a-day pill blocked that high. "We didn't expect that at all," Dackis says. Potentially more important, he says, modafinil seems to increase activity in the prefrontal cortex, the brain's decision-making command center and the spot that allows reasoning to override impulse or emotion. Cocaine reduces activity in that key brain region, making it even harder for would-be quitters to ignore cravings and resist another hit. Modafinil also increases the ability to think strategically, a means of weighing variables and risks to make decisions, says Frank Vocci, NIDA's pharmacotherapy chief. "The effects on cognitive processes are very subtle, and very interesting," Vocci says, and the reason that of a half-dozen medications being studied as potential cocaine treatments, the government's biggest emphasis is on modafinil. Cocaine is highly addictive: About 16 percent of people who try it become hooked, often rapidly. In 2003, the latest data, the government estimated that more than 1.5 million Americans were dependent on or abusing cocaine, and more reported recently experimenting with it. Addictions in general rewire the brain, says Volkow, the NIDA director. Drugs cause a feel-good rush by increasing amounts of the brain chemical dopamine. The brain reacts by tamping down regular dopamine production, making users feel lousy between hits and setting up the cycle of addiction. At the same time, the dopamine surge also creates memory circuits that eventually establish so-called "cue-induced cravings": If an addict passes the crack house or sees friends he did drugs with, his brain literally sends a strong impulse to use again. "One of the strategies of course, in terms of treatment ... is how can we help recover the function of the dopamine system, so the person that's addicted can become sensitive to natural stimuli," Volkow explains. Modafinil seems to affect chemicals that in turn regulate dopamine production, a different pathway than cocaine takes to strike dopamine, and thus one that might counter it, adds Dackis. "You can't assume this is going to work," he cautions. But if it pans out, a drug that could help cognition instead of just numb cravings would "be a big benefit in treatment." EDITOR'S NOTE Lauran Neergaard covers health and medical issues for The Associated Press in Washington. LOAD-DATE: April 25, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 Associated Press All Rights Reserved 388 of 998 DOCUMENTS Agence France Presse -- English April 16, 2006 Sunday 9:12 AM GMT No planned comeback for disgraced sprinter White LENGTH: 322 words DATELINE: SAN FRANCISCO, April 16 2006 Disgraced American sprint star Kelli White will not return to competition when her two-year doping ban expires next month, her attorney confirmed. White was stripped of her two gold medals from the 2003 world championships and banned for two years in May 2004 after admitting using banned steroids and doping methods. Her ban expires on May 17. "She does not intend to return to competition," attorney Jerrold Colton told The San Francisco Chronicle. "At this point it's unlikely. These last two years have been tough on her and she doesn't want to deal with this anymore." White's rise was as rapid as her fall. Although she won a bronze medal in the 200m at the 2001 world championships, it was not until 2003 that she dominated when, helped by the doping programme of BALCO founder Victor Conte, she became the first American woman to win both sprints at the world championships in Paris in personal best times. Soon after the victories, White tested positive for the drug modafinil, which she claimed she needed to treat a sleeping disorder. She later admitted using several banned substances, including the designer steroid THG, the endurance-boosting drug EPO, a form of testosterone and the stimulant modafinil. At the time White insisted she would return to competition but now aged 29 and recovering from major surgery to her knee cap she has seen the rise of sprint stars Allyson Felix and Lauryn Williams. "She feels pretty good but she's not sure if she wants to get out there and test it," her father Willie White said. "A lot of people wish things hadn't happened, but they did," he said. "You've got to move on. Everybody makes decisions. People make choices. You have to live with them and deal with them." All of White's competitive results from December 15, 2000 were wiped out as a result of the ban. She last competed on May 14, 2004 in Doha where she ran the 200m in 23.42, 1.37 seconds slower than her best time. bur/ea06 LOAD-DATE: April 17, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 Agence France Presse All Rights Reserved 389 of 998 DOCUMENTS Family Practice News April 15, 2006 FDA Panel: Modafinil Is Not Safe for Treating ADHD in Teens BYLINE: Alicia Ault, Associate Editor, Practice Trends SECTION: Pg. 38 Vol. 36 No. 8 ISSN: 0300-7073 LENGTH: 821 words    GAITHERSBURG, MD. - A Food and Drug Administration advisory committee said modafinil is not safe for treating ADHD in children and adolescents by a 12-1 vote, although committee members unanimously agreed the drug was effective for that indication.    At a meeting of the FDA's Psychopharmacologic Drugs Advisory Committee, the panel members were mainly concerned about modafinil's potential to cause Stevens-Johnson syndrome (SJS). The severe rash, which is often due to a hypersensitivity reaction to a drug, can be fatal in up to 5% of cases, according to Dr. Michael E. Bigby of the dermatology department at Harvard Medical School, Boston, and consultant to the panel.    Among 933 children and adolescents exposed to the drug during trials, there were 12 cases that could have been definite erythema multiforme (EM) or SJS, early prodromal EM or SJS, or suggestive of prodromal EM or SJS-a rate of 1.29%, said Dr. Glenn B. Mannheim, a medical reviewer in the FDA's division of psychiatry products.    The panel's discussion focused on one case that seemed most likely to be SJS-indicating a 1 in 1,000 risk. But they were not certain that was the true risk.    Dr. Bigby and Dr. Mannheim said more cases could occur once modafinil (Provigil) is more widely used-even though there have been no reports of SJS in the 36,000 children who were prescribed the drug off-label in 2002-2005.    Given the trial data and the assumption that modafinil could capture 10% of the market for children under age 19 (based on other stimulants' sales), there could be 500-3,250 cases of EM or SJS, and 25-488 deaths, said Dr. Mannheim.    The dichotomy between the postmarketing experience and the trial data prompted the FDA to seek its advisers' input, said Dr. Robert J. Temple, director of the FDA's office of medical policy.    The FDA usually follows the advice of its panels.    The FDA has received six reports of serious skin reactions in adults, said Dr. Mannheim.    "I'd like to see an opportunity for the company to come back with additional data. That will give us additional assurance that this case was a fluke," said panel chair Dr. Wayne K. Goodman, chair of the department of psychiatry at the University of Florida, Gainesville.    The committee said modafinil's manufacturer, Cephalon Inc., should conduct a 3,000-patient, open-label study to further clarify the risk of SJS.    After the meeting, Dr. Thomas Laughren, director of the FDA's division of psychiatry products, told reporters that if a case turns up in such a study, "then they have a problem."    It was not clear why children had higher rates of skin-related adverse events than adults, but Dr. Mannheim noted that lab tests indicated that they had a 7-16 times higher area under the curve ratio of modafinil sulfone, a metabolite. The levels could not be explained by higher milligram-per-kilogram dosing, he said.    In two of the three phase III studies, children were given a flexible dose with weekly titration (170 mg, 255 mg, 340 mg, or 425 mg). In the third study they were given a fixed dose, with those under 30 kg receiving 340 mg daily, and those over 30 kg receiving 425 mg daily.    The primary outcome was the total score on the school ADHD rating scale. In all three trials, children taking modafinil had a more significant drop in scores than those taking placebo. The total score for modafinil recipients-just over 20-was close to the normative score for a 10-year-old male, according to a Cephalon statement.    Panelists did not dispute the drug's efficacy, although many said it would not be a first-line choice.    Lesley Russell, Cephalon's senior vice president of worldwide clinical research, said modafinil offers clinicians an alternative, especially when children don't respond to other marketed drugs.    But Dr. Temple said that even though it's plausible that modafinil might work in nonresponsive children, the company had not proved that.    "The mere fact that people given a second drug respond after failing to respond to the first tells you nothing at all," he said.    According to a company statement, modafinil may be less addictive and less apt to be diverted because it does not offer a "high" to recreational users. Jeffrey L. Vaught, executive vice president of research and development at Cephalon, said the drug is not water soluble and is not stable at high heat, which makes it difficult to crush for injection or smoking. Studies have shown that modafinil does not activate reward centers in the brain, and that it does not cause release of dopamine in vitro or in vivo.    The Drug Enforcement Administration has deemed modafinil a schedule IV drug; other stimulants used to treat ADHD, such as Ritalin, are schedule II.    Despite potential advantages, the panel did not want modafinil to be marketed for children yet.    "I think we did err on the side of consumer protection," said Dr. Goodman. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: FPNEWS Copyright 2006 Elsevier Inc., International Medical News Group All Rights Reserved 390 of 998 DOCUMENTS CNS Drug News Pharmaceuticals April 6, 2006 Alfresa/Tanabe to co-develop modafinil in Japan LENGTH: 225 words Alfresa Pharma ( Alfresa Holdings ) and Tanabe have concluded a co-development agreement regarding the right to co-market modafinil for the treatment of narcolepsy, as well as to co-develop other new indications for the product in Japan. Application for manufacturing and marketing approval of modafinil for narcolepsy has been filed by Alfresa. Modafinil is a wakefulness-enhancing agent, to which Alfresa acquired the right to develop, manufacture and market in Japan from Cephalon in June 1998. Products containing modafinil are currently marketed in over 30 countries in the world as treatment for the excessive daytime sleepiness associated with narcolepsy. It has also been approved in the US and certain major European countries as an agent for obstructive sleep apnoea and excessive sleepiness in shift-work sleep disorder patients. In Japan, Alfresa has been developing it for the treatment of narcolepsy as an orphan drug designated by the Ministry of Health, Labour and Welfare and is currently waiting for early approval. Upon approval, each of the companies will market modafinil using its own sales channel under the same tradename, Modiodal . The companies also plan to seek necessary approvals for further indications of modafinil in Japan, such as obstructive sleep apnoea syndrome and paediatric attention deficit hyperactivity disorder. LOAD-DATE: April 7, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2006 ESPICOM Business Intelligence Ltd. All Rights Reserved 391 of 998 DOCUMENTS Japan Corporate News Network April 05, 2006 Wednesday 06:45 PM JST Alfresa Pharma, Tanabe Seiyaku to Collaborate in Development and Sales of Narcolepsy Drug Modafinil BYLINE: jcn LENGTH: 118 words DATELINE: Tokyo, Japan Tokyo, Apr 5, 2006 - (JCN) - Alfresa Pharma, a wholly owned subsidiary of Alfresa Holdings, has signed an agreement with Tanabe Seiyaku on modafinil, an agent for treating narcolepsy. Upon receiving approval, the two companies will co-promote the agent under the trade name of Modiodal in Japan. Further, they will proceed with research on the agent with the aim of expanding indications including obstructive sleep apnea syndrome and pediatric ADHD (attention-deficit hyperactivity disorder). Modafinil is an arousal-enhancing agent for which Alfresa Pharma has obtained rights to develop, manufacture and develop in Japan from US company Cephalon. Currently, the agent is available in over 30 countries worldwide. LOAD-DATE: April 6, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 Japan Corporate News Network All Rights Reserved 392 of 998 DOCUMENTS Breaking News from globeandmail.com April 1, 2006 6:47 PM EST Sleep no more BYLINE: Alexandra Gill; From Saturday's Globe and Mail SECTION: CAT6,B; specialScienceandHealth; Front LENGTH: 1646 words HIGHLIGHT: If you're having trouble getting decent shut-eye, why bother? Pharmacists say they have a remedy Every morning, I wake up to a pounding wail of thunder, feeling shaken, spent and thoroughly unsatisfied. Then I roll over, hit the snooze button, and do it again. This bleary-eyed ritual, which must be repeated several times to drag my weary body out of its deprived state of slumber, is the symptom of a widespread hunger. "Sleep is the new sex." So says Arthur J. Spielman, a New York psychologist and co-author of The Insomnia Answer. "People want it, need it and can't get enough." This weekend, as we spring forward to daylight time, and lose yet another precious hour of shut-eye, it's the same old story: We're getting less and less sleep. The National Sleep Foundation (NSF) estimates that the average sleep time in the United States has dropped by more than 20 per cent in the past century. By last year, 71 per cent of people were getting by with less than the eight hours of sleep the body needs (up from 63 per cent in 1998). According to the latest numbers from Statistics Canada, one in seven Canadians -- 3.3 million people -- have trouble going to sleep and staying asleep. Things are now so bad that the Monday after the annual switch to daylight time has been declared National Napping Day, and this year the goal is to have us catch 40 winks while on the job. "We live in a time famine," says Harvey Moldofsky, director of the Centre for Sleep and Chronobiology at the University of Toronto. "There isn't enough time in our waking periods to accomplish all of the expectations industrialized society requires of us." The 24/7, BlackBerry-buzzing, on-demand lifestyle is taking its toll. We pummel ourselves through a vicious cycle, jolting up on caffeine during the day and knocking ourselves out with hypnotics at night. Last year, 42 million sleeping-pill prescriptions were filled in the United States, up 60 per cent since 2000, according to a study by Forbes magazine. This cranky, edgy, worn-out state of being leaves us vulnerable to anxiety, depression and weakened immunity. Studies have shown that a lack of sleep affects memory loss and dexterity and has contributed to rising rates of obesity. Not surprisingly, it also diminishes our sex drive. In last year's Sleep in America poll conducted by the NSF, nearly one-quarter of partnered adults said they have lost interest in sex, or have it less often because they are just too darn tired. There has to be a better way. Perhaps there is. What if you were offered a magic pill that made you feel alert throughout the entire day, without the jitter, buzz, euphoria, crash, addictive qualities or potential for paranoid delusion that come with amphetamines and caffeine? Would you be interested in a pill that lets you bounce back from a late night, bright-eyed and bushy-tailed, after just four hours of sleep? Meet modafinil, "the first wave of new lifestyle drugs that promise to do for sleep what the contraceptive pill did for sex -- unshackle it from nature," New Scientist magazine trumpets in a recent cover story. "Modafinil has made it possible to have 48 hours of continuous wakefulness with few, if any, ill effects," Graham Lawton writes, almost giddily, about the brave new world of 24-hour living. "New classes of sleeping pills are on the horizon that promise to deliver sleep that is deeper and more refreshing than the real thing," he continues. "Further down the line are even more radical interventions -- wakefulness promoters that can safely abolish sleep for several days at a stretch, and sleeping pills that deliver what feels like eight hours of sleep in half the time." Modafinil, a stimulant trademarked as Provigil in the United States and Alertec in Canada, was approved by the U.S. Federal Drug Administration in 1998 to treat narcolepsy, a chronic neurological disorder that causes excessive daytime sleepiness, loss of voluntary muscle tone, vivid hallucinations and brief episodes of total paralysis. The way modafinil works is not clearly understood. It seems to target regions of the brain believed to regulate normal wakefulness and cognitive functions, perhaps by slowing the release of GABA (a sleep promoter in the brain) or acting on the histamine pathways (connected to sleep regulation). And unlike amphetamines, cocaine and most other pick-me-ups, it doesn't appear to fire up the neurotransmitters that cause dopamine to flood the brain, which then sets the heart racing, makes you feel high and causes twitchiness. "It works," Dr. Moldofsky says. "It's not a panacea, but our studies have shown that, for narcolepsy, it can be very helpful. It literally can change the lives of these people overnight." Although modafinil is still approved only for narcolepsy, there are many who would like to put it to other uses. The U.S. Defence Department has been testing it heavily as a replacement for dexedrine, the "go pill" taken by the two U.S. Air Force bomber pilots who accidentally killed four Canadian soldiers in Afghanistan. Last winter, researchers at the University of Pennsylvania published the results of a small study, which found that modafinil may help recovering cocaine addicts fight their addiction. Some professional athletes were using it to enhance their performance, until the International Olympic Committee and World Anti-Doping Agency listed it as a banned substance in 2004. And increasingly, sleep-deprived professionals are using it to pursue a more active lifestyle. In 2002, the FDA issued a warning to Cephalon, the Pennsylvania-based pharmaceutical company that licensed the drug from France's Laboratoire Lafon and conducted its clinical trials, about misleading promotional materials that encouraged off-label use for general sleepiness, lack of energy and fatigue. As reported by The Washington Post, Americans bought $150-million (U.S.) worth of modafinil in 2001; three-quarters of the pills were swallowed by people who didn't have narcolepsy. Cephalon amended its marketing, but modafinil's underground use shows no sign of slacking. "If I take a dose just before I go to bed, I can wake up after four or five hours and feel refreshed," one user told the New Scientist reporter. "The alarm goes off and I'm like, 'Let's go!' " The 31-year-old old software developer from Seattle, who has been popping the pills for three years and buys them on-line, says the drug doesn't make him any more alert or less sleepy. "It's just that thoughts of tiredness don't occur to me. I find I can be very productive at work. I'm more organized and more motivated. And it means I can go out partying on a Friday night and still go skiing early on Saturday morning." Hmm, that sounds awfully seductive. I must try to get some -- after I take a nap. "I've never heard of it," says the doctor on duty at my neighbourhood walk-in clinic. "They say it's quite safe," I implore, pushing the article into his hands, after explaining the travails of my restless nights and daytime exhaustion. Frowning, he skims through the piece, then picks up the hefty 2005 edition of the Canadian Pharmacists Association's Compendium of Pharmaceuticals and Specialties, and starts flipping. "Oh, it's here," he says, mildly surprised. "Can cause headaches, nausea, dizziness, overconfidence and psychosis. Do you have any problems with your liver? Well, there are no big red flags." Psychosis isn't a big red flag? "Lots of drugs cause psychosis," he says, peering sternly over the book. "Pot makes some people psychotic, but we seem to think that's okay." Jonathan Fleming, co-director of the Sleep Disorder Clinic at the University of British Columbia Hospital, warns that doctors must be cautious in their dispersal of modafinil. "The research evidence shows it works, and, as a drug, it's very safe. But the research protocols were very clear. This is not for people who have been out until 5 a.m., and have to get work the next day. That's a misuse," he says, sighing impatiently over the phone. "Having said that, people misuse medication all the time," he continues. "And we all self-medicate with coffee or Wake Ups. But if you're using it for sleep deprivation, at some point, you're going to have to address that sleep debt. Getting adequate sleep is the appropriate response." Modafinil, which doesn't prevent you from falling asleep when you want to, cuts the recovery time of sleep debt in half. You can stay awake for 48 hours and need only eight hours of sleep, instead of 16, to catch up. But researchers are doubtful that anyone could take it every day without consequences. Sleep is necessary for the endocrine system, immune function and hormonal growth. Yet, there is already a new class of drugs being developed that may, it is hoped, eliminate sleep debt altogether. A trial compound called CX717, one of the "ampakine" drugs originally developed to fight Alzheimer's, has shown remarkable restorative powers. According to New Scientist, the Defence Advanced Research Projects Agency plans tests this year "that will push volunteers through four consecutive nights of hard work with only four hours of recovery sleep in between." But even if Mother Nature is conquered some day, there are still big societal questions to contend with. If we can safely skip on sleep, what's to keep us from working around the clock? Will people who choose to sleep be overlooked for promotions? Will the super sleep drugs, which are not likely to be covered by health insurance, cause even greater class divisions? Back at the clinic, the doctor says he is uncomfortable prescribing modafinil. "How's your thyroid?" he asks, filling out a laboratory requisition for a battery of blood tests. Then he hands me several photocopied pages, modafinil's monograph from the pharmaceutical encyclopedia. "We'll see how the tests go. And in the meantime I want you to read this. Maybe it will scare you to sleep." Alexandra Gill is The Globe and Mail's western arts correspondent, based in Vancouver. LOAD-DATE: April 12, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Web Publication Copyright 2006 Bell Globemedia Publishing Inc. and its licensors. All Rights Reserved 393 of 998 DOCUMENTS Clinical Psychiatry News April 2006 Treatments for Sleepiness Vary in Cost, Side Effects BYLINE: Sherry Boschert, San Francisco Bureau SECTION: Pg. 54 Vol. 34 No. 4 ISSN: 0270-6644 LENGTH: 677 words    SAN DIEGO - All three main treatments for problem sleepiness can perk patients up, but they differ in cost and side effects, Dr. Milton Erman said at a psychopharmacology congress sponsored by the Neuroscience Education Institute.    Caffeine is the cheapest, most accessible, and most widely used stimulant. The two other treatment options are prescription medications, which are more expensive: modafinil or CNS stimulants (most commonly amphetamines or methylphenidate).    Caffeine tolerance develops rapidly, however, and there's a moderate risk for dependence. Stopping a daily caffeine habit too quickly can trigger a "caffeine headache." Side effects from regular caffeine use include nervousness, irritability, insomnia, and GI problems, said Dr. Erman of the University of California, San Diego.    "Many of my insomniac patients tell me proudly that they aren't using caffeine" to indicate that caffeine can't be blamed for their insomnia, he said. Ironically, a bit of caffeine in the morning may be just what they need. "The problem with many of these insomniac patients is that they can't get going, get functioning in the morning," he said. Limited caffeine use in the morning may help them function better.    Use of CNS stimulants also leads to tolerance, and there is a high potential for dependence. Side effects include nervousness, headaches, insomnia, anorexia, GI problems, and mood changes. General CNS stimulants such as amphetamines have a high risk of abuse and hyperactivity because of their broad mechanism of action.    One experimental study of sleep deprivation that compared amphetamines with modafinil treatment to maintain wakefulness suggested that the two drugs are equally potent. In real life, however, "I think amphetamines are more potent," he said. Patients with narcolepsy who have used amphetamines in the past often aren't satisfied with the effects of modafinil.    Modafinil works more specifically on wakefulness circuits and has fewer side effects than other stimulants. Tolerance is not an issue-it maintains most of its efficacy over time-and use of the drug does not lead to dependence. Side effects include headache, nausea, dry mouth, insomnia, and hyperactivity.    The risk of headache relates to the dosing of modafinil. In early research on the drug, headache appeared primarily in patients who titrated up to a dose of 400 mg/day by the third day. In subsequent research that gave patients 7-9 days to titrate up to 400 mg/day, headache was much less of a problem, Dr. Erman said.    "Modafinil works quite well, particularly if we're not talking about the most severely hypersomnolent patients," such as narcoleptics who have become accustomed to taking stimulants, he said.    Dr. Erman is a speaker and consultant for, and has received research funding from, the company that makes modafinil, Cephalon Inc. Modafinil is approved to treat sleepiness from shift work, narcolepsy, and sleep apnea.    The most common cause of problem sleepiness is sleep apnea, which occurs in perhaps 10% of the population, he said. Restless leg syndrome can interrupt sleep and lead to daytime sleepiness. Narcolepsy is fairly uncommon. Insomnia can cause excessive sleepiness, but more often, insomniac patients are hypervigilant. "If anything, they are more alert" than they want to be, he said.    Secondary causes of sleepiness include chronic pain and any medical condition that causes pain or discomfort, which may interrupt sleep. Medications used to alleviate pain also can lead to daytime sleepiness because they affect breathing during sleep and increase the risk for sleep apnea.    Check to see if patients who complain of sleepiness are taking drugs that cause sedation or that disrupt sleep, Dr. Erman added, and consider alternative therapies.    Lifestyle issues, such as graveyard shift work, also contribute to excessive sleepiness,. The pace of U.S. culture commonly leads to chronic sleep deprivation that affects daytime function. "As a society, we really haven't dealt with this," he said. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: CPNEWS Copyright 2006 Elsevier Inc., International Medical News Group All Rights Reserved 394 of 998 DOCUMENTS The Globe and Mail (Canada) April 1, 2006 Saturday HEALTH; If you're having trouble getting decent shut-eye, why bother? Pharmacists say they have a drug that can keep you awake for two days without side effects, ALEXANDRA GILL reports. And on the horizon: pills that could make bedtime completely a thing of the past BYLINE: ALEXANDRA GILL SECTION: FOCUS; Pg. F9 LENGTH: 1654 words Every morning, I wake up to a pounding wail of thunder, feeling shaken, spent and thoroughly unsatisfied. Then I roll over, hit the snooze button, and do it again. This bleary-eyed ritual, which must be repeated several times to drag my weary body out of its deprived state of slumber, is the symptom of a widespread hunger. "Sleep is the new sex." So says Arthur J. Spielman, a New York psychologist and co-author of The Insomnia Answer. "People want it, need it and can't get enough." This weekend, as we spring forward to daylight time, and lose yet another precious hour of shut-eye, it's the same old story: We're getting less and less sleep. The National Sleep Foundation (NSF) estimates that the average sleep time in the United States has dropped by more than 20 per cent in the past century. By last year, 71 per cent of people were getting by with less than the eight hours of sleep the body needs (up from 63 per cent in 1998). According to the latest numbers from Statistics Canada, one in seven Canadians - 3.3 million people - have trouble going to sleep and staying asleep. Things are now so bad that the Monday after the annual switch to daylight time has been declared National Napping Day, and this year the goal is to have us catch 40 winks while on the job. "We live in a time famine," says Harvey Moldofsky, director of the Centre for Sleep and Chronobiology at the University of Toronto. "There isn't enough time in our waking periods to accomplish all of the expectations industrialized society requires of us." The 24/7, BlackBerry-buzzing, on-demand lifestyle is taking its toll. We pummel ourselves through a vicious cycle, jolting up on caffeine during the day and knocking ourselves out with hypnotics at night. Last year, 42 million sleeping-pill prescriptions were filled in the United States, up 60 per cent since 2000, according to a study by Forbes magazine. This cranky, edgy, worn-out state of being leaves us vulnerable to anxiety, depression and weakened immunity. Studies have shown that a lack of sleep affects memory loss and dexterity and has contributed to rising rates of obesity. Not surprisingly, it also diminishes our sex drive. In last year's Sleep in America poll conducted by the NSF, nearly one-quarter of partnered adults said they have lost interest in sex, or have it less often because they are just too darn tired. There has to be a better way. Perhaps there is. What if you were offered a magic pill that made you feel alert throughout the entire day, without the jitter, buzz, euphoria, crash, addictive qualities or potential for paranoid delusion that come with amphetamines and caffeine? Would you be interested in a pill that lets you bounce back from a late night, bright-eyed and bushy-tailed, after just four hours of sleep? Meet modafinil, "the first wave of new lifestyle drugs that promise to do for sleep what the contraceptive pill did for sex - unshackle it from nature," New Scientist magazine trumpets in a recent cover story. "Modafinil has made it possible to have 48 hours of continuous wakefulness with few, if any, ill effects," Graham Lawton writes, almost giddily, about the brave new world of 24-hour living. "New classes of sleeping pills are on the horizon that promise to deliver sleep that is deeper and more refreshing than the real thing," he continues. "Further down the line are even more radical interventions - wakefulness promoters that can safely abolish sleep for several days at a stretch, and sleeping pills that deliver what feels like eight hours of sleep in half the time." Modafinil, a stimulant trademarked as Provigil in the United States and Alertec in Canada, was approved by the U.S. Federal Drug Administration in 1998 to treat narcolepsy, a chronic neurological disorder that causes excessive daytime sleepiness, loss of voluntary muscle tone, vivid hallucinations and brief episodes of total paralysis. The way modafinil works is not clearly understood. It seems to target regions of the brain believed to regulate normal wakefulness and cognitive functions, perhaps by slowing the release of GABA (a sleep promoter in the brain) or acting on the histamine pathways (connected to sleep regulation). And unlike amphetamines, cocaine and most other pick-me-ups, it doesn't appear to fire up the neurotransmitters that cause dopamine to flood the brain, which then sets the heart racing, makes you feel high and causes twitchiness. "It works," Dr. Moldofsky says. "It's not a panacea, but our studies have shown that, for narcolepsy, it can be very helpful. It literally can change the lives of these people overnight." Although modafinil is still approved only for narcolepsy, there are many who would like to put it to other uses. The U.S. Defence Department has been testing it heavily as a replacement for dexedrine, the "go pill" taken by the two U.S. Air Force bomber pilots who accidentally killed four Canadian soldiers in Afghanistan. Last winter, researchers at the University of Pennsylvania published the results of a small study, which found that modafinil may help recovering cocaine addicts fight their addiction. Some professional athletes were using it to enhance their performance, until the International Olympic Committee and World Anti-Doping Agency listed it as a banned substance in 2004. And increasingly, sleep-deprived professionals are using it to pursue a more active lifestyle. In 2002, the FDA issued a warning to Cephalon, the Pennsylvania-based pharmaceutical company that licensed the drug from France's Laboratoire Lafon and conducted its clinical trials, about misleading promotional materials that encouraged off-label use for general sleepiness, lack of energy and fatigue. As reported by The Washington Post, Americans bought $150-million (U.S.) worth of modafinil in 2001; three-quarters of the pills were swallowed by people who didn't have narcolepsy. Cephalon amended its marketing, but modafinil's underground use shows no sign of slacking. "If I take a dose just before I go to bed, I can wake up after four or five hours and feel refreshed," one user told the New Scientist reporter. "The alarm goes off and I'm like, 'Let's go!' " The 31-year-old old software developer from Seattle, who has been popping the pills for three years and buys them on-line, says the drug doesn't make him any more alert or less sleepy. "It's just that thoughts of tiredness don't occur to me. I find I can be very productive at work. I'm more organized and more motivated. And it means I can go out partying on a Friday night and still go skiing early on Saturday morning." Hmm, that sounds awfully seductive. I must try to get some - after I take a nap. "I've never heard of it," says the doctor on duty at my neighbourhood walk-in clinic. "They say it's quite safe," I implore, pushing the article into his hands, after explaining the travails of my restless nights and daytime exhaustion. Frowning, he skims through the piece, then picks up the hefty 2005 edition of the Canadian Pharmacists Association's Compendium of Pharmaceuticals and Specialties, and starts flipping. "Oh, it's here," he says, mildly surprised. "Can cause headaches, nausea, dizziness, overconfidence and psychosis. Do you have any problems with your liver? Well, there are no big red flags." Psychosis isn't a big red flag? "Lots of drugs cause psychosis," he says, peering sternly over the book. "Pot makes some people psychotic, but we seem to think that's okay." Jonathan Fleming, co-director of the Sleep Disorder Clinic at the University of British Columbia Hospital, warns that doctors must be cautious in their dispersal of modafinil. "The research evidence shows it works, and, as a drug, it's very safe. But the research protocols were very clear. This is not for people who have been out until 5 a.m., and have to get work the next day. That's a misuse," he says, sighing impatiently over the phone. "Having said that, people misuse medication all the time," he continues. "And we all self-medicate with coffee or Wake Ups. But if you're using it for sleep deprivation, at some point, you're going to have to address that sleep debt. Getting adequate sleep is the appropriate response." Modafinil, which doesn't prevent you from falling asleep when you want to, cuts the recovery time of sleep debt in half. You can stay awake for 48 hours and need only eight hours of sleep, instead of 16, to catch up. But researchers are doubtful that anyone could take it every day without consequences. Sleep is necessary for the endocrine system, immune function and hormonal growth. Yet, there is already a new class of drugs being developed that may, it is hoped, eliminate sleep debt altogether. A trial compound called CX717, one of the "ampakine" drugs originally developed to fight Alzheimer's, has shown remarkable restorative powers. According to New Scientist, the Defence Advanced Research Projects Agency plans tests this year "that will push volunteers through four consecutive nights of hard work with only four hours of recovery sleep in between." But even if Mother Nature is conquered some day, there are still big societal questions to contend with. If we can safely skip on sleep, what's to keep us from working around the clock? Will people who choose to sleep be overlooked for promotions? Will the super sleep drugs, which are not likely to be covered by health insurance, cause even greater class divisions? Back at the clinic, the doctor says he is uncomfortable prescribing modafinil. "How's your thyroid?" he asks, filling out a laboratory requisition for a battery of blood tests. Then he hands me several photocopied pages, modafinil's monograph from the pharmaceutical encyclopedia. "We'll see how the tests go. And in the meantime I want you to read this. Maybe it will scare you to sleep." Alexandra Gill is The Globe and Mail's western arts correspondent, based in Vancouver. LOAD-DATE: September 15, 2006 LANGUAGE: ENGLISH GRAPHIC: Illustration PUBLICATION-TYPE: Newspaper Copyright 2006 The Globe and Mail, a division of CTVglobemedia Publishing Inc. All Rights Reserved 395 of 998 DOCUMENTS Pediatric News April 2006 FDA Panel: Modafinil Not Safe for Children BYLINE: Alicia Ault, Associate Editor, Practice Trends SECTION: Pg. 7 Vol. 40 No. 4 ISSN: 0031-398X LENGTH: 955 words    GAITHERSBURG, MD. - A Food and Drug Administration advisory committee said modafinil is not safe for treating ADHD in children and adolescents by a 12-1 vote, although committee members unanimously agreed the drug was effective for that indication.    At a meeting of the FDA's Psychopharmacologic Drugs Advisory Committee, the panel members were mainly concerned about modafinil's potential to cause Stevens-Johnson syndrome (SJS). The severe rash, which is often due to a hypersensitivity reaction to a drug, can be fatal in up to 5% of cases, according to Dr. Michael E. Bigby of the dermatology department at Harvard Medical School, Boston, and consultant to the panel.    In a group of 933 children and adolescents exposed to the drug during trials, there were 12 cases that could have been definite erythema multiforme (EM) or SJS, early prodromal EM or SJS, or suggestive of prodromal EM or SJS-a rate of 1.29%, said Dr. Glenn B. Mannheim, a medical reviewer in the FDA's division of psychiatry products. The panel's discussion focused on one case that seemed most likely to be SJS-i.e., a 1-in-1,000 risk. But they weren't certain that was the true risk.    Dr. Bigby and Dr. Mannheim said more cases could occur once modafinil (Provigil) is more widely used-even though there have been no reports of SJS in the 36,000 children who were prescribed the drug off-label in 2002-2005.    Given the trial data and the assumption that modafinil could capture 10% of the market for children under age 19 (based on other stimulants' sales), there could be 500-3,250 cases of EM or SJS, and 25-488 deaths, said Dr. Mannheim.    The dichotomy between the postmarketing experience and the trial data prompted the FDA to seek its advisers' input, said Dr. Robert J. Temple, director of the FDA's office of medical policy. The FDA usually follows its panels' advice.    The FDA has received six reports of serious skin reactions in adults, said Dr. Mannheim.    "I'd like to see an opportunity for the company to come back with additional data. That will give us additional assurance that this case was a fluke," said panel chair Dr. Wayne K. Goodman, chair of the department of psychiatry at the University of Florida, Gainesville.    The committee said modafinil's manufacturer, Cephalon Inc., should conduct a 3,000-patient, open-label study to further clarify the risk of SJS.    After the meeting, Dr. Thomas Laughren, director of the FDA's division of psychiatry products, told reporters that if a case turns up in such a study, "then they have a problem."    The committee was less concerned about cardiac and psychiatric side effects, partly because both had a thorough airing at a hearing on ADHD drugs the day before (see p. 1). There were five psychosis events and six suicidal events in the modafinil trials, said Dr. Mannheim.    Cephalon proposed to add warnings to modafinil's label on the potential for psychiatric adverse events. Modafinil's label already warns against use in patients with hypertrophy or bicuspid aortic valve.    It was not clear why children had higher rates of skin-related adverse events than adults, but Dr. Mannheim noted that lab tests indicated that they had a 7-16 times higher area under the curve ratio of modafinil sulfone, a metabolite. The levels could not be explained by higher milligram-per-kilogram dosing, he said.    In two of the three phase III studies, children were given a flexible dose with weekly titration (170 mg, 255 mg, 340 mg, or 425 mg). In the third study they were given a fixed dose, with those under 30 kg receiving 340 mg daily, and those over 30 kg receiving 425 mg daily.    The primary outcome was the total score on the school ADHD rating scale. In all three trials, children taking modafinil had a more significant drop in scores than those taking placebo. The total score for modafinil recipients-just over 20-was close to the normative score for a 10-year-old male, according to a Cephalon statement. Panelists did not dispute the drug's efficacy, although many said it would not be a first-line choice.    Lesley Russell, Cephalon's senior vice president of worldwide clinical research, said modafinil offers clinicians an alternative, especially when children don't respond to other marketed drugs.    But Dr. Temple said that even though it's plausible that modafinil might work in nonresponsive children, the company had not proved that. "The mere fact that people given a second drug respond after failing to respond to the first tells you nothing at all."    According to a company statement, modafinil may be less addictive and less apt to be diverted because it does not offer a "high" to recreational users. Jeffrey L. Vaught, executive vice president of research and development at Cephalon, said the drug is not water soluble and is not stable at high heat, which makes it difficult to crush for injection or smoking.    Studies have shown that modafinil does not activate reward centers in the brain, and that it does not cause release of dopamine in vitro or in vivo.    The Drug Enforcement Administration has deemed modafinil a schedule IV drug; other stimulants used to treat ADHD, such as Ritalin, are schedule II.    Despite potential advantages, the panel did not want modafinil to be marketed for children yet.    "I think we did err on the side of consumer protection," said Dr. Goodman.    In a statement after the meeting, Dr. Paul Blake, Cephalon's executive vice president of worldwide medical and regulatory operations, said, "We are obviously disappointed with the recommendation of the advisory committee. We will continue our discussions with the FDA to determine the next steps in the review of this drug application." LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: PDNEWS Copyright 2006 Elsevier Inc., International Medical News Group All Rights Reserved 396 of 998 DOCUMENTS Rheumatology News April 2006 Modafinil Held to Be Unsafe for Treating ADHD in Children BYLINE: Alicia Ault, Associate Editor, Practice Trends SECTION: Pg. 42 Vol. 5 No. 4 ISSN: 1541-9800 LENGTH: 584 words    GAITHERSBURG, MD. - A Food and Drug Administration advisory committee said modafinil is not safe for treating ADHD in children and adolescents by a 12-1 vote, although committee members unanimously agreed the drug was effective for that indication.    At a meeting of the FDA's Psychopharmacologic Drugs Advisory Committee, the panel members were mainly concerned about modafinil's potential to cause Stevens-Johnson syndrome (SJS). The severe rash, which is often due to a hypersensitivity reaction to a drug, can be fatal in up to 5% of cases, according to Dr. Michael E. Bigby of the dermatology department at Harvard Medical School, Boston, and consultant to the panel.    In a group of 933 children and adolescents exposed to the drug during trials, there were 12 cases that could have been definite erythema multiforme (EM) or SJS, early prodromal EM or SJS, or suggestive of prodromal EM or SJS-a rate of 1.29%, said Dr. Glenn B. Mannheim, a medical reviewer in the FDA's division of psychiatry products.    The panel's discussion focused on one case that seemed most likely to be SJS-indicating a 1 in 1,000 risk. But they weren't certain that was the true risk. Dr. Bigby and Dr. Mannheim said more cases could occur once modafinil (Provigil) is more widely used-even though there have been no reports of SJS in the 36,000 children who were prescribed the drug off-label in 2002-2005.    Given the trial data and the assumption that modafinil could capture 10% of the market for children under age 19 (based on other stimulants' sales), there could be 500-3,250 cases of EM or SJS, and 25-488 deaths, said Dr. Mannheim.    The dichotomy between the postmarketing experience and the trial data prompted the FDA to seek its advisers' input, said Dr. Robert J. Temple, director of the FDA's office of medical policy.    The FDA usually follows its panels' advice.    The FDA has received six reports of serious skin reactions in adults, said Dr. Mannheim.    "I'd like to see an opportunity for the company to come back with additional data. That will give us additional assurance that this case was a fluke," said panel chair Dr. Wayne K. Goodman, chair of the department of psychiatry at the University of Florida, Gainesville.    The committee said modafinil's manufacturer, Cephalon Inc., should conduct a 3,000-patient, open-label study to further clarify the risk of SJS.    After the meeting, Dr. Thomas Laughren, director of the FDA's division of psychiatry products, told reporters that if a case turns up in such a study, "then they have a problem."    It was not clear why children had higher rates of skin-related adverse events than adults, but Dr. Mannheim noted that lab tests indicated that they had a 7-16 times higher area under the curve ratio of modafinil sulfone, a metabolite. The levels could not be explained by higher milligram-per-kilogram dosing, he said.    In two of the three phase III studies, children were given a flexible dose with weekly titration (170 mg, 255 mg, 340 mg, or 425 mg). In the third study they were given a fixed dose, with those under 30 kg receiving 340 mg daily, and those over 30 kg receiving 425 mg daily.    The primary outcome was the total score on the school ADHD rating scale. In all three trials, children taking modafinil had a more significant drop in scores than those taking placebo. The total score for modafinil recipients-just over 20-was close to the normative score for a 10-year-old male, according to a Cephalon statement. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: RHNEWS Copyright 2006 Elsevier Inc., International Medical News Group All Rights Reserved 397 of 998 DOCUMENTS Akron Beacon Journal (Ohio) March 24, 2006 Friday In the Nation SECTION: BRIEFS; Pg. 3 LENGTH: 445 words WASHINGTON Drug's use opposed The narcolepsy drug modafinil should not be approved as a treatment for attention deficit hyperactivity disorder in children until more is learned about a possible link to a serious skin disease, federal advisers said Thursday. A Food and Drug Administration advisory committee voted 12-1 against recommending modafinil as safe for children with ADHD. China-trade tension The Bush administration told China on Thursday that it will be looking for concrete actions to lower trade tensions between the two nations in advance of a U.S. visit next month by Chinese President Hu Jintao. Commerce Secretary Carlos Gutierrez, who will hold talks with Chinese officials next week in Beijing, said his message will be that the administration is looking for China to play a responsible role in the global-trading community. Bush signs trade law President Bush signed a law Thursday that ended Cold War-era trade restrictions on Ukraine, opening the way for the former Soviet republic to join the World Trade Organization. ATLANTA TB resistance rises Federal and international health officials said Thursday they are seeing what appears to be a disturbing increase around the world in tuberculosis infections resistant to both the first- and second-line antibiotics used against TB. ``It's basically a death sentence. If people are failing first- and second-line drugs, and we don't have in the pipeline a new drug for immediate use, that's a crisis,'' said Dr. Marcos Espinale, executive secretary of the World Health Organization's Stop TB Partnership. SELMER, TENN. Pastor shot dead A minister was found shot to death in his parsonage, and authorities searched Thursday for his wife and three young daughters. The family of Matthew Winkler was found safe later Thursday in southern Alabama. Police said they want to find out what his wife, Mary, may know about the slaying. MELBOURNE, FLA. 3 die in plane crash A small plane crashed into a parking lot about a mile from an airport runway Thursday, killing all three people aboard, officials said. Witnesses said the plane's engines appeared to have shut down before the crash. J.D. Byrider Systems Inc., a used-car finance company based in Carmel, Ind., identified two of the passengers as James DeVoe, the company's founder, president and CEO, and Steele Gudal, DeVoe's son-in-law. The company didn't know the pilot's identity. TOPEKA, KAN. House overrides veto The Kansas House on Thursday overrode Gov. Kathleen Sebelius' veto of a concealed-weapons bill, allowing it to become law this summer. The vote was 91-33, giving supporters seven votes more than the required two-thirds majority. Compiled from wire reports. LOAD-DATE: March 24, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2006 Akron Beacon Journal All Rights Reserved 398 of 998 DOCUMENTS The Associated Press State & Local Wire March 24, 2006 Friday 12:47 AM GMT Committee says drug needs more study as possible ADHD treatment BYLINE: By ANDREW BRIDGES, Associated Press Writer SECTION: BUSINESS NEWS LENGTH: 361 words DATELINE: WASHINGTON The narcolepsy drug modafinil should not be approved as a treatment for attention deficit hyperactivity disorder in children until more is learned about a possible link to a serious skin disease, federal advisers said Thursday. A Food and Drug Administration advisory committee voted 12-1 against recommending modafinil as safe for children with ADHD. Earlier Thursday, the psychopharmacologic drugs panel agreed unanimously that the modafinil works in treating ADHD. The FDA is not required to follow the recommendations of its advisory committees but usually does. The committee recommended that Cephalon Inc. undertake a 3,000-patient trial to determine what risk modafinil may pose for Stevens-Johnson Syndrome. Drug reactions cause nearly all cases of the sometimes fatal skin disease, which can produce widespread blistering and rashes, according to The Merck Manual. The FDA's drug chief, Dr. Robert Temple, said one out of roughly 900 children involved in earlier studies of the drug developed the disease. Temple and Cephalon spokeswoman Jenifer Antonacci said the agency and company would discuss the committee's recommendation. The Frazer, Pa.-based company does not see a "clear link" between its drug and the skin disease, Antonacci said. In December 1998, the FDA originally approved modafinil, under the brand name Provigil, to treat adults with sleepiness associated with narcolepsy. The company has proposed calling a higher-dose version of the pill Sparlon when used to treat ADHD. Other drugs already approved by the FDA for ADHD include Ritalin, Strattera and Adderall. A different advisory committee recommended on Wednesday that the FDA add warnings to the labels of those and other ADHD drugs on the market alerting doctors and parents to the possible risk of hallucinations in the more than 3 million children receiving the popular medications. Narcolepsy is marked by recurring episodes of daytime sleep, lasting from a few seconds to an hour. The disease can be merely inconvenient to some people, but disabling and dangerous to others who may fall asleep while driving or operating machinery. On the Net: Food and Drug Administration: http://www.fda.gov LOAD-DATE: March 24, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 Associated Press All Rights Reserved 399 of 998 DOCUMENTS CNS Drug News Pharmaceuticals March 24, 2006 FDA Advisory Committee recommends against approval of Sparlon LENGTH: 211 words The FDA's Psychopharmacologic Drugs Advisory Committee has voted not to recommend FDA approval of Sparlon ( modafinil ) Tablets [C-IV], Cephalon 's investigational medication for the treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents. The Committee voted unanimously that Sparlon is effective for its intended use, but recommended that the company collect additional data to support the safety of the drug in children and adolescents with ADHD. Cephalon is to continue its discussions with the FDA, to determine the next steps in the review of the drug application. The Committee's recommendation will be considered by the FDA in its review of the sNDA that Cephalon submitted for Sparlon in December 2004. Cephalon received an approvable letter from the FDA with respect to Sparlon in October 2005. Sparlon is a new formulation and proprietary dosage strength of modafinil, the active ingredient in Provigil Tablets [C-IV], which is approved for the treatment of adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnoea/hypopnoea syndrome and shift work sleep disorder. Sparlon is chemically distinct from currently approved therapies and if approved, would provide a unique option for ADHD treatment. LOAD-DATE: March 24, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2006 ESPICOM Business Intelligence Ltd. All Rights Reserved 400 of 998 DOCUMENTS FDAnews Drug Daily Bulletin March 24, 2006 Friday REVIEWER RECOMMENDS 'NONAPPROVABLE' ACTION FOR PROVIGIL ADHD INDICATION SECTION: Vol. 2 No. 311 LENGTH: 347 words An FDA reviewer is urging the agency not to approve Cephalon's bid to market its narcolepsy drug Provigil as a treatment for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents, arguing the drug presents unacceptable risks to that patient population. The agency's Psychopharmacologic Drugs Advisory Committee is scheduled to convene March 23 to consider Cephalon's supplemental new drug application (sNDA) for an ADHD indication for Provigil (modafinil). The company submitted its sNDA in December 2004, and the FDA issued an approvable letter in October 2005. The agency decided to hold the advisory committee meeting to address reported risks associated with the drug, including incidents of skin rash and psychiatric adverse events. In background documents released recently, one FDA reviewer said clinical studies show modafinil was "significantly better than placebo in terms of efficacy" for treating children and adolescents with ADHD. But another FDA reviewer said the studies identified "worrisome safety signals," including Stevens-Johnson Syndrome and other rashes of unclear significance, a possible Reye's Syndrome case, and various psychiatric disorders such as suicidality, depression, agitation, psychosis and phobias. Other safety signals associated with the drug versus placebo included insomnia (27 percent versus 4 percent), anorexia (16 percent versus 3 percent) and headaches (20 percent versus 13 percent), the reviewer said. "Despite the demonstration of clinical efficacy, the safety profile demonstrates increased and -- in this reviewer's opinion -- unacceptable risks to children and adolescents, resulting in the recommendation that the agency take a nonapprovable action on this submission," the reviewer said. The FDA is not required to follow the advice of its advisers, but usually does. For background materials on the meeting, access http://www.fda.gov/oc/advisory/accalendar/2006/cder12544d032306.html (http://www.fda.gov/oc/advisory/accalendar/2006/cder12544d032306.html). (http://www.fdanews.com/did) Release date: March 24, 2006 LOAD-DATE: March 23, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2006 Washington Business Information, Inc. All Rights Reserved 401 of 998 DOCUMENTS National Public Radio (NPR) March 24, 2006 Friday SHOW: Morning Edition 10:00 AM EST FDA Committee Rejects ADHD use for Modafinil ANCHORS: RENEE MONTAGNE REPORTERS: JON HAMILTON LENGTH: 659 words RENEE MONTAGNE, host: An expert panel has advised the Food and Drug Administration not to approve a new drug for attention deficit hyperactivity disorder. Panel members say the drug isn't safe enough to give to millions of children. NPR's Jon Hamilton reports. JON HAMILTON reporting: Modafinil is already approved for people with sleep disorders. It helps them stay alert. The company that makes Modafinil, Cephalon, was hoping to expand into the much larger market for ADHD drugs. The advisory panel has dimmed that hope. Its recommendation came at the end of an all-day meeting in Gaithersburg, Maryland. But the tone was set by the day's first speaker. Dr. Glen Manheim(ph), an FDA scientist, described children who developed severe skin rashes after taking Modafinil. Mr. GLEN MANHEIM (scientist for the Food and Drug Administration): One subject had peeling and blistering over the entire body, with lips and urinary tract involvement. The drug was stopped, but the rash progressed to involve peeling, blistering, mucosal involvement, over days. HAMILTON: Manheim said the drug appeared to have caused an extremely rare skin problem called Stevens-Johnson syndrome. This was a mild case, but Manheim says the condition often requires treatment in a hospital burn unit, and some patients die. Manheim says there might be big problems if even 10 percent of the 2.5 million children on ADHD drugs switched to Modafinil. Mr. MANHEIM: Based on the known mortality associated with (unintelligible) with Steven-Johnson, we would expect from 25 to over 400 deaths to occur. HAMILTON: Other FDA officials were less concerned. And Cephalon argued that millions of people around the world have taken the drug without problems. It was also unclear just how many children had actually developed severe skin problems. Dr. Daniel Pine, a panel member from the National Institutes of Health, asked for help during the discussion. Dr. DANIEL PINE (Chief, Section on Development and Affective Neuroscience): So do we have three cases where everybody would agree that these are concerning dermatologic issues? Do we have one case? Do we have two that are somewhat concerning, a third that's suggestive? And, you know, can we get some agreement on that? HAMILTON: In the end, the panelists could only agree about the one case. And records showed the boy's skin condition never even kept him home from school. The panelists also heard an impassioned plea from Dr. Joseph Biederman, a Harvard Psychiatrist who's done research on Modafinil for Cephalon. Biederman says ADHD patients need choices beyond the traditional stimulants they're usually prescribed. Dr. JOSEPH BIEDERMAN (Professor of Psychiatry, Harvard Medical School): Although the stimulants are clearly an effective treatment for ADHD, a sizable number, in the order of 40 percent are non-responsive or not tolerating this treatment, calling for alternative treatment for this condition. HAMILTON: Ultimately, the panel took the cautious road. Twelve of thirteen panelists said the FDA should not approve Modafinil. Their recommendation came a day after a different FDA committee heard a litany of concerns about existing drugs for ADHD. These drugs have been linked to heart problems and suicidal thoughts. The recommendation is a major blow for the drug company, Cephalon. Gary Nachman is a pharmaceutical analyst for the investment company, Leerink. He said approval would have meant a lot of money for Cephalon. Mr. GARY NACHMAN (Director Analyst, Equity Research at Leerink Swann & Company): I forecast sales of about 120 million this year, growing to a little bit over 400 million in 2010. And, at that point, it would represent about 20 to 25 percent of the company's total sales. HAMILTON: Nachman said the FDA panel didn't slam the door on Modafinil. Members suggested that a new study of several thousand children could show whether severe skin problems are a major issue or just a rare occurrence. Jon Hamilton, NPR News. LOAD-DATE: April 17, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Transcript Copyright 2006 National Public Radio (R) All Rights Reserved 402 of 998 DOCUMENTS The Washington Post March 24, 2006 Friday Final Edition Use of Drug to Treat ADHD in Children Opposed BYLINE: Associated Press SECTION: A Section; A11 LENGTH: 227 words The narcolepsy drug modafinil should not be approved as a treatment for attention-deficit hyperactivity disorder in children until more is learned about a possible link to a serious skin disease, federal advisers said yesterday. A Food and Drug Administration advisory committee voted 12 to 1 against recommending modafinil as safe for children with ADHD. Earlier, the psychopharmacologic drugs panel unanimously agreed that modafinil works as a treatment for ADHD. The FDA is not required to follow the recommendations of its advisory panels but usually does. The committee recommended that Cephalon Inc. undertake a 3,000-patient trial to determine the risk modafinil may pose for Stevens-Johnson syndrome. Drug reactions cause nearly all cases of the sometimes fatal skin disease, which can produce widespread blistering and rashes, according to the Merck Manual. The FDA's drug evaluation chief, Robert J. Temple, said one out of 900 children involved in earlier studies of the drug developed the disease. He and Cephalon spokeswoman Jenifer Antonacci said the agency and the company will discuss the committee's recommendation. In December 1998, the FDA approved modafinil, under the brand name Provigil, for treating adults with sleepiness associated with narcolepsy. Other drugs approved by the FDA for ADHD include Ritalin, Strattera and Adderall. LOAD-DATE: March 24, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2006 The Washington Post 403 of 998 DOCUMENTS Xinhua General News Service March 24, 2006 Friday 1:15 AM EST FDA panel recommends against treating ADHD with modafinil SECTION: WORLD NEWS LENGTH: 149 words DATELINE: WASHINGTON A U.S. Food and Drug Administration (FDA) advisory committee on Thursday recommended against using the narcolepsy drug modafinil to treat attention deficit hyperactivity disorder (ADHD) in children and teenagers. The psychopharmacologic drugs panel voted 12-1 against the recommendation. It concluded that the drug is effective against ADHD, but can't be regarded as safe for the use by children for the time being, reports reaching here said. The panel was most concerned about a possible link with skin rashes and recommended that the drug's manufacturer, Cephalon Inc., conduct a 3,000-patient trial to measure the risk. The drug is also found in link with psychiatric effects including mania and aggression. Modafinil is being marketed as Provigil for treating sleep disorders. Cephalon is seeking to sell the drug under the name Sparlon for children with ADHD. LOAD-DATE: March 25, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 Xinhua News Agency 404 of 998 DOCUMENTS Associated Press Online March 24, 2006 Friday 10:10 PM GMT Panel: Drug Shouldn't Be Used for ADHD Yet BYLINE: By ANDREW BRIDGES, Associated Press Writer SECTION: WASHINGTON DATELINE LENGTH: 361 words DATELINE: WASHINGTON The narcolepsy drug modafinil should not be approved as a treatment for attention deficit hyperactivity disorder in children until more is learned about a possible link to a serious skin disease, federal advisers said Thursday. A Food and Drug Administration advisory committee voted 12-1 against recommending modafinil as safe for children with ADHD. Earlier Thursday, the psychopharmacologic drugs panel agreed unanimously that the modafinil works in treating ADHD. The FDA is not required to follow the recommendations of its advisory committees but usually does. The committee recommended that Cephalon Inc. undertake a 3,000-patient trial to determine what risk modafinil may pose for Stevens-Johnson Syndrome. Drug reactions cause nearly all cases of the sometimes fatal skin disease, which can produce widespread blistering and rashes, according to The Merck Manual. The FDA's drug chief, Dr. Robert Temple, said one out of roughly 900 children involved in earlier studies of the drug developed the disease. Temple and Cephalon spokeswoman Jenifer Antonacci said the agency and company would discuss the committee's recommendation. The Frazer, Pa.-based company does not see a "clear link" between its drug and the skin disease, Antonacci said. In December 1998, the FDA originally approved modafinil, under the brand name Provigil, to treat adults with sleepiness associated with narcolepsy. The company has proposed calling a higher-dose version of the pill Sparlon when used to treat ADHD. Other drugs already approved by the FDA for ADHD include Ritalin, Strattera and Adderall. A different advisory committee recommended on Wednesday that the FDA add warnings to the labels of those and other ADHD drugs on the market alerting doctors and parents to the possible risk of hallucinations in the more than 3 million children receiving the popular medications. Narcolepsy is marked by recurring episodes of daytime sleep, lasting from a few seconds to an hour. The disease can be merely inconvenient to some people, but disabling and dangerous to others who may fall asleep while driving or operating machinery. On the Net: Food and Drug Administration: http://www.fda.gov LOAD-DATE: March 25, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 Associated Press All Rights Reserved 405 of 998 DOCUMENTS Associated Press Financial Wire March 23, 2006 Thursday 11:22 PM GMT Narcolepsy drug needs more study as possible ADHD treatment, federal advisers say BYLINE: By ANDREW BRIDGES, Associated Press Writer SECTION: BUSINESS NEWS LENGTH: 381 words DATELINE: WASHINGTON The narcolepsy drug modafinil should not be approved as a treatment for attention deficit hyperactivity disorder in children until more is learned about a possible link to a serious skin disease, federal advisers said Thursday. A Food and Drug Administration advisory committee voted 12-1 against recommending modafinil as safe for children with ADHD. Earlier Thursday, the psychopharmacologic drugs panel agreed unanimously that the modafinil works in treating ADHD. The FDA is not required to follow the recommendations of its advisory committees but usually does. The committee recommended that Cephalon Inc. undertake a 3,000-patient trial to determine what risk modafinil may pose for Stevens-Johnson Syndrome. Drug reactions cause nearly all cases of the sometimes fatal skin disease, which can produce widespread blistering and rashes, according to The Merck Manual. The FDA's drug chief, Dr. Robert Temple, said one out of roughly 900 children involved in earlier studies of the drug developed the disease. Temple and Cephalon spokeswoman Jenifer Antonacci said the agency and company would discuss the committee's recommendation. The Frazer, Pa.-based company does not see a "clear link" between its drug and the skin disease, Antonacci said. In December 1998, the FDA originally approved modafinil, under the brand name Provigil, to treat adults with sleepiness associated with narcolepsy. The company has proposed calling a higher-dose version of the pill Sparlon when used to treat ADHD. The ADHD drugs include Ritalin, manufactured by Novartis Pharmaceuticals Corp. and in generic form by other companies; Adderall, made by Shire Pharmaceuticals Inc.; and Strattera, produced by Eli Lilly and Co. A different advisory committee recommended on Wednesday that the FDA add warnings to the labels of those and other ADHD drugs on the market alerting doctors and parents to the possible risk of hallucinations in the more than 3 million children receiving the popular medications. Narcolepsy is marked by recurring episodes of daytime sleep, lasting from a few seconds to an hour. The disease can be merely inconvenient to some people, but disabling and dangerous to others who may fall asleep while driving or operating machinery. On the Net: Food and Drug Administration: http://www.fda.gov LOAD-DATE: March 24, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 Associated Press All Rights Reserved 406 of 998 DOCUMENTS The Associated Press March 23, 2006 Thursday 11:22 PM GMT Narcolepsy drug needs more study as possible ADHD treatment, federal advisers say BYLINE: By ANDREW BRIDGES, Associated Press Writer SECTION: BUSINESS NEWS LENGTH: 381 words DATELINE: WASHINGTON The narcolepsy drug modafinil should not be approved as a treatment for attention deficit hyperactivity disorder in children until more is learned about a possible link to a serious skin disease, federal advisers said Thursday. A Food and Drug Administration advisory committee voted 12-1 against recommending modafinil as safe for children with ADHD. Earlier Thursday, the psychopharmacologic drugs panel agreed unanimously that the modafinil works in treating ADHD. The FDA is not required to follow the recommendations of its advisory committees but usually does. The committee recommended that Cephalon Inc. undertake a 3,000-patient trial to determine what risk modafinil may pose for Stevens-Johnson Syndrome. Drug reactions cause nearly all cases of the sometimes fatal skin disease, which can produce widespread blistering and rashes, according to The Merck Manual. The FDA's drug chief, Dr. Robert Temple, said one out of roughly 900 children involved in earlier studies of the drug developed the disease. Temple and Cephalon spokeswoman Jenifer Antonacci said the agency and company would discuss the committee's recommendation. The Frazer, Pa.-based company does not see a "clear link" between its drug and the skin disease, Antonacci said. In December 1998, the FDA originally approved modafinil, under the brand name Provigil, to treat adults with sleepiness associated with narcolepsy. The company has proposed calling a higher-dose version of the pill Sparlon when used to treat ADHD. The ADHD drugs include Ritalin, manufactured by Novartis Pharmaceuticals Corp. and in generic form by other companies; Adderall, made by Shire Pharmaceuticals Inc.; and Strattera, produced by Eli Lilly and Co. A different advisory committee recommended on Wednesday that the FDA add warnings to the labels of those and other ADHD drugs on the market alerting doctors and parents to the possible risk of hallucinations in the more than 3 million children receiving the popular medications. Narcolepsy is marked by recurring episodes of daytime sleep, lasting from a few seconds to an hour. The disease can be merely inconvenient to some people, but disabling and dangerous to others who may fall asleep while driving or operating machinery. On the Net: Food and Drug Administration: http://www.fda.gov LOAD-DATE: March 24, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 Associated Press All Rights Reserved 407 of 998 DOCUMENTS Drug Industry Daily March 23, 2006 Thursday FDA Reviewer Recommends 'Nonapprovable' Action for Provigil ADHD Indication SECTION: Vol. 5 No. 58 LENGTH: 661 words An FDA reviewer is urging the agency not to approve Cephalon's bid to market its narcolepsy drug Provigil as a treatment for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents, arguing the drug presents unacceptable risks to that patient population. The agency's Psychopharmacologic Drugs Advisory Committee is scheduled to convene March 23 to consider Cephalon's supplemental new drug application (sNDA) for an ADHD indication for Provigil (modafinil). The company submitted its sNDA in December 2004, and the FDA issued an approvable letter in October 2005. The agency decided to hold the advisory committee meeting to address reported risks associated with the drug, including incidents of skin rash and psychiatric adverse events. In background documents released March 22, one FDA reviewer said clinical studies show modafinil was "significantly better than placebo in terms of efficacy" for treating children and adolescents with ADHD. But another FDA reviewer said the studies identified "worrisome safety signals," including Stevens-Johnson Syndrome and other rashes of unclear significance, a possible Reye's Syndrome case, and various psychiatric disorders such as suicidality, depression, agitation, psychosis and phobias. Other safety signals associated with the drug versus placebo included insomnia (27 percent versus 4 percent), anorexia (16 percent versus 3 percent) and headaches (20 percent versus 13 percent), the reviewer said. "Despite the demonstration of clinical efficacy, the safety profile demonstrates increased and -- in this reviewer's opinion -- unacceptable risks to children and adolescents, resulting in the recommendation that the agency take a nonapprovable action on this submission," the reviewer said. By contrast, Cephalon said the treatment of modafinil is "generally safe and well tolerated" in children and adolescents with ADHD. The drug has been tested in 933 ADHD patients from this population group, the firm said in a document prepared for the advisory committee meeting. Studies found a low occurrence of serious adverse events and adverse events leading to withdrawal, the company noted. The most common adverse events -- insomnia, anorexia and headache -- are common to drugs that affect the central nervous system, Cephalon said. "These events were usually mild to moderate in severity and seldom required discontinuation of treatment with the study drug," the firm noted. The firm also reported few adverse events of "special interest" such as skin rash and psychiatric episodes. There were two cases of children with possible Stevens-Johnson Syndrome, which is manifested as skin blistering, the firm said. Neither of those patients was hospitalized. There were a "relatively small number of psychiatric adverse events" in all modafinil development programs, the firm said. In addition, the studies found no cardiovascular safety issues. "Because current medications for ADHD may not be optimal for up to 40 percent of patients, there is a need for additional safe and effective pharmacologic treatment options for children and adolescents with ADHD," Cephalon said. The company is proposing to market the drug under the brand name Sparlon. FDA advisers will vote on whether modafinil has been shown to be effective and "acceptably safe" in the treatment of ADHD in this population. Assuming the drug is to be considered for approval, the agency also will ask the panel's advice on what kind of risk management plan should be implemented regarding the serious skin rash signal, how the concern about skin rashes should be addressed in product labeling, and if there should be a requirement for a postmarketing study to better understand serious skin rashes. The FDA is not required to follow the advice of its advisers, but usually does. For background materials on the meeting, access http://www.fda.gov/oc/advisory/accalendar/2006/cder12544d032306.html. -- Neal Learner Release date: March 23, 2006 LOAD-DATE: March 22, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2006 Washington Business Information, Inc. All Rights Reserved 408 of 998 DOCUMENTS Drug Industry Daily March 23, 2006 Thursday Full Issue SECTION: Vol. 5 No. 58 LENGTH: 3081 words Vol. 5, No. 58 FDA Reviewer Recommends 'Nonapprovable' Action for Provigil ADHD Indication An FDA reviewer is urging the agency not to approve Cephalon's bid to market its narcolepsy drug Provigil as a treatment for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents, arguing the drug presents unacceptable risks to that patient population. The agency's Psychopharmacologic Drugs Advisory Committee is scheduled to convene March 23 to consider Cephalon's supplemental new drug application (sNDA) for an ADHD indication for Provigil (modafinil). The company submitted its sNDA in December 2004, and the FDA issued an approvable letter in October 2005. The agency decided to hold the advisory committee meeting to address reported risks associated with the drug, including incidents of skin rash and psychiatric adverse events. In background documents released March 22, one FDA reviewer said clinical studies show modafinil was "significantly better than placebo in terms of efficacy" for treating children and adolescents with ADHD. But another FDA reviewer said the studies identified "worrisome safety signals," including Stevens-Johnson Syndrome and other rashes of unclear significance, a possible Reye's Syndrome case, and various psychiatric disorders such as suicidality, depression, agitation, psychosis and phobias. Other safety signals associated with the drug versus placebo included insomnia (27 percent versus 4 percent), anorexia (16 percent versus 3 percent) and headaches (20 percent versus 13 percent), the reviewer said. "Despite the demonstration of clinical efficacy, the safety profile demonstrates increased and -- in this reviewer's opinion -- unacceptable risks to children and adolescents, resulting in the recommendation that the agency take a nonapprovable action on this submission," the reviewer said. By contrast, Cephalon said the treatment of modafinil is "generally safe and well tolerated" in children and adolescents with ADHD. The drug has been tested in 933 ADHD patients from this population group, the firm said in a document prepared for the advisory committee meeting. Studies found a low occurrence of serious adverse events and adverse events leading to withdrawal, the company noted. The most common adverse events -- insomnia, anorexia and headache -- are common to drugs that affect the central nervous system, Cephalon said. "These events were usually mild to moderate in severity and seldom required discontinuation of treatment with the study drug," the firm noted. The firm also reported few adverse events of "special interest" such as skin rash and psychiatric episodes. There were two cases of children with possible Stevens-Johnson Syndrome, which is manifested as skin blistering, the firm said. Neither of those patients was hospitalized. There were a "relatively small number of psychiatric adverse events" in all modafinil development programs, the firm said. In addition, the studies found no cardiovascular safety issues. "Because current medications for ADHD may not be optimal for up to 40 percent of patients, there is a need for additional safe and effective pharmacologic treatment options for children and adolescents with ADHD," Cephalon said. The company is proposing to market the drug under the brand name Sparlon. FDA advisers will vote on whether modafinil has been shown to be effective and "acceptably safe" in the treatment of ADHD in this population. Assuming the drug is to be considered for approval, the agency also will ask the panel's advice on what kind of risk management plan should be implemented regarding the serious skin rash signal, how the concern about skin rashes should be addressed in product labeling, and if there should be a requirement for a postmarketing study to better understand serious skin rashes. The FDA is not required to follow the advice of its advisers, but usually does. For background materials on the meeting, access http://www.fda.gov/oc/advisory/accalendar/2006/cder12544d032306.html. -- Neal Learner FDA Advisory Committee Considers Psychosis Warning for ADHD Drugs The FDA's Pediatric Advisory Committee discussed the need for new warnings about the increased risk of psychosis and mania events associated with attention deficit/hyperactivity disorder (ADHD) drugs at its March 22 meeting, but the panel had not made any recommendations by DID press time. FDA drug-safety reviewers earlier had called for new warnings regarding these conditions (DID, March 16). According to the agency, the predominance of patients reporting hallucinations involving insects, snakes or worms is striking and deserves further evaluation. In many patients, the events ceased after they stopped taking the drug, the FDA reviewers added. The committee's scheduled recommendation late March 22 follows its recommendation last month to include a black box warning that highlights possible links to heart attack and stroke (DID, Feb. 13). Over the past year, ADHD drugs have been linked to hypertension, chest pain, arrhythmia and tachycardia, among other conditions. The ADHD drug market generated more than $3 billion in sales in 2004 and ACHD drugs are prescribed to 2.5 million children between the ages of 4 and 17. These drugs also are increasingly prescribed to young adults between the ages of 20 and 44, according to Medco Health Solutions. The number of adults taking these medicines grew more than 139 percent from 2000 to 2005, outpacing increases in children 19 years and younger by a margin of 82 percent, Medco said. Adult use of these drugs can lead to heart problems, the group added. "The possible cardiovascular issues associated with ADHD drugs should be weighted very seriously when prescribing these drugs for adults since they're at a greater risk of heart disease and stroke than children," said Robert Epstein, Medco's chief medical officer. An executive with Eli Lilly, which makes the ADHD drug Strattera (atomoxetine), could not comment on the financial effect of a potential black box warning for psychosis. "I don't know the impact, because [Strattera] is still a top seller" even with existing warnings, Albert Allen, Eli Lilly's medical director, told DID. FDA Extends Review Period for Reintroduction of Tysabri The FDA will extend its review period for the reintroduction of Elan and Biogen Idec's multiple sclerosis (MS) drug Tysabri by up to 90 days, according to the companies, which pulled the drug last year following reports that it may be linked to a rare brain disease. The agency requires additional time to review the company's information for a Tysabri (natalizumab) risk management plan, the firms said March 22. Under the revised timeline, Elan and Biogen anticipate a decision from the FDA by June 28. The firms withdrew Tysabri in February 2005 following reports that three patients taking the drug had developed progressive multifocal leukoencephalopathy (PML), a rare and deadly nerve disease (DID, March 1, 2005, Page 1). On March 8, an FDA advisory panel voted unanimously in favor of returning the product to the market under certain conditions (DID, March 9). The panel recommended the companies establish a patient registry to monitor side effects. The advisers also voted 7 to 5 to allow Tysabri on the market as a first-line treatment. FDA reviewers have suggested various restrictions for Tysabri if it is reintroduced, including limits on prescribing and dispensing the drug (DID, Feb. 7). One pharmaceutical analyst said the FDA may take a more conservative view of the drug's risks and benefits than the advisory committee. There is a 25 percent probability the agency will only reapprove Tysabri as a second-line therapy to treat MS patients who have shown intolerance or failed to respond to other MS therapies, Merrill Lynch research analyst Erica Whittaker said in a March 22 research note. Elan's share prices are in line with peak Tysabri sales of over $2 billion, which means treating over 100,000 patients, Whittaker noted. "We believe this scenario is only possible if prescribing and distribution restrictions are lifted following no further cases of PML or other serious infections, which we think is unlikely," she said. Merrill Lynch's sales forecast for Tysabri remains about $500 million in 2010, based on the firm's discussions with multiple clinicians who say they would use Tysabri on average in less than 10 percent of their patients, Whittaker said. -- Neal Learner Bristol-Myers, Sanofi-Aventis Settle With Apotex Over Plavix Bristol-Myers Squibb (BMS) and sanofi-aventis have reached a settlement with Apotex over the generic firm's patent challenge to the blood thinner Plavix. But the brand firms also acknowledged there is a "significant risk" the FTC will not approve the agreement because of antitrust concerns. If the FTC does not approve the settlement, Apotex will receive an undisclosed payment from the two companies and litigation will resume, BMS and sanofi-aventis said March 21. BMS distributes Plavix (clopidogrel bisulfate) in the U.S. for sanofi-aventis. The drug had sales of $5.9 billion in 2005, according to IMS Health. A patent trial had been scheduled for June in the U.S. District Court for the Southern District of New York, BMS and sanofi-aventis said. Under the agreement, Apotex would be able to launch generic Plavix eight months before the Plavix patent expires in November 2011, or in May 2012 if Plavix receives a pediatric extension of the patent. Apotex also could launch its generic earlier if another generic enters the market before this time. BMS and sanofi-aventis have proposed a similar settlement with generic firm Dr. Reddy's. The FDA granted final approval to Apotex' application to market generic Plavix in January. But analysts have said Apotex would not launch the product until the U.S. litigation was resolved (DID, Jan. 26). Apotex unsuccessfully challenged the Plavix patent in a Canadian court in 2005 (DID, March 24, 2005, Page 1). Meanwhile, Teva Pharmaceutical and Canadian drugmaker Cobalt Pharmaceuticals have also challenged the Plavix patent. BMS and sanofi-aventis said they will "communicate with them in due course." -- Dar Haddix Study Finds Levitra Effective in Men Taking Blood Pressure Drugs A clinical study has found GlaxoSmithKline (GSK) and Schering-Plough's erectile dysfunction (ED) drug Levitra is effective in men taking high blood pressure drugs, the firms announced. According to data published in the Journal of Sexual Medicine, patients treated with Levitra (vardenafil HCl), a PDE5 inhibitor, experienced an 83 percent overall success rate in erectile function while also receiving one or more antihypertensive drugs, the companies said March 22. "This study demonstrated that Levitra was well-tolerated when used concomitantly with antihypertensive medications in patients not previously treated with PDE5 inhibitors," said study author Hermann van Ahlen of the University of Munster in Germany. Hypertension is a major risk factor for ED and affects 29.4 million men in the U.S., according to the firms. Many blood-pressure-lowering drugs may adversely affect erectile function, the companies added. The study gave either Levitra or a placebo to 354 men who were taking hypertension drugs -- not including alpha blockers -- and had experienced ED for more than 6 months. In the Levitra group, 83 percent of men reported having an erection compared to 58 percent of men taking the placebo. NitroMed Executives Quit; Sales of BiDil Lag Two top executives at NitroMed have resigned amid slow sales of the heart-failure drug BiDil, the first product indicated specifically for African Americans. NitroMed announced the resignations March 21 of CEO Michael Loberg and chief financial officer (CFO) Lawrence Bloch. The company has appointed Argeris Karabelas as interim CEO and Kenneth Bate as CFO. During a conference call March 22, Karabelas said NitroMed's board "felt it was time for a course correction." Sales of BiDil (isosorbide dinitrate/hydralazine hydrochloride) have not met expectations because of problems with insurance reimbursement, sales productivity and product promotion, executives said during the conference call. BiDil sales were only $4.5 million in 2005, well below analyst estimates. The drug was launched last July after a study found that black patients with heart failure experienced a 43 percent improvement in survival after taking BiDil, compared to those taking standard heart-failure therapy plus a placebo (DID, July 17, Page 2). NitroMed has struggled to get insurance companies to put BiDil on their list of preferred drugs, because it is composed of two generics already available to patients. "There is absolutely no question of the value of BiDil in the treatment of congestive heart failure in African Americans," Karabelas said. "We need to forcefully get this point across to managed care and also to be flexible in our contracts so we can achieve access, which is what we need to drive sales." Karabelas said the company has appointed a senior manager with "exceptional leadership" who "has the right ideas for increasing the productivity of the sales force." The company downsized its sales force in January from 195 to 144 sales representatives, eliminating positions in less productive sales territories. Another problem has been getting doctors to switch patients to BiDil if their condition has already stabilized on their current drug regimen. "What's been difficult to explain is that patients who are stabilized need the benefit of this drug," Karabelas said. "Doctors are not comfortable switching a patient's prescription when they're stable," he noted. The company's key objectives include exploring copromotion opportunities for BiDil -- especially in hospital settings where many cardiologists are based -- and improving BiDil's formulary status with managed care companies, Karabelas said. -- Dar Haddix PBM Disclosure Proponents Lose State Ballot Initiatives, But Predict Long-Term Success A national push to increase the transparency of financial dealings between drugmakers and pharmaceutical benefit managers (PBMs) in Medicaid negotiations has suffered numerous setbacks in state legislatures this year, but proponents argue that upcoming legal battles could turn the tide. The National Legislative Association of Prescription Drug Prices (NLARX) is undertaking a multistate effort to pass legislation that would require PBMs to disclose the prices they pay for different drugs and require any rebates they receive be sent to the states. NLARX is a nonprofit organization managed by state legislators working across state lines to make prescription drugs more affordable and accessible to consumers, with its primary focus on lowering drug prices. The organization's effort comes as states face higher costs for their Medicaid programs, which are growing by 8 to 9 percent per year and accounting for a bigger chunk of state budgets than education (DID, Jan. 3). But many such efforts have failed, with defeats this year in Colorado, Connecticut, New Hampshire, Oklahoma, Virginia and Washington State. What had seemed like a trend toward greater disclosure in recent years -- with victories in Maine and Washington, D.C. -- seems to have dried up, according to opponents such as the Pharmaceutical Care Management Association (PCMA), which represents the PBM industry. These efforts are failing "literally from coast to coast," said Phil Blando, PCMA's spokesman. Maine's Unfair Prescription Drug Practices Act, enacted in June 2003, requires PBMs to disclose pricing information negotiated with drugmakers and pass on the savings to consumers to avoid conflicts of interest. But PCMA believes recent efforts have been defeated because state legislatures have realized that greater disclosure would result in higher prices for health plans, employers and PBMs and actually lead to higher drug costs for consumers. It is "very clear there is a cost impact," said Blando, noting that the recent push for disclosure is "failing to gain traction at the state level." Greater disclosure creates an artificial price floor that drug companies will not go below, Blando said. Making this information public is "like playing poker with all your cards up," he added, and tilts "contracts and bargaining in favor of the drug companies." PCMA will continue lobbying state legislatures to oppose future disclosure proposals, Blando said. But proponents argue there are key legal battles that could change the tide toward greater disclosure. Currently, PBMs are challenging the Maine and Washington, D.C., plans in court and are using the legal uncertainty this is causing to undermine efforts in other states, said Sharon Treat, NLARX's executive director. "When there's uncertainty, there's a tendency to just vote 'no,'" on legislation, Treat said. But if NLARX wins in these two cases, the group will argue that there is no longer the legal uncertainty about disclosure laws, which should enhance state legislative support for these bills, she said. The group also disputes PCMA's contention that greater disclosure equals higher prices. Proposed state legislation contains confidentiality requirements that prevent negotiating parties from revealing the prices they paid. These bills include heavy fines for disclosure of this data so that competitors will not know what the other is paying, and there will therefore be no artificial price floor, Treat said. Greater disclosure puts the client -- the states -- "in a better bargaining position and that's what [PBMs] don't want," Treat said. A track record of price savings is becoming evident in states that require disclosure, she noted. The multimillion-dollar settlements PBMs have paid for improper Medicaid negotiations with states are another sign of the savings that would be reaped if these dealings were transparent, according to Treat. Meanwhile, PCMA is appealing to the U.S. Supreme Court a decision by the U.S. Federal Court of Appeals for the First Circuit last November to uphold the Maine law. Their petition for review will be submitted by April 10, Blando said. The group also is waiting for the U.S. District Court for the District of Columbia to decide whether the Washington, D.C., law represents an illegal taking of PBM trade secrets and represents improper state regulation of areas -- such as the Employee Retirement Income Security Act of 1974 -- which are under the purview of the federal government. -- Stephen Langel Release date: March 23, 2006 LOAD-DATE: March 22, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2006 Washington Business Information, Inc. All Rights Reserved 409 of 998 DOCUMENTS FDA Advisory Committee Meetings No license is granted to the user of this material other than for research. User may not reproduce or redistribute the material except for user's personal or internal use and, in such case, only one copy may be printed, nor shall user use any material for commercial purposes or in any fashion that may infringe upon Data Licensing, LLC's copyright or other proprietary rights or interests in the material.; provided, however, that members of the news media may redistribute limited portions (less than 250 words) of this material without a specific license from Data Licensing, LLC, so long as they provide conspicuous attribution to Data Licensing as the originator and copyright holder of such material. This is not a legal transcript for purposes of litigation. March 23, 2006 Thursday FDA ADVISORY COMMITTEE DISCUSSES NEW ADHD DRUG APPLICATION PROVIGIL SECTION: FDA ADVISORY COMMITTEE MEETING LENGTH: 53395 words DATELINE: GAITHERSBURG, MARYLAND FOOD AND DRUG ADMINISTRATION PSYCHOPHARMACOLOGIC DRUGS ADVISORY COMMITTEE DISCUSSES NEW ADHD DRUG APPLICATION PROVIGIL MARCH 23, 2006 SPEAKERS: PSYCHOPHARMACOLOGIC DRUGS ADVISORY COMMITTEE: WAYNE K. GOODMAN, M.D., CHAIR CICELY REESE, PHARM.D., EXECUTIVE SECRETARY JORGE ARMENTEROS, M.D. JEAN BRONSTEIN, R.N., M.S. ANDREW C. LEON, M.D. DANIEL S. PINE, M.D. DELBERT ROBINSON, M.D. PHILIP WANG, M.D., DR.P.H. BARBARA WELLS, PHARM.D. TEMPORARY VOTING MEMBERS: MICHAEL BIGBY, M.D. DEBORAH DOKKEN, MPA RICHARD MALONE, M.D. CYNTHIA PFEFFER, M.D. MARSHA RAPPLEY, M.D. NON-VOTING MEMBER: DILIP MEHTA, M.D., PH.D. FDA PARTICIPANTS: ROBERT TEMPLE, M.D. THOMAS P. LAUGHREN, M.D. PAUL J. ANDREASON, M.D. GLENN MANNHEIM, M.D. SPONSOR REPRESENTATIVES: VICTOR RACZKOWSKI, M.D. JOSEPH BIEDERMAN, M.D. SRDJAN STANKOVIC, M.D. LESLEY RUSSELL, M.R.C.P. [*] GOODMAN: We expect a few more people to join us around the table but I want to make sure that we start on time. Welcome, everyone, to the Psychopharmacologic Drugs Advisory Committee, or the PDAC. We have been asked today by the FDA to advise them on a new drug application for modafinil in the treatment of attention deficit hyperactivity disorder, ADHD. Most of the questions, as will be articulated by the FDA, concern safety issues. Yesterday there was a meeting of the Pediatric Advisory Committee which discussed a range of safety issues concerning medications used in the treatment of ADHD, the stimulants as well as Strattera, and actually some data emerged on modafinil as well during those discussions. I was present as an observer during those meetings. I am glad I was there. Some of the members of the committee that are here today were also present yesterday so I think a lot of heavy lifting was done yesterday on some of these important side effect issues that will help inform us in our deliberations today. My remarks are going to be unusually brief, in part because my voice is strained. My voice has not been cooperating for the last few days. In fact, sometimes I am not sure it is my voice -- I don't know what kind of symptom that would mean. But we have a backup plan. Danny Pine, when he comes here, in case my voice fails, he will become my voice. I also want to put you on notice that Cicely Reese may deliver at any moment! I am not kidding! So, we have plans for her transportation and replacement should that occur. Please bear with us under these circumstances. Now I would just like to go around the table and ask everyone to introduce themselves. Let's start from the FDA end. LAUGHREN: Tom Laughren, from the Division of Psychiatry Products. ANDREASON: Paul Andreason, Division of Psychiatry Products. MANNHEIM: Glenn Mannheim, Division of Psychiatry Products. BIGBY: I am Michael Bigby, dermatologist from Boston. RAPPLEY: Marsha Rappley, Developmental Behavior Pediatrics, Michigan State University. WANG: Phil Wang, psychiatrist and epidemiologist from Harvard Medical School. REESE: Cicely Reese, executive secretary. GOODMAN: Wayne Goodman, chair of this committee as well as chair of the Department of Psychiatry, University of Florida. LEON: I am Andrew Leon, professor of biostatistics at Cornell Medical School. ROBINSON: I am Delbert Robinson. I am a psychiatrist at the Zucker Hillside Hospital and the Albert Einstein College of Medicine. PFEFFER: I am Cynthia Pfeffer, child and adolescent psychiatrist at Weill Medical College of Cornell University. ARMENTEROS: Jorge Armenteros, child and adolescent psychiatrist in Miami, Florida. WELLS: Barbara Wells, I am dean of the School of Pharmacy at the University of Mississippi. DOKKEN: I am Deborah Dokken. I am the patient family rep. on the Pediatric Advisory Committee. MALONE: I am Richard Malone, a child psychiatrist from Drexel University College of Medicine. MEHTA: Dilip Mehta, retired physician from the drug industry. I am the industry representative on the committee. GOODMAN: Thank you all very much. I think Daniel Pine will be joining us shortly. I would now like to turn the microphone over to Cicely Reese to go over some housekeeping, particularly the conflict of interest statements. REESE: The following announcement addresses the issue of conflict of interest and is made part of the record to preclude even the appearance of such at this meeting. Based on the submitted agenda and all financial interests reported by the committee's participants, it has been determined that all interests in firms regulated by the Center for Drug Evaluation and Research present no potential for an appearance of a conflict of interest at this meeting with the following exceptions: In accordance with 18 USC, Section 208(b)(3), Dr. Wayne Goodman has been granted a full waiver for his employer's related contract with a competitor, funded between $100,001 and $300,000 per year. His employer also has related contracts with another competitor, funded for less than $100,001 per year. Dr. Andrew Leon has been granted a waiver under 21 USC, 355(n)(4) for his ownership of stock in a competitor. This stock is valued from $5,001 to $25,000. A copy of the waiver statements may be obtained by submitting a written request to the agency's Freedom of Information Office, Room 12A-30 of the Parklawn Building. We would also like to note that Dr. Dilip Mehta has been invited to participate as an industry representative, acting on behalf of regulated industry. Dr. Mehta's role on this committee is to represent industry interests in general and not any one particular company. Dr. Mehta is retired from Pfizer. In the event that the discussions involve any other products or firms not already on the agenda for which the FDA participant has a financial interest, the participants are aware of the need to exclude themselves from such involvement and their exclusion will be noted for the record. With respect to all other participants, we ask in the interest of fairness that they address any current or previous financial involvement with any firms whose products they wish to comment upon. Thank you. GOODMAN: Dr. Daniel Pine just joined us so I wonder if you could introduce yourself. PINE: Danny Pine, Chief of Developmental Studies, Mood and Anxiety Disorders Program, National Institute of Mental Health Intramural Research Program and I am a child and adolescent psychiatrist. GOODMAN: In a moment I will turn over the floor to Dr. Laughren who will give us the introductory remarks. I think for all of us who have read through these briefing materials one of the issues that emerges, that didn't surface during yesterday's discussions, are questions about dermatological reactions. I see that we will also have the benefit of an intensive review of those issues as well to help us in our decision-making today. So, Tom, would you please come forward? Thank you. LAUGHREN: I would like to welcome everyone to today's meeting. Before I introduce the topics for today's meeting I would like to acknowledge the service of one of your colleagues on this committee whose term is ending in June, and that colleague is Wayne Goodman. This has been a particularly busy time for the committee, as you know, and Wayne has, of course, been the chair of the committee for much of this time. Serving on this committee, again as all of you know, is a very demanding and sometimes stressful task and I hope that you all understand how much we appreciate the help that you give us. Now, Wayne told me after the September, 2004 meeting on antidepressants and suicidality in pediatric patients that he didn't have any friends anymore in the academic and clinical community. I just want to assure him that he always has friends here, at FDA. (LAUGHTER) So, thank you, Wayne. This is a small token of our appreciation. GOODMAN: Thank you very much. I used to have a voice before I started this! (APPLAUSE) LAUGHREN: Now, on to the topic for today's meeting, we are going to focus on NDA 20-717, supplement 19. This is for modafinil in the treatment of attention deficit hyperactivity disorder. As you know, modafinil is marketed as Provigil to improve wakefulness in adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnea syndrome and shift work sleep disorder. It is a Schedule IV drug and the recommended dose in these disorders in adults is 200 mg. Now, Cephalon has provided us data in support of a claim for the safety and the short-term effectiveness of modafinil in the treatment of ADHD at a slightly higher dose, at a dose of 340 mg per day in children less than 30 kg and 425 mg per day in children greater than 30 kg. This supplement was submitted in December of 2004 and, as you know, we issued an approvable letter in October of last year. Though we did issue an approvable letter, the letter addressed three concerns that we wanted to have further addressed. One of those was serious skin rashes; a second was psychiatric adverse events; and, finally, there were three patients with transaminase elevations for which we wanted additional data. The sponsor responded to our approvable letter, in November of last year, and today you will hear from several FDA staff. You will hear from the primary reviewer, Glenn Mannheim who, as you know having seen his review, has recommended against approving this drug based on his concerns about rash and several other adverse events. You will also hear from Dr. Paul Andreason who will provide some additional comments on safety. Our presentations are going to focus entirely on the safety issues because we agree with the company on efficacy. But you will hear from the company on efficacy and, as well, you also have our reviews. In addition, we have obtained advice on the dermatologic problems from our own internal consultants from Dermatology. You have their reviews, and Dr. Markham Luke, from the Dermatology Division, is here to address any questions you might have. In addition, we have Dr. Michael Bigby, who is the chair of the Dermatology Advisory Committee, who will be making a presentation on serious drug-related rashes and he will be participating in the discussion as well. Now, I want to be clear that the Division of Psychiatry Products has not reached a conclusion yet about this application. We have these concerns and that is precisely why we are coming to you to ask for your advice. After you have heard the findings and the arguments we are going to ask you to vote on two questions. The first question is focusing on efficacy questions, whether or not you believe that the company has demonstrated that this product is effective in the treatment of ADHD. Secondly, we will ask you to vote on the question of whether or not it has been shown to be acceptably safe in the treatment of this disorder. In addition, we are going to be asking for your comments on several other issues related mostly to rash. First of all, if the drug were to be approved for this indication we would like your advice on a risk management plan. We would like your advice on labeling, particularly for rash. Finally, we would like your advice on any postmarketing studies that you think might be useful to further clarify this problem. I think I will stop there and Dr. Mannheim will be presenting his findings. Thank you. MANNHEIM: As Dr. Laughren explained, I reviewed the initial submission for modafinil for this indication. I will review with you today the information specific to safety. Here is an outline of what I will be covering. I will be reviewing a little bit of the background and history of modafinil; an overview of the safety database; common adverse events in Cephalon's clinical trial; other adverse events of significance; psychiatric adverse events; and, most importantly, rashes and what I think the potential public health impact may be. Then I will give you some closing comments, and I will be followed by Dr. Andreason. In 1998 modafinil was approved as a wakefulness-promoting agent in adults with excessive daytime sleepiness associated with narcolepsy. Additional indications were granted by FDA in 2003 for excessive daytime sleepiness associated with obstructive sleep apnea/hypopnea syndrome and shift work sleep disorder. The important thing that I would like you to notice from this slide is the dose. The recommended dosing was 200 mg once a day which, based on a 65 kg adult, comes to about 2.67 or 2.7 mg/kg. I want you to remember those numbers since we will come to it in other slides. Recommendations were to give modafinil, Provigil, as a single morning dose for narcolepsy or obstructive sleep apnea or for shift work sleep disorder one hour prior to the start of the work shift. No additional benefit was shown for doses more than 200 mg. The current application is for use of modafinil in children and adolescents with ADHD. Two doses have been proposed by Cephalon. For children less than 65 lbs or 30 kg, they would be getting a single daily dose of 340 mg. For children or adolescents more than 65 lbs or 30 kg, they would be getting a dose of 425 mg a day. Now, remember the number 2.6. For the highest dose in children, on a milligram/kilogram basis, the children would be getting 21 mg/kg or about 8 times higher than the adult dose. For those over 65 lbs or 30 kg the highest dose would be 5.3 times higher than the adult dose. Cephalon is recommending that children or adolescents start the drug at initial doses of 85 mg and slowly titrate up, based on tolerability, by incremental steps of 85 mg to the targeted dose of 340 mg or 425 mg a day. This shows the population which was studied in the submission. It was children and adolescents 6-17 years of age with DSM-IV ADHD who attended a full-time school. These were moderately to severely ill children. They had minimal learning difficulties. As it relates to adverse events, children with psychiatric comorbidities were excluded. Stimulant non-responders were not allowed in the trial. Those with abnormal laboratory or medical conditions one month prior to the start of the study were also excluded. There are three studies which are called the pivotal studies for this. Study 309 and 311 were 2 9-week, double-blind, flexible dose, weekly titration studies. Study 310 was a 7-week, double-blind, fixed dose study, followed by a 2-week randomized withdrawal to modafinil or placebo. Children less than 65 lbs went on 340 mg a day and those over 65 lbs went on 425 mg a day. This slide shows the total number of subjects and doses used in the Phase 3 double-blind, placebo-controlled trial. Of note, 420 subjects were treated with modafinil and 213 subjects were treated with placebo. The important thing to note here is the numbers 102, 256 or 358. Children and adolescents only received the proposed labeled efficacious doses. This slide comes from Cephalon's briefing document which was submitted for your consideration by Cephalon. It summarizes the pediatric trials. The 420 comes from the Phase 3 double-blind exposure. The number I want to show here is the number 933 because this constitutes the core safety database of this supplemental NDA. This slide indicates that additional 303 children were exposed to modafinil in an open-label ongoing Phase 3 trial. About 400 other children for obstructive sleep apnea and narcolepsy are the legacy studies. As far as the purposes of this submission, we are only considering the number 933 since we don't have an integrated safety database for the other 689 children and they were not part of this submission. It certainly would be reassuring if there were no adverse events in these subjects but we really don't know at this point. This slide is a little busy and I apologize for that. It shows exposure to modafinil and modafinil metabolites and compares it with what one sees in clinically used doses in adults with those proposed for children. What I want to bring your attention to is the exposure of the modafinil sulfone as measured by the total exposure area under the curve. In adults, with an initial dose of 200 mg, the average area under the curve is 38 or close to 40. Going to the highest child, receiving 425 mg, the area under the curve of the sulfone is about 250. This is 6.5 times higher than the exposure seen in adults. Going to the lowest dose of children receiving 340 mg, the average area under the curve is around 630. This is 16 times higher than that seen in adults with clinical dosing. This cannot be explained by differences in dosing on a milligram/kilogram basis. These are clinically used doses and with them one sees that the sulfone metabolite is much higher compared to adults. Now we are going to look at the adverse event data. The incidence of common treatment-emergent adverse events in the Phase 3 double-blind, placebo-controlled trial is listed. Of note, insomnia occurred in 27 percent of subjects on modafinil and 4 percent of subjects on placebo. Anorexia occurred in 16 percent of subjects on modafinil and 3 percent of subjects on placebo. Perhaps associated with that, there was weight loss in 4 percent of subjects on modafinil and 1 percent of subjects on placebo. Notable psychiatric adverse events include psychosis in 0.5 percent, as listed here, and suicidal events in 6 subjects, 0.6 percent. The suicidal events included 5 ideations; 1 attempt. None were completed. Yesterday Dr. Mosholder reported on a pooled analysis of the ADHD trials and that suicidal behavior was infrequent among the non-medicated ADHD placebo subjects. Other clinically significant adverse events which were noted in this trial consisted of gastric or duodenal ulcers in 2 subjects. One case of note was a child who was admitted to the hospital with a moderate metabolic acidosis who had an H. pylori infection. There were 9 cases of syncope in the total exposure. Of note is a child who, according to the vignette information, had a 40-minute bradycardia, hypotensive syncopal episode and one week later an EKG was performed which showed AV dissociation with adjunctional rhythm. There were 24 children who were quoted as having asthma. Of note is a subject in one of the pivotal trials, 310, who, 8 days after being started on modafinil at a dose of 340 mg collapsed at school during gym, stopped breathing momentarily and was given an inhaler and began breathing normally. This was diagnosed as an acute asthma attack and the child was discontinued from the study on day 9. There were 3 subjects who had dehydration, and of note is a subject in the open-label continuation trial who, on day 147 of treatment, was admitted to hospital with severe dehydration, moderate ketoacidosis and hypoglycemia which was found secondary to a strep. throat. Sixteen subjects had laboratory evidence of hepatocellular injury based on transaminases being greater than 3 times the upper limit of normal. Of note, there were no cases of jaundice or liver failure, or no significant bilirubin elevations. Now I am going to talk to you about the rashes but I am not a dermatologist and I am relying on FDA's dermatologist, Dr. Porres who did a consult, and someone from FDA from Dermatology is here to answer some questions. When you look at all the subjects who were exposed, rashes were present in 5 percent of all subjects compared to 4 percent that you saw in the Phase 3 double-blind, placebo-controlled trial versus 2 percent in placebo. Only 1 subject dropped out in the double-blind, placebo- controlled Phase 3 trial, which was an 8-week, study, because of a rash. When you look at all the studies, including the open-label safety study, 101 subjects dropped out because of an adverse event, of which 26 percent were noted to have a rash in their vignettes although it may not have been coded as a reason for discontinuation. In one-half of these subjects, or 13 subjects, the rash was coded as a primary reason for discontinuation. The rashes varied in spectrum of severity. Eight with rash also had fever; 2 with rash had elevated liver function tests, one with a transaminase of 17 times the upper limit of normal. I am now going to discuss some of the serious skin rashes, primarily the erythema multiforme, Stevens-Johnson which, from my standing as a pediatric neurologist are usually hypersensitivity reactions to drugs. There were 2 rashes which were thought to be erythema multiforme, Stevens-Johnson. One subject had peeling and blistering over the entire body, with lips and urinary tract involvement, in study 311. The drug was stopped but the rash progressed to involve peeling, blistering, mucosal involvement over days. In another subject in study 207 the drug was stopped but the rash progressed. The child was hospitalized. Other rashes of note included a child in study 207 with vesiculobullous cheeks with severe lip blisters. In study 312 another subject had a rash where there is no clear description but the rash was obviously severe enough that he was treated with systemic steroids, prednisone and given Benadryl. The rash recurred when restarted at 85 mg on day 34. There are two cases of positive, you know, rechallenge. Other skin reactions of note -- there were possible allergic events in about 22 of the subjects out of the total exposure of 933 subjects, at 2.4 percent. They included hives, urticaria; facial edema; pruritus; allergic reactions; red lips; eczema with increased LFTs. There were some non-allergic events of alopecia, tongue blotches, Herpes zoster, plantar warts and ringworm. Now I would like to give some more details about the index cases here. Case number one was a young girl with an unremarkable medical history who had attention deficit disorder. She was started and then titrated over 2 weeks to a target dose of either 340 mg or 425 mg a day, but it differs in 2 different vignettes. Two days later, on day 16, the child developed a fever of almost 102, sore throat, mild rash which was described as red bumps. The next day the child was seen in the emergency room. My understanding is they thought the child had strep. throat and they gave one dose of amoxicillin which was subsequently stopped. The next day, day 18, the modafinil was stopped. Over the next 4 days the rash worsened and progressed. There were multiple pruritic areas over the arms and stomach. On day 22 the rash progressed to involve the face. On day 23 mucosal involvement was said to be present in 2 areas. It burned when the child urinated so there was involvement of the urethra. The child had swollen and crusty lips. At some time later -- the exact course is uncertain from the vignettes -- there was extensive skin peeling involving the palms and soles. No new lesions were said to be present by day 30 and the event was said to be resolved. By day 31 or day 26 -- it differs in 2 vignettes -- the child was given 1 more dose of modafinil by the mother for unclear reasons and the itching returned. On day 44 the child was withdrawn from the study and the vignette indicates the Stevens-Johnson syndrome resolved but the erythema multiforme continued. This case involves a young child with inattentive deficit disorder who also had Turner's syndrome and bed-wetting, who was on somatotropin for the Turner syndrome for 7.5 years prior and desmopressin for the bed-wetting for 4 months prior. She was started, titrated on modafinil 200 mg a day for week 1 of the study and then 100 mg a day for week 2 of the study. By day 4 she developed fever, abdominal pain and diarrhea. This lasted for 9 days. By day 14 the child was seen in the emergency room for pruritic urticaria involving the face and chest. The drug was stopped. The child was treated with diphenhydramine. The rash worsened by day 15. The child was then hospitalized with a provisional diagnosis of Stevens-Johnson. The child was seen by a dermatologist who found no evidence of mucosal involvement but was diagnosed as a moderate morbilliform rash. The child was treated with hydroxyzine. This rash resolved in 1 week. This case was accepted by Cephalon as being compatible with Stevens- Johnson syndrome. Another subject of note is a young boy who was started on modafinil at 400 mg a day for 2.5 weeks, and on day 14 developed fever and a moderate rash on the cheeks. The rash progressed. By day 17 there was severe blistering on the lips. The rash was described as vesiculobullous. On day 19 the modafinil was stopped. The time course of everything else was not specified in the vignette and no more information is available. The child was treated with cephalexin for the rash and Tylenol with codeine for fever and pain. Dr. Porres, of the Division of Dermatology at FDA, reviewed the 21 cases identified in my initial review and the entire safety database of this submission. He divided the cases into three categories, definite cases representing erythema multiforme, Stevens- Johnson. There are 2 subjects there or 0.2 percent; subjects who had a history consistent with early prodromal erythema multiforme and Stevens-Johnson, there were 3 subjects, 0.32 percent; and then there were 7 additional subjects who had a history suggestive of prodromal erythema multiforme, Stevens-Johnson. So, 10 more subjects plus the 2 subjects, or 12 subjects, so this is a total of 1.25 percent of subjects with definite and potential erythema multiforme, Stevens-Johnson. When one looks at the postmarketing experience with modafinil, there were 6 reports of serious skin reactions. All occurred in adults 18 and over. There were 5 biopsy confirmed cases of erythema multiforme, Stevens-Johnson. Four were hospitalized and 1 died, but this case was really confounded by other medications and medical conditions. There was 1 dermatitis bullous. Because of the under-reporting, the true number of cases is probably likely to be greater. But the take-home message that I would like to say is that this slide shows that biopsy confirmed Stevens- Johnson syndrome occurred in adults at lower exposures than those received by children. Erythema multiforme or Stevens-Johnson syndrome is generally thought to be hypersensitivity reactions to drugs. One of the cases which was really interesting involved a child who developed urticaria, facial edema, fever and a 17-fold elevation in transaminase between 10-14 days after starting the drug. The child had a history of allergy to sulfamethoxazole trimethoprim. Sulfamethoxazole is a sulfonamide and is one of the drugs known to cause Stevens-Johnson. It is structurally similar to modafinil sulfone, which raises the question of a possible cross-sensitivity to the sulfone metabolite. What is the potential public health impact of these findings? Two recent estimates of the background rate for erythema multiforme, Stevens-Johnson was 1-2/million/year. In this submission there were 2 subjects with erythema multiforme and 10 other possible cases of a significant rash. The total range of risk is anywhere between 0.2 percent to 1.3 percent. A recent CDC study estimated that 2.5 million children, ages 4- 17, were on ADHD medication. Now, if we assume that only 10 percent of these children will try modafinil at some point, then we ask the next question, how many cases would result. We estimated that there would be a range between 500 and 3,000 cases which will occur based on the 0.2 percent to the 1.3 percent incidence among the 10 percent who are switched to modafinil. Based on the known mortality associated with erythema multiforme, Stevens-Johnson, we would expect from 15 to over 400 deaths to occur. We conclude that even though a crude estimate can only be made at this time, a potential exists for a significant number of cases to occur post-approval since ADHD is so prevalent. The question is can one label for this? Can we prevent this? Dr. Le Grenade and her co-authors at FDA recently published a paper on Stevens-Johnson syndrome and toxic epidermal necrolysis in association with selective COX-2 inhibitors. I quote from her and I italicized certain areas: There is no satisfactory method for determining who is at greatest risk for developing drug-associated Stevens-Johnson syndrome and toxic epidermal necrolysis and hence of preventing it, short of avoiding drugs altogether. There has been a single study suggesting that early withdrawal of the agent at the first sign of illness may improve the outcome. Although this intuitively makes sense, this study needs to be replicated. Even if it is proven correct, its practical application will be limited because it is very difficult to identify the very earliest lesion in a timely manner because of the rapidly progressive nature of this illness and the non-specific features of its prodrome. In the cases observed with modafinil in this submission in children no deaths occurred. The rash progressed after the drug was stopped and the children recovered. It may not be so next time. ADHD is a serious condition -- I will give you closing comments -- it is a serious condition which is usually not considered to be associated with a fatal outcome. Exposure to a sulfone metabolite is significantly greater, up to 16 times more in children than in adults. This raises questions about the relevancy of the adult safety experiences to pediatric use. The relationship of this metabolite to rash is purely speculative but it has structural similarities to drugs known to cause erythema multiforme and Stevens-Johnson syndrome which can be fatal. The incidence of erythema multiforme, Stevens-Johnson syndrome observed in these studies is, at a minimum, hundreds of times the background. The age ranges of the rashes appear skewed towards subjects less than 12 years, those having a higher sulfone exposure. Doses lower than 340 mg have been shown to limit efficacy, hence, dose reduction is not a reliable option. Although some cases with rash got better, there were 2 positive rechallenges and one case progressed after discontinuing the drug. One subject with rash was hospitalized but there was disagreement about the diagnosis. One child with a history of reactions to sulfa drugs developed a hypersensitivity reaction with transaminase elevation 17 times the upper limit of normal, with urticaria, fever and facial edema 10 days after starting modafinil, which raises the hypothesis of cross- sensitivity with sulfa drugs. Psychosis and suicidality, although not standardly significant, were more frequent in subjects on modafinil than with placebo. Insomnia was present in 27 percent of subjects on modafinil versus 4 percent in placebo, and anorexia occurred in 16 percent of subjects on modafinil versus 3 percent on placebo in the double-blind, Phase 3 trials. This review was very much a team effort of my many colleagues at FDA, some of whom I am blessed to call my friends. Thank you. GOODMAN: Before you step down, could you review any cardiovascular effects, effects on heart rate and blood pressure? MANNHEIM: Dr. Andreason is going to do that. ANDREASON: Good morning. My name is Paul Andreason and I am the Acting Deputy Director of the Division of Psychiatry Products. I would like to talk to you this morning about modafinil in the treatment of ADHD. Dr. Mannheim has outlined the concerns that he has about modafinil in the treatment of ADHD, and I think what we are faced with as we look especially at the skin rashes is what I like to call incongruity of data. I will get into that in a little bit. I would also like to acknowledge the Neurology Products Division where the drug resides -- it is kind of its home since it was approved there first -- and the safety team for helping us out with the background rates for Stevens-Johnson and looking at the adverse event reports through the Adverse Event Reporting System and their epidemiologic expertise. Glenn did the primary review on the first submission. June Cai helped out with the review of the response to the approval letter. In the Division of Dermatology, I would like to thank Joe Porres and Markham Luke, who is here with us today -- Markham is here with us today. Joe took another job and he is not with the Division of Dermatology right now. Then, in the Division of Drug Risk Evaluation, I would like to thank Andy Mosholder and Kate Gelperin who, as part of their presentation yesterday, did an analysis of the psychiatric adverse events that are associated with modafinil use. Just as a quick review of how we workup safety problems with drugs or safety profiles of drugs, I should say, when we look at a drug we look at deaths, serious adverse events, adverse dropouts, potentially clinically significant labs, ECG and vital signs and then we develop information on comparative common and drug-related adverse events, all these things from controlled trials. We also do special searches, especially in this case with modafinil and many psychiatric drugs -- well, all psychiatric drugs, for psychiatric adverse events; in this case, for Stevens-Johnson syndrome and neutropenia because these were things that kind of popped up; and then the recent interest in blood pressure, pulse and cardiovascular adverse events. Then with the response to the approvable letter we get a safety update. In that safety update we focus on serious adverse events and deaths, if they occur. We develop our profile of the common and drug- related adverse events from the controlled trial data, as well as the comparative information on labs, ECGs and vital signs. Modafinil is a marketed product and we got some information from Verispan about the exposure to modafinil at this point. These are numbers not in patient-years but in unique patients. At all ages at this point between the years 2002 to 2005 there were 1,087,000, roughly 1,088,000 exposures in all ages, and for children ages 0-17 there were roughly 36,000 exposures. I kind of want you to keep that in mind because this is the first piece of what I would call inconsistent data about rash. It is almost unheard of to see cases of Stevens-Johnson syndrome in controlled trial data and here we have at least nominally 2 cases that have been identified as such. At that kind of a rate you would expect to see something in the adverse event reporting data. Dr. Mannheim said, well, based on these numbers, these would be the projected number of cases that we would see after marketing. The piece of incongruity here is that the drug is already marketed. We have 36,000 exposures in the age ranges that were studied, and in the 0-12 group right around 11,000 and we have no AERS-reported cases. Now, one of the cases from the controlled trial data actually is a duplicate case. It got reported in AERS but there are no spontaneous reported cases. So, given that kind of projection, I would expect to see some cases reported in AERS and we haven't seen that yet. This is, again, a review of patient exposure in the controlled trial database. In the safety update we did get some information on serious adverse events and dropouts, as well as deaths, and Stevens- Johnson syndrome would be considered in that group. So, as more and more information comes in, you know, that denominator of cases reported per amount of exposure changes, however, even with 2 cases in 1,600 that would still be a large number. I think the problem that comes about when we look at Stevens- Johnson -- and we will hear more from Dr. Bigby in a moment about how that ascertainment is made -- is that in these two cases one was hospitalized and one was not. Neither of them were in a burn unit or the ICU and we don't have biopsy information on those kids. These are tables that you have already seen. It reviews the numbers of patients exposed in the three pivotal trials. Now, this is a table that shows you the common adverse event profile. Our usual definition of common and drug-related is adverse events that occur at least 5 percent of the time and occur at a rate that is twice placebo. In italics you will see that anorexia and insomnia meet that criteria. There are a couple of other adverse events that are close but don't quite make that cutoff. This is the table actually that is proposed in labeling and is the usual kind of table that we have in labeling. Just as a quick overview of the safety results from the controlled trials, there were no deaths and, of the adverse events of note, there were these 2 cases that were identified as either Stevens- Johnson or erythema multiforme. There were no new cases of leukopenia in the AERS system update, and we could see no real signal for leukopenia in the controlled trial data. As far as psychiatric events, there were 4 suicide-related adverse events, no completed suicides. I will talk more about those in a moment. There were none in the placebo group. As far as mean blood pressure changes, modafinil actually showed a slight decrease compared to placebo in mean blood pressure. However, the numbers of patients that met the outlier criteria of systolic blood pressure of greater than 130 and an increase in greater than 20 mmHg were 9/420 for modafinil and 1/213. With pulse there was no difference in the mean value either, and the numbers for outliers are 6/420 versus 2/213. The 6 versus 2 in those 2 groups is, in my opinion, not terribly different. There was some weight loss, 0.7 kg weight loss with modafinil versus 1.0 kg mean weight gain in the placebo group. So, did that answer your question about blood pressure? GOODMAN: Yes. ANDREASON: Great! As far as psychiatric adverse events, this is drawn from one of Andy Mosholder's slides from yesterday. These were the comparative numbers with patient-year exposure, and these are real years. They are not multiplied. So, with 33 patient-years exposure in placebo you have no cases of mania or psychosis or suicide-related adverse events. But there were 5 cases of aggression, spontaneously reported aggression. Zero cells are kind of tough to deal with when you are doing statistical analysis, but oftentimes you can use a Fisher's exact test to get at least some idea of whether or not something is statistically significant. I will show you that for the suicide-related adverse events on the next slide. You will notice that numerically the cases of aggression are slightly less with modafinil than they are with placebo. As Dr. Mosholder stated yesterday, that was not a significant difference but it is not, by the same token, greater. In the open-label data it shows that the rates are lower. That doesn't necessarily mean -- well, let me put it this way, these are patients, once they reach open-label, who have tolerated the drug and I think that probably the best comparison for this is the controlled trial data. These are the results of the Fisher's exact test for suicide- related adverse events. You see here that you have the 4 cases in the modafinil and that is compared to no suicide-related adverse events in the 660 in placebo. So, that ends up with a 2-tail value of p of 0.31 and 1-tailed p of 0.22. Just to give you kind of a comparison with, say, Strattera that has received labeling for suicide-related adverse events, with Strattera there were 6/1357 versus 0/851. Because of the increased sample size, those numbers ended up being statistically significant. There were 5 cases of ideation and 1 attempt in the FDA defined cases. I would like to note that Eli Lilly has slightly different numbers because they had a slightly different definition of the suicide-related adverse events. They had 7 versus 1 out of 1357 and 851 respectively. That p value ended up being 0.07. Traditionally, for safety-related topics we don't necessarily use a p of 0.05 like we do for efficacy. We use a p of 0.1. So, using a cutoff of a p of 0.1, the 0.7 would still be statistically significant. And, Strattera has a boxed warning. Now, with the modafinil there are 4/664 versus 0/308. This is not statistically significant by Fisher's exact and all were cases of ideation and 3 of the cases actually resolved without discontinuation of the drug. The sponsor proposes warning language in labeling as opposed to boxed language. As far as the cases of severe rash that are identified as Stevens-Johnson syndrome, we will hear more about that, again, from Dr. Bigby, and Dr. Markham Luke is here today to talk about the cases individually if people have questions on those. The problem that we have with almost any adverse event report ascertainment, there was no histopathology with either of these cases. With Stevens-Johnson syndrome admission to burn units and ICUs is common. One of the kids was hospitalized but not in an ICU or burn unit. The other child was treated as an outpatient. You have heard about the cases. I can go back to those if anyone has any questions. Again, there were no children in the postmarketing Adverse Event Reporting System, other than the one case that is the duplicate from the controlled trial. There were 4 adults in the AERS postmarketing database, and it turned out that 3 had confirmatory histopathology and the other one was erythema multiforme without histopathology. There were no adults with Stevens-Johnson identified in the adult controlled trial database. So, what we are left with from this controlled trial database, along with the open-label material that goes with it, is 2 serious cases, one admitted to the hospital, neither to the ICU or burn unit; none in the placebo group; 10 dropouts due to rash versus no dropouts due to rash in the placebo group. Spontaneous adverse events in the controlled trial, about 4 percent for modafinil versus 1 percent for rash, for all kinds of rash. But then, the incongruity here is that there are no other children with either Stevens-Johnson syndrome in the postmarketing adverse event database with about 36,000 kids exposed. Again, with that kind of exposure and the projected numbers of cases of SJS, based on 2/933 or even 2/1,600, one would expect to see more in the Adverse Event Reporting System. So, just to compare and contrast labeling with Lamictal that carries a boxed warning for Stevens-Johnson syndrome, in that boxed warning there are some fairly hard numbers. For example, they did a prospective registry study and there was one death due to Stevens- Johnson syndrome with Lamictal out of 1983 patients. There was also information on rates in adults with different kinds of diagnoses, for example, 8/1000 in children with Lennox Gasteau and 3/1000 adults. Then in the bipolar population it was 1.3/1000 adults on adjunctive therapy for bipolar disorder. So, those are some fairly hard numbers. On the modafinil side, the sponsor proposes warning language and I have listed under here the points to compare and contrast with Lamictal. There are no deaths reported. Actually, on one of the slides that Dr. Mannheim presented, he said there was one death. That case was a fellow who came in to the hospital and had a subarachnoid hemorrhage and was treated with several drugs, one of which was phenytoin, known to be associated with Stevens-Johnson syndrome. He developed Stevens-Johnson syndrome as part of the course of his hospitalization and apparently was treated with modafinil prior to that hospitalization. So, I think that case is terribly confounded and I wouldn't count that as drug related, or I don't think we could count that one as a good drug-related case. So, based on my exclusion of that case, there would be no deaths so far due to Stevens-Johnson. The child cases were not severe enough to require burn unit or ICU. Now, again back to this, there are at least 2 nominally identified cases out of the 933 in the submission that were identified but there is no biopsy confirmation. Back to the other part of the incongruity, there are 36,000 exposures already with no cases. Then back to the other side, you have 3 confirmed cases of adult SJS in the postmarketing but that is with 1.5 million. So, that is getting close to the background. Depending on how you factor in under-reporting, you know, there could be association and increased risk for Stevens-Johnson. So, I guess in the end the question that you need to think about is if there is an increased risk of Stevens-Johnson syndrome associated with modafinil, what would be an acceptable risk. And, if modafinil were considered for approval, what kind of risk management program would you want to implement, and how should the concern about serious skin rashes be addressed in product labeling. Again, you have the examples of labeling and I can go over those a little more if you would like. And, should there be a requirement for postmarketing studies, if approved, to better understand the skin rashes? There was one slide, as a bit of a digression that Dr. Mannheim showed about liver enzymes, he included GGT in a slide, along with ALT and AST as a percentage of increased liver enzymes under the heading of hepatocellular injury. Usually we look at ALT, AST and bilirubin as signs of hepatocellular injury and don't necessarily include GGT. Excluding GGT, there were 3/420 cases of elevation of ALT and AST of greater than 3 times the upper limit of normal, for a percentage of 0.7. In placebo there was 1/213, for a percentage of 0.5, and I don't see that as meaningfully different. So, that concludes my remarks about modafinil and I would be happy to entertain any questions. GOODMAN: Thank you. I understand there is going to be a change of technology before the next presentation. Is that correct? Yes? So, why don't we start doing that but I wonder if you can stay for questions that this committee may have. Let me start that off. Of the 35,000 or so children who have been exposed to modafinil postmarketing, how many of them were on the doses that are proposed to be used in ADHD? I would suppose further that that would be mostly for Mexico where it is already approved. ANDREASON: I am not sure. By the way, those numbers are for the United States only. GOODMAN: So, if they are for the United States only let me go back and rephrase it. How many of them would be in the dose range that is proposed for ADHD? ANDREASON: Yes, we tried to track that down and found that it was impossible to get that kind of information. I think the only thing you could do would be to assume that they had received the maximum recommended dose, which was only 200. GOODMAN: We have one of our committee members that I would like to see introduce herself, Jean Bronstein. BRONSTEIN: Good morning. I am Jean Bronstein. I am a nurse and consumer representative for the committee, and I apologize for being a little late. But I do have a question. I am trying to understand some 300 patients, I believe, that have dropped out of the study, and I am wondering if the rash numbers are also representative of all patients having dropped out of the study at some point. Is that clear? ANDREASON: The patients who dropped out due to rash are included in those numbers, yes. BRONSTEIN: They are? Thank you. GOODMAN: Any other questions around the table or are we ready to proceed with the presentation? WANG: It is actually a follow-up to Wayne's question. In the negotiations for these pivotal trials how were the doses chosen? Why was, you know, 300 mg, 400 mg chosen? For the wakefulness indication it is 200 with no additional benefit. LAUGHREN: Paul, you may be able to say more about this, but my understanding is that there was a Phase 2 study, a fixed dose study that looked at different doses, I think running from 100-400, that basically showed effects only at the higher doses and that was the basis for focusing on the higher doses in the pivotal trials. ANDREASON: I am sorry, I thought you were looking at Cephalon when you asked that question. But, yes, that is correct. Two of the studies were flexible dose studies in the pivotal trials and one of them was a fixed dose study. WANG: There is no data in here to suggest something that you have raised, Dr. Mannheim, that there is no potential benefit to trying lower doses. They don't look to be, you know, sort of clinically efficacious, which these data don't suggest. MANNHEIM: My understanding from the earlier Phase 2 trials was that lower doses didn't work and they had to get to these doses in order to show efficacy in ADHD. Cephalon can respond to that. GOODMAN: Yes, maybe we can hear more about that from the sponsor during their presentation. We have Dr. Leon and then Dr. Mehta. LEON: I would like to follow-up on the number of exposed. Is that based strictly on the 7- or 9-week clinical trials out of which maybe about 40 percent dropped out? Or, does that include the follow- up as well? Is there slide on person-week exposure? ANDREASON: Oh, as far as the number of patients that are exposed for an adequate amount of time to count, I think what we came up with was as an estimate that was around 600. Again, if you say 2 cases out of 600, that makes the rate of it seem even higher. Then, it even makes it seem more implausible that we don't see anything in postmarketing. So, I think you are right, if Stevens-Johnson is something that shows up in the first 2-8 weeks of treatment the numbers in the controlled trials would be right around 600. The 900 includes patients that dropped out. It includes patients that were in Phase 2 studies -- excuse me, I take that back. The 933 includes patients that were in the open-label trials, so patients that were exposed for much longer. When we looked at postmarketing data and estimates of exposure we didn't look at patient-year exposure because we wanted to focus on the fact that Stevens-Johnson we probably likely to show up in the first 2-8 weeks and if we looked at patient-year exposure the rate of background would start to drop with extended exposure if you looked at patient years instead of unique patients. That is why we chose to look at it that way. GOODMAN: Dr. Mehta? MEHTA: Is the dose of the drug relevant to the occurrence of Stevens-Johnson syndrome? I would have thought that this is a sensitivity reaction so it doesn't matter what came out of the drug that is used, that is, the dosage is irrelevant for the occurrence of SJS. ANDREASON: You will see from the presentation coming up from the company that it didn't appear that the sulfone metabolite was increased any higher, than in other patients that didn't have rash, in the 2 patients that were identified as having rash. The expert is here to talk about that. BIGBY: Can I just make a quick comment about that? GOODMAN: Go ahead. BIGBY: It shouldn't make any difference in terms of the incidence of the rash. I think you are correct in that regard. The only way that I think it could affect the disorder is in outcome in terms of at a higher dose it will take a little bit longer to be cleared from the body so that the prognosis might be worse if you start with a higher dose because it may take longer to be eliminated. GOODMAN: Dr. Malone? MALONE: I just had a question about dosing. The stimulants are also used for daytime sleepiness disorders. Is the dose used for ADHD a lot different than the dose used for daytime sleepiness? ANDREASON: Yes, it is higher. Daytime sleepiness and obstructive sleep apnea doses are 200. Right, Glenn? Then, for ADHD it is 300 and 425. RAPPLEY: No, I think he is asking about comparing the other stimulants? So, are the doses for Adderall or Ritalin higher for ADHD than they are... ANDREASON: I am sorry, I don't have that right at the top of my head. GOODMAN: Dr. Pfeffer? PFEFFER: I have a question about the pharmacokinetics of this drug, with the dose being so much higher in children, especially younger children, how is the drug metabolized? Also, is there a way of understanding if there are children who are slower metabolizers of this drug and, therefore, this is higher? Can we understand that? Is there a way of understanding also if there are certain children that might be assessed in terms of the metabolism and understand that relative risk? ANDREASON: I can't really answer that question. I think we have somebody who can answer that question. Let me preface it by this though, I don't necessarily believe that ruling out the sulfone would be necessarily a guarantee of safety. In my opinion, I think the sulfone may be a bit of a red herring. I think with Lamictal we have no real idea why SJS occurs and it is much more common in kids than it is in adults. If they could come up with some kind of marker that would show what the risk was, that would be wonderful. I don't think in this case the sulfone reaches that kind of state. First of all, we have to identify whether or not there is a signal. Then, if one came to the conclusion that there was a signal, I still don't think that the sulfone would give us any assurance of safety regardless at this point. GOODMAN: Dr. Temple and then I want to go to Dr. Bigby's presentation. TEMPLE: I just wanted to observe that on the dose relatedness matter it is sort of unusual to have almost an order of magnitude difference between what one group gets and what the other group gets. So, a lot of our experience with drugs will be looking at, you know, one- or two-fold differences and things like that. I am not sure one really could say that a marked difference in blood levels or exposure might not be related to rate. It could. ANDREASON: Ron Cavanaugh was the human biopharmacologist on this. GOODMAN: But then definitely Dr. Bigby. CAVANAUGH: Thank you. I agree with Dr. Andreason that at this point for the sulfone we really don't know any relationship for certain. It is purely at this point a plausible hypothesis. It is very structurally similar to the one drug which causes the highest incidence of Stevens-Johnson, blethamide, which is slightly different than many of the other sulfonamides in that it has a third oxygen in addition to the nitrogen and the sulfone. Modafinil also has that third oxygen in the same position. We do not know. Basically, the only reason we looked at the sulfone was because of the dramatic higher amounts, as well as when Glenn asked me about the sulfone I immediately thought Stevens-Johnson and immediately thought sulfonamide. So, at this point we don't know. In terms of the kinetics, from what I have seen, the metabolism does not seem to be particularly well defined. So, I really do not know at this point, you know, anything in terms of could specific metabolic pathways result in higher sulfone concentrations in some kids versus others. The concentrations that I see, and it is very poor, do not lead me to believe that the sulfone concentrations in these particular children -- and there was only one child who had any measurement of the sulfone who had any of the Stevens-Johnson or other severe dermatologic reactions, and that sample was taken several days after the drug was discontinued. If I back calculate, it basically seems that for that one child the concentration was in the approximate range. In terms of dose response, which was raised, we really have too few numbers here. You are also dealing with, you know, population numbers and you are dealing with 0.1 percent difference, 0.2 percent differences. There is no way you can be certain. In terms of a dose related to hapten and degree of what is the likelihood of Stevens-Johnson or a hypersensitivity of any sort, I am not an immunologist; I do not know. One of the reasons we focused on AUC is because that gives you an idea of total exposure. When someone has already developed hypersensitivity and they have already had a history with a sulfonamide, they can get Stevens-Johnson with the very first dose of a drop, and there have been deaths in cases like that. Really we are more talking about the development of hypersensitivity, and what you are developing as it being a hapten, my understanding is that it is the combination of, you know, developing hypersensitivity to the combination of the drug bound to certain proteins, or other things in the body. So, with the higher exposure you are going to get more of this binding and, therefore, more antigenic exposure. The numbers are so small, we don't know. Also, with longer duration you would expect more stimulation. I would really refer you to an immunologist. I really don't know, but the whole issue of dose response and everything else in terms of developing hypersensitivity, to me, is not clear. GOODMAN: Thank you. Thank you for being patient, Dr. Bigby. We are running behind schedule but the way I hope we may be able to make up some time is that I am going to cut lunch and I don't think we have that many public speakers. But I am determined to end at least at our scheduled time. During the sponsor presentations I would ask the committee members to restrict their questions to ones of clarification. BIGBY: Good morning. I am always impressed when I come down to sort of work in FDA committee meetings about the seriousness of what goes on here, and also the dedication that people have to trying to make rational decisions, and I hope my comments are helpful in your deliberations. What I was going to talk about is serious adverse cutaneous reactions to drugs, and in order to do so I am going to cover three things. One is how to identify a drug eruption as a drug eruption and pin it down to a specific drug. We will look specifically at common eruptions, the serious eruptions, and I will end by showing you some things that are commonly mistaken for drug eruptions. This is sort of a gold standard for determining that a rash is due to a drug. First you have to be sure that the rash you are looking at is a morphology that can be caused by drugs. You have to exclude alternative causes. You have to examine the relationship between the exposure to the development of a rash in terms of the time interval; note the response to drug withdrawal, i.e., the rash will go away. For many drugs there is information known about their proclivity to produce rashes, so what the frequency of rash is for a particular drugs. Then, in those rare cases where you actually do have a re- exposure, to determine what happens on re-exposure so you can be positive that it is a drug rash and looks like an eruption that is a classic eruption for drugs. You have excluded alternative causes; the interval from exposure to the development of a rash is correct in terms of what is known about that drug and that eruption. It goes away. Often I think the mistake people make about the response to withdrawal is that you expect it to go away very quickly when you withdraw the drug. For most eruptions that is not the case and the rash will actually take much, much longer than most people think to go away after you withdraw the drug. Then, oddly enough, re-exposure doesn't always produce the rash but when it does, then you can be absolutely sure that you are looking at a definite cause. Where some of these things are missing, are judged to be probable or unlikely or not due to the drug at all. Very quickly, we are going to look at these three common drug eruptions: exanthem which is the most common, urticaria and fixed- drug eruption. This is a patient with a widespread exanthematous drug eruption. It usually starts within the first 3 days after exposure to the drug. For some drugs like antibiotics and allopurinol that exposure window can be up to about 2 weeks. The rash is best described as small, erythematous papules that may coalesce. These patients have pruritus but they are not generally ill. Mucous membrane involvement is rare. It is a benign condition in that as the drug is withdrawn the patient gets better. They can often later in the course of the disease desquamate but they don't develop blisters and they don't have epidermal detachment. There is very good data about this type of reaction. It has been studied in several prospectively collected data sets. One was the Boston Collaborative Drug Program. There is data on I think something like 35,000 exposures over about, you know, a 10- year period, collected in many hospitals. You can say with fair certainty that there are certain drugs that have higher rates than others, and in this list the highest tends to be antibiotics. The highest rates are for amoxicillin and co- trimoxazole. It is also helpful to know that there is a large list of drugs that are almost never associated with reactions. So, if a patient is on multiple drugs, which they often are, it is useful to refer to this type of list to exclude the ones that are least likely to be the culprit. Urticaria you all know how to recognize. It is areas of swelling. There are usually plaque type lesions, and the key about urticaria is any individual lesion generally will last for less than 24 hours. Here is one of the perfect examples. If you identify the cause and you withdraw it patients will often have urticaria after such an exposure for weeks and even months even though you have identified the correct drug and withdrawn it. The list of drugs that cause urticaria is very similar to the ones that produce exanthem. Lastly, this is a fixed-drug eruption. A fixed-drug eruption is a really peculiar thing in that it tends to occur only on certain areas and to recur in those areas on re-exposure. It is the one instance where people will often be re-exposed because it is not so clear to the providers that this was, in fact, a drug eruption. The other reason that this is quite relevant is that the histopathology of a fixed-drug eruption is very similar to what you see in erythema multiforme and, to a lesser degree, in Stevens-Johnson syndrome and toxic epidermal necrolysis. Again, if you look at the drugs that cause fixed-drug eruptions, there is a lot of overlap between the drugs that most commonly cause all of these types of eruptions. The three serious drug reactions that I want to talk about are the ones that I think are the most relevant to this question that you are asking today, and that is toxic epidermal necrolysis, Stevens- Johnson syndrome and the drug hypersensitivity syndrome. Of all of the things which I have to say today, this is the slide that I want you to remember the most. These are two patients that I saw personally. These are people with toxic epidermal necrolysis. The most obvious and important thing about these patients is, number one, that they are sick. They often have multiple mucous membranes involved. In severe cases not only are the sort of distal mucous membranes involved, but it can affect the trachea and even the bronchi. The second most important thing is that they have widespread areas of cutaneous involvement and, in the case on the right, they often shed full-thickness necrotic skin over very large areas, and they have basically the equivalent of a widespread burn. The summary of toxic epidermal necrolysis in terms of its clinical features is also a prodrome of fever and malaise. This usually lasts one to two days. The eruption is predominantly on the face and torso. The lesions are best described as pruritic plaques. They can have bullae. Multiple mucosa are commonly involved. Patients with toxic epidermal necrolysis, however, do not have true target lesions. Probably by the best definition of toxic epidermal necrolysis, it has to involve at least 30 percent of the body surface area, and the mortality for such described toxic epidermal necrolysis is quite high, around 30 percent. The majority of deaths are due to either infection or problems with respiratory distress that are either due to pneumonia or to the fact that the airway linings are involved. As has already been mentioned, it is a relatively rare phenomenon so that in most population studies the incidence is about one case per million patient years; 95 percent of the cases clearly have a drug etiology, and there are certain drugs for which the incidence is much higher. Based on a case-controlled study that was published in the New England Journal years ago, this was a study that carefully ascertained cases in France, Germany and Italy and to drug exposure histories from patients in three age and gender matched controls, and came up with an estimate of the number of cases per million exposures that one would see per week. It was highest for sulfonamides. If you do the arithmetic, this turns out to be something in the order of 1 case in 200.00 or 250,000 for some of these drugs. The drugs commonly associated with TEN are listed here. Again, these lists are very similar to the ones that cause benign eruptions and the same sort of drugs keep showing up: sulfonamides, hydantoins, some but not all of the nonsteroidals and allopurinol. This is a patient with Stevens-Johnson syndrome, Stevens-Johnson syndrome and toxic epidermal necrolysis are dissimilar disorders in a continuum. The difference between Stevens-Johnson and TEN is one of degree of epidermal detachment. The symptoms are very similar. There is prodrome often of fever and malaise. The lesions are very similar. In Stevens-Johnson syndrome the area of involvement is usually defined as being less than 10 percent. It has a much lower mortality. The other interesting thing is that if you look at the etiology of Stevens-Johnson syndrome, it can be attributed to drugs in only about 50 percent of cases. Now, that seems to be in congress with TEN and SJS being part of a spectrum. I think the problem is that there is a lot of confusion about mixing up cases of erythema multiforme, which I think is a quite separable disease, with Stevens-Johnson syndrome. I think that explains why drug etiology is less commonly identified. I will have more to say about erythema multiforme at the very end. Again, the incidence is about one per million per year, drug induced in about 50 percent. There is a higher incidence with some drugs and it is that same list of drugs, you should note. Now, what I was saying about the relationship between SJS and TEN, TEN is defined as those cases where the area of involvement is more than 30 percent. SJS is less than 10 percent. Then, there are people who are kind of in the middle, between 10- 30 percent, that are called SJS/TEN overlap. The other thing to note is that erythema multiforme is not mentioned anywhere on this slide or in my previous comments because, as I said, I think it is a distinct disorder. The last serious reaction that I wanted to talk to you about is the hypersensitivity syndrome. That is what this slide is an example of. It looks very similar to exanthem except for two things. When you have seen a few of these patients it always strikes you that the color in the hypersensitivity syndrome is a much brighter and darker red and the amount of confluence of the rash is much higher. Symptomatically, these people have exanthem. They have fever, lymphadenopathy, often have hepatitis, some of them have arthritis. This is a disorder that has a significant mortality. It is not clear how patients should be treated and, again, the list of drugs that cause this that are already known and sort of identified as such is very similar to the list of drugs that cause drug rashes in general. This is a slide from a paper that was done by Roujeau and Stern, in the New England Journal, and it is a very busy slide. The only thing I want you to note is that the fatality rate for the hypersensitivity syndrome is about 10 percent. For TEN it is about 30 percent. For Stevens-Johnson syndrome, because of the area of involvement and severity it is much less; it is lower. Finally, exposure to rash for TEN and SJS is in the order of weeks, so 1-3 weeks is noted in the third column in this slide. Skin biopsies are very helpful because in TEN and SJS they tend to show full-thickness epidermal necrosis, detachment of the skin at the dermal/epidermal junction, and often there is very, very little inflammation in the dermis associated with the rash. Finally, I would like to conclude by showing you examples of things that are often called drug eruptions but are not, primarily erythema multiforme. Now, erythema multiforme -- you can't make that diagnosis unless patients have typical target lesions. Typical target lesions have three rings, either a dusky or bullous center, an area of erythema around that and then a surrounding area of edemous skin. You can often actually have rings beyond that but if you have the three rings it is I think easily identifiable as erythema multiforme. In terms of the distribution, another thing that is helpful is that erythema multiforme predominantly affects the face and the extremities. The torso is much less commonly and much less extensively involved. The majority of cases of erythema multiforme are actually associated with infection, herpes simplex being the most common one and, although it can be caused by drugs, drugs are a much, much less common etiologic factor for erythema multiforme. The other thing is that erythema multiforme, by and large, is a benign disorder. Patients recover and deaths are extremely rare for erythema multiforme. I think people shouldn't combine erythema multiforme, even erythema multiforme major with mucosal involvement with Stevens- Johnson because I think they are distinct entities. Grover's disease is another one that looks to the world like a drug eruption. It tends to occur commonly in hospitalized males on their back and, you know, a lot of the times we get called for drug eruptions and it turns out to be just this scenario, elderly men with Grover's disease predominantly on their back. Lastly, extensive cases of pityriasis rosea can be mistaken for drug eruptions. The key there is that, you know, the history is usually pretty classic. The distribution is classic as well and if you have the herald patches, as noted in the right-hand slide, there is not a lot of confusion. The last two things on this list, the viral exanthem and graft versus host disease, no one can really distinguish those from drug exanthems or several other drug eruptions and it is a matter of great difficulty. That is where I will stop. Thank you. GOODMAN: Thank you. Questions from the committee? Dr. Pine? PINE: I guess I am struggling a little bit, kind of like Dr. Andreason was. On the one hand, you know, the rashes were very concerning that were described. On the other hand, there are no cases in the spontaneous reporting. I was just wondering, given your background as somebody who sees this kind of thing every day presumably, or frequently, what was your impression when you reviewed the cases in terms of how convincing they were, number one and, number two, when you combine that with what you would expect to see how concerned, as a dermatologist who spends a lot of time thinking about this, were you about the data that you saw and the cases that you saw? BIGBY: I think that the 7 year-old child that was described, to me, was a probable case of SJS that was drug related. After looking at the material, I think that the drug is going to be, and probably already is, associated with sort of an excess of cases of SJS/TEN. PINE: Thanks. GOODMAN: Dr. Rappley? RAPPLEY: I looked over 26 cases, I think it was, that had rash and I noted that many of those cases presented on a continuum that included fever, pharyngitis, rash, and it went from very mild to very severe. That is something in pediatrics that we see as a reaction with immunosuppression or reaction that, you know, reminds of Kawasaki's -- not exactly but it makes me think of that. It reminds me of drug reactions. It reminds me of neutropenia. So, my question is do you see that as a continuum, those symptoms as related? BIGBY: I am actually not sure I understand your question. I mean, of the material that I saw, I think that there was one case that probably had SJS. I think that the other sort of rashes described... RAPPLEY: So, you don't see that as a continuum? (UNKNOWN): No... RAPPLEY: You see Stevens-Johnson as a very discrete... BIGBY: Yes, right. You know, I think that eruptions are sort of specific things to dermatologists and these things don't sort of fit together as a gestalt for a kind of reaction to that drug, no. RAPPLEY: OK. GOODMAN: What I would like to do is take an unscheduled quick break, seven minutes. Before we do that, just an admonishment, I would like to remind the committee that, in the spirit of the Federal Advisory Committee Act and Sunshine Amendment, discussions about today's topic should take place in the forum of this meeting only and not during lunch breaks or in private sessions. We ask that the press honor the obligations of the committee as well. If you will allow the committee members to exit the room first to take their break, we will reconvene in seven minutes. Thank you. (RECESS) GOODMAN: We are resuming now with a series of presentations from the sponsors. Please, committee members, restrict any burning questions to those of clarification. I think that we will go to lunch at 12:30 instead of 12:00, which means that we save time for more detailed questions of the sponsor after the public presentations. Please go ahead. RACZKOWSKI: Good morning. Dr. Goodman, members of the advisory committee, Dr. Laughren, FDA representatives, ladies and gentlemen, today we will be discussing the application for Sparlon tablets for approval for treatment in pediatric patients with ADHD. My name is Victor Raczkowski and I am the vice president for worldwide regulatory affairs at Cephalon. Our proposed indication for Sparlon is for the treatment of ADHD in children as well as adolescent patients. We filed our application in December of 2004 and we received an approvable letter about 10 months later. We submitted a complete response then to the agency in November of last year. Sparlon contains the active ingredient modafinil which is also contained in Provigil tablets. So, modafinil is not a new chemical entity. Sparlon tablets have been formulated to facilitate administration to pediatric patients. That is, on a milligram/kilogram basis of modafinil they are smaller than Provigil tablets. They come in dosage that ranges in strength from 85-425 mg and are intended for once daily administration in the morning. Provigil has been marketed in the United States since 1999 and is currently marketed in 28 countries worldwide. Provigil is a wakefulness promoting product and it is approved in the United States in adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome or shift work sleep disorder. We have estimated exposure globally through the end of February 2006 as being approximately 780,000 patient-treatment years, of which 30,000 patient-treatment years are in pediatric patients. Modafinil is also listed in Schedule IV of the Controlled Substances Act. You have been asked to address a number of questions today and the two voting questions are on the efficacy and safety of Sparlon. We hope to be able to show you with our data today that not only is Sparlon effective for the treatment of ADHD, but it has also been shown to be acceptably safe for the treatment of ADHD in pediatric patients. We have also been asked to address the dermatological safety of Sparlon tablets. Just by way of orientation, this slide represents cases of SJS in pediatric patients in clinical trials as well as in our postmarketing experience. Other speakers are going to go into this in much more detail. This is just to orient you that an earlier review by our experts indicted that there was one case of probable SJS in our clinical trial program out of 1622 patients exposed. However, that case is of uncertain etiology. In addition, if the committee has questions or interest in the clinical course of that patient, we do have the investigator here at the meeting today who can describe the clinical course of that patient. In our pediatric postmarketing experience we have seen no pediatric cases of SJS in over 30,000 pediatric patient-treatment years. We will have a number of presentations today, beginning with an overview of attention deficit hyperactivity disorder by Dr. Joseph Biederman. That will be followed by a review of both the clinical pharmacology and efficacy by Dr. Lesley Russell. Dr. Srdjan Stankovic will then provide an overview of the safety and then Dr. Russell will conclude with an overall benefit-risk assessment. We have a number of consultant experts in the field with us today representing various disciplines including psychiatry/ADHD, dermatology, addiction medicine, cardiology, child development as well as epidemiology. I would just like to highlight one name since dermatology is a major issue in today's presentation, we do have an individual, Dr. Neil Shear, with us today who has published extensively in peer reviewed journals on SJS as well as other dermatological disorders. I would also like to note, as you can see on this slide, that we have a number of investigators with us today. With that, I would now like to introduce Dr. Joseph Biederman, who is professor of psychiatry at Harvard Medical School. Dr. Biederman? BIEDERMAN: It is a pleasure to be here. I would like to offer you a very brief overview of ADHD as a very serious illness of genetic etiology affecting the brain that has a bad prognosis. I strongly believe that without understanding the assessment of benefit-risk alternative treatment is impossible. First of all, I think that it is important to note that ADHD is a highly heterogeneous illness like all psychiatric illnesses. We know that genes are important, as I am going to show you in moment -- perhaps the most important risk factor. We know quite a bit about heterogeneous neuroanatomy and neurochemistry. We know that CNS insults, if affecting key regions of the brain like the prefrontal cortex, can produce very similar problems as those produced by genes. Even environmental factors can be important in ADHD. We need to consider that environmental factors are not bad mothers or bad teachers, like frequently thought, but include things like poverty, exposure to parental psychopathology, et cetera, et cetera, things that in themselves can be driven by genes. So, heterogeneous illness requires different treatment. Different patients require different alternative therapeutic options. Another thing that has been highlighted today but I would like to stress again is that ADHD is a worldwide condition, not only an American invention. It affects children in the 5-10 percent range worldwide. Data are coming from Asia now, from China and Japan and data from South American, Western and Eastern Europe and, of course, North and South American point to the fact that no matter what criteria you want to use, it is an extraordinarily common disease. You have to remember that at least 50 percent -- at least 50 percent of the children of today are going to be adults tomorrow and we now know that ADHD affects at least 4 percent or 5 percent of adults in this country, not only that it affects them but it is very morbid and dysfunctional. I would like to stress that the yardstick of considering the severity of an illness just by mortality may not be an adequate yardstick. Many conditions are devastating to our patients, even though they are not necessarily lethal in the traditional sense, like malignancies. This is a condition that profoundly affects the lives of those affected and everybody around them. Many of the MRI studies that have been conducted have been small and many of the children participating in them have been medicated, creating the suspicion that perhaps what we see in MRI studies may reflect the toxic effects of medications. Therefore, this study that I briefly want to review for you is extraordinarily important. This study is large. It was published in a very prestigious medical journal, JAMA. It was done by colleagues at the National Institute of Mental Health. The lead author is Dr. Castellanos. And, 152 children and adolescents of both genders and a similar number of controls of both genders were assessed longitudinally. The specific objective of the study was to assess the issue of medication status, whether medication is important in brain abnormalities. What this study found is that the brain of children and adolescents with ADHD was significantly smaller, in the 3 percent range, independently of medication status. These volumetric abnormalities were persistent over time so this is not a neurodegenerative disease. It is early disease that persists into adult life. There were no gender differences and there was some evidence of an association between severity of ADHD and brain findings. The visual of this study shows the brains -- these are males up to the age of 20; females out to age 15. You can see that both genders have significantly smaller brains and the lines are flat over time. The conclusion of this study is that either genetic or early environmental influences on brain development are operant in ADHD. These are fixed, nonprogressive and unrelated to stimulant treatment. If you look at key regions of the brain that are involved in attention and executive function, anyone of us in this room irrespective of having or not having ADHD, we have this area of the brain -- this is the cingulate gyrus; this is the dorsal anterior cingulate associated with executive control; dorsolateral prefrontal cortex associated with selective attention; and the right frontal lobe associated with alerting. These are interconnected areas, key regions for cognition and attention. Their disruption will cause symptoms of ADHD. This is a recent study that we just submitted for publication from our program at the Mass. General. This is a three-dimensional reconstruction of the anterior cingulate. What you see here is a study of adults with ADHD. The anterior cingulate area is 13 percent smaller in individuals with ADHD compared with controls. With imaging studies you can do not only volume, as I just showed you with the three-dimensional reconstruction so you can measure volume of this region -- this is the cingulate gyrus again -- but you can also measure the thickness of the cortex, how thick or thin is the cortex in critical brain regions. So, this is another study that we have done in our program of cortical thickness. This has not yet been published but I promise you it will be published. What you see, first of all, in red here is a statistical comparison between the brains of ADHD individuals compared with controls. What this depicts, in orange and yellow, is significant differences in cortical thinness. These areas are selectively thinner in these regions. So, you don't see thinness across the entire brain; you see thinness in critical cortical regions involved with executive control and attention. This is the dorsal anterior cingulate. This region hovers between the cognitive and emotional division of the anterior cingulate -- very important issues for clinical understanding of the symptoms of this condition. This is, of course, the dorsolateral prefrontal cortex that is clearly involved in cognition and in the symptoms that subserve this illness. We have also done this analysis. It is very exciting. This is diffusion tensor imaging that measures white tracts. What you see here is that we are documenting disruptions in the perigenual area of the anterior cingulate and dorsal anterior cingulate selectively. So, this area of the brain that is involved in cognition, executive functions and regulatory controls is smaller in volume, is thinner in cortical thickness and has other abnormalities as well. I am not aware of many other psychiatric illnesses can claim such conversion of information, focusing on the same brain regions that could certainly account for the clinical picture. If you look at functional MRI in the same region, if you look at the coronal view of the brain, if you put people without ADHD on the scanner you can very nicely activate anterior cingulate doing a very mild cognitive task. If you put adults with ADHD, they fail to activate the same region and, instead, they activate insular so these adults can do the task but they are not using the part of the brain that is specifically wired to do the task at hand. We have very exciting new data that you can correct this malfunction with medications. These findings on neuroimaging are extraordinarily congruent with conceptualization from neuropsychology. As you know, ADHD is considered a neuropsychological disease. What is called directed attention, the circuit that allows people to pay attention to things that they are not interested in is disrupted. Inhibitory deficits, the person fails to inhibit when destructions occur; and executive dysfunction issues of planning and organization, working memory, et cetera, et cetera are disturbed. These are the regions that are in this part of the brain where we are documenting abnormalities. Another circuit that is involved in ADHD is called fascination reward circuit. People with ADHD have difficulties with delayed gratification; difficulties with regulating mood. This kind of hot temper that characterizes people with ADHD and some of the road rages that lead to accidents, and so on and so forth, may be accounted for by these neuropsychological deficits. Another key aspect to document that ADHD is a neurobiological disorder is genetic research. ADHD clearly runs in families. There is a 5- to 7-fold increased risk of ADHD in first-degree relatives of children with ADHD. Of course, that is not evidence for genetics so we need to have additional information to make a genetic hypothesis or genetic claim. Twin studies are very important because twins come from two varieties, monozygotic and dizygotic twins. For genetic illnesses, you expect that monozygotic twins will have a higher level of concordance than dizygotic or fraternal twins. Twin studies are also very important because they can allow us to compute coefficients of heritability that I will tell you about in a moment. Adoption studies are important because with genetic illness you expect to have a higher rate of the disease in biological rather than adopting relatives. Finally, molecular genetic studies will look at specific genes that may be associated with this condition. Coefficients of heritability are based on twin studies. I would like to point out to you that there are a lot of twin studies in ADHD. Coefficients of heritability range from zero/zero percent of the variance accounted for by genes to 100/100 percent of the variance accounted for by genes. The congruence of the genetic studies for the coefficient of heritability in ADHD is remarkable. Even though the studies use different methods, parent support, teacher support, structured interviews questionnaires, look how consistent this is. On average, coefficients of heritability are close to 80 percent, in other words, 80 percent of the variance of ADHD can be accounted for by genes. For example, height, a very genetic trait, is about 90 percent genetic; schizophrenia and bipolar illness, very genetic. Recognized genetic illnesses are equally genetic as ADHD, 80 percent. Panic disorder and major depression are genetic as well, about 50 percent, 0.5 for coefficient of variability; other medical conditions like asthma or breast cancer at 0.3, 0.4 coefficients of heritability. So, we are dealing with a very genetic brain disorder here. Specific genes have been associated with ADHD. The first genes that were looked at in ADHD are genes that are associated with the dopamine system, candidate genes because the drugs that we usually use to treat this condition are dopaminergic drugs. Mutation in a dopamine transporter gene, what is called DAT1 or DAT10; mutation in the dopamine receptor of D4 and D5 genes -- these are cortically distributed receptors. There is also an association between a very rare thyroid disease on chromosome 3. People that have this mutation also have ADHD, but this probably accounts for very little of ADHD out there. So, the genes that have bee associated with ADHD in a consistent fashion are the dopamine transporter genes that bring back dopamine to the presynaptic neuron. This gene over-expresses the dopamine transporter, make more it active or more transported, too much dopamine to the presynaptic neuron. Cortically distributed genes are the D4 and D5. There is also a gene, SNAP25, that is involved in the presynaptic encapsulation of dopamine. Well, I see this slide is totally degenerated. I am very sorry. But what I would like to say is that Dr. Faraone published in Biological Psychiatry a review of a meta-analysis. There are certain genes, about seven genes that consistently have been associated with ADHD, several genes in the serotonergic system, DBH, dopamine transporter gene and also dopamine receptor DR D4 and DR D5. These genes have been found in multiple studies in meta-analyses of these specific genes to be associated with ADHD. You probably have these details in the handout, as well as the reference for the paper that support these claims. The treatments that we have available are clearly effective. This study was not done by industry. It was funded by the NIMH on the multi-modal treatment of ADHD. This study studied close to 600 children 7-9 years of age in this country, in 5 sites. This was a study in which children were randomized to very aggressive medication management, very aggressive, comprehensive behavioral treatment, a behavioral treatment that was so comprehensive that you could not possibly improve on it, and it is so expensive that it is not doable. But that was the purpose of the study. Children received both medication and behavioral management and community-based treatment. What this study found, and I would like to point this out to you, is that these two arms, the very aggressive medication arm and combination treatment were superior to just behavioral treatment and community based treatment that consisted largely of communication too. This group, here, is a group that received the best treatment that we can offer, very aggressive pharmacotherapy and very aggressive behavioral treatment. And, even using the best we can, the response is 60 percent, leaving 40 percent of our patients inadequately treated with intolerable side effects or with difficulty tolerating this treatment. Stimulants are Schedule II drugs. About 40 percent or perhaps more do not tolerate or to not respond to these treatments. The side effect profile of sleep, appetite, difficulties with mood and anxiety can seriously hinder our ability to treat all the patients that otherwise could benefit, and concerns about growth suppression and tic development continue to plague stimulant treatment in ADHD, although the data is generally reassuring, people continue to be concerned about these issues. ADHD not only affects school and school performance, it is clearly a life disease. For example, ADHD has been shown to be associated with a significantly increased risk for automobile accidents, and automobile accidents, as you know, are the leading cause of death in our young. So, patients not only have poor grades in school or may not reach college but may not reach adult life altogether or may kill somebody in the process of driving and not paying attention to the road. So, if you look at the morbidity of ADHD as a serious -- perhaps not a lethal illness but a very devastating illness to the individual, the family and society secondary to under-achievement, under- employment, marital difficulties, drugs and substance abuse, legal difficulties, or morbidity, we are dealing with an extraordinarily morbid disease that can profoundly affect those afflicted with this condition. So, in summary, ADHD is a neurobehavioral disorder with complex etiology. It is a disorder that affects the brain; has a strong genetic component, as I alluded to; affects millions of people worldwide, both sexes. It is highly persistent in the majority of those affected. It has a negative impact on the life of the individual affected and everybody around. Although the stimulants are clearly an effective treatment for ADHD, a sizeable number, in the order of magnitude of 40 percent, are non-responsive or not tolerating this treatment, calling for alternative treatment for this condition. Thank you very much for your attention. The next presentation will be by Dr. Lesley Russell who will be talking about clinical pharmacology and efficacy. RUSSELL: Thank you, Dr. Biederman. Today I would like to briefly overview the clinical pharmacokinetics of modafinil in children, and then summarize for you the efficacy findings of our program in ADHD. Just to begin with, here is an outline of the development program that Cephalon undertook in children and adolescents with ADHD. The three Phase 3 studies, studies 309, 310 and 311, formed the basis of the efficacy and safety that will be discussed today. In addition, we had two pharmacokinetic studies, studies 113 and study 206, that outline the pharmacokinetic parameters of modafinil in children. In addition, we conducted two studies, 207 and 213, to help us define the dose required for the Phase 3 studies. All patients in the Phase 3 studies and some from the Phase 2 studies were allowed to enroll into study 312 which is an ongoing open-label extension program. Following submission of the sNDA, we initiated a further study, study 3044, in which 303 patients were enrolled. This study is still ongoing. I would now like to briefly summarize the pharmacokinetics of modafinil in children. As shown on this slide, the pharmacokinetics and exposure are dose-proportional over the dose range studied. The absorption is rapid, with a maximum concentration observed 2-3 hours after administration. When administered with food, there is an approximate 1 hour delay in the time to Cmax although the overall absorption is not affected. The volume of distribution increases in children linearly with their weight. The metabolism of modafinil is primarily hepatic, with less than 10 percent excreted unchanged in the urine. There are 2 primary metabolites, modafinil acid and modafinil sulfone. As you heard earlier, we did observe higher levels of modafinil sulfone in the younger children. The elimination of modafinil is time- and age-dependent. We observe a decrease in clearance over time with steady state being reached by about week 6 of treatment. There is a gradual decrease in clearance with age, with a pronounced shift between 9-11 years of age. So, we see that there is a half-life in the younger children of approximately 7 hours which is compared to a half-life of 15 hours in the adults. I would now like to outline for you the basis of the dose selection that we used in the Phase 3 studies. Study 207 was a relatively small, double-blind, randomized, 4-period crossover study, and this was the first program undertaken to assess the efficacy of modafinil in the treatment of ADHD. The results shown for you are the total scores on the ADHD rating scale as assessed by the parent. With the caveats of this being a small study, you can see that those patients who received 100 mg barely discriminated from placebo. A slightly larger treatment effect was seen with the 200 mg dose group and a larger treatment effect was seen with the 300 mg or 400 mg dose group. And, I should reiterate here that the 300/400 mg doses were administered based on weight, with the 300 given to children less than 30 kg and the 400 to those children weighing at least 30 kg or more. The next study we undertook was study 213, and this was designed to see the best way of administering a single dose of 300 mg either as a single dose administered first thing in the morning, which is depicted in blue, or as a split dose of 200 mg in the morning and 100 mg at lunch, depicted in orange, 100 mg in the morning and 200 mg at lunch time, depicted in pink and compared to placebo. As you can see from the slide, there appeared to be little benefit to splitting the dose and the largest response we saw was in the 300 mg dose group administered as a single dose. As you can see on the right-hand side of the slide, this is for all patients, but when we looked at it stratified by weight you can see that it is clearly the younger and lighter children that had the larger response. So, from this study we concluded that older and heavier children may require a higher dose. This slide identifies the systemic exposure that we saw following these dosing regimens. In the middle, here, are those children weighing less than 30 kg who received 300 mg. Here are those children weighing more than 30 kg who received. You can see that the systemic exposure associated with the lighter children is clearly higher than the systemic exposure with the heavier children. Using these data and the clinical efficacy results from the Phase 2 studies, we developed a pharmacokinetic/pharmacodynamic model and estimated that the systemic exposure which would be associated with a consistent pharmacodynamic effect would be in the order of 150 mcg/hour/ml, and that the doses that would be required to achieve this exposure at steady state would be 340 mg for those children weighing less than 30 kg and 425 mg for those children weighing 30 kg or more. Following the Phase 3 program which included sampling from population pharmacokinetics, we went back to test this hypothesis. As you can see from this slide, we pretty much got it right in that here are the children weighing less than 30 kg who received 340 mg and here are those heavier children who received 425 mg, and the systemic exposure in those groups is pretty similar, around 150 mcg/hour/ml. As you will see from the next slides, these doses were associated with substantial efficacy. Here are the designs of the 3 pivotal studies that were undertaken. All studies were double-blind, randomized, placebo- controlled and had a 2:1 randomization. Study 309 and 311 were identical in design. Both were 9 weeks in duration and employed a flexible dose titration regimen whereby children could be titrated from a minimum dose of 170 mg to a maximum dose of 425 mg based on perceived efficacy and their tolerability to treatment. The dosing increments occurred on a weekly basis at 85 mg. Study 310 was slightly different. This study had a 7-week efficacy period and a 2-week period that assessed abrupt discontinuation of the drug, the results of which I will not show you today. This study was also a fixed dose study and patients were titrated at 85 mg increments every 2 days to their target dose based on weight, so 340 mg for the children weighing less than 30 kg and 425 mg for those children weighing 30 kg or more. The patients enrolled in the study were very similar. All patients were 6-17 years of age with a diagnosis or ADHD according to the Diagnostic and Statistical Manual of Mental Disorders. The children were required to be at least moderately ill on the Clinical Global Impression of severity and have an ADHD rating scale which was at least 1.5 standard deviations above the norm for age and gender. Patients were required to be of normal intelligence with no learning disability and attend school full time. Patients were excluded from study if they failed to respond to 2 or more adequate courses of stimulant therapy, although it should be noted that patients who had failed one stimulant therapy were allowed to be enrolled. Patients were also excluded if they had psychiatric comorbidities requiring current pharmacotherapy and were well controlled with their current ADHD therapy and had no good reason to change treatments. The efficacy assessments were identical for each of the 3 studies. The primary outcome measure was the change from baseline in the Total Score ADHD Rating Scale as assessed by the teacher. Secondary outcome measures included a change from baseline in the Home ADHD Rating Scale as assessed by the parents in the evening between 6:00 and 8:00 at night; the Clinical Global Impression of change as assessed by the treating physician; the Conners' Parent Rating Scale as assessed by the parent; the test of Variables of Attention, which is a continuous performance test; the Social Skill Rating Scale and the Child Health Questionnaire. As you can see, the average age of patients entering into the program was around 10, with the majority of patients being less than 12 years of age. The majority were boys and white, and about two- thirds of the patients actually weighed 30 kg or more. As per inclusion criteria, patients were required to be at least moderately ill on the Clinical Global Impression of severity and, as you can see from the slide, about 50 percent of the patients were considered to be moderately ill and the other 50 percent were considered to be markedly or severely ill. Around two-thirds of the patients had the combined inattentive and hyperactive subtype of ADHD. About a third were predominantly inattentive and very few were purely hyperactive. The baseline ADHD rating scale at entry was on average 37, which is well above the norm for a 10-year boy which is roughly 18. A total of 638 patients were randomized into the study and 630 received treatment, 420 in the modafinil treatment group and 213 in the placebo treatment group. Around two-thirds of the patients completed the double-blind treatment period, with the reasons for discontinuation outlined here. As you can see, some of the main reasons for discontinuation were lack of efficacy with a much higher proportion in the placebo treatment group, and adverse events with the higher proportion in the modafinil treatment group. The other reasons are listed for you here. The following three slides will show the outcomes of the primary efficacy variables for each individual study. Here are the results for study 309, the first of the flexible dose studies. Just to orient you, on the Y axis is the Total ADHD Rating Scale with the lowest score showing benefit, and across the X axis is the duration of the treatment period in weeks. Just as a reminder, the primary outcome variable was the change from baseline to endpoint using the last observation carried forward analysis. As you can see from this slide, there was a statistically significant difference in favor of those patients being treated with modafinil. More specifically, the treatment effect on the modafinil treatment group was 17.5 points with the treatment effect on the placebo group of 9.7 points for an effect estimate, which is the difference between the 2 treatment groups using the Lee squared means of 7.4. In addition, statistically significant results were seen using the observed cases analysis. A similar result was seen in study 311 which is the second flexible dose study. At endpoint the treatment effect on the modafinil treatment group was 15 points and a treatment effect on the placebo group was 7.3 points for an effect estimate of 8. Again, this is statistically significant both at endpoint and using the observed case analysis. The last study is study 310 and, again, a very consistent treatment effect was seen in this study, with a treatment effect of minus 17.2 points on the modafinil group versus 8.2 points on the placebo treatment group for an effect estimate of 9. Outlined for you on this slide is just another way of viewing the data. On the left-hand side of the screen is the modafinil treatment group at baseline and at endpoint. On the right-hand screen is the placebo group at baseline and at endpoint. This slide illustrates the remarkably consistent effect seen not only in the modafinil treatment group but in the placebo treatment group. The red line depicts what would be considered to be a normative value on the ADHD rating scale for a 10 year-old boy. As you can see, those patients treated with modafinil are beginning to approach this normative value. We also assessed the effect of treatment using a responder analysis on the School ADHD Rating Scale with those patients who had at least a 30 percent reduction in their scores from baseline to endpoint or a 50 percent reduction from baseline to endpoint. As you can see, in all 3 studies a significantly higher proportion of patients treated with modafinil had either a 30 percent or a 50 percent reduction in their ADHD symptoms. This slide shows for you in all 3 studies the home version of the ADHD Rating Scale. As a reminder, this was assessed by the parents in the early evening. The results seen here very much mirror the results we saw using the school version of the ADHD Rating Scale, with significant differences seen both at endpoint and in the observed case analyses in all 3 studies in favor of the modafinil treatment group. Depicted here is the responder analysis on the Clinical Global Impression of improvement. Outlined for you are those patients who were either considered to be much or very much improved by the treating physician. Again, in all 3 studies we see a very consistent treatment effect, with a significantly higher proportion of patients considered to be much or very much improved on this scale by the treating physician. Another commonly used scale for assessing ADHD and their response to medication is the Conners' Parent Rating Scale. Again, you can see in each of the 3 studies, using this scale, a very similar effect to the observation seen using the ADHD rating scale, with improvements on the modafinil treatment group in cognitive problems and in attention, hyperactivity and their total ADHD index. This scale also allows the assessment of treatment on the oppositional behavior. As you can see, in all 3 studies there appears to be a treatment effect in favor of modafinil, although this is only statistically significant in study 311. The one inconsistent effect that we saw was using the Test of Variable Attention. Outlined for you in this study is the pooled analysis using data from all 3 studies. Although you can see that those patients treated with modafinil tend to do better than those patients treated with placebo, it should be noted that this is actually a decline in performance rather than an improvement in performance over time. Children with ADHD often have poor peer to peer relationships and difficulties with socialization. We wanted to assess the effects of treatment on these parameters and we used the Social Skills Rating Scale. Again, this is the data from all 3 studies pooled. The individual studies did show a consistent treatment effect. As you can see, there appears to be an improvement in many of these parameters when treated with modafinil, including the Social Skills Total Scale. A similar improvement was seen in other problem behaviors as measured by this scale. It should be noted that these results were only seen in the children in grades kindergarten to 6th grade and we observed no major differences between treatment groups in the older age groups. Lastly, here are the results of the Child Health Questionnaire, a global sort of quality of life instrument that assesses many behaviors that can be impaired with ADHD. Again, this is the pooled analysis of all 3 studies. As you can see from this slide, there appears to be an improvement in many of the behavioral aspects seen for those patients treated with modafinil -- including an improvement in the total psychosocial summary. We did not see significant improvements in the physical functioning domain, although it should be noted that these values were normal at baseline. We have undertaken many subgroup analyses, many of which are outlined in your briefing document. Here I just want to show for you the subgroup analysis for those patients who were either stimulant naive at study entry, and that was for about 50 percent of the patients, and those patients who had received a prior stimulant before enrolling into the study, which was again about 50 percent of the patients. Here you can see that treatment with modafinil was effective even in those patients who had had prior stimulant therapy, although it should be noted that the treatment effect appears to be larger in those who were stimulant naive. In conclusion, we saw consistent efficacy results across 3 pivotal studies. The improvement in ADHD symptoms was seen by the teachers, the parents and the treating physicians. Improvements were seen at school, at home and across the day. As well as improvement in the core ADHD symptoms, we did observe improvement in other psychosocial domains. Finally, we saw efficacy in stimulant naive patients and in patients who had had prior stimulant experience. I would now like to hand over to Dr. Srdjan Stankovic who will outline safety for you. STANKOVIC: Thank you. My name is Serge Stankovic and I am with the Cephalon clinical research group. My presentation this morning on modafinil safety is organized as follows: I will review overall modafinil exposure in clinical trials. Following that, I will review the safety data for the modafinil ADHD program in children and adolescents, and this will include review of general safety and events of special interest such as skin reactions and psychiatric events. In the balance of my presentation I will briefly summarize high level safety information from our development program in excessive sleepiness in pediatric patients. Finally, I will review modafinil information coming from our postmarketing safety surveillance. Overall, safety data for 933 patients with ADHD were included in the supplemental NDA, submitted in December of 2004. Of these, in the 3 Phase 3 placebo-controlled trials, 420 patients were treated with modafinil and 213 patients were treated with placebo. Please note these numbers as I will often refer back to them when I am presenting data from our controlled trials. Following the sNDA submission, one additional open-label study in children with ADHD was initiated. With that, as of February, 2006, a total number of pediatric ADHD patients exposed to modafinil was 1236. Additional pediatric exposure comes from our development program in excessive sleepiness, 270 pediatric patients, and from pediatric patients exposed to a variety of foreign studies for various indications, 116 patients. Finally, just a reminder that 4000 adult patients were exposed to modafinil in the development program for excessive sleepiness and in other clinical trials. Looking at patient exposure in the pediatric ADHD program, this slide presents exposure by modal dose and duration for 933 patients as of February 1, 2006. A total of 246 patients were treated with modafinil for a minimum of 12 months, and as many as 164 were on drug for 18 months or longer. About half of the patients received modafinil at the modal dose of 425 mg a day, while about one-third at the modal dose of 340 mg a day. The total exposure to modafinil in the pediatric ADHD program is 575 patient-years. Next I will discuss adverse events observed in ADHD studies of children and adolescents. A general overview of adverse events reported in 3 Phase 3 placebo-controlled studies is presented on this table. While the majority of patients in both groups experienced at least one adverse event, a higher incidence was observed in the modafinil treatment group. Relatively few of these events were reported to be severe, were reported to be a reason for study discontinuation or were reported to be a serious regulatory definition of that word. The most commonly observed adverse events in the Phase 3 placebo- controlled studies were insomnia, headache and anorexia. The COSTART term of anorexia used here includes both loss of appetite and decreased appetite. In fact, about 70 percent of patients reporting anorexia experienced decreased appetite. Insomnia and anorexia were reported at a substantively higher rate in the modafinil group compared to placebo. Review of these two events indicated that very few were reported as severe, specifically 9 out of 115 events for insomnia and 1 event for anorexia. Likewise, only 5 events in insomnia led to discontinuation, while 2 patients reporting anorexia discontinued study due to that adverse event. In most instances, these 2 events first occurred in the initial 2 weeks of treatment and the median duration reported was about 2 weeks. Out of 933 patients included in the sNDA, 18 patients experienced at least one serious adverse event by the time of the 10-month safety update submitted in November of 2005. Four of these patients were enrolled in the 3 placebo-controlled Phase 3 studies and all of them were in the modafinil treatment group. From the 2 ongoing pediatric studies in ADHD, 3 patients experienced a serious adverse event during the period up to February, 2006. Discussion of serious skin adverse events as well as psychiatric events in more detail with be part of the discussion of special safety. In the next four slides I will review relevant information related to laboratory evaluations from the pediatric ADHD studies. Data for selective hematology and blood chemistry parameters will be reviewed in more detail. Although included in your background package, data for other laboratory parameters did not raise questions or concerns and, therefore, will not be presented here today. Based on some early observations from the Phase 2 studies, concern was raised regarding modafinil treatment effects on absolute neutrophil count and white blood cell count in children. Our Phase 3 controlled data did not show a meaningful difference in mean change from baseline or incidence in clinically significant values between modafinil and placebo. Furthermore, as presented on this slide, when the lowest on treatment values are grouped by range there was no meaningful difference between modafinil and placebo treatment groups. With respect to serum chemistry, as in adults, we did observe a difference in mean change from baseline between modafinil and placebo for alkaline phosphatase and GGT. In the Phase 3 placebo-controlled studies there were few patients experiencing a clinically significant change on any of the parameters, with no apparent imbalance between treatment groups. On the next slide we will discuss LFT elevations highlighted in the background document as cases of possible concern. These cases are included in this table in the column for all modafinil studies. In the FDA approvable letter it was stated that although controlled trials data did not reveal a signal for drug-related mean increase in transaminase values or in drug-related outliers, there were 3 modafinil-treated patients who had transaminase increases of concern, but insufficient other information to further assess the significance of these changes. Details related to these 3 patients are presented on the slide. In all 3 cases, total bilirubin values both at the time of observation of abnormal LFT values and throughout the study were normal. In one case laboratory abnormalities returned to normal while patients continued treatment with modafinil. In the second case treatment was continued for an additional 6 months prior to study discontinuation. At that time, all abnormal LFT values returned to normal except for a mild elevation in ALT. In the third patient abnormal values returned to normal after withdrawal of modafinil. This case will be discussed later in relation to possible hypersensitivity reactions. The next segment of the safety presentation is focused on cardiovascular safety. I will review blood pressure and pulse data, ECG information including QTc interval and cardiovascular adverse events from the Phase 3 placebo-controlled trials. It should be noted that the vital signs measurements in ECGs were recorded in these studies at variable time points during the day and in relation to the intake of study medication. With respect to blood pressure, no notable effects in sitting blood pressure were observed in the Phase 3 controlled studies. Presented on this slide are box plots for systolic blood pressure on the left side of the screen and diastolic blood pressure on the right side of the screen in modafinil and placebo treatment arms respectively. Changes from baseline for both systolic and diastolic blood pressure were similar in the 2 treatment groups with respect to both mean values, overall distribution and extreme outliers. This graph presents the distribution of observed change from baseline in sitting pulse for the 2 treatment groups. As presented, we observed similar distribution between the 2 treatment arms and the occurrence of outliers. Review of the ECG tracings from the ADHD pediatric studies did not reveal specific concerns both with respect to morphology or interval measures. This slide presents an overview of QTc interval data from the 3 placebo-controlled trials expressed as maximum change from baseline or as maximum duration observed. The slide presents data for QTc using the Fridericia correction, but the findings are similar when other corrections are used. Either way, there is no apparent effect on QTc interval or imbalance between treatment arms. Finally, when reported adverse events are reviewed, we observe relatively few cardiovascular events. Only a small fraction of these, 2 patients on modafinil and 1 on placebo, reported events leading to treatment discontinuation. In all 3 cases the stated reason for discontinuation was tachycardia. None of the reported cardiovascular events were reported to be serious. Important consideration in the safety evaluation of any ADHD compound is assessment of its effects on growth. In the placebo- controlled Phase 3 studies modafinil treatment of up to 9 weeks duration led to relative weight loss compared to weight gain observed in the placebo group. Similarly, a significantly higher proportion of modafinil-treated patients experienced clinically significant weight loss, defined as at least 7 percent in weight reduction. To be precise, 9 percent of modafinil-treated patients versus 1 percent of placebo-treated patients experienced significant weight loss during the study. Naturally, we did look at the longer term treatment data related to weight and growth in general. As you know, for accurate evaluation of growth effect in children, we need to evaluate them relative to norms. To achieve this, we expressed changes in weight and height using Z-scores. Just a quick reminder, Z-score is a statistical measure that quantifies the distance measured in standard deviations of a patient data point, in this case individual weight or height, from the population mean, in this case CDC growth norm for corresponding age and gender. This graph presents mean weight and height Z-scores over 12 months of treatment with modafinil. A decline in Z-score is observed initially in the first 3 months of treatment consistent with the reported weight loss in our short-term trials. In the following months the line remains horizontal, meaning that the normative pattern of growth is regained. Using the same presentation, it is apparent that there was no indication of adverse effects on height over the 12 months of treatment with modafinil. In the course of the modafinil ADHD pediatric development cases of serious skin reactions were reported. Some of these were indicative of a possible Stevens-Johnson syndrome or hypersensitivity reaction, generally a rare but very serious complication of treatment. Cephalon shares the important concerns raised by our colleagues at FDA in regard to these events. Therefore, I will review skin events in greater detail. To bring everybody on the same page with respect to cases of interest, I will start with the list of events, included in the FDA briefing document, in the second dermatology consult report dated February 27, 2006. In this report the events were grouped in 3 categories based on the level of diagnostic confidence. The 3 groups are events representing EM, SJS or TEN; events somewhat suggestive but lacking confirmation; and events resembling prodromal presentation but without sufficient information for diagnosis. Cephalon has performed a similar review and in the next two slides I will review cases from the first two groups. With respect to the third group, our review did not support the conclusion that any of these cases should be classified as SJS or prodrome. We based this on the low specificity and low predictive value of reported symptoms. Additionally, many of the symptoms are quite common and many were not reported concomitantly or concurrently. First, we will review the clinical trial cases. Patient number 1 is a 7 year-old boy who, on day 16 of treatment with a 340 mg dose, presented with symptoms described by the investigator as erythema multiforme, Stevens-Johnson syndrome and both FDA and Cephalon reviewers agreed that the diagnosis of Stevens-Johnson syndrome is likely accurate, with less consensus on the possible etiology. I am sure that this case will be discussed in more details later and, as Dr. Raczkowski said, we have the investigator here who was treating the patient, as well as members of our panel of dermatologists who can talk more about the case. Patient number 2 is an 11 year-old girl reported with morbilliform rash on day 15 with treatment of a 200 mg dose of modafinil. This patient was hospitalized and the SJS diagnosis was excluded. FDA review indicated that this was a case representative of EM/SJS. Cephalon's panel of independent reviewers, on the other hand, was unanimous that the reported diagnosis of morbilliform rash is probably correct and the event did not represent Stevens-Johnson syndrome. Patient number 3 is a 6 year-old boy who reported rash, fever and vomiting 2 weeks after initiation of treatment. Review of the source documentation received from the investigator indicated that this event was diagnosed as fifth disease. Patient number 4 is an event in an 8 year-old boy described as rash on the cheeks and blisters on the lips, and was reported as erythema multiforme. The event occurred on day 23 of treatment with a 300 mg dose of modafinil. This case is considered by the FDA reviewer as somewhat suggestive but not representative of EM/SJS or TEN. Cephalon's reviewers, on the other hand, agreed that this is unlikely erythema multiforme, but did not agree on the alternative diagnosis. One considers this event to be possible SJS. A second reviewer considered it to be probable herpetic gingivostomatis and a third independent reviewer attributed to the event as either viral etiology or SJS. Patient number 5 is a 9 year-old boy with reported symptoms of urticaria, fever and facial edema. This patient also had elevated transaminases. Cephalon's review indicates that this is a possible case of hypersensitivity reaction and it is not consistent with SJS. In the review of postmarketing reports both FDA and Cephalon concluded that there were 4 reports of serious skin reactions, 1 SJS/EM and 3 SJS reports. Of the 12 suggestive but not confirmed cases on the FDA list, Cephalon has identified 8 reports considered suggestive of possible hypersensitivity but not indicative of EM, SJS or TEN spectrum. The other 4 cases were also not considered suggestive of SJS. In the Phase 3 placebo-controlled trials the incidence of rashes coded by the COSTART coding system was 4 percent in the modafinil treatment group and 2 percent in placebo. As we all know, the preferred term "rash" in the COSTART coding system does not include many terms that could be considered non- urticarial rash. Therefore, Cephalon undertook an additional analysis to ascertain the incidence of non-urticarial rash. In collaboration with 2 external dermatology experts, we defined a category of non-urticarial rash which included all adverse events indicative of rash, excluding urticaria and related reactions. Using this definition, cases of non-urticarial rash in the pediatric ADHD studies, as well as in the pediatric studies for excessive sleepiness and in all adult studies with modafinil were identified and frequency tables were constructed. Additionally, all reported adverse events of urticaria, hypersensitivity reactions and all allergic reasons in the pediatric ADHD studies were reviewed for possible underlying causality and prior medical history. Based on the described methodology, we calculated the incidence of non-urticarial rash across treatment groups in controlled pediatric ADHD trials and in all pediatric patients. This table presents the incidence in the placebo-controlled trials. We also present the incidence of those described as severe and those leading to treatment withdrawal. The overall incidence of rash was higher in the modafinil treatment groups, with few being described as severe or leading to treatment discontinuation. In the ongoing open-label study in ADHD initiated after the supplemental NDA submission a total of 303 additional newly exposed patients entered the study, with 188 receiving modafinil for at least 4 weeks. Presented on this slide is the observed incidence of non- urticarial rash in that study. As in the previous slide, we also present the incidence of events described as severe or those leading to discontinuation. As seen on this slide, the reported incidence is somewhat lower compared to the modafinil group in the controlled studies. One patient reported a severe rash on day 10 and discontinued the study on day 13 due to this rash which was described by the investigator as rash. The overall incidence of non-urticarial rash reported in the controlled pediatric studies for excessive sleepiness was similar between modafinil treatment groups and placebo. These are much smaller studies Additionally, the observed incidence was lower compared to ADHD pediatric studies. Only one event was reported as severe for events described by the investigator as fifth disease. No events led to discontinuation or were serious by regulatory definition. The observed imbalance in incidence of non-urticarial rash in the controlled ADHD pediatric studies prompted further evaluation for possible association with treatment. We approached this in 3 ways. We evaluated the relationship between rash and dose; relationship between rash and modafinil plasma exposure; and, finally, we evaluated the relationship between rash and modafinil sulfone exposure, one of the metabolites known to be present in higher concentrations in children. With respect to relationship of non-urticarial rash and dose, we conducted a case-control analysis where patients with rash were matched with controls based on the study protocol, time in the study to event and weight. Based on this analysis, we did not find statistical evidence for association between rash and modafinil dose. A second analysis looked at the modafinil plasma exposure by comparing area under the curve between patients reporting non- urticarial rash, in the far left box on the slide, controls, in the middle box, and overall patient population in Phase 3 studies, in the far right box. Areas under the curve were calculated based on sparse sampling data from the Phase 3 trials and PK modeling. As presented on this slide, no difference was apparent between the 3 groups. An assessment of the relationship between non-urticarial rash and exposure to modafinil sulfone was also conducted. Here we graphically depict the distribution of modafinil sulfone concentrations in patients developing rash -- small red boxes at the bottom, and in patients not developing rash -- blue boxes. On the Y axis the number of patients is depicted and different modafinil sulfone concentration ranges are depicted on the X axis. We observed that the distribution of sulfone concentrations in patients with rash appears to closely mimic the distribution of sulfone concentrations in the full population of treated patients in placebo-controlled studies. We conclude, therefore, that there appears to be no correlation between non-urticarial rashes and systemic exposure to modafinil sulfone. One additional piece of information is that 2 cases in question had modafinil sulfone concentration of less than 6 mcg/ml. We have also examined the adverse events database from the controlled ADHD pediatric studies for COSTART preferred terms indicative of urticaria, hypersensitivity reactions or allergies. This slide presents a tabular summary of the reviewed preferred terms and associated medical history reported prior to treatment initiation. One can easily see from the table that the vast majority of these events was reported in patients with prior history of seasonal allergies or asthma. Psychiatric adverse events related to ADHD treatment have enjoyed special interest in the recent months, culminating in some important discussions as recently as yesterday. In response to the request from the Division issued to all ADHD drug manufacturers, Cephalon has performed a full analysis of psychiatric events from all pediatric studies and from our pharmacovigilance database as per prespecified methodology. In addition, we have reviewed serious adverse events occurring after the last safety update cutoff in October, 2005, covering the period through February 1, 2006. The results will be presented in the next several slides. GOODMAN: Excuse me just a moment, I want to ask a question of clarification on the previous metabolite levels that you showed. What was the relationship between the timing of obtaining the sulfone metabolite level and the dosing? Obviously, there can be a lot of noise contributed by relationship between time of assay and dose. STANKOVIC: We obtained the values for concentrations of modafinil sulfone closest to the event for those patients that reported a rash. GOODMAN: But it might not have been the same relationship to the time the dose was actually taken. Right? STANKOVIC: That is right, yes. That is correct. A brief introduction on methodology of the psychiatric evaluation, all adverse events reported in the ADHD and excessive sleepiness pediatric programs were subject to a review by a string search for COSTART preferred terms of investigator verbatim terms indicative of psychiatric events. Once identified, all events are classified in the following groups, psychotic events including mania, suicidal ideation and behavior, aggressive and violent behavior and miscellaneous psychiatric events that were serious by regulatory definition. A similar string search approach was employed in the review of our psychovigilance reports. Event terms and narratives from the ongoing pediatric studies for serious adverse events were reviewed in order to identify psychiatric events as well. We present here psychiatric adverse events from the ADHD pediatric program. Just a quick note, this table includes both events that occurred during treatment as well as those that occurred 48 hours following last dose of modafinil. As I will be discussing these cases, we put them together. This is somewhat different than the methodology applied in the tabulations presented yesterday. In the controlled studies all psychotic events, as well as all events of suicidal ideation or behavior were reported in modafinil treatment groups. Reports of aggression or violent behavior were relatively balanced between treatment groups, with a slight higher proportion of these events occurring in placebo. Additionally, no serious miscellaneous events were reported in either group. When the smaller pediatric program in excessive sleepiness was examined, no psychotic or suicidal events were found. Obviously, even few events or a psychotic or suicidal nature are a great concern so we will review them in more detail. A total of 5 patients reported psychotic symptoms while on modafinil treatment, all within 48 hours post last dose. Three of these events were relatively short in duration and why patients continued modafinil in one case or following withdrawal of the drug in two cases. One additional case, described as psychotic disorder aggravated, was also relatively short in duration but did require hospitalization and led to withdrawal from study. This case, also in the narrative, we learned reported as suicidal verbalization but it is included in this table in the psychotic disorders. The fifth case was an interesting case of reported ideas of reference that apparently did not require any specific treatment -- yes, sir? GOODMAN: We have a question. PINE: I want to understand both of these cases because the last two cases don't really make sense to me and I am wondering if you could go into them in a little detail, really the last case more than the second to the last one. When it says psychotic disorder aggravated, that implies to me that there was either a pre-existing psychotic disorder or some other factor that was contributing and it sounds concerning that the child was hospitalized. So, that is one question. The second question is that this is a case of ideas of referential control which, again, sounds somewhat concerning and the event lasted ten months, which is also somewhat concerning if those are really ideas of referential control, but the action taken was to continue with modafinil. So, that doesn't make any sense to me. I wondered if you could explain those situations. STANKOVIC: Yes, I can talk a bit about those cases additionally. The psychotic disorder aggravated is an 8 year-old boy with ADHD. He presented with severe psychosis beginning on day 19 of the open-label study. He was hospitalized and at the time of hospitalization we learned that there was a prior history of a psychotic disorder that was not reported at the time of the entry to the study. The second case is a very interesting case to us as well. Unfortunately, we do not have quite a clarification of continuing modafinil treatment in ten months of continued ideas of reference. We don't have any additional details. It is interesting and somewhat confusing but that is what happened. The investigator continued treatment for an additional 10 months. PINE: Just to make a comment about that, I mean, not only does that raise questions about this case but it raises questions about the nature of the data in general because it just wouldn't make sense that somebody would see something like this, and idea of reference, that would be ongoing for ten months but not feel the need to take any treatment. Anyway, I guess it speaks for itself. STANKOVIC: We have here a similar presentation for the 5 patients reporting adverse events classified as suicidal ideation or behavior. The first 3 patients experienced brief episodes of suicidal ideation, described as suicidal statement. In 1 patient this happened on 2 occasions. None of these events required either treatment for the event or study drug discontinuation. One patient verbalized a suicidal threat which was resolved after study drug was discontinued. One case, however, is a case of aggressive behavior reported initially as normal behavior. The case narrative described suicidal behavior in a 6 year-old girl with a psychiatric history and possible family history. The event occurred 2 days following the last dose of study medication and required hospitalization and prolonged treatment. Between the last safety update in November, 2005 and February, 2006 4 serious adverse events indicative of suicidality of psychotic symptoms were reported in the ongoing pediatric studies. These include both ADHD studies and ongoing pediatric studies in excessive sleepiness. Three patients reported events that were classified as suicidal events, ideation or gesture. In 2 of these cases no treatment intervention was required and the patients continued in the study. Treatment was withdrawn for 1 patient. One additional patient reported paranoid reaction following 16 days of treatment. The event lasted 5 days and the study drug was withdrawn. In the request from the Division for analysis of psychiatric adverse events, we have been asked to review postmarketing reports received during the period January, 2000 to June, 2005. We estimate that for this particular period the total pediatric exposure approximates 24,700 patient-treatment years. A total of 7 psychiatric reports were received during this period. These are the events reported. The events were reported in a wide ranges of ages, as you can see, from 6 to 17 years, and across both genders. Four events involved psychotic symptoms. One event was reported as a suicide attempt. However, in this case modafinil was not taken prior to the event but was only taken as a part of the cocktail of drugs used in the multi-drug overdose. The 2 remaining cases are events of aggressive symptoms and violent behavior. You may wonder at this time how does the safety profile of modafinil observed in pediatric ADHD studies compare to other programs in children. We have one additional program, smaller, completed as a part of the pediatric retail request in narcolepsy and obstructive sleep apnea for excessive sleepiness. I will review here the general safety profile observed during the pediatric development program in this indication. Overall, a similar safety profile was observed in the small patient population; a similar AE profile, effects in vital signs or laboratory parameters were observed. Notably, no adverse effects on weight were observed during the short-term trials in this patient population. Lower incidence of non-urticarial rash was observed compared to ADHD studies, and no events led to discontinuation or were serious in nature. One serious adverse event from the pediatric studies in excessive sleepiness requires discussion as it was mentioned as a point of concern in the FDA clinical review as a possible case of Reye's syndrome. The clinical picture in a 6 year-old boy was that of a non- specific viral syndrome -- nausea, vomiting, pharyngitis, followed 3-4 days later by a change in mental status characterized by somnolence, delirium, hallucinations and seizures. The patient had elevated serum ammonia but not transaminases. The case was reviewed at Cephalon's request by two external consultants, one pediatric neurologist and one pediatrician. The consensus opinion was that the most likely diagnosis was viral encephalitis or inborn error of metabolism. Urea cycle disorder was mentioned. Reye's syndrome was considered unlikely because of normal LFTs. According to the FDA briefing package, the FDA consultant also concluded that this case is not drug related. Some of the postmarketing information has been reviewed earlier as part of the discussion on skin and psychiatric reactions. Here we will review the profile of the reported events through our pharmacovigilance system from the perspective of different system organ classes. First, review of estimated postmarketing exposure, we estimate that as of February, 2006 total postmarketing exposure to modafinil was 780,000 patient-treatment years. This includes worldwide exposure for the period since drug approval in the first country in 1999. As it appears, based on the prescription data market research that we have, 4 percent of these exposures included individuals less than 18 years of age so we estimate that the overall pediatric exposure is about 30,000 patient-years. Based on some information that we have available, the estimated median duration of treatment with Provigil in the market is approximately 3 months. So, using those numbers, one can estimate exposure to modafinil to be higher than a million, up to 3 million adults and in excess of 100,000 children. Presented on this graph are comparative profiles of postmarketing adverse drug reactions reported for adult patients, in blue rectangles, and pediatric patients, in orange. The total number of reported adverse drug reactions in a particular system organ class is presented on the Y axis while different system organ classes are presented on the X axis. We had a total of 105 adverse drug reaction reports for all pediatric patients. As you can see, although it is a little hard on this slide, the two profiles appear largely similar across different organ systems. It should be noted, however, that the we do not have reliable information on how the two populations relate with respect to underlying indications for which the drug is prescribed or doses used. Based on the postmarketing reports, the Provigil label is continuously reviewed and updated as deemed necessary. This slide is a reminder of 3 label changes initiated by Cephalon within the past 3 years. As you can see, some of the safety events observed in the pediatric ADHD program are fairly consistent with the postmarketing experience that resulted in label changes. I have reviewed a considerable amount of safety information and will try in the next two slides to briefly summarize the main points. We believe that it is fair to say that modafinil is generally well tolerated at doses studied. Not unusual for ADHD medication, the most frequently reported adverse events were insomnia, headache and anorexia. These events were seldom severe and few led to treatment discontinuation. Likewise, few significant laboratory abnormalities were observed. No effects on mean systolic blood pressure, diastolic blood pressure, pulse or QTc interval were observed in the controlled trials. Beyond initial weight loss, there were no consistent adverse effects on growth observed over 12-month treatment with modafinil. We did observe events of suicidal ideation and psychotic events in the ADHD pediatric patients treated with modafinil. These events were short in duration in general and did not require additional treatment in many cases. We believe that there is one case of probable Stevens-Johnson syndrome reported in the pediatric clinical program so far at this point, at an exposure of 1622 patients. This case resolved without any adverse sequelae. As I mentioned, I am sure that there will be more discussion of this case and we will hear from the investigator and consultants on this. In the next presentation Dr. Lesley Russell will review... GOODMAN: Before you go to that presentation, Dr. Rappley? RAPPLEY: I have two questions; the first, in the 30,000 children that you expect were exposed in the postmarketing period, do you expect that most of them received the 200 mg dose? STANKOVIC: As I said, it is very difficult to know exactly what dose was prescribed and for what indication it was prescribed so I cannot comment on that. I don't really know. As Dr. Temple mentioned earlier, one can assume a variety of things. Whether it was 200 mg or higher, we don't know. RAPPLEY: And, in your study 310 it was cited for not obtaining hematologic values, and one of the sites was with 21 patients. In looking at your table on slide 76 which describes neutrophilia, to what extent did those missed samples affect your data? How many samples were missed? STANKOVIC: I can't give you the exact number; I don't know it off the top of my head, but I think that the number of analytes may be 390 or maybe 20 or 30 patients that don't have all of the analytes, but I am not positive about that. I can find you that number. RAPPLEY: Thank you. GOODMAN: Dr. Leon? LEON: I would like clarification on the case control analysis you did. In the sponsor book it is on page 64-65. You very briefly made reference to your analyses... STANKOVIC: Yes. LEON: ... in your slides, that you found no risk of a variety of dosing factors for the rash. It was a dependent variable. It was a case control where you had 39 cases and 3 times that number, 117, controls apparently matched on 3 variables. I have some questions. First of all, it looks like you entered about 14 variables that were very highly correlated simultaneously. I mean, that is what it says here. The effects were measures of dose entered at one time. RAPPLEY: Will you show us the document you are referring to? Is it this one? LEON: Yes. Sponsor's book page 64-65. I mean, this is being used as evidence of no association when the analyses were not conducted in the way that I believe an association would be detected. So, my first question has to do with entering all those variables simultaneously, very highly correlated measures of dosing. My second question has to do with what is the statistical power you would have with this sample size? You would have statistical power to detect what effect? The sample size is only 39 versus 117. Would that be an odds ratio of maybe 2 or 2.5? You could miss some pretty substantial associations. Third, did the analyses account for the clustering of these sets of 4 who were matched? In what way did it account for it? KINGSBURY: Let me address these one at a time. First of all, let me inform you that we did not use all 14 variables at a time. This was just different approaches to explore those and they were done one at a time. OK? First of all, let me describe the matched control analysis that we did. There were 39 cases. We found 3 matched controls, as described in the briefing document. As already indicated they were matched by the study they came from; by the weight stratum they were in; and also by having been in the study at least as long as the time taken for the event to take place. So, in that set, using each of those 14 variables one at a time, we looked at the distribution of whatever the dose was in quartiles and tried to ascertain whether there was a relationship, but understanding the limited power. This is more of an exploratory analysis... LEON: What was the way that you accounted for the clustering of these quartets of case controls there? What was the analysis? KINGSBURY: I am sorry? LEON: Well, you have groups of people, as you would in a paired T-test if you had diads, and you have sets of 4 people who are matched on these criteria that you just described, and I want to know what is the statistical analysis that was used to account for this clustering, the correlation among these sets, these quartets. KINGSBURY: We did essentially a conditional logistic regression in which we defined this stratum as the case. We identified each case and the corresponding matched controls. Then we looked at the odds ratios of each of the various increasing quartiles relative to the fist quartile just to get a sense -- I mean, this was very much a descriptive statistical approach to see if there was any evidence of a consistent dose response. We did not find that. LEON: So, you acknowledge limited power. You have power here with 150 subjects total to detect what size odds ratio? Just so you can let us know the magnitude that might have been missed there. KINGSBURY: Because it was not an a priori designed analysis, we did not focus on that issue. We actually did not test anything; we were just obtaining confidence intervals because that is all we felt would be appropriate. As I mentioned before, although the confidence intervals overlapped 1, the odds ratios extended from 0.09 to a little over 2. LEON: But when you are looking to see if confidence intervals are overlapping 1, then you are doing tests, exactly the same as looking at p values. You are getting more information as well about the magnitude of the change and about the variability of that change, that association. KINGSBURY: We don't claim to have shown no association. All the conclusion we are making is that -- by the way, consistent with the limitation in the numbers that we have no compelling evidence of an association, we did an additional analysis based on the randomized clinical trial data, and from that analysis we found an odds ratio of 1.4 with a confidence interval extending from 0.678 to 3.094. Going back to the case control analysis... GOODMAN: Thank you very much. Let's go on to our next speaker. Thank you. STANKOVIC: The next speaker is Dr. Lesley Russell. RUSSELL: Thank you, Dr. Stankovic. We have presented a lot of information this morning regarding the efficacy and safety profile of modafinil in the treatment of ADHD. Following your deliberations, you will be asked to answer two questions, the first being has modafinil been shown to be effective for the treatment of ADHD in children and adolescents? We believe that the answer to this first question is yes. In the 3 pivotal studies consistent benefit of treatment with modafinil was seen in all 3 studies, with these effects observed by the teacher, the parent and the treating physician across different rating scales and instruments, and with effects being observed both at home and at school. You are also going to be asked today whether modafinil has been shown to be acceptably safe for the treatment of ADHD in children and adolescents. In the Phase 3 clinical program modafinil was generally well tolerated. The most common adverse events reported, insomnia and anorexia, were generally mild to moderate in severity and rarely a cause for treatment discontinuation. No adverse signals were observed in the Phase 3 program with respect to pulse, blood pressure or growth. We were asked in the approvable letter to provide more information on 3 cases of liver transaminase elevations. As outlined in our response to the approvable letter and presented here today, in 2 of these cases the transaminase elevations were resolving on continued treatment with modafinil with, in 1 case, ALT values returning to normal whilst continuing treatment. In the third case the transaminase levels were returning to normal on discontinuation of treatment. We do not believe that an adverse signal with respect to liver function has been observed. Concerns have been raised over the reporting of psychiatric adverse events. As you are aware, these events were fully discussed yesterday at the Pediatric Advisory Committee for all ADHD products. Although no consensus was reached on how to label aggression, psychosis, mania and suicidality, Cephalon has proposed language in the warning section of the label which we believe provides appropriate information regarding these events seen in our clinical program. Concerns have also been raised over the reporting of serious skin reactions, and in the approvable letter we were asked to provide you with more information on 3 cases of interest seen in the clinical trials and 4 cases reported in adults in the postmarketing setting. As suggested by FDA, these cases were reviewed by experts in the field and there appeared to be general concurrence reached by these reviews and Dr. Porres, from the FDA, with respect to the first case, the 7 year-old boy with possible SJS. But there does appear to be some diversity of opinion regarding the other 2 clinical trial cases. This seems to be in keeping with the diagnostic and etiologic uncertainty surrounding the diagnosis of these types of skin reactions. However, we acknowledge that an association with modafinil cannot fully be excluded. In all 3 of these cases, however, the events did abate following discontinuation of drug and no adverse sequelae occurred. In assessing the risk for SJS and reviewing the totality of the data in the clinical trials and postmarketing database for both adults and children as reviewed, we believe that the risk for SJS is low. However, we have proposed language to be included in the warning section of the label. Based on your deliberations today, we will be happy to modify this as appropriate in order to provide patients and health care providers with adequate information concerning these events. Lastly, modafinil is not a new chemical entity and to date there have been 780,000 patient-years of exposure which, when looking at actual patients exposed, may equate to approximately 3 million exposures since introduction of the drug in France, in 1994. Pharmacovigilance is undertaken to assess risks associated with modafinil usage and, as you have heard today, this has led to 3 labeling changes, one regarding the incidence of severe skin reactions. Cephalon is committed to improving these risk assessments further by undertaking a more structured case ascertainment with respect to skin adverse events. So, in conclusion, we believe we have shown you today that modafinil is an effective treatment for ADHD with an acceptable safety profile, with the benefits of treatment outweighing its risks. Thank you for your attention. GOODMAN: Thank you. May I suggest that your team stay at the podium to address some questions? I am going to assume that most of the committee members are going to have questions for you. If we start to run out of time, we are going to have more opportunity to ask those questions later this afternoon. Let me start off with what may be the easier of the two questions we are asked to vote on today, the one regarding efficacy. From the FDA standpoint and what I read, they were satisfied with the efficacy data. I certainly feel satisfied from what I have seen. Yet, before we move on to the harder question of evaluating issues of safety, it is very important to have the context in mind of the benefit. So, I want to give you an opportunity to answer, from your perspective, where you see this medication fitting in; where is it going to add value or options in the marketplace? Is it going to be advantages in the area of efficacy, tolerability? I wonder if you could just expand on those issues to give a little bit of a framework to think about the benefits of this medication. RUSSELL: Well, as you heard from Dr. Biederman with the MTS study, despite treatment with drugs that are considered to be very effective -- and we certainly don't doubt that -- there does remain a group of patients that still either cannot tolerate drugs or don't respond to them. We saw in our program that, although maybe not considered refractory, patients who had failed on a prior stimulant therapy did appear to benefit from the drug. We also saw that if you are stimulant naive you respond slightly better to the drug. So, we see this as a viable treatment alternative to other drugs that are obviously commonly used and considered to be effective agents. However, I would like to have a treating physician in the field come up and maybe give you that from his perspective. So, if I could ask Dr. Biederman? GOODMAN: Sure, go ahead. BIEDERMAN: I think that in clinical practice we need alternative treatments to treat our patients. The idea that the most efficacious treatment treats all our patients is not true to life. So, clinicians in practice need to have options to allow us to better serve the people that consult with us. The issue of adverse effects is a statistical issue. That means that even if side effects are similar within a class of drugs, some patients clearly tolerate one versus another even if on average they have a similar spectrum of adverse effects. So, patients that have poor tolerability may benefit from a drug that may have on average similar issues but may be better tolerated for them. Finally, the issue of scheduling -- I think that even though many of the new generation stimulants that are available today are clearly less of an issue for diversion and abuse, many clinicians and many families do not want their children to be on a Schedule II drug. So, I think that this gives an option for clinicians to use a lesser scheduled drug in cases where they choose not to use a scheduled compound. GOODMAN: Joe, before you step down, has it been your impression so far that there is less abuse potential, less potential for diversion as, say, compared to stimulants? BIEDERMAN: Yes. I am not an expert on abuse and we have here a colleague that specializes in that. The abuse and diversion -- first of all, let me comment on abuse and diversion. There are different publics that use these drugs recreationally and therapeutically. Our battles in clinical practice are to encourage our patients to remain in treatment. There is a very severe problem of non-adherence to these treatments. So, it is not something that our patients look forward to taking. The attraction of the stimulants is when the tablet can be crushed and snorted for an IV-like experience. It is the parenteral intake that produces the euphoria, not the oral intake. So, this drug is not snortable, injectable, and so on and so forth, so it is not a drug that the addict community on the street would pay a high price for to get it. But maybe we can get some of our colleagues that are here with better expertise than mine on diversion and abuse to give a perspective. RUSSELL: Does that answer your question? GOODMAN: I would like to hear a little more on that issue. RUSSELL: Dr. Dackis? DACKIS: With regard to the abuse potential of modafinil, I think it is important to note that it is chemically unrelated to central stimulants and has a very weak effect on the dopamine transporter so that it is extremely unlikely to increase dopamine levels, except in very high dosages. There have also been a number of studies in humans to assess what the subjective effects of this agent are and these studies, which have been conducted by Jasinski demonstrate that in males there is no effect of modafinil. There was a smaller study in females that did show some stimulant effects using these various rating scales. Two other studies, again, showed that there was not a significant high; that the subjects were not willing to pay money for modafinil, et cetera. In addition, animal studies, looking at things like self- administration and condition-place preference showed very weak stimulant-like effect of this agent. So, there is some reinforcing quality but it is very, very weak. GOODMAN: I thought monkey studies showed preference. DACKIS: Yes, that is correct. Gold and Balster's study did show that monkeys, trained to self-administer cocaine, if given modafinil would continue to self-administer large doses of this agent, as they would with other compounds like ephedrine. So, large doses are required to continue to self-administer. GOODMAN: Thank you. Dr. Temple? TEMPLE: I am sympathetic to the idea that drugs with different pharmacology may have different usefulness, but I want to address the question of whether they have documented the ability of this drug to work in people who are resistant to stimulant drugs, and the answer is that they have not. There is a perfectly simple, never done kind of study design to do that. You take people who fail on whatever it is you want to test and then you randomize back to that drug and to the new drug. It is a perfectly simple study. That is how clozapine came to the market because we wouldn't have approved clozapine unless it worked in failures because of the 1.5 percent agranulocytosis. That study could be done. You might even think about whether it is something that ought to be done, but it has not been done. The mere fact that people given a second drug after failing the first respond to it tells you nothing at all. We have many examples where drugs don't particularly work in non-responders to other therapy but the second time around the people do better. So, I just want to make it clear they have not shown that. It might be true. It is plausible even but it hasn't been shown. PINE: Can I ask a question about that? Of course, there have been other medications that have been discussed over the last couple of years for new indications for ADHD and I am sure that that issue came up. I think that those studies have not been done and what was the thinking and discussion around that? TEMPLE: Well, they are almost never done. We don't usually have a reason to say, for example, only use this drug in people who have failed on other therapy, if one thought that was an appropriate thing because I am not saying you should or not -- you are going to get to that. I am just making the point that they have not documented in a rigorous way that the drug would actually work in those people. You might think that there is a little evidence that it does, and you might think the pharmacology difference suggests that it might, all of which I agree with but that hasn't been studied and it can be studied, and it never is studied. PINE: For what it is worth, my take on it would be that that would only be one of the potential uses of the medicine clinically, and it seems like some of the other issues are, you know, kind of bigger in terms of thinking about the medicine as opposed to, you know, is it primarily for people who don't respond to stimulants. REESE: We are going to get to everyone's questions. First we are going to have Dr. Bronstein and then we will have Dr. Wang. Thank you. BRONSTEIN: My question is a fairly straightforward, easy one. On slide 93, in the Phase 3 study you have one person who had a severe event and withdrew from the study. What kind of rash was this? RUSSELL: Unfortunately, the only description on the case report form, which reflects the source documents, is just a verbatim of rash so I am unable to describe it further for you. BRONSTEIN: We can assume though that it was severe. RUSSELL: It certainly led to discontinuation of the drug. That is all the information I can give you. BRONSTEIN: Thank you. REESE: Ms. Dokken? DOKKEN: Yes, I apologize, I thought we were supposed to hold our questions until the end so my question really goes back to slides 30 and 31 and this issue of the 40 percent who are non-responders or had intolerable side effects. I am wondering whether anyone can sort of unpack, you know, how many people are in which category because it seems to me that what we have been hearing is that one of the marketing messages for modafinil will be that it is an alternative. If it is an alternative and we are talking about whatever percentage of that 40 percent are ones who suffered "intolerable" side effects, certainly this particular drug -- and those of us who were fortunate or unfortunate enough to be present yesterday, you know, the side effects are present in almost all. Then that leads me to the worry about the next step which is, you know, if it were approved how is it marketed and what are the messages because probably it was the Pediatric Advisory Committee that has seen, you know, other situations where something is marketed as being free of something else, suggesting that there are no risks and to say that because it is a non-stimulant it has no risk would be a concern for me. TEMPLE: Drug advertising reports to me so I have to worry about this. We are fairly careful about making claims when you don't have a direct comparison and there aren't any direct comparisons. However, if one is scheduled at a different place, or something like that, that is true and they would be allowed to claim that. There are some cases in which the difference in certain side effects is so obvious -- like it never happens with this and it happens all the time -- where we might allow something like that. But we are very careful about comparisons in the absence of actual comparative data across study comparisons and treat it with suspicion. REESE: Dr. Pfeffer? PFEFFER: Thank you. I am not questioning the efficacy but I have some questions on slides 52, 53 and 54, please. Maybe you can help us understand the longitudinal process of the three studies. For example, it looks as if in slide 52 I guess efficacy was being demonstrated by week 5. Then in slide 53 and 54 it seems that it was earlier, although on slide 53 at week 5 there was perhaps less of that. I don't know if that is due to dropouts and then resumption. So, my question is on the early phase of these, week 3 and even week 2 on slide 54, what were the general doses that the children were on at that point in time? Then, if you can tell us what happened in week 5, on slide 53? Finally, if you could tell us a little bit about when were blood tests taken in the process of the study and when did the side effects emerge, especially skin reactions, et cetera? I am trying to link the time course with the doses and the longitudinal course. RUSSELL: In study 10, which is the slide up here, this is the fixed dose study so that by the second week patients would have been titrated to that target dose. That would have occurred by day 7 for those randomized to 340 and day 9 respectively. PFEFFER: I thought I understood that but my concern is if, in slide 53 and 54, you see earlier efficacy is that at the target dose or less than the target dose? RUSSELL: In this study, which is the fixed dose study, they would have been at target dose. Could you go back to the previous slide for 311, please? This is one of the flexible dose titration studies. So, in the earlier weeks they would have still been titrating up. PFEFFER: Do you know approximately the average doses at the early phase? RUSSELL: Probably around 255 mg by the second week and up to the 340 mg by the fourth week. PFEFFER: And on slide 54 it is similar. Is that right? RUSSELL: Slide 54, which I think is study 310, is where they titrated up more quickly so they would have been at target dose by day 7 and 9 respectively. REESE: Dr. Armenteros and then Dr. Malone? ARMENTEROS: Just to follow-up a little bit on the dosing question, I understand the model that you used to dose the two groups of children, you know, below 30 kg and above. Now, most of the children that got into the study were above 30 kg, like 68 percent that you mention here. Now, when you presented data on efficacy there wasn't a differential response between these two groups by weight. The reason that I ask that question is that we already know from your previous studies that at lower doses you do get response for daytime sleepiness, and so forth. So, I don't know if we may be missing perhaps different points in dosing at which these kids may respond. Because at the end of the trial I come out with a very fuzzy impression of what the actual dosing should be and I hope I can get a better understanding. RUSSELL: First let me answer the excessive sleepiness programs first because what we do find is a very different pharmacodynamic response when we are treating excessive sleepiness than when we are treating ADHD. So, in the excessive sleepiness programs and the pediatric narcolepsy, although we looked at doses of 100 mg through 400 mg, doses of 400 mg were clearly efficacious in that model. Then we did some PK/PD work and the target exposure needed for an effect in narcolepsy is substantially lower than the target plasma exposure associated with effect in ADHD -- so very different pharmacodynamic response which I don't think I can explain, but it is very different. In terms of looking at the doses and how did they respond to efficacy, what we did was to look at the different quartiles of dosing and in the third and fourth dosing quartiles, which are the higher dose groups, you see numerically a slightly higher response but it is only a point or two. So, I would say that the dose response, with all the caveats because we were titrating to a target dose, is flat in the doses that we looked at here. REESE: Dr. Malone? MALONE: I have two questions. One is on efficacy. The stimulants wear off every day by the end of the day. Is that true for this drug? I am just wondering if it is like the stimulants, that you have to dose it every day; you dose it in the morning and then it wears off by the evening. RUSSELL: The only data we have with respect to that is actually in the 2-week withdrawal period where the patients who had received modafinil during the double-blind treatment period were randomized to either stay on modafinil or were randomized to receive placebo. What we see is not an immediate return to baseline in symptoms but a more gradual return towards baseline and their symptoms. So, based on the limitations of that data which I acknowledge here, there doesn't appear to be a sort of complete rebound effect. REESE: Dr. Bigby? BIGBY: I have a question about the ADHD rating scale. If you gave this test to a group of normal kids who don't have ADHD, what would their score be? RUSSELL: The average for a 10 year-old boy I think is 18.8, and the children going into our study had an average of around 37. So, they were clearly much higher than what would be considered to be normative for a 10 year-old boy, which was the average population in our study. It does differ a little bit based on whether you are a boy or a girl or your age, but that appears to be the average for a 10 year-old boy. GOODMAN: Dr. Temple? TEMPLE: In one of the studies you actually did a withdrawal phase but I believe the data weren't shown. RUSSELL: That is right. TEMPLE: You must have a slide of it. That would answer the question of how soon it wears off. RUSSELL: If I could have the slide, please? This is over the 2-week withdrawal period. You can see on the right-hand side that the placebo at the end of the 7-week period and the end of the 9-week period obviously stays the same. In the modafinil group there is a point difference, but for those who were on modafinil and then got changed to placebo you can see that there is a beginning of deterioration of their symptoms over that 2-week period. It is not huge but there is a deterioration and it looks like they are returning towards baseline. But there doesn't appear to be a sort of instantaneous effect. TEMPLE: And you don't have it day by day or anything like that? RUSSELL: Unfortunately, we don't. REESE: Dr. Malone, your second question and then Dr. Rappley. MALONE: It was really I guess partly answered. It had to do with the abuse potential for modafinil. I think, from the reading, it did say that it can cause euphoria and that animals would work for this drug. If that is true, I just have a question why would a stimulant be a Class II and this a Class IV? How do they decide that? GOODMAN: Dr. Temple or Dr. Laughren? I have a very similar question about the classification. Currently this drug is classified Schedule IV compared to the stimulants which are Schedule II. Could you just explain that distinction? It would be in the context of a quick follow-up I was going to do and ask sponsor how they would best characterize or classify their compound. LAUGHREN: Actually, FDA doesn't decide that classification. The decision is made by the Drug Enforcement Administration. They do an 8-factor analysis. I haven't looked at that. Maybe the company could respond to, you know, how it is that the DEA arrived at a Class IV rather than a Class II. TEMPLE: There is a very sharp distinction between the level of control. I think we are about to hear about that. II is, you know, locked cabinets and all the rest; IV is much less. GOODMAN: Yes, please, could we hear about that? RUSSELL: The difference between a Schedule II and a Schedule IV, is that what you are asking? LAUGHREN: How it got a Schedule IV rather than a Schedule II. RUSSELL: I wasn't with the organization at the time of the original scheduling. Perhaps I could ask Dr. Vaught, who was here, to explain how that happened. VAUGHT: Good morning. My name is Dr. Jeff Vaught, executive vice president for research and development for Cephalon. I would like to very briefly just go over the aspects of scheduling which, certainly the agency knows as well as I do, has to do not only with the physical chemical characteristics of the compound but also testing that is done in human beings to suggest that there is a reinforcing property. So, if we look at the overall physical chemical activity of modafinil, it has very, very low water solubility which is incompatible with intravenous injection. It is very unstable at high temperature, therefore, it is incompatible with smoking. Importantly, it is structurally unrelated to other agents that are known to be abused. While it does have a very, very weak -- and it is really the only neurochemical effect that we have been able to demonstrate in blood receptor binding assays, et cetera -- with dopamine. It doesn't appear to cause elevations of dopamine of nucleus accumbens, which is markedly related to drugs of abuse, as well, it has not releasing properties as do other Schedule II stimulants. There is also lack of activation, as I mentioned, of reward centers, and really the results, as Dr. Dackis described to you, from preclinical studies suggest that if there is a signal it is very, very weak. Now, all this is theoretical because that is all nonclinical data. Perhaps more importantly and something that we undertook at Cephalon spontaneously, is a postmarketing surveillance, starting in 1999 with the Haight Ashbury group. The Haight Ashbury group monitors a variety of areas worldwide where drugs may be diverted to, including rave scenes, medical professionals, et cetera. Now that we have had six years we still have reporting on this. There have been limited to no reports of euphoric effects. There are no reports of reinforcing effects. There has been a very large increase since the drug has been approved for wakefulness for mainstream publicity regarding the use of modafinil, including in The New Yorker magazine, college newspapers, et cetera, and across the Internet every now and then we will see postings of potential use but nothing that is consistent. In fact, the Haight Ashbury concludes after evaluating this for the last six or seven years that if there is abuse potential for modafinil at all, it is very, very low. So, all of this is consistent with what is seen as an agent with low abuse potential. We now have considerably more experience with the substance than we did five or six years ago when we were getting approval and we thought that was consistent with the regulatory standards for Schedule IV. GOODMAN: Thank you. Apart from how DEA will classify your drug, how would you internally classify it? Would you say it is a stimulant or is it distinct based upon its mechanism of action, which I understand is unknown. Although I know at one time it was thought to be mediated through orexin receptors, I guess that is not as firmly established at this point. The reason I ask is not just a semantic question but whether it gets counted or considered a stimulant may have labeling implications. As revealed by discussions yesterday, for example, Strattera, should that be considered a stimulant and, if so, should it have certain warnings attached to it that go with the rest of the class of stimulants? So, I would just like the sponsor's perspective on whether you would classify this medication as a stimulant or not. VAUGHT: We approach this from a couple of levels. One is the preclinical data that we have, as well as the clinical information. In direct answer to your question, I would not classify it as a traditional sympathomimetic stimulant. It is a CNS activating agent and we have all been taught, prior to the introduction of modafinil, that, in fact, most of our CNS activators are psychostimulants. Nonclinically, modafinil has a profile of wake-promoting activity that, unlike the classical stimulants -- its wake-promoting activities are not blocked by haloperidol which has been characteristic of wake, if you will. As far as the orexin component that is involved, we have been able to demonstrate it has no interaction with the orexin system because in knock-out animals, as well as human beings and dogs it is highly effective. When we move to human beings, we similarly don't see the typical types of profile that one sees with the stimulant population. If we include this with methylphenidate and amphetamines this includes sympathomimetic-like effects as well as generalized excitation reinforcing properties, euphoric effects, et cetera. So, overall the pharmacology would suggest that if we want to classify it as CNS activating agent it is certainly a non-traditional agent. GOODMAN: Would you say that it has less peripheral -- if you look at the relationship between CNS, there is relatively more CNS to peripheral activation? VAUGHT: Yes. GOODMAN: That was my last question. REESE: Dr. Rappley? RAPPLEY: My question goes back to the safety area and pharmacodynamics. Dr. Mannheim noted that we don't have information about steady state for the sulfone metabolite. We know it accumulates to a much greater extent in children but we don't know quite when that steady state is achieved and I wonder if you have more information about that. RUSSELL: The sulfone metabolite appears to reach steady state at about 2 weeks and then it actually plateaus thereafter. REESE: Dr. Wang? WANG: I have one more housekeeping question about efficacy. Are these effect sizes and response rates -- I guess this is either for the sponsor or maybe our pediatric colleagues -- are these response rates comparable to what is seen with other treatments for ADHD or is there some differential response here? RUSSELL: Dr. Biederman? BIEDERMAN: I believe that the computed effect size is about 0.7, very similar to the effect size of Strattera; lower than the effect sizes of the stimulants that are about 0.9. So, it is lower than the stimulants but potent enough to treat ADHD. WANG: Then this is actually a question for the FDA. The sponsor is already proposing warning language and I am curious what are the potential actions you can take. I mean, bolded warning; black box warning? Are those the same thing? Are there other intermediate warning language actions you can take? Because the sponsor is already proposing potential language. ANDREASON: I am sorry, I missed the first part of your question. WANG: Firstly, I should know this but is there a difference between bolded warning language and a black box warning? And, are there intermediates between them and what other options are there? ANDREASON: Yes, they are different. Which adverse event are we talking about here? WANG: They are already proposing language for, it sounds like, psychiatric adverse events and also for skin rash. LAUGHREN: Well, there is a difference between bolded language and unbolded language in warnings. I mean, sometimes if we want to give particular emphasis to something we will bold it. That is different than a box. A box goes as the first thing in labeling and it is surrounded by a box. So, that is very different than just bolding language in warnings. So, there is a continuum. TEMPLE: In the context of the CNS warnings, you need to think about it in the setting of the consideration of all of the drugs that went on yesterday, and so on. The skin is their own baby. So, if we were very worried about it we could put it in a box. Usually you put things in a box when you want to be very sure that the doctor absolutely, positively considers this before prescribing it. There are other things you can do. Ziprasidone, because of the QT prolongation, says you really think should think about using other drugs before you do this. You can go further, you can say this is absolutely only for people who fail other therapy. Sometimes we do that even if we don't know for sure, as I said earlier, that it absolutely works in people who failed other therapy. You know, because of its different properties, you assume there might be a population that responds that way. There are a variety of things you can do to try to direct therapy. We like to say we don't practice medicine but we do sometimes try to influence the way a drug is used if we are worried about its safety. The black box is the loudest statement. There is at least a perception that it affects use because it scares people. That is why some people like it and some people don't like it. Bolding is more prominent than non-bolding, and so on. REESE: Dr. Leon? LEON: Dr. Biederman, I would like to clarify what you said about the Strattera effect relative to what we saw in this trial. It is my understanding that the Strattera effect size was about 0.80 and in these data it was 0.56. So, this is quite a bit smaller. It is still a minor effect size but it is not as large as was seen in the Strattera trial. BIEDERMAN: To my knowledge, and I don't remember those numbers by memory, but I think between 0.6 to 0.7 is the effect size of modafinil. The company may have that information better than me. I understand as well that the effect size of Strattera on average is very much similar at about 0.7. In the meta-analysis of non-stimulants that Dr. Faraone did a relatively short time ago, that is shared by other non-stimulants as well, like tricyclics and things of that type, on the order of magnitude of 0.7, a low effect size of stimulants at about 0.9. REESE: Dr. Pine? PINE: I would like to go to slide number 89. I guess the thing that I am struggling with most, and I think a lot of people might be, is the dermatologic issue. On the one hand, I don't want to start a fight but, on the other hand, I guess I am struggling a little bit with some of the inconsistencies in terms of the way three of the cases on slide 89 are being discussed. So, I guess what I want to do is point out what I see as the inconsistencies and then maybe hear from Dr. Bigby about do I have it right; do I not have it right; and then maybe also try to clarify some of those inconsistencies. So, the way that I heard it is that case number 1 or patient number 1 everybody agrees had Stevens-Johnson but there is disagreement about the etiology, I heard, which confuses me a little bit because I don't understand what the etiology possibly could have been except for the medicine or except for the modafinil. So, I would like to hear discussion about that. For patient number 4, at least what I heard was that Dr. Bigby did think it was Stevens-Johnson and I heard that two out of the three experts at Cephalon thought it was at least possible Stevens-Johnson. So, at least in the way I am thinking about it, I would think of those as two at least likely cases. Then, for patient number 5 I am a little blurry in terms of the magnitude of concern as a non-dermatological clinician. If I see a possibly suggestive hypersensitivity reaction or whatever Dr. Bigby classified it as, is that equally concerning, or slightly less concerning, or how much less concerning than Stevens-Johnson? So, do we have three cases where everybody would agree that these are concerning dermatologic issues? Do we have one case? Do we have two that are somewhat concerning and a third that is suggestive? You know, can we get some agreement on that? REESE: Dr. Bigby? BIGBY: What I would say is that case number 62338 is a case of Stevens-Johnson syndrome and, based on the information that is provided, I would say it is drug related. PINE: What about the other two? For case 18004 would you also say that? And, what is the disagreement? BIGBY: I would say that that case is more likely to be due to something else other than a drug. So, I don't actually count that as a drug-related case. What was the third one? PINE: The third one was case 056003. You said fever, urticaria, swollen eyes, vomiting, increased ALT/AST and the Cephalon review said possibly suggestive of a hypersensitivity reaction -- I guess level of clinical concern in terms of a serious adverse effect related to the medicine. BIGBY: You are going to have to give me a little time for that one. PINE: OK. Dr. Goodman is whispering in my ear that he wants to know what made you conclude on case number 18004 that it was not medication related. BIGBY: For that case it is just not so clear to me what the diagnosis is. I mean, it is hard in sort of spottedly reported case reports to figure things out and I just am not convinced that that is a drug rash at all. PINE: Then I guess the last question, when I asked you before about your level of concern you seemed fairly clear that there is, quote, a signal here in terms of dermatologic risk. Based on what you just said, my conclusion would be that you are basing it on this one confirmed case out of 923. BIGBY: Plus, there is a signal for exanthems. Those aren't serious reactions but there is also a signal of exanthems occurring with the drug. PINE: But I also understood you to say that there is not necessarily a relationship between exanthems and incidence of Stevens- Johnson. BIGBY: This is correct. PINE: So, again, I guess what I am hearing is that it is really the one case out of the 923. BIGBY: I think that that is a good summary of how I feel about it. RAPPLEY: But there are also the four cases in adults. Is that correct? PINE: I think those were in adults. RAPPLEY: That is right, in adults. PINE: And it was consistent with the base rate. When we looked at the patient-years exposure it was consistent with the base rate of Stevens-Johnson syndrome, the four adults. REESE: Dr. Robinson? ROBINSON: Could we go to slide 112? I just want to clarify a few things because in Dr. Andreason's presentation it said that we were finding some dermatologic signal within the clinical trials but not in the postmarketing, and I just want to clarify a few things on this slide. In the pediatric subgroup you didn't find a signal for rash in the postmarketing. Is that correct? RUSSELL: Certainly, in the postmarketing setting in children we have had no reports of any serious skin reactions. That would be correct. ROBINSON: OK. Then, one of the questions about that is, is that because there is none or is it that you are unable to detect that? So, that is why I would like to ask a question about the psychiatric signal that you do have in the pediatric subgroup because in the clinical trials it seemed that there is some signal about suicide and psychosis, and in the postmarketing data for pediatrics were you picking up that signal? RUSSELL: In the postmarketing data we saw seven cases that Dr. Stankovic highlighted for you. ROBINSON: That was in pediatrics? RUSSELL: That was in pediatrics, yes. ROBINSON: And it was which ones? Psychosis or suicide? RUSSELL: If I remember right, there were three psychosis, one suicidal ideation. Perhaps you can clarify? STANKOVIC: There were four cases of psychotic symptoms. There were two cases of aggression and violent behavior and there was one case of a suicide attempt. That was the patient that overdosed and used modafinil as one of the cocktail drugs but it was not modafinil prior to the event. RUSSELL: Thank you for clarifying. ROBINSON: Thank you. REESE: Dr. Temple? TEMPLE: Back to derm., I think it would be helpful to be clear on what the appropriate denominator is because there seems to be one case everybody agrees on. This 933 number that has been used includes some very short exposures. Dr. Bigby can tell us what kind of exposure is enough, but let's say we wanted to say how many of those 933 or some of the people from the other studies had, say, at least two weeks or whatever the right amount is. That would help. Maybe it doesn't matter whether it is one out of 900 or one out of 600 but it would be good to have a number. So, how many people who were on it long enough to have had a nasty skin reaction actually were there for that one to be the numerator for? BIGBY: That is a very good question. You know, I think that the best data available about the window of exposure where TEN/SJS is going to occur comes from that study that I cited. It was sort of a consensus panel in three countries, and the majority of cases occur within the first one to four weeks. It is probably one to three weeks. And, if you sort of include in your denominator patients that have been on it steadily for months and months and months you actually probably come up with a lower rate than the actual because the time that you are going to get it in is in that first month. REESE: We can have the response and then Dr. Armenteros. RUSSELL: I can get Dr. Shear to come up and comment on these cases with respect to etiology and all the other aspects we have been discussing. SHEAR: Thank you very much. From a dermatologic point of view from somebody who has been doing this for 20 years, first of all, I would like to thank Dr. Bigby for his excellent presentation because I agree with what he said and this is an area that has been really messy over the years and you can see the confusion that led us here. So, I would really focus on that one case of Stevens-Johnson syndrome. Going through that case extensively -- the panel went through it but I also went through it with the panel again, with Amy Paller who was the leader of the panel -- to try and figure out exactly what was going on with that case and how we could best characterize it. I think we see enough to call it either Stevens-Johnson syndrome or maybe erythema multiforme major. You could then argue about which it is, and does it really matter since both of those can be viral induced? Speaking with the investigator and looking through the case records, there were clear viral-looking lesions that suggested Coxsackie very highly in the pharynx prior to the patient getting this. The clinical course was very compatible with a viral-induced either erythema multiforme major or Stevens-Johnson syndrome because actually the patient was not that sick and was able to continue going to school and continue with other activities. Part of the problem was getting the full history, and much of it was retrospective and there was a language barrier, but the patient wasn't sick enough to be admitted to hospital or really to be seen very carefully during the actual event. But still, piecing it together, I would certainly put viral etiology well within the mix. I don't know what percent I would give it but, you know, drug is in there and virus is in there so it is not a completely clear case of either Stevens-Johnson syndrome nor is it a completely clear case that it was drug induced. GOODMAN: Dr. Bigby, would you concur? BIGBY: I think the patient had SJS. PINE: But the suggestion is that it could potentially have been Coxsackie virus induced SJS, which would be a very different thing. Again, I mean I get the impression that you do not think that that is likely. BIGBY: You know, it is really impossible, never having seen a patient, to do this. I don't think you should call things EM if the patient doesn't have typical targets. There is no description -- the data is inadequate to be very dogmatic or firm about this. I mean, I would say that none of the dermatologists involved here would go out and have a big fight about what this case is because the description is just not good enough. SHEAR: Yes, I should mention that in one of the papers it did describe target lesions. So, that was helpful but, again, there are all these bits and pieces in trying to look at the source documents. From the source all the way to the narrative, you get different bits and pieces. Some are quite extensive. The MedWatch report has different data, but piecing it all together, there is uncertainty but it is in that EM major and Stevens-Johnson spectrum that overlap, if you will. GOODMAN: Hold your questions. We are going to break for lunch and come back at one o'clock. We will have the public hearing component at that time. (RECESS) GOODMAN: We are going to begin the afternoon proceedings. I am going to ask Dr. Pine to read the description of the process for the benefit of the individuals who are presenting at the public hearing segment of today's proceedings. PINE: Both the Food and Drug Administration and the public believe in a transparent process for information gathering and decision-making. To ensure such transparency at the open public hearing session of the advisory committee meeting, the FDA believes that it is important to understand the context of an individual's presentation. For this reason, the FDA encourages you, the open public hearing speaker, at the beginning of your written or oral statement to advise the committee of any financial relationship that you may have with any company or any group that is likely to be impacted by the topic of this meeting. For example, this financial information may include a company's or a group's payment of your travel, lodging or other expenses in connection with your attendance at the meeting. Likewise, FDA encourages you at the beginning of your statement to advise the committee if you do not have any such financial relationships. If you choose not to address this issue of financial relationships at the beginning of your statement, it will not preclude you from speaking. REESE: We will have the first speaker, who will have five minutes and when there is one minute remaining we will let you know your time. RAVENEL: Dr. Ravenel. As a pediatrician with 36 years experience -- by the way, I have no financial disclosure; no connections; no funding. I am here independently as a private practitioner. With 36 years combined experience in academic and private practice with a heavy emphasis on behavioral pediatrics, I want to share some concerns with the committee concerning the pending new indication for Cephalon's modafinil, to be marketed as Sparlon. My concerns include the potential for abuse and diversion, as well as data questioning its effectiveness for ADHD, along with counterbalancing risk of adverse effects. Although being promoted as a drug with low potential for abuse, a substantial risk is actually suggested by the following: One, the FDA posted a warning letter on January 14, 2002 which compared the abuse potential of modafinil with that of methylphenidate in an inpatient study of individuals experienced with drugs of abuse. Quote: Results from this clinical trial demonstrated that modafinil produced psychoactive and euphoric effects and feelings consistent with other scheduled CNS stimulants (methylphenidate). Number two, an Internet drug information database source states, quote: Modafinil may be habit forming. You should discuss the abuse and dependence potential of modafinil with your doctor. Number three, as reported in the New York Times, the United States Olympic Committee includes modafinil in a list of banned stimulants and raises the spectra of widespread diversion and even more problem with, quote, lifestyle and cognitive enhancement and recreational use as has already been seen with traditional stimulants. Several psychiatrists and other professionals with experience with substance abuse by teenagers and young adults have warned that off-label use of this drug is, quote, staggering already, and warned that modafinil is very likely to become the next popular drug for its perceived cognitive enhancement or other perceived benefits enabling users to remain awake and alert for prolonged periods. Marketing claims for the drug's effectiveness for ADHD appear to be exaggerated. A recent study in the Journal of Pediatrics of the American Academy of Pediatrics proclaims that at the final visit 48 percent of the modafinil-treated subjects were rated as much or very much improved compared to 17 percent of placebo subjects. One can see that 52 percent of subjects were not improved significantly. This compares to 75-85 percent comparable improvement on traditional stimulants. Insomnia was reported in 29 percent of the treated subjects, and it is noteworthy that drug tolerability was evaluated only by spontaneously reported adverse events. This can be expected to minimize adverse events significantly below their actual occurrence. The New York Times article quotes experts as being concerned that manipulating natural sleep by reducing it may have serious consequences such as chronic sleep depravation damages health, immune system and is associated with life span. All of these references are provided in my speech. The aforementioned FDA warning letter to Cephalon pointed out that the putative mechanism of action being claimed by the company was misleading, noting that the PI states that, quote: The precise mechanisms of action through which modafinil promotes wakefulness is unknown, period. In summary, claims for potential effectiveness are exaggerated and the risks of adverse events are minimized for a drug which has been shown to have a potential for abuse and for recreational use that far exceeds even that for traditional stimulants. Approval at this time for ADHD is premature considering the emerging controversy and public awareness of issues of adverse events, diversion and abuse related to stimulants. It is ironic that this very phenomenon is being used by those promoting modafinil for ADHD. That is... REESE: One minute. RAVENEL: ... looking at the problems with the stimulants. The FDA would be better served by exercising caution and by opening the door to even more of the same criticisms that have emerged recently about stimulant drugs. Thank you for your consideration. GOODMAN: Thank you. REESE: We will have speaker number two. JACKSON: If you could hold on putting up the first slide, I might do those towards the end. Thank you. My name is Dr. Grace Jackson. I am here independently as a private practice psychiatrist from eastern North Carolina. I am here today to actually begin by correcting some of the misinformation which has been disseminated to committee members over the past 48 hours. The first point I would like to make is about some of the concerns I have as a doctor and who has actually worked in the prison system and as a former Naval physician. One of the first things I would like to point out is that I think that the precautions which should be described are basically the elephants that nobody seems to be looking at in the room. I would like to talk about some of those elephants. The first elephant has to do with the fact that stimulants rewire the brain. This is what Harvard University and McLean Hospital clinicians have referred to as neuronal imprinting. Basically, what this means is that we shouldn't be focusing just upon the potential for current diversion or current recreational abuse, but we should be looking at the fact that these drugs are altering the plasticity of the brain in children and adolescents in a way which increases the likelihood of future chemical dependencies, particularly to nicotine and to cocaine. I would like to direct your attention to the papers by Nadine Lambert at the University of California Berkeley, papers published by Russell Berkeley in which statistical manipulations have been used to try to conceal this correlation, and also a recent publication from the University of Michigan which has demonstrated the same kinds of findings, that people who are arriving on college campuses who have received stimulants in middle school, high school or college have a 3- 7 times higher likelihood of taking prescription stimulants illicitly, and a higher rate of actually using cocaine in the past year. The second elephant that I would like to talk about which we haven't really been hearing enough about, I don't believe, is the effects of stimulants on growth suppression. While it used to be the case that doctors took seriously the growth curve, it seems that this is now something which is casually dismissed. I believe it is time for the FDA and physicians to begin seriously considering the suppression of growth not only on the long bones of the legs and the arms, but also potential impact on the skull which continues development through adolescence and particularly the growth effects upon the brain, a point to which I will return in a few moments. The third elephant I would like to talk about is the fact that no one yet here, at the FDA or at these hearings in the past two days, has discussed the effects of stimulants on cortical blood flow, specifically frontal cortex, parenteral cortex and temporal cortex. I believe that if you will actually pay attention to the medical literature there is a real vascular effect which actually deserves a black box warning, at the least, so that physicians and family members are aware of the fact that these stimulants have the potential to shrink the cortex, especially the frontal cortex, and if they are not doing that, at the very least, they are not benefiting children who, some practitioners believe, begin life with smaller brain volumes initially. The next point I would like to make is that we hear so much about the FDA needing to balance the risks and the benefits of drugs. Well, I would like to just point out the fact that I have heard numerous references to the MTA study in the past two days. Fourteen-month outcomes have been emphasized repeatedly. I would like to just say something that was misrepresented yesterday and again today. If you will actually go into a paper which was in the Archives of General Psychiatry in 1999, called "Mediators and Moderators of the Outcomes of the MTA Study," you will find about two sentences in that whole article where they actually have done a subgroup analysis of the children who began that study in an unmedicated condition and who remained in an unmedicated condition. Those children actually had superior numerical improvements compared to the children who began unmedicated and were placed on stimulants. While that finding was not standardly significant, that may have been an effect of the study being under-powered. Even more important though is the fact that in the Pediatrics journal, in the year 2004, 24-month outcomes were published for the MTA study. The findings at that point demonstrated that the effects of medication deteriorated; that the trajectories for symptomatic improvement reversed; and, in fact, the benefits of behavioral therapy -- a modality that consisted mostly of one 8-week summer camp -- actually had enduring effects. So, I would like to suggest that this implies that a lot of the treatments that we are hearing so much about as being so necessary are, in fact, futile when one carries out the studies to a long enough duration of time. Finally, I would like to return to the misinformation which continues to surround the classification of medications that we keep hearing as they are not really stimulants; they are just central nervous system activators... REESE: One minute. JACKSON: I would like to suggest to the committee that they need to talk to the World Health Organization. Stimulants are classified not on the basis of potential addictiveness; they are classified as stimulants on their potential to be CNS activators. Actually, the World Health Organization classifies drugs on the basis of three properties: One, chemical structure. You ignore the fact that atomoxatine is a chemical derivative of phenylpropanolamine, a chemical structure which was removed from the market by the FDA in 2000 because it caused hemorrhagic stroke. I would like to point out the fact that the World Health Organization also classifies stimulants on the basis of pharmacological properties, none of which require dopamine re-uptake inhibition to meet the criteria of being a stimulant, and I would like to see that everybody drinking coffee here to recognize the fact that caffeine, which is an adenosine-2 antagonist, is not something that you would classify by Dr. Andreason's standards as a stimulant. Yet, I think Starbucks would say something else. Finally, I would like to say... REESE: Time. JACKSON: Thanks. GOODMAN: Thank you very much. BAUGHMAN: I am Fred Baughman, a neurologist. I have discovered and described a handful of real neurological and genetic diseases. I am speaking on the chemical imbalance lie as it applies to modafinil and other ADHD drugs. If one goes to a physician or takes a child or parent to a physician, if there is a gross microscopic or chemical abnormality a disease is present. If there are no abnormalities no physician should say that there is a disease. In psychiatry there are no physical abnormalities, which means there are no actual diseases and here we speak of the risk side of the risk-benefit equation. Psychiatric drugs appeared in the '50s. Psychiatry and big PhRMA married and gave birth to the chemical imbalance lie. At a 1970 congressional hearing the chemical imbalance strategy was already in place. Lippman, of the FDA, argued hyperkinesis is a medical syndrome. In 1994 Leber, of the FDA, in a letter to me confessed no pathophysiology has been delineated. At the 1998 consensus conference William Kerry concluded ADHD appears to be a set of normal behaviors. At the consensus conference James Swanson reviewed anatomic MRI research, concluding ADHD subjects have on average 10 percent atrophy. I challenged Dr. Swanson, saying why didn't you mention that virtually all of the ADHD subjects were on stimulant therapy? The research had proven 14 times over that the drugs, not the fictitious disease ADHD, had caused the brain atrophy. Caught in this lie, the consensus conference panel confessed, quote: We do not have an independent valid test for ADHD. There are no data to indicate that ADHD is a brain malfunction. Unlike real epidemics, once psychiatric diseases are found not to exist, the epidemics flourish nonetheless. In 2002 Castellanos published the one and only MRI study of an ADHD untreated group but, inexplicably, they failed to use matched controls, voiding the study. So, I would hope that this study is not referenced as the proof that ADHD is an actual disease. While the FDA's Goodman acknowledged that claims that SSRIs correct serotonin and imbalance go too far, he had the gall to suggest, quote, this is reasonable shorthand for expressing that this is a chemical or brain-based problem. Saying any psychiatric diagnosis is a brain-based problem and that medications are normalizing the function is an absolute lie. There is nothing more despicable than a physician or physicians who knowingly tell normal patients that they are diseased for profit... REESE: One minute. BAUGHMAN: ... yet, this has become standard practice throughout medicine and FDA, APA, AMA, AACP, AAP, AANCNS, AAFP. The right to informed consent universally abrogated must be restored. You are mandating the medical treatment of ADHD. Where is the proof that ADHD is a disease? Give us that reference, that citation right now, please. Give us the reference citation to the test that demonstrates an objective abnormality child by child, please. REESE: Calling for speaker number four. HANSON: Good afternoon. My name is Ben Hanson. I am from Traverse City, Michigan. In the interest of full disclosure, I suppose I should mention a few things. In March, 2000 I was appointed to the Michigan Department of Community Health Recipient Rights Advisory Committee, a state watchdog panel that meets in Lansing. I received no compensation for serving on this committee, other than mileage for travel expenses. Also, I am the Michigan contact person for Mind Freedom International, a non-profit organization which advocates for the rights of individuals stigmatized by psychiatric labels. This is a volunteer position for which I receive no compensation. I am also a proud member of the International Center for the Study of Psychiatry and Psychology, icspp.org, and I was one of the principal organizers of yesterday's ICSPP press conference here, in the Hilton. It is possible I may be reimbursed for some of my travel expenses by ICSPP but to date I have not received one dime of compensation from ICSPP, which is fine. I am happy to do this work for free. Finally, I have been contracted on a part-time basis by another non-profit organization, the Law Project for Psychiatric Rights, psychrights.org, founded by Alaska's attorney Jim Godstein. To date, I have received a total of not over $1000 for various services like updating the mailing list, working on the web page, et cetera. I want to make it clear that I am speaking on my own behalf today. I am not speaking for anyone else, including these organizations I just mentioned. I am here before you as a private citizen, a taxpayer of the U.S. I want to say a few words about the drug Sparlon, also known as Provigil, also known as modafinil. My interest in this drug began a few years ago when I learned that modafinil had been approved for treatment of a new disease called shift work sleep disorder. This interested me personally because for nine years, from 1995 through 2003, I worked for the Michigan Department of Natural Resources as a ranger in a state park located in northern Michigan. I worked the night shift, from 7:00 p.m. until 4:00 a.m. five nights a week. Basically, my job was to walk around in the woods after dark, which I loved because I love the outdoors. It was a dream job except for those hours and I never got used to it. I can testify to the fatigue, to the irritability, to the general clumsiness and inattentiveness which is caused by working those late night hours, especially that last hour from 3:00 a.m. to 4:00 a.m. The rangers call it the "dead hour," the dead of night when the whole world except you seems to be asleep, nothing stirred, not even the crickets, not even the mosquitoes. I can testify to this mental dullness. In fact, I would say if you work those hours and you don't grow a little groggy and a little clumsy, the only reason I can think is that you are probably on some kind of drug. I believe consenting adults should have the right to take any drug they wish but I condemn the FDA for endorsing a fictitious disease, created most likely by some pharmaceutical marketing department as a way to sell more drugs. What is next, FDA? Are you going to approve jet lag as an official disease? Perhaps it is only a coincidence but I understand the formulary patent on modafinil expires this month, March, 2006 -- a minor inconvenience to Cephalon and its stockholders. But one way around that problem would be to change the name of the drug, call it Sparlon and approve it for the treatment of ADHD, which is a larger market than shift work sleep disorder anyway. Isn't that what Eli Lilly did when Prozac's patent was about to expire? They changed the color of the pill from green to pink. They changed the name to Sarafem and they marketed it for another invented disease, PMDD, and the FDA approved that. No problem. I flew down here from Michigan... REESE: One minute. HANSON: ... because I couldn't believe -- I can't believe that you people are really going to approve this pep pill, which reportedly allows people to get by on two hours of sleep a night, for children diagnosed with ADHD. If you do this I want to be here to see you do it with my own eyes. Thank you for this opportunity to express my opinion. GOODMAN: Thank you. At this point I would like to invite our committee members to ask questions of both the FDA and the sponsor. At a time when I think it is probably the appropriate moment we will put the questions up on the screen, but before we do that let's have more free-ranging questions, including some that may have been carried over during lunchtime. I remember that a few people didn't get an opportunity to ask their questions. REESE: Dr. Armenteros? ARMENTEROS: Yes, a question to the sponsor pertaining to the most common side effect in the list, which is insomnia, could you tell us a little bit more? For example, does this start happening in the very beginning? Do kids get used to it? Does it change during the time of treatment under observation? And, does it have anything to do with dosing? RUSSELL: In the main, the insomnia appears to start with treatment initiation, and the highest incidence of first reports of insomnia occurred during the first two weeks of treatment and then it does appear to taper off. As Dr. Stankovic mentioned, I think we had seven withdrawals from the drug because of insomnia. So, there appear to be people who either learn to get used to the insomnia or habituate to it, as with many of the other drugs that I think have this as a side effect. I am sorry, I know there was a third part to the question but I have forgotten it. ARMENTEROS: Yes, what is the relationship to the dose? RUSSELL: We did look at the doses and there doesn't appear to be a major difference with the doses of 340 mg or 425 mg. REESE: Dr. Mehta? MEHTA: Actually, it is just a comment on Dr. Temple's earlier remark. All the studies are two-week or longer. There is only one study in 24 subjects which is a single dose. So, the denominator should be somewhere around 920 or something like that. GOODMAN: I have a question for the sponsor about the pharmacokinetics. If you took two children, same age, and one was being administered 400 mg modafinil, the other 200 mg modafinil obviously the plasma levels would be higher in the one that is receiving the 400 mg, but would the levels of the metabolite be proportionate or disproportionate to those levels as well? You may have covered that and I may have missed it. RUSSELL: Yes is the answer. GOODMAN: They would be proportional? RUSSELL: Yes. GOODMAN: In a linear fashion? RUSSELL: Yes. GOODMAN: Thank you. REESE: Dr. Leon? LEON: Could the sponsor please show us a slide of the weekly retention rates? I notice there is a big difference between the LOCF results and the endpoint and I am curious to see how those retention rates look, and if there are differences. I know maybe about 50 percent more people dropped out of placebo than active medication. RUSSELL: The biggest time of dropout was between weeks three and five. This largely may have had something to do with the design of the protocol that did allow patients who were going to come off for an adverse event to roll over into the open-label program at that time. The reason for that allowance was based on a lot of input from investigators who found that it would be difficult to keep children on a placebo for that length of time. So, there was a dropout between week three and week five. LEON: Do you have a slide that shows the weekly retention rates? Could we see that, please? RUSSELL: I am looking at my colleagues and they don't seem to have it. LEON: I didn't see it in the materials. Is it in the book maybe? It is pretty important when we are trying to draw inferences about efficacy. RUSSELL: I think in your briefing document there are by week numbers. LEON: I didn't see it. Maybe you could tell us what pages to look on. RUSSELL: Let me try and find the page. If you look at figure 4 on page 31 of the briefing document, there are the numbers for the CGI that are actually the numbers -- sorry, they are not; I am misleading you. I am afraid we don't have it. REESE: Dr. Wells? WELLS: I have a question about the source of the postmarketing adverse events that were reported, a question to the sponsor. These postmarketing events, do these come from all of the postmarketing studies, all events from all studies? Also, do they include voluntary reports from practitioners in a more naturalistic setting? RUSSELL: I am sorry, could you repeat the question? WELLS: The question is about the source of the postmarketing reports of adverse events. Where do these comes from? Presumably postmarketing studies are included of the drug used in other indications. Would it also include voluntary reports of practitioners... RUSSELL: Yes, it would. The spontaneous reports would be reports from health care providers, consumers. Any study that we undertake we include in our clinical trials information. WELLS: So, it is data from studies as well as voluntary reports from practitioners? RUSSELL: In the postmarketing it doesn't include the studies; it includes the voluntary reports. WELLS: Just the voluntary reports? RUSSELL: If I could clarify the previous question, on figure 3 on page 29 of the briefing document there are numbers at the bottom of each of the graphs. REESE: Dr. Pine? PINE: I guess two issues, and one of them I think maybe we will just come back to. That is the issue that Dr. Leon just raised about the sample sizes for each week on page 25 efficacy data. I realize you don't have it now but, you know, I think a few of us are a little concerned about differential attrition in terms of the efficacy data and it would be very helpful to see those data but, again, I know that you don't have that right now but maybe if you could get them and give them to us sometime in the next half hour or so. The second issue is a question on psychosis. I guess there are really two things that -- yes, that slide, right there. If you could just give us the Ns in each group at each data point. RUSSELL: This is the ADHD rating scale. Actually, the numbers are here the teachers versions so you can see that there are dropouts as the weeks go by. PINE: Yes, they are very small. RUSSELL: They are pretty small. I am afraid I can't see those from here. PINE: You can barely make them out in the document but you can see them; they are there. But the issue of psychosis, there was an extensive discussion about this yesterday, for people who weren't here and I don't know that we need to repeat the whole discussion. I guess I would just like to raise two issues. One is that I seem to recall on one of the slides from yesterday that there was a hint -- and I can't remember which event it was, that one of the adverse psychiatric events looked to be more prevalent in modafinil or Sparlon relative to the other agents. If somebody from the FDA could either point that out or bring it up, that would be helpful. Then I have one other point about that. GOODMAN: Which event was it? Dr. Mosholder would know. Do you remember? MOSHOLDER: Andy Mosholder, Office of Drug Safety at FDA. For the suicidal event category there were four events in my analysis of modafinil, zero on placebo. I wonder if that is the one. For psychosis there were two and none on placebo. Those are just the double-blind. PINE: And I guess my take on it is that I don't feel any differently looking at the data here for this compound than I felt about the broader discussion yesterday, on the one hand. On the other hand, I think it is important, particularly for people who weren't here yesterday, to know that similar concerns that were raised in general for other compounds should also be acknowledged or discussed here. I guess the last thing to say is that the quality of the adverse event reports in general always concerns me. But I guess on slide 102, case number 312592271 with 10 months of ideas of reference concerns me. I realize it is one case and I don't think we should make too much out of it, on the one hand. On the other hand, in terms of discussing the medication I do think that we need to at least bring up the point again that there needs to be some acknowledgement that these are potentially concerning adverse events. GOODMAN: As long as you are on that subject, Dr. Pine, it reminds me that in the review of the correspondence between the FDA and the sponsor there was a description of one case that seemed to be misclassified or mis-coded. It was an individual who was said to have had a personality change or personality disorder and, in fact, they had a noose around their neck. Could somebody from either the sponsor or the FDA side clarify? Obviously, if you read a case like that it harkens back to early concerns we had about previous problems in appropriate reporting of those kinds of AEs. RUSSELL: Yes, I can comment on this case. This was a six year- old girl who after two days of discontinuing the drug -- she stopped the drug on day 91 and then on day 93 engaged in what her mother calls bizarre behavior but there was some suicide intent by putting a rope around her neck. The patient was hospitalized. The inpatient assessment says that the patient had major separation anxiety and admitted to trying to hurt herself with grave references to suicide. This was a girl who had a history of mood swings and a family history including maternal depression and a suicide attempt. So, that is that case which was originally thought by the investigator to be abnormal behavior but, as you saw today, we included it on the slide with the suicidal cases. REESE: Dr. Bigby? BIGBY: I have a question about response of the placebo group. You have a figure that was in the CD that you sent and it was a summary slide for the three studies looking at the ADHD rating scale school version for all three studies. I think it went out to eight weeks, and it is really striking how much the placebo curve drops down. Also, if you can find and put that slide up -- I don't know if you have that slide, it has the numbers of people still in the study at the various time points. So, I have two questions. The first one is for anybody who knows about ADHD trials. Is this kind of effect in the placebo group sort of universally seen in ADHD trials? RUSSELL: Dr. Biederman? BIEDERMAN: I am not sure whether I know what you are asking, but placebo response in ADHD is on the order of magnitude of 30 percent on average in the literature. You are asking if this placebo effect is typical of other studies of ADHD. It is pretty much within that range. BIGBY: Then, the second question I think sort of goes back to the question about numbers of dropouts. Now, at each of these time points you have listed the number of patients in the treated and the control group. For the control group you start out with 210 and by the time you get to the seventh week there are 71. So, basically two-thirds have dropped out. Is the score with the bracket at each one of those time points just the people still in the trial, in which case the same would be true for the treatment group and it is sort of a per-protocol trial and not an intent-to-treat trial. RUSSELL: Depicted on these figures is the by week analysis so those are the patients that are actually in the study at that particular time. The endpoint is the last observation carried forward analysis so all values are included in the endpoint analysis. REESE: Dr. Wang? WANG: Yes, I want to explore some more this differential in effect size between modafinil and other ADHD treatments. Particularly, you mentioned Strattera. What I am interested in is the clinical significance of that decrement. Is this decrement of clinical significance? Is it of a size where it would warrant making modafinil a second-line treatment? I think it will have some bearing on how desirable we think it is to warn about the safety issues. RUSSELL: The overall effect size across all three studies was 0.69. WANG: I am talking about the differential between the effect size in your pivotal trials and what is known about the effect sizes for other ADHD treatments and what is the clinical significance of the difference. PINE: Can I ask a question about that 0.69? That is a Cohen's D for the difference in active versus placebo? Is that what that difference is? RUSSELL: Dr. Kingsbury, can you comment? PINE: You know, typically most people go by Cohen's D criteria so stimulants have Cohen's D effect of somewhere in the low 1s, 1 to 1.2. Strattera I think is frequently quoted as 0.7 to 0.8. So, if it is 0.7, if that is a Cohen's D for the difference in the change of active that accounts for placebo and that would be a reasonable effect size. But I would like to hear if that really is the effect size they are quoting. KINGSBURY: Specifically calculated as the difference in treatment effect divided by the pooled estimate of the standard error. PINE: The pool of the placebo? KINGSBURY: The placebo. PINE: So, that is a reasonable effect. It is not huge but it is within the realm of an effective agent. WANG: Would you say it is getting to the point where this would be a second-line treatment? PINE: I would not say that. Clinically, based on an effect size of 0.69, I would not say that that would make it a second-line agent necessarily. It is clearly less than what you would expect in stimulants but I would think about it similarly as I would about atamoxatine. LAUGHREN: I think if you are going to be comparing effect sizes for different drugs you ought to be looking at it in the same trial because it varies a lot from trial to trial. It is going to depend on the sample size and on the placebo response. So, I think it is really hazardous to compare effect sizes, whatever measure you are using, whether it is Cohen's D or anything else, to cross-study comparisons. PINE: On the other hand, since we all know of multi-drug trials where people obviously are grappling a little bit with the efficacy data I think we have to say something about, you know, in the universe of studies of ADHD, is this in the realm of a reasonable treatment or not. Again, I would agree; I wouldn't quibble with what you said. WANG: And I am not arguing. I am just trying to kind of qualitatively understand whether if there is a warning, whatever shape or form it takes, and it drives down use or effectively turns modafinil into a second-line treatment, is that a terrible thing? Is it a good thing? Is it neutral? That is what I am trying to kind of understand. REESE: Dr. Rappley? RAPPLEY: I want to go back to the skin issue so if anybody else wants to talk about the effect -- keep going? OK. I would like to ask Dr. Bigby if he might have some insight about how we might think about the spontaneous reports of Stevens-Johnson syndrome and how that compares to the actual incidence. BIGBY: Actually, that is a very good question. Neil actually did a study in Canada where he ascertained cases of TEN, and he can give you the details of the study, and compared it to the spontaneous reporting system they have in Canada. I think that it is vastly under-reported. I looked at that paper last week and I think it was 10 percent or less than the cases that he found that had actually been reported. I think the same is true for other researchers that have looked at reporting of TEN vis-a-vis drug usage in an attempt to try to determine rates of reactions. SHEAR: That is correct. We tried to look at patients with TEN and contacted burn units across the country to see patients who were coming in versus what was actually reported to Health Canada through the spontaneous reporting system, and we came up with a number of around 10 percent that were actually reported. So, we realized it wasn't necessarily the burn doctors but probably hospital pharmacists who were reporting it or other health care professionals but still it was about a 10 percent reporting rate. REESE: Dr. Pfeffer? PFEFFER: Again a clarification, Dr. Bigby. Maybe you can help us. You said that the Stevens-Johnson was dose related. BIGBY: No, no. PFEFFER: Then if you could clarify a little bit more about the onset of this type of skin problem. BIGBY: I mean, I think SJS and TEN are idiosyncratic hypersensitivity reactions. I tend to shy away from talking about mechanism because I don't think anybody really knows what the mechanism is. Developing the disorder I think is not dose related but the point I was trying to make about the dose perhaps being a factor is that I am aware of at least two studies that have shown that the patient prognosis is better if the drug is identified and stopped, and it has mostly to do with the half-life of the drug and the body's ability to clear the drug. I think that if you start with a greater concentration it will take you longer to have undetectable levels and it might affect prognosis. I don't think it has anything to do with the incidence. PFEFFER: One other question about the syndrome, if a child develops this on a medication such as modafinil, would that child be at increased risk in the future for the syndrome? In other words, would the exposure to this particular drug increase the risk or would that not be an issue? BIGBY: Increase the risk if they were exposed to any drug? PFEFFER: Either any drug or whatever causes the syndrome, yes. Does it lead to sensitization? BIGBY: Well, the only definite thing that i can tell you is that if they got the same drug again it might be that they would have the same reaction. Whether it identifies them as someone who is more likely than the general population to do develop TEN to other drugs, particularly drugs that are known to be associated with TEN, I can't answer that question although there is some suggestion, not entirely convincing, that that might be the case. But it is not clear to me that the exposure to the drug and the fact that they developed the TEN as the cause of that identifies them as someone who has that potential. So, I don't know if I am answering your question. I think that a patient that develops TEN to a drug -- there is some evidence that they are more likely to develop that type of reaction to drugs. But I think probably they were that way before the exposure. Actually, again, this is a subject that Neil has done more work on than anyone I know. I mean, I think it would be useful for you to hear his comment on it as well. SHEAR: Thanks, Michael. It is a difficult question because you are not going to get enough data ever to really do that, especially if a child has had TEN. For every drug they get in the future the parents ask can this drug cause TEN, it is no longer a hypothetical possibility and if the answer is yes, but don't worry that couldn't possibly happen in a billion years, you know they are not going to get the drug. So, you are not going to collect that data. What we did show was that among the aromatic anticonvulsants there was a risk of cross-reactivity and that is even hard to explain structurally. We don't know why that is but we showed in vitro and in vivo that it does seem to exist. But otherwise, usually people who have had Stevens-Johnson don't get it again. REESE: Dr. Malone? MALONE: I know you said that dose probably was not related to Stevens-Johnson but I guess it is a similar question, is there any mechanism that will explain why a group of children getting 340 mg of the drug might have a higher rate of Stevens-Johnson than those being treated for daytime sleepiness getting 200 mg or less? BIGBY: The only thing I can do is repeat I don't think the development of TEN, as far as anyone knows, is a dose-dependent phenomenon. GOODMAN: I think you are being appropriately cautious but there is the other factor we discussed of the sulfone metabolite. Although there is no proven relationship, there is certainly a suggestion based upon other compounds that have been associated with Stevens-Johnson that have that sulfone group. So, is it at least conceivable or plausible that the higher levels of that metabolite could pose a greater risk for development of Stevens-Johnson syndrome? BIGBY: Is it conceivable? Yes. But, I mean, I think the threshold for whatever it is that is the mechanism for developing TEN is exceeded by all of the doses that you are talking about here. I mean, yes, what you said is hypothetically true. The problem is I don't have any evidence to say that it is or isn't. VAUGHT: Mr. Chairman, if I could address that for you, please? REESE: You may. VAUGHT: Thank you. What I would like to do is just perhaps orient the panel a bit. Because of the inference of the sulfone to agents that have been directly associated with the occurrence of SJS -- I am not going to do a chemistry lecture today but on the right-hand side of the slide is the modafinil sulfone. With the structural characteristics there is, in fact, a similarity across two agents that have been directly related to SJS. Obviously with the sulfa drugs and the aryl-sulfonamide valdecoxib, the only similarity is the sulfone group. I think what you will notice is -- and I agree with Dr. Bigby that while the mechanism is not well-known, in general with the sulfa drugs the amine group becomes activated and it is believed to be one part of the overall syndrome that is created, as well as the fact of the close association of the sulfone group to the aromatic ring. Valdecoxib is similar to this in that it has a sulfonamide group again associated with the phenyl group. While this is not a conclusive relationship, there seems to be a very broad preponderance of this type of structural feature being associated and directly related to SJS. We can see that with the modafinil sulfone moiety this is structurally simply not similar to these agents. MANNHEIM: We have a similar slide I would like to show. CAVANAUGH: We also looked and I have to say I am very impressed with the level of discussion today from everybody. When Dr. Mannheim asked me about Stevens-Johnson and I heard that there was a sulfone, I said, well, you know, sulfonamide, as you know, is classically thought of and it is in the labeling. Sulfonamides in general are labeled as 0.1 to less than 1 percent. You can again see the sulfone here with the amine, and that is the sulfonamide; this is sulfanilamide and you can see it here and, again, sulfamethoxazole. As you pointed out, there is some similarity with the sulfone but the amine is separated by two carbons and there is also a ketone here. If you look at sulfacetamide, and here you see a 3D structure rendering so you can see it a little clearer with the two oxygens, two carbons separated, a third oxygen and then the nitrogen which is going to be withdrawing electrons. If you look at sulfacetamide, the difference is that instead of the nitrogen being on this side, it is basically substituting for this carbon. So, this is a sulfonamide but it has a third oxygen, it is a third atom away. The interesting thing about sulfacetamide is that it has been reported to cause Stevens-Johnson, at least in the labeling, at 3 percent -- I believe it is in the labeling; it might be in other places -- and that is an eye drop. You know, people have died with even the first dose of eye drop where they have a history of sensitivities to sulfonamide. So, you know, this whole issue of is it the sulfone, isn't it, I think what you have been hearing is that it is very, very muddy. We don't know. You have heard factual information and we don't know. The same with the dose. It is too small numbers. We don't know. It is plausible. Is there cross-reactivity? Maybe yes, maybe no; we don't know. So, these are some of the issues that we have been struggling with and I am glad the committee is dealing with them. Let's see, was there any other point I wanted to make? The only thing that I wanted to point out is, you know, we have been talking about Stevens-Johnson and there has been talk about other hypersensitivity reactions, and I went through the various cases of rash and you heard earlier about the PK and the exposures not being any different, and that is about what you would expect. But a lot of those rashes also were just general rashes. When you look at cases that could be possible hypersensitivity, you have several cases of allergic reactions. You have the vesiculobullous possible SJS. You have increased LFTs. One of them was a hypersensitivity. You don't have anything up here in the teens but it also could be due to the numbers. But in general the percentage for possible hypersensitivity is kind of consistent. These are the individual cases and you can see the combination of symptoms. Here is an allergic reaction. Here is an allergic reaction with nothing else. Here is an allergic reaction with a rash. Here is the increased LFTs with eczema and that is the individual -- oh, I am sorry, here is the increased LFTs with edema and urticaria and that is the individual who was 17-fold higher. You also have hives, fever, whatever. So, there is some evidence of additional hypersensitivity. We are just arguing about numbers at this point in time. GOODMAN: That is helpful. Thank you very much. I have a more global question for anybody on the FDA side about the safety data. Is the FDA in general satisfied that there is sufficient long-term safety data at the doses being used for the pediatric population? We have focused a lot on the acute trials, individual areas of concern, but just in terms of a kind of more panoramic view do we have sufficient long-term safety data at this point for this dose in this population? LAUGHREN: I think I remember from the earlier slide that we now have about 240 patients greater than six months. Is that right? That is about as much as we usually have. Again, this is not a new compound. If there were some adverse event that we thought was related that had a long latency we might be more worried about it. I think the event that we are most concerned about here is one that probably has a short latency. GOODMAN: That satisfies me. I would like to turn to the questions, if we could have those projected. There are two questions for which we must take a vote. The first question is has modafinil been shown to be effective for the treatment of ADHD in children and adolescents? Number two, has modafinil been shown to be acceptably safe in the treatment of attention deficit hyperactivity disorder in children and adolescents? When we get to number two I would like to break that down in the following way, starting first with dermatological issues because those have been the most salient features; then with cardiac, growth and psychiatric. Let's begin with the first question pertaining to efficacy. I think I already shared my view earlier and that has not changed, that I am satisfied that there is sufficient efficacy data as we have heard. You know, we don't have a direct head-to-head comparison with an active comparator. That is unfortunate but it is not an atypical situation. When we have looked at the effect sizes, I think most of the experts in the room said it is probably not quite at the level of the stimulants. It is probably closer to the range of Strattera, yet it is still quite effective and has certain features that I think would make it a valuable addition to the armamentarium. I just shared my opinion but I want us to have a discussion and hear from around the room, from all of you, regarding the efficacy question. Anybody can volunteer. REESE: Dr. Wang? WANG: I would just second that one caveat about the comparative efficacy. I think it would be useful to have additional data just to understand where in the armamentarium this would fall. That is number one. Number two, another big area of a question mark is the dose. I think it is unfortunate and it would be helpful if there were more data to suggest whether you have fathomed the lower bound of the dosing range because, as Dr. Bigby said, maybe the development of these skin rashes isn't necessarily dose dependent but the prognosis may be dose related. So, getting kids on the smallest dose possible would be optimal. I don't know if this is additional trials but some way to understand if a lower dose might be useful. REESE: Dr. Pfeffer? PFEFFER: I share that idea and concern and I asked the question previously. It seems that trial 309 was a fixed dose and is the dose that was proposed, which was the higher doses. Trial 311 was a flexible dose and it looked to me, in slide 53, that there was demonstrated efficacy early on and I am assuming it is at a lower dose. Then, on slide 54, while it was a flexible dose we heard that it was a very rapid increase of dose early on. So, there wasn't enough sense in that trial if a lower dose might also have been effective. So, while I think there is definitely demonstration of efficacy, the efficacy is demonstrated on the high dose and the question about would a lower dose serve the purpose is not answered clearly. REESE: Dr. Temple? TEMPLE: Well, I think it would be helpful if, maybe with another look, you took a look at the Phase 2 study that led to the conclusion that you need the high dose, number one. I mean, we press people for dose-response data all the time but apparently we were satisfied that that had ruled out usefulness of lower doses. The other thing to do is look at the average dose or maybe even dose groups in the titration studies to see whether, while the dose is still quite low, there is some separation. I mean, that wasn't the planned analysis but the company may have that. Early on there is not much separation so at least for the earliest part of the titration you really don't see much. Then at either three weeks, four weeks, five weeks you do, but we don't know the doses or the average doses or the subsets of dosing by that time. So, perhaps one could look at that and see if we have an answer already. REESE: Dr. Armenteros? ARMENTEROS: That is fine, but it could also be an artifact of the time lag between administration of the drug and response. TEMPLE: I totally agree. If you didn't see something you wouldn't really know whether a lower dose might -- but it was the Phase 2 study that I think is what convinced the Division that the dose-finding was sufficient. So, I think if you don't think that is adequate we need to know why. REESE: Dr. Pine? PINE: I guess just briefly to second some of the statements, it looks at least to me fairly clear that there are not a lot of questions about efficacy. It sounds like the data have been reviewed a few times. Just in looking at the three studies, on the face of it there can be a reasonably strong case made for efficacy here, and I don't know that I have a big need to discuss it much further although I would be happy to hear other people's thoughts. REESE: Dr. Rappley? RAPPLEY: Speaking from the point of view of a clinician, I would say that this is a medication that looks to be somewhat less effective than the other options available to me to treat attention deficit hyperactivity disorder, and it has the common side effects, common and mild side effects that are very similar to the other agents. So, it would probably be perhaps a fourth or even a fifth line of medication that I might turn to in order to treat a child who was not responding to the other medications. GOODMAN: I wondered if you would revise that positioning of the medication if you had a sense of abuse potential, diversion potential. We can talk about that a little bit more today, but I have heard a variety of different views on this. It would appear that the abuse potential is less than with some of the stimulants but it is certainly true we often don't find out about abuse potential until a medication becomes widely available in a particular population. So, I was just wondering if you might revise that if you felt that the abuse or diversion potential was less. RAPPLEY: Well, I would like to answer that in two ways. One is that we have heard that one reason a physician might want to use this is so that the physician would not have to deal with controlled substances. I don't like that argument. That is not about what is best for my patient in terms of their condition and their treatment. That is about a system that makes it difficult for me to deliver care effectively. So, I would rather educate my families that this is not a narcotic and it is controlled for some legitimate reasons and it is the best set of medications I can use and, therefore, I will work with that. So, I don't see that as persuasive. The other suggestion that it would be less likely to be abused as an agent itself, I think that might be attractive to me if, in fact, I was looking at a family where I thought abuse by other family members or my patient was possible, which is not an unusual case for my practice. But I have other agents in the classification of stimulants that I could turn to for that purpose. GOODMAN: Other comments on the issue of efficacy before we take a formal vote? Dr. Temple? TEMPLE: I am actually embarrassed to have to ask this, but outside of maybe psychiatry this Cohen's D is not widely used. Could somebody dilate on that a little bit? To divide effect size by some kind of measure of variance seems to give you something that doesn't have tangibility. PINE: It is not dividing the effect size. Maybe Andy can talk more about this. It is dividing the mean. So, it is a difference in means divided by pooled standard deviation. It kind of goes back to the in the social sciences, in a widely cited book in the mid '80s, about statistical power for that particular metric, which was the difference in means divided by the pooled standard deviation in the two groups. Standards were kind of put forth that were somewhat arbitrary at the time, in the mid '80s, for a small, medium and large effect. And, there are standard deviation units so up to 0.3 was a small difference; from 0.3 to 0.8 was medium; and above 0.8 was large. Then, what has happened over the last 15 years, particularly among pediatric psychopharmacologists but also adult psychopharmacologists, is that those standards have been applied and they tend to fit in terms of how people think about medications clinically. Typically, medications that physicians tend to think about as powerful tend to have large standardized differences or a difference in standard deviation of approximately one unit between an active treatment and an inactive treatment. Similarly, medium treatments tend to follow in the 0.5 to the 0.8 range. TEMPLE: It sounds, for example, like making your study larger makes your effect size look bigger. PINE: No, it will not. TEMPLE: Won't decrease the standard deviation? PINE: No, it will not do that. In fact, one of the nice things about the Cohen's D is that it is independent of sample size. TEMPLE: We will talk off-line. GOODMAN: Other comments before we call the vote? (NO RESPONSE) In that case, we are voting on the first question on efficacy. We have three options, yes, no or abstain. Let's start with Dr. Mehta. Although officially his vote doesn't count, in my mind his non- vote is extremely persuasive. MEHTA: On this drug it is not an issue but I think it is a pleasure not to be able to vote on most of the drugs! I think there is clear and persistent evidence of efficacy so efficacy-wise I don't think I have an issue. MALONE: I don't have any issue with efficacy either. I think that all the studies were positive and overall it looks effective. REESE: Ms. Dokken? DOKKEN: Yes on efficacy. REESE: Could you say your name before you give your vote? Thanks. WELLS: Barbara Wells, yes. ARMENTEROS: Dr. Armenteros, yes. PFEFFER: Dr. Cynthia Pfeffer, yes. ROBINSON: Delbert Robinson, yes. LEON: Andrew Leon, yes. PINE: Danny Pine, yes. GOODMAN: Wayne Goodman, yes. BRONSTEIN: Jean Bronstein, yes. WANG: Phil Wang, yes with those two caveats earlier. RAPPLEY: Marsha Rappley, yes. BIGBY: Michael Bigby, and if you really want my opinion about the efficacy of a psychiatric drug, yes. (LAUGHTER) GOODMAN: Do you want to recap for us Cicely? REESE: Well, "the yes" have it. It is unanimous. GOODMAN: Let's turn to question number two, which is a bit more thorny... BIGBY: Could I ask a question? GOODMAN: Who has a question? BIGBY: Me. Is there a definition for acceptably safe? GOODMAN: It is the same that you would use in dermatology! (LAUGHTER) REESE: Dr. Temple? TEMPLE: Well, this goes back to the law and various elaborations of it. What the law asks is that safety be assessed by all tests reasonably applicable -- a very broad standard that you could drive any sort of truck through; and that it show the drug to be safe for its effective use, which has generally been interpreted to mean that the benefits appear to outweigh the risks. But it goes on to make it clear that something can be unacceptable either because it shows something bad or because you haven't done enough. We have elaborated on that in various risk management things but it is always the same -- have you done what you need to do or enough of what you need to do? A judgment call obviously. And, can you conclude that in light of what it does that is good for you, you have acceptable risk? That is what it always means. GOODMAN: As we return to this question, I would like to break it down to different categories. Let's start with the dermatological issues first. I wonder if I could turn to you, Dr. Bigby, to offer your opinion on whether you think this drug is reasonably safe in this population, given what we have heard today about possible dermatological complications? BIGBY: I think that the drug should be put in the context of other currently available, marketed and highly used drugs where over time it has become clear that they are associated with the development of severe adverse skin reactions, such as TEN and SJS, and I think that this drug will find itself among that group. PINE: Can I ask you a question about that? I actually found, and I don't know what the number of the slide is from Dr. Andreason -- I found the slide that gives the labeling of Lamictal interesting and relevant and I wondered if you might comment on that. For Lamictal it says Stevens-Johnson syndrome -- it gives 8/1000, that is what it gives in children. It is page 8, on the bottom. Because I do think your comment about placing it in the context of other medications is very helpful and lamotrigine is a medication that there is some familiarity with and I wondered if you might comment on the comparison. It has a black box below age 15, lamotrigine. Is that right? I think that is right. That is my recollection, anyway. BIGBY: You know, the problem that I think you are going to have is that you are going to have a difficult time coming up with and agreeing on a number, but I do think that the drug should be labeled as one where people should be aware that it could be associated with SJS/TEN. Actually, I am quite surprised at the 8/1000 number because you are pretty close to one percent. You know, that is a pretty high rate for TEN. So, I don't know, I mean, I have a hard time believing that the number is really that high. Is it really that high? PINE: I don't know. I am just looking at what Dr. Andreason... GOODMAN: The numbers have come down over time. Is that correct? ANDREASON: Well, it is hard to say. If you look at the prospective registry study that was done, there was one death of Stevens-Johnson syndrome in that prospective registry with 1983. So, the idea that it is more common in children than in adults is fairly well accepted. I think that the numbers are reasonable from what we know. I think they are reasonable estimates. GOODMAN: It was placed in a black box and even though over time it would appear that the incidence is lower for lamotrigine it has maintained its black box position. Is that correct? ANDREASON: I am not aware that the numbers have actually been documented to come down. TEMPLE: But if you had one death in a thousand people you wouldn't remove the black box. That is an impressive number for most drugs. GOODMAN: Dr. Bigby, I have a follow-up question too. I agree with your position but I just want to clarify the basis of it. It seems like it is largely on one case, one case in which you have fair degree of suspicion or confidence that there is a bona fide case of Stevens-Johnson syndrome and, given the denominator, that was enough for you to be concerned. Is that fair? BIGBY: Yes. GOODMAN: And there was some exanthem as well. BIGBY: That is fair. I mean, that is a fair statement of my position. GOODMAN: Let me just follow up then. There is this disconnect that we have all talked about -- the real concern here is the extrapolation to large numbers and there is the disconnect with the postmarketing surveillance. But it would seem to me that that could in part be explained by dosing. I think I understand that dosing may not determine the incidence but it may have played a role in the persistence of the problem. So, we don't know whether the sulfone metabolite is relevant or not, nevertheless, we don't have a lot of postmarketing data in that age range at that dose and that could, indeed, explain the lower than expected rate in that population, in my mind at least. I just want to see others' reflection on that position. BIGBY: Can I just make a comment? You know, I have been involved in quite a few of these discussions about incidence of side effects postmarketing, and one of the things that is really striking about postmarketing studies is that unless they are very rigorous they don't detect much. So, when you are relying on spontaneous reports I think that you are going to miss a lot of the cases that were, in fact, cases and it is striking how poor, in terms of pickup of adverse reactions, postmarketing studies are unless they are really done with some sort of design in mind. TEMPLE: Obviously a problem is that nobody can answer the question of what the degree of under-reporting is and it is estimated widely. However, there is a lot of reason to think it is less bad when events occur that are likely to be drug related. So, for example, we have been pretty good at picking up acute hepatic necrosis in cases like that because when that happens the drug is highly suspect. When we approved a drug that was a major 3A4 inhibitor we got cases of rhabdommyolysis because it inhibited the metabolism of a couple of statins. We get cases very rapidly. Now, I don't know whether we got them all but these kinds of things you probably do better than things that happen regularly in the background -- seizures, things like that -- where why would a person decide that the drug did it. So, it is not that discouraging for things that are obvious and that deepens the mystery to me because, you know, the fact that the dose is about half what you would recommend now, that doesn't make it seem like there shouldn't be any cases. I mean, that is why it is here, because we find it a little surprising that there are no cases and yet there was one. CAVANAUGH: In terms of your question, Dr. Andreason showed a slide where he estimated about 11,000 children 6-12 years old who were probably getting modafinil from the postmarketing experience. If you take that 1/900, that is just about 0.1 percent. So, if you take 0.1 percent of 11,000, that would be about 10 cases. Now, it is commonly quoted that reporting rates are about 10 percent. That is based upon drugs where they may have been on the market a while but, all of a sudden, somebody publishes an article with a case-control series and then everybody else starts reporting it. In that case, after people are, you know, kind of all reporting cases, that is where you get the 10 percent. You know, if you even took 10 percent of 11 cases or 10 cases you might expect one case to be reported. Now, yesterday you heard that psychosis and aggression was about one percent consistently with the various drugs used for ADHD. Back in June, we also discussed this with Concerta specifically and you have about 1.25 million kids on Concerta and we know now that it is about one percent in terms of psychosis. Yet, you were dealing six months ago -- say, one percent out of 1.25 million is 1250 and yet you were only dealing with -- I can't remember the number but maybe 30 cases. So, it was less than one-half of one percent that was the reporting rate. BRONSTEIN: My question is to the FDA. What kind of requirement does manufacture of Lamictal have for postmarketing studies and reporting of incidence? ANDREASON: I am not sure what the requirements are. Right now, they have already completed the registry study. That is in labeling. There is already a black box. I think that the risk has been capped. I am not sure exactly what more one would want. It is also noted in the black box that it is only approved in children for Lennox Gasteau even though it is approved for other things in adults. I think that is about all we could expect. BRONSTEIN: Thank you. REESE: Dr. Laughren? LAUGHREN: I want to come back to the point that Dr. Cavanaugh was making. I think there is a real problem in knowing what the extent of under-reporting is and it probably varies so much depending on what the event is. With something like psychosis, especially depending on how you define it and if you are defining it just as hallucinations, a lot of those probably aren't going to get reported because it is a fairly common event in the background. Something like Stevens-Johnson, which is an extremely unusual event, a very alarming event, is probably much more likely to get reported. But the truth is we don't know what the extent of under-reporting is so you have to factor that into this. It is hard to know what it means that you don't have any reports among roughly 35,000 kids who have been exposed to it postmarketing but it is a disconnect and you just have to figure that in, in your overall deliberations on this matter. REESE: Dr. Mehta? MEHTA: I think it is just a comment to Dr. Cavanaugh too, essentially reiterating what Dr. Laughren said. I can't believe that 90 percent of the Stevens-Johnson syndrome which occurs in patients, either in Europe or in this country, is not reported. ANDREASON: Also, those numbers on exposure are unique patients between the years 2002 and 2005 only in the United States. REESE: Dr. Temple? TEMPLE: This is right at the heart of all this. If you really believe the one case is likely to be drug related you are talking about a rate with a point estimate of something like 1/1000 and a lower bound that is a lot worse than that. That is one problem. One question is how reassured to be by the fact that the pediatric use in the outpatient setting hasn't produced any, and I guess if you follow what Dr. Cavanaugh said you shouldn't take any reassurance from that at all because people report so poorly. My own view is that I take a little bit of reassurance but it is very hard to know. But that is what is at the nub of this. Just to make it obvious in case it isn't from the questions, the things you can do is try to manage that risk, taking some estimate of it, or ask for more data. That is the question. That is what question two is about. PINE: I guess thinking out loud a little bit, and in many ways my comments are similar to what Dr. Temple just said, I think if you listen to anybody who knows about dermatologic issues and who has talked about it today there is clearly a concern among everybody I think -- you know, the sponsor's dermatologist was concerned; Dr. Bigby is clearly concerned. I guess the thing I am struggling with is, you know, what is the level of concern. I think the other thing we would say, and I think everybody would agree with this and Dr. Bigby himself said this, that we really do not have enough data clearly to specify what the level of concern would be because there is this one case out of 923 but, when pushed, I totally agree with what you said, that you haven't examined the patient. So, I guess what it brings things down to and it makes me somewhat uncomfortable is that there is a lot of judgment call going on here for a potentially incredibly important decision. I just feel somewhat uneasy with that because, you know, you miss it either way and you could screw up big time. I don't know if that says we need to get more data. I don't know what that says but it just seems to me that we are stuck in a way. GOODMAN: Let me take it from there. So, I think the real question I would like to discuss now about this issue among the committee is whether it warrants a black box for that concern about Stevens-Johnson syndrome. I think that is really what you are alluding to there, Danny. We have efficacy. We have agreed upon that. We have already voted it. We have concerns about Stevens-Johnson but we have only one case that we can really hang our hat on. We don't have the postmarketing yet. It might be appropriate use for a black box given that it is something that will alert the prescriber and the patient to recognize it early. I think it is that early recognition that could make a difference in terms of outcome. I am not emphatic about it. I think that there might be other ways of addressing the warning without it being put in a black box because we have so little data at this point. Perhaps the highlighting would be a step below that. There is no question I think at this point that it should be included among the warnings. So, it is really a matter of does it wind up in a box or is it highlighted. Those are probably the two choices in my mind. Dr. Temple, help us. TEMPLE: Well, I would say, not to try to preempt the discussion, it at least gets a black box. PINE: Why do you say that? TEMPLE: That is the least because the only data we have says the rate is something like 1/1000. It is life-threatening. Everybody has to know about this and we don't know the rate. It could be 1/300; it could be worse. I have discussed this with Tom and I am virtually certain that would be what we would do. There are two other things to do though that you need to think about and address for us. One is whether it should be in some form or another recommended as not first-line therapy or think about other things first. There are various levels of subtlety in how to do it. We also are going to ask you whether we should ask for more data before we say yes. But maybe you think we are just wacky about the black box. That is all right, feel free to tell us. GOODMAN: Dr. Wang? WANG: I think there are several lines of argument that all point towards at least a black box. I mean, Lamictal sets the standard. If you are willing to put a black box for one Stevens-Johnson death out of 2000, here our best estimate is about 1/1000. The fact that, you know, with Lamictal the case was a fatal one doesn't really hold much weight. I mean, there are black box warnings for suicidality even though none of the cases were fatal. So, the fact that this one case didn't die is just fortunate I think. GOODMAN: I am sorry to interrupt, but the big difference there is we also didn't have efficacy, or at least very much efficacy. WANG: Granted. I think this whole issue of should this, on efficacy grounds, be a second-line treatment again pushes you. There appears to be less of a downside in putting something like a black box because if that de facto has the effect of causing it to be used second after failing a stimulant, then maybe that is, on efficacy grounds, also justified. TEMPLE: I have to say we would be very uncomfortable without a direct comparison asserting -- I mean, even though everybody loves this measurement and everything, we would be very uncomfortable asserting that it is second line because it is not as good, without direct comparisons. You can come back and say why don't you ask for direct comparisons all the time. That is another story. REESE: Dr. Rappley? RAPPLEY: Have we rendered an opinion about whether or not this is acceptably safe? I think in some ways we have taken a jump here and talked about what kind of labeling. Also, something you said made me think the black box label, or whatever warning is on the label is not related to efficacy and that is not a risk-benefit judgment. That is just a statement of risk. Am I correct? PINE: The way it was discussed yesterday, and it would be nice to hear that again, in what makes a black box it was a risk-benefit consideration and efficacy does go into the consideration, at least the way it was discussed yesterday. RAPPLEY: So, approval for use in children I see as weighed risk and benefit. TEMPLE: The decision to include a box has something to do with what the drug is for. If there were only one treatment for this and it was considered urgent to treat it, I don't know whether you would put a black box in. We don't box most anti-cancer drugs, but they are all lethal in one degree or another, because that is an expected part of the deal. So, what it is for and what it does has at least something to do with it. So, there are several other classes of drugs that work; you have choices; and here is one particular liability. But feel free to tell me I am all wet. GOODMAN: Let me stay with Dr. Rappley's comment. I didn't mean to short-circuit the discussion. I was offering my opinion but you are welcome to express the opinion if you feel, based upon the dermatological issues, it is not reasonably safe. RAPPLEY: The way I am thinking about this is I understand that there is a particular metabolism of this medication in children and we have one case of Stevens-Johnson, perhaps 1/1000. We have plausibility that this medication can be linked to this serious condition. My understanding of under-reporting is that it is significantly under-reported and it is more likely to be common and I am reflecting comments from Dr. Bigby that we will find it associated in the future, and my faith in postmarketing studies is somewhat small. So, given those things, I think that children are at risk for serious side effects with this medication and, if you ask me to do the cost benefit analysis, I think it is not adequately balanced by what we have to offer in bringing this to treatment of children for ADHD. GOODMAN: I would like to hear if others would share that point of view. REESE: Dr. Malone? MALONE: I think I partly share that point of view. I don't think it is safe enough to recommend it as a first-line treatment, especially when we have a number of effective, well-known first-line treatments -- with the data that we have right now. It may turn out that this isn't going to be an issue but I think with the data that we have now it is hard to recommend as a first-line treatment something that could have such a dangerous side effect. REESE: Dr. Laughren? LAUGHREN: I just want to come back to a point that Dr. Temple was making earlier about what acceptably safe means. Part of what is inherent in that concept is having enough information to make a judgment about safety so I really want to make sure that you consider the full range of options. You might, looking at what you have, decide that you don't have enough information to make a judgment about safety but if you are going down that path, then tell us what more information you would like to see. But I just want to make sure you consider the full range of options other than, you know, black boxes and whatever. REESE: Dr. Bigby and then Dr. Robinson. BIGBY: I actually enjoyed the comment at the end of the table here because I don't know if you figured this out but I like to try to make things simple. You know, thinking about it that way does actually make it simpler. The statement about we don't have enough information to say that it is safe, I would actually say it the other way and that is that we have reason to worry but we don't actually have enough data to say it is not safe. REESE: Dr. Leon? LEON: Well, I am concerned about a couple of comments I have heard in the last 10 or 15 minutes. Dr. Pine said right now it is just a judgment. Without putting words in his mouth, I think we are basing this without enough data. Dr. Bigby is predicting that once this is used widely we will see more Stevens-Johnson; Dr. Temple is saying we need more data and suggesting we should look at more data. I don't feel comfortable saying it is safe until we have more data. There is at least one ongoing study. When are those results going to be in? There are 303 children, if I am correct, being followed right now. It is certainly worth waiting for them, and that is still a very small number. BIGBY: But those children aren't going to help you with the issue that you have. LEON: That is a good point, yes. But in my opinion we just have inadequate data. In the first 1000 there was a case. Is the next 1000 going to have 20 cases or zero cases? I don't think we can guess yet. REESE: Dr. Robinson? ROBINSON: Actually, it is interesting, what Andy is saying. I guess my question is, OK, we have 1/1000, how many more kids do we have to do to where we really say the estimate really changed dramatically, either going down or going up, that would be clinically meaningful either down or up? Are we talking about having another 1000 kids? Another 10,000 kids? Because we are dealing with what seems to be a rare event with all drugs. So, that is the question. It is always good to say we would like more data but is that in the actual realm of doability? LAUGHREN: Actually, you can figure out how many patients you need to follow to cap the risk at whatever level you want to be comfortable with. We have this rule of 3 which, you know, estimates the upper bound of the confidence interval for the finding of no cases. For example, if you wanted to be comfortable with a level of 1/1000 you would have to follow 3000 for whatever period of time was of interest. If you found no cases, that would cap the risk at 1/1000. So, you can use that method to calculate how many patients you would have to look at, at the doses of interest and for the time period of interest, with the finding of no events that would cap the risk. Now, if you wanted to cap the risk at somewhere near the background rate, that is not a doable experiment but you could at least figure out, say, with 3000 that the risk is no greater than 1/1000 if you found no cases. REESE: Dr. Pine? PINE: I guess two things. I want to bring up one point that we haven't spent much time talking about, and that is kind of the need for more treatments in ADHD. You know, the important thing to remember is, yes, clearly stimulants are effective. No question, and they are good treatments and there are other treatments around. Again, no question. But even when medications are effective the amount of improvement that you get even when treatments work well is often not necessarily what you want, and there are not nearly enough treatments available for kids with ADHD. You know, I think it is hard to say where this is going to fit in and I would totally second what Dr. Temple said, you know, to base a decision on limited use on efficacy would not be a good thing to do because it is a yes/no question. The medication clearly works. And, I am uneasy about withholding treatment that could be potentially efficacious given the availability of treatments, such as they are, for ADHD. So, that is the first thing. I don't think we have spent enough time recognizing that fact, that there are clearly needs for other treatments. Number one. Number two, thinking about that on the one hand, with capping the risk on the other hand, just personally, off the top of my head, I would be much more comfortable if we could cap the risk at 1/1000. I would feel much more comfortable about making a statement or decision or conclusion about whatever the word -- what is the word, relatively safe? -- acceptably safe. If I knew that a good estimate of the risk was 1/1000 I would feel a lot better. If you are saying that 3000 cases treated for two weeks openly and we see no cases would answer that question, I would feel a heck of a lot better. TEMPLE: That is our rule of 3, and I am sure Dr. Leon can explain why it is not quite right but it has been considered close enough. Just another way to look at this, suppose you thought that the risk could be as great as 1/500 -- I mean, the data we have now has a confidence interval and it probably goes down to 1/300 or something like that, where would you be comfortable? You just said 1/1000 properly labeled and everybody knowing it would probably be OK. But I think it is important to discuss that. PINE: One in 950. REESE: Dr. Pfeffer? PFEFFER: I think there are several other considerations. I certainly agree that if we can enlarge our treatment spectrum for this disorder it would be wonderful. But I also think that we in a way have concern about the potential risks in this case without sufficient data, and I am thinking also about what happens in the real world once a drug is approved. Many of the children with this disorder are treated with multiple medications, unfortunately, and I would wonder about what drugs might have potential for cross-reactivity that might increase the risk for these children. And, I tend to think that we have a disorder that is severe, there is no doubt. We have carefully tried to develop approaches to treat these children and perhaps a careful approach is to ask for more data and to sort of place that in abeyance for the time being until we can answer this question with a little bit more assuredness. It just raises a new issue because we did talk about some medications, one of which I think is commonly used, which could have cross-reactivity. GOODMAN: Let me clarify. We have 1/1000 and there was an estimate of -- what was it? -- 5 percent of cases of Stevens-Johnson lead to mortality? BIGBY: Yes. GOODMAN: Let's start with that just as a figure. How many open cases would you need to treat, for what period of time, in order to gather those data with some degree of confidence? TEMPLE: I don't think you could imagine getting good mortality data... GOODMAN: No, I am not talking about mortality data. TEMPLE: Well, to take a simple task, as Tom said, if you wanted reasonable reassurance that it was not greater than 1/1000, if you had data on 3000 people and no cases that would provide that. I mean, the tension we have had is here is this one case in 1000. Here are 30,000 people treated, no cases. Is this just some wild, weird fluke or is that close to the true rate? You might even decide -- I mean, you did say even if that is the true rate, that might be OK. Maybe you would make it second line or do something else. That might be OK. But at the moment, one of the reasons this was brought to you is we don't know what the rate is. We don't have enough data to know what the rate is and it could be rather high or maybe it is really low and this is just a fluke and that is our uncertainty. PINE: Speaking only for myself, that is what I would want to know and I would be comfortable with that, but until I know that it is going to be hard for me to make a decision. REESE: Dr. Rappley? RAPPLEY: I could ask it another way. Is anybody comfortable with the amount of data that we currently have? Then we could move to discussing what additional data we need if there is further discussion on that. I don't mean to push. GOODMAN: No, that is good. TEMPLE: Just one thing, as you discuss that I think it is important to think of enough data for everybody, enough data for a fairly scary statement that says this is only for people who haven't responded well to other things, not that we have data on that but, I mean, there are a number of things to think about as you discuss this. PINE: Again, related to the discussion we have had I don't think the questions are really about efficacy or what the niche is going to be so, personally, I would care less about who receives the medication in terms of what narrow type of condition they have, and I would be more concerned with capping the risk estimate. Based on what Dr. Bigby said, it seems to me 3000 patients treated for a month openly would be what you would want to do. GOODMAN: We are not finished with this obviously. I would like to move on to some of the other concerns we have and see if we can go through a list and perhaps even identify where we think that this medication might have some advantage, some possible niche. In terms of cardiac issues, those were discussed at some length yesterday. I think in the context of stimulants it was decided that an individual who had known structural cardiac abnormalities should not be prescribed a stimulant. Would we be having similar concerns about this agent? In the data that I have seen there wasn't very much evidence for increases in cardiac parameters such as heart rate or blood pressure and, therefore, would it be in that context perhaps a safer alternative? REESE: Dr. Andreason? ANDREASON: I just wanted to add that in the Provigil labeling already it warns against using modafinil in patients with hypertrophy and bicuspid aortic valve. GOODMAN: So, you would already put it in the same category with the stimulants? ANDREASON: Well, it kind of already is. It is already in labeling. Unless you felt that the data that was presented should remove that. GOODMAN: I don't see anyone saying yes. REESE: Could you come to the microphone and state your name? Thank you. HERSKOWITZ: Norman Herskowitz, medical officer in DMP. In the labeling, as I recall, it really discusses the limitation -- I think this is the initial studies -- to issues of mitral valve stenosis and regurge type of syndromes, but not to any other sorts of cardiac history. So, that is just for information sake. ANDREASON: I am pulling up that labeling for you; I am not as fast as I thought I would be. HERSKOWITZ: It mentions some very subtle changes in blood pressure, but extremely subtle. In the adult studies there seemed to be a pattern of increase in anti-hypertensive use although no changes in mean blood pressure. ANDREASON: I have it. This is under cardiovascular system in the Provigil labeling. It says in clinical studies of Provigil signs and symptoms, including chest pain, palpitations, dyspnea and transient ischemic T-wave changes on ECG were observed in three subjects in association with mitral valve prolapse or left ventricular hypertrophy. It is recommended that Provigil tablets not be used in patients with a history of left ventricular hypertrophy or in patients with mitral valve prolapse who have experienced the mitral valve prolapse syndrome in previously receiving CNS stimulants. Such signs may include but are not limited to ischemic ECG changes, chest pain or arrhythmia. GOODMAN: And that is at a lower dose than is being proposed. ANDREASON: Correct. REESE: Dr. Rappley? RAPPLEY: The discussion yesterday from Dr. John Moore who is a pediatric cardiologist on the Pediatric Advisory Committee and, Deborah, add to this if you can, we talked about how the increases in blood pressure and pulse were perhaps not clinically significant for children but statistically significant and, yet, the concern persists because of the idiopathic hypertrophic subaortic stenosis being a condition that really cannot be detected in the population until the serious adverse event occurs, and that it is plausible that increasing sympathetic tone could contribute to that in the same way that running track or becoming dehydrated does. GOODMAN: After Dr. Pine makes a comment I would like to take a ten-minute break before we come back for further discussion and vote on the second question. I need a few minutes to deliberate. Dr. Pine? PINE: I guess with a lot of these secondary adverse effects -- the cardiac effects, the psychiatric sequelae, the growth effects -- for some of the same reasons that people were uncomfortable making statements about comparative efficacy, I would be uncomfortable making statements about comparative adversity unless there have been head-to- head trials, which there haven't been. You know, my take from looking at all the other data, besides the dermatologic data, I am slightly concerned with the psychiatric adverse effects, no more concerned here than the discussions yesterday, and I just think it is probably not fair, given the data, to make statements that this is better or not better than any other agent unless they have been compared head-to-head. I think it is, you know, is it safe enough or not for all of these secondary issues and, again, in my mind it seems safe enough, whatever that means. GOODMAN: I would agree. Let's take a 10-minute break. (RECESS) GOODMAN: It seems to me that a lot is hinging on one case and I still haven't decided which way I want to go based upon that pivot point. So, let me just go back to that case for a moment. First I would like to hear from Dr. Bigby. I think I have already heard, but I need him to repeat, that there was definitely a case of SJS but I would like to hear again his opinion on the association between the drug and that case of Stevens-Johnson syndrome. BIGBY: My opinion about that reported case is that it is probably a case of Stevens-Johnson syndrome related to the drug. Now, that doesn't mean that it is definitely related to the drug. And, I think that the difficulty would be for anybody to say with any certainty that it is not drug related. But, you know, am I absolutely certain that it was due to the drug? No. But I wouldn't want to be put in the position to argue that it is not drug related. That is the problem we have. GOODMAN: I understand that the investigator who treated that subject is here. Could that person identify himself or herself? Would you mind coming forward and just describing your impressions of the case? REESE: Could you please be sure to identify yourself, sir? BELNOR: I am Samuel Belnor, a pediatric neurologist and I was the principal investigator on this case that was a 7 year-old Asian boy who is perhaps the most compelling case for Stevens-Johnson. My impression on this patient -- and then I will go into detail, but my impression was that the most likely diagnosis was erythema multiforme, possibly Stevens-Johnson. The most likely etiology was a viral infection, possibly drug related. The patient had shown improvement in the clinical symptoms of ADHD after one week on drug and was seen on the 14th day. On the 14th day the patient presented with fever of 101.9, a sore throat and feeling bad. I was out of town but the sub-investigator, a pediatrician, saw the patient. The mother complained of two lesions on the leg which she thought were possibly a brown spider bite but there was no rash. The next day the sub-investigator put the patient on amoxicillin and did a rapid screen for strep. which was negative. The throat, he felt, looked like a viral throat infection. There was no exudative pharyngitis but papules in the throat. The patient was seen the next day by a pediatric group locally. The pediatric group saw typical lesions of Coxsackie B virus in the posterior pharynx and diagnosed this patient as having a Coxsackie B virus infection. The rash was over most of the areas of the body but it was more marked on the face and extremities. Also, they felt that the two lesions on the legs were the target lesions of erythema multiforme. The patient did not develop any apparent -- there were no lesions in the mouth at that time and no mucous membrane involvement. About six days later -- I apologize, we have a real lack of data because the mother did not bring the patient back to us until four weeks after the rash developed, in spite of being called on numerous occasions. She had a single family business and was the only employee and would not bring him back. He went to school many of these days. We told the family the day of the rash to stop the drug. The teacher recommended, on day 23, that she felt that he should go back on the drug because his behavior was much worse and the mother gave him one dose of the drug and nothing really changed much except that she felt that he was maybe pealing more and did not give any more. No one saw the lesions in the mouth, other than the mother, and she thought that there were lesions in the mouth because he would not eat well. No physician see mucosal involvement. He did complain of burning when he urinated, which is a possibility. The patient really felt quite good during this four-week period from the onset of the rash until we saw him next. He went to school about half the time. The mother was really unconcerned. When I saw him four weeks after the rash onset I saw no lesions in the mouth. There was no evidence of any previous lesions in the mouth. He was happy; no stress. And, his skin was pealing. There was no evidence of any dermal involvement other than just some pealing of the skin, mainly on the extremities. There were no lesions in the posterior pharynx of the Coxsackie B virus. If we had seen the patient earlier we obviously would have done a skin biopsy. We did a RAS test later to modafinil and to amoxicillin -- of course, it is of limited value, but it did not show any positive reaction. GOODMAN: I would like comments on what you have just heard from either Dr. Rappley or Dr. Bigby. Does that help one way or the other in the diagnosis? BIGBY: Given the description, I don't think that anybody can say that that was not a case of SJS. You know, it would be nice to know if the patient had typical targets or not but I don't think you are going to get that described in this case. RAPPLEY: I guess for me it is the degree of uncertainty that we have at every point; it is sort of the added uncertainty that makes me uneasy; that makes me unwilling to say that it is just fine, let's go forward and treat everybody. GOODMAN: Can you repeat that? RAPPLEY: It is the degree of uncertainty that we have that makes it difficult for me to say that it is fine or perfectly acceptable to proceed with just having people make sure they report rashes. GOODMAN: Dr. Pine? PINE: I want to go back to the statement Dr. Temple made. You obviously seemed very taken with this when you said it is at least going to get a black box and we moved away from you fairly quickly. Could you just spell out your thinking, what made you react that way? I mean, I think it is more than just this one case or maybe it is just this one case but I would like to hear that. TEMPLE: Well, it goes without saying that I have no credible, sensible view about whether this is a bona fide case or not. I am listening to people who do though. So, what we are seeing is that in something like 1000 people, but perhaps when you look at exposure it may be 700 or 800, you have one case that is at least statistically compatible with rates that are high enough to be worrisome, you know, down to one in a few hundred and up to whatever, and a condition that is very scary and is life- threatening. So, it all turns on believing the case. I mean, if this was dismissable I wouldn't have said that but everything I have heard up to now, both internally and even from the company, says that this is a plausible case. So, when your best estimates of something very worrisome are in the neighborhood of 1/1000, you know, of it was agranulocytosis or something we are accustomed to taking full note of those. That is really all I meant. PINE: Yes, that is helpful. Thanks. GOODMAN: Dr. Mehta? MEHTA: Actually, I have two questions of the investigator. One is was the patient hospitalized? And, what surface area of the body was affected by Stevens-Johnson syndrome? BELNOR: I am sorry, will you repeat the first question? MEHTA: Was the patient hospitalized? BELNOR: No. Although most of the areas of the body were involved, the total surface area of the body involved, according to the mother's history and the pediatrician that saw him and our examination when he came back, was less than 10 percent. MEHTA: Can I ask Dr. Bigby a question? GOODMAN: Sure, go ahead, Dr. Mehta. MEHTA: What percentage of Stevens-Johnson syndrome patients would be hospitalized? BIGBY: Excellent question to which I do not know the answer. GOODMAN: Ms. Bronstein? BRONSTEIN: I think there is another signal we can't forget and that is the adult population on the low dose having three cases in a little over a million, which is two cases more in a million than the general population on the same drug. So, you know, even if there is some question there is also some other linking stuff, at least in my mind. GOODMAN: Dr. Laughren? LAUGHREN: Could we get some clarity, maybe from Dr. Bigby, on what the background rate of Stevens-Johnson is? Then, what the reporting rate is in this experience with this drug in adults? BIGBY: If you look at sort of population-based studies the estimate is one case in a million or 500,000. If you look at the case-control study that was done in Germany, Italy and France where they sort of specifically tried to identify all of the cases over a period of time and they took detailed drug histories from the patients and they limited the definition to SJS and TEN the way I defined it in my talk, it was in the order of 1/100,000 to 1/400,000. LAUGHREN: So, it sounds like it varies anywhere from 1/100,000 to 1/million. Do we have clarity on what the reporting rate is for those three or four cases in adults? Maybe the company would know that. CIVIL: Yes, for the person taking the transcript, my name is Rich Civil, C-I-V-I-L. Our reporting rate for events coded as SJS and TEN, the number of cases we have has been discussed. There are five. Each of them can be looked at individually and, indeed, the discussions up to this point have already excluded largely from consideration one of the cases, that being the patient with subarachnoid hemorrhage who developed the cutaneous skin reaction in association with the apparent initiation of treatment we phenytoin and phenobarbital. Subtracting that case out, we have four cases in approximately 750,000 adult patient-treatment years of exposure. Given the described hazard profile which suggests a greater risk in the first four weeks perhaps, we recognize that a better denominator for that exposure would be patients rather than patient- treatment years. Based on what we have estimated as an average treatment duration of approximately 2.5 months on average in the postmarketing environment, we would then calculate that the 750,000 patient- treatment years translate to the rough equivalent, based on IMS estimates and survey data, of approximately three million patients treated. LAUGHREN: So, the reporting rate with that denominator is roughly one per million. So, there you have it. I mean, you have a reporting rate of one in a million; background rate somewhat less than that. TEMPLE: Well, that doesn't take in the under-reporting. LAUGHREN: Right, but we usually compare reporting rates to background rate, understanding that there is under-reporting. We generally take some comfort if the reporting rate is well below the estimated background rate. PINE: I guess my question is what is the downside of capping it at 1/1000 by studying 3000 more patients? As far as I can hear, the only downside is that we are going to delay putting the treatment on the market for six months or a year, which seems like a risk worth taking if we really want to be sure that, you know, 1/1000 is really the risk of Stevens-Johnson. I mean, that seems like a fairly fair trade, you know, to be sure that the rate is really no higher than 1/1000 and we delay approving a treatment for however long that takes, six months or a year. LAUGHREN: That is precisely what we are asking the committee. TEMPLE: Right, and people have to weigh the cost of the delay and the consequences of not doing that. MALONE: Most of the talk has focused on the one Stevens-Johnson. What about the other case? I didn't quite understand the case where there was urticaria. Was that thought to be drug related or a signal of anything else related to serious skin reactions? BIGBY: I think that that case is less than 50 percent likely to be drug related. GOODMAN: If this were a new molecular entity with no prior marketing experience and I was presented with these data, with the degree of uncertainty that we are all facing, I would say we needed additional data, for sure. And, I think one of the reasons that I have been on the fence in the last hour or so is because it is an agent that has been out there for a long period of time. But, given the fact that it is at a higher dose and it is going to be given to a population that metabolizes it differently, perhaps I should be taking it more as if it were new rather than a different indication for the same compound in the same population. So, I would have to say I am leaning at this point to recommend additional safety testing. I don't feel, as I re-read this question, that modafinil has been shown to be acceptably safe given the doubts that we have in our minds. If it turns out to be 2/1000 I think we would all regret the decision to go forward. I don't want to do that experiment in the postmarketing arena. I think, that said, if we are to recommend the studies -- hopefully, the FDA would be the ones to really design this -- that we don't set the bar too high. I don't want to be disingenuous. I think that this is a drug that we all agree is efficacious. There may be certain advantages over existing compounds. Some of those are yet to be proven. I would like to see an opportunity for the company to come back with those additional data that would give us an extra degree of assurance that this case was a fluke, and that could exactly be what it was. LAUGHREN: I think it is important to be clear about what level of comfort we could gather from the study that I proposed earlier. The most you would be able to do is to cap the risk at 1/1000. So, even if you did that and you were comfortable with that as a cap, I think the drug would still have fairly strong labeling. I just want to be clear about that. It is not going to make the problem go away. PINE: Related to that, there probably would be some discussion about, you know, let's say you could do a larger study and cap the risk even lower. You know, maybe people would want to do that. There could be some discussion about that. I think that is probably going a little far based on the data we have right now. I think the question is, is it safe enough or not and that is kind of what we are debating. GOODMAN: Dr. Wang? WANG: I am a little bit less sanguine. You feel that with a study of another 1000 patients maybe you will cap it at 1/2000. It quantitatively gives you reassurance; it won't qualitatively necessarily give you maybe the reassurance we are looking for. One thing in favor of additional studies is an active comparator, a study that actually could maybe sort out sort of where in the armamentarium this might fit in. GOODMAN: Dr. Bigby? BIGBY: Somebody has to clarify to me then what is the black box labeling for Lamictal. If they have a rate of 8/1000 in children what does the label say? ANDREASON: Let me put it up. PINE: The other thing to remember about the labeling for Lamictal is that it is for Lennox Gasteau syndrome so it is a different disorder fundamentally. TEMPLE: And for which I believe there is no other treatment. PINE: There is no other treatment, that is right. TEMPLE: It makes a difference. I am confident if there were no other treatment here our discussion would be different. ANDREASON: Here is the lamotrigine black box, or at least the part that has the data and the warning up front. This is for Lennox Gasteau in kids and then adjunctive therapy for epilepsy in adults and bipolar in adults. GOODMAN: Dr. Temple? TEMPLE: Well, I am sure you are going to want people to discuss what you just said but I just want to throw one other thing into the mix, and that is, suppose the company did a study showing definitively the way I want it shown that it really did work in people who failed on other therapy -- a properly designed study, not that hard to do if it really does work in that setting, would that make any difference in all this? GOODMAN: It would make a difference. It would definitely wind up with a black box. PINE: I don't think it is an either/or though. I would want to cap the risk. TEMPLE: Well, that is what I am asking. What you have just been discussing is capping the risk before it gains approval for this use. What I am asking is if, before doing that, they knew that it unequivocally works in people who failed on other therapy would that make you want to make it available even before you capped the risk, with an appropriate box, or not? PINE: You know, that is a theoretical debate. I would have to see how well does it work; does it really beat a stimulant head-to- head; who are these people... TEMPLE: That is the test. It would have to beat the drug they supposedly failed on, presumably a stimulant, in a randomized trial and it would have to beat it. PINE: That would be great. I mean, I can't tell you that I would definitely say forget about the risk if you show me that, but it definitely changes the discussion we are having right now quite appreciably. GOODMAN: I would echo Dr. Wang's point earlier that not having the comparative data I think is a weakness of this application. PINE: But, personally, I don't think you have to have that. I mean, I think if it worked just the way it does work and you knew that the risk was 1/1000, again just speaking for myself, I would be comfortable with that. TEMPLE: No, I just meant whether you could truncate further characterization of the risk if you knew that thing about it. Maybe that is such a hard study nobody is even interested but you don't know until you ask. GOODMAN: Dr. Bigby, has your question been answered? BIGBY: Yes. REESE: Dr. Malone? MALONE: If you did such a study, then would the label reflect that it was approved for the treatment of patients who failed other treatments or would it not include that in the label? TEMPLE: Excellent question. With clozapine where we had those data the labeling said you should have failed on other therapy because the 1.5 percent rate of agranulocytosis was considered unacceptable in a first-line population. So, if there were no further characterization of risk you might very well say that it is for people who failed other therapy, and maybe you wouldn't have to wait for the further characterization of risk. If the risk were then further characterized and everybody was comfortable, maybe then we would feel it could just be thrown into the mix and they would have this particular piece of information. MALONE: How well do post-approval registries help resolve a question like this because it won't be that easily resolved? And, how would you do that? TEMPLE: Yes, that is a hard question. There are probably people better able to answer. The most successful registries are ones where you are controlling distribution so, for example, the clozapine registry, in my view, is a huge success because you can't get the drug without going to the right pharmacies and your name goes in it, and one of the purposes of it is to keep people who have already gotten agranulocytosis from ever getting the drug again and, as near as we can tell, it has been very, very successful and there have been analyses, but that is because you have to sign up to get the drug. Registries ordinarily in many other cases are voluntary and whether people stick to them or not is uncertain, and they have varying degrees of success. We would have to get some people who know more about it than I do to answer that though. MALONE: Currently, with stimulants you almost have to see a patient fairly regularly because you have to keep writing the prescription. Could a registry be developed by requiring a script from a doctor? At least they could ask if they had a rash. TEMPLE: Well, any system that limits distribution -- first of all, it is very difficult if the drug is already available in another form. Second, they are a lot of trouble. I mean, we do those things for drugs we are really worried about. There is one being set up for Accutane that is more rigorous than before; thalidomide -- I mean, those are the things we are talking about. You don't do them lightly because there is actually some evidence that they interfere with use. We have distribution system for a drug called dofetilide that is used to maintain normal sinus rhythm and a study, I guess out of Duke, showed that people are using solatol or quinidine instead. Well, that was not what we had in mind. So, you have to fit it into the system and it has to work out. GOODMAN: Dr. Malone, by this line of questioning, are you suggesting that our target would be to vote in favor of the compound but to put in place a rigorous registry program to monitor for rashes, particularly Stevens-Johnson? MALONE: No, I wasn't trying to suggest that. I don't think it is going to be easy to answer how often a rare event occurs if you do more patients. So, I think in the end you are going to have to have a longer way of answering that question. I wasn't trying to suggest that you would approve it and then handle it that way. GOODMAN: Any members of the committee that would like to argue in favor of this being shown acceptably safe, and we are focusing on the dermatological complications? (NO RESPONSE) I would like to give a representative of the company a chance to argue that point before we take a vote. RUSSELL: I would just like to ask Neil Shear to give his opinion on the risk of Stevens-Johnson. SHEAR: Well, I guess I can perhaps add strength to your difficulty. The question of this single case is exactly the way I would have explained it, that there was a single case that was sort of convincing. It didn't meet a definition of Stevens-Johnson because the body surface area of epidermal detachment was not high enough. It would probably meet a definition of erythema multiforme major, and it probably is post viral. The other issue you can look at is it is not 1/1000 because it was 10/10,000 -- it was one and that one could easily be zero and that one could be two. So, in terms of it perhaps being a fluke, I think there is some strength to that argument. Then trying to do the balance that you are talking about, I think, you know, you have raised various possibilities. I don't feel it is up to me to tell you what to do on that. But keeping track of reactions has been done before for other drugs. I would also say that because of its already accumulated experience, the pediatric dose notwithstanding, this is not Lamictal. This is not a drug that had started right from the beginning -- Lamictal, when it was started in England out of Burroughs Wellcome, was causing problems immediately and continued to cause issues. Now, some of those are probably over-ascertainment because people were jumping on the bandwagon in terms of diagnosis but, still, it is a drug that has a very different risk and I think that has been managed over the years, actually many years now. Here is a drug that was on the market. It is not a new chemical entity but is being used in a broader population in children so you have the balance there. What I have seen so far has not convinced me. I think where I would differ from Dr. Bigby is that I don't feel that I can absolutely -- and I don't think he said absolutely, but I don't know if I can really confidently say that there are going to be cases of Stevens- Johnson/TEN with this. I just don't see that based on the exposures we have but that is, again, just personal after looking at many of these drugs for many years. If you look at dilantin, if you look at sulfonamide, they were recognized in the '30s. When they first came on the market it was clear that these drugs were causing these kinds of problems right away. I do want to make one more comment since I have the microphone for a second, the sulfonamide allergy story -- for the severe reactions to sulfonamide it is the aromatic amine at the end of the molecule and not the sulfonamide moiety that is considered to be responsible. There is certainly no evidence to the contrary and the only evidence that exists on a metabolic basis is that the aromatic amine is hydrolyzed to a hydroxylamine which goes on to become a nitroso, which is a P450 pathway through 2C19, and that is what appears to lead in vivo and in vivo to toxicity. PINE: I would like to ask you a question about your statement about where you would disagree with Dr. Bigby. How confidently would you assert that you doubt that we would see additional cases? I understand that you said that there is not a lot of evidence to support that. SHEAR: Well, I guess what I would do is look at the cases that exist. What is real? What am I comfortable with? We do see that there are some cases in the adult literature. It is hard to tell but, you know, we do have some numbers that are low, like background, and they are in the 1/100,000 to 1/million type of range. Though adults don't usually get Stevens-Johnson syndrome that often, we do see it. We do see people come in; they have no drug and they get a real Stevens-Johnson syndrome. So, that is probably out there. The pediatric exposures of at least 30,000 children -- Dr. Andreason showed the numbers for people who were getting the drug through various programs, and they had none in 30,000 exposures. Again, if this case was rock-solid Stevens-Johnson, which it doesn't appear to really be by the usual case definitions that we use nowadays, but if it is erythema multiforme major, which is something that kids do get and something that suggests viral from what we heard about the case, the more you dig into this the more I am getting more comfortable that it isn't. And, until I had a chance to actually talk to the investigator I don't think I would have been saying this, but looking at it in its totality and trying to balance it against the other known hard-core data, that is what makes me more comfortable and I think I have had that information maybe hours longer than Dr. Bigby, but not much more, and I think you do get more comfortable, and we sat down as a group of experts to talk about it and we did become more and more comfortable where that probably fit. REESE: Dr. Bigby? BIGBY: Do you have a response to the question that was asked about what percentage of patients with Stevens-Johnson syndrome get admitted to the hospital? SHEAR: Yes, your answer was a good answer; it is a good question. I mean, we do sometimes see people who come in who we think have Stevens-Johnson admitted to the emergency departments, but I would say that if they actually had some real epidermal detachment they would be admitted not only to hospital but probably to a burn unit. I mean, we are talking about some pretty sick people and if you see a kid with truly Stevens-Johnson syndrome, well, you are not going to send them home. Unless you want to, you know, not only potentially kill the child but end your career, you are not going to do that. This is a serious event and it is easy to recognized. This is not a subtle diagnosis really. I mean, these people have mucosal blistering that is not only horribly painful but is hemorrhagic, and that is not what we saw in this case and, again, we have not seen any reports in the larger pediatric population or the postmarketing surveillance. GOODMAN: Further discussion? Dr. Mehta? MEHTA: I have worked in the drug industry for about 40 years and I must say that I have worked with a lot of different drugs and I have seen during clinical studies about 20 patients with toxic epidermal necrolysis or Stevens-Johnson. I don't recall a single patient not being hospitalized. Every single patient is hospitalized. It is such a serious disease because mortality now is about 5-15 percent. Ten or 20 years ago it used to be 50 percent. So, every patient was hospitalized. GOODMAN: Dr. Rappley, do you have a comment? RAPPLEY: All day we have dealt with the uncertainty before us but now we hear a lot of confidence that it is not Stevens-Johnson. I, myself, am not changing my view on this. GOODMAN: Dr. Temple? TEMPLE: Well, let me offer a suggestion or a question. My assumption is that to the extent confidence that this case really represented Stevens-Johnson, you would be more comfortable with going directly to approval perhaps with language in the labeling, and I don't think we are going to be able to fully do that here. So, let us tell you -- you know, we might telephone you or something, but we will look more at this. We have experts around even though none of us personally knows about it. If the case starts to look very weak, that is going to change things and i think we understand what you think about that. But if the case stays reasonable strong, not 100 percent but reasonably strong then I think we have heard your advice. GOODMAN: I find that acceptable. I would like to call the vote on the question based upon what we know now. RAPPLEY: Will you clarify what it is that we are voting on? GOODMAN: Has modafinil been shown to be acceptably safe in the treatment of attention deficit hyperactivity disorder in children and adolescents? You have a comment, Dr. Andreason? ANDREASON: Yes, Dr. Luke had a question about the case report versus the report given by the investigator. LUKE: Yes, in the original written case report it stated that it covered the entire body. It was described very differently from how the investigator describes it today. I think that contributed somewhat to the relative uncertainty that we are now hearing within the last half hour or so. So, the question is what is the real story, was it the written report provided by the sponsor or is it the investigator's testimony given now at today's meeting? BELNOR: I don't think we have changed the story. The implication was that it was on all areas of the body but it didn't cover every area of the body completely. It was less than 10 percent of the total body surface area. It was on the trunk, the face, the extremities and the back. LUKE: So, you are saying the pealing is less than 10 percent but perhaps the rash itself... BELNOR: No, the rash. The rash was around 10 percent by the history that we obtained from the pediatrician. LUKE: Oh, so it is by history. You did not yourself observe this? BELNOR: No, the peeling looked like it was obviously less than 10 percent when we saw the patient. LUKE: So, then there is still some doubt. It is really hard for a dermatologist, and I know other dermatologists in the room can attest to it, to make an assessment from hearing a story, especially if it is not carefully written up. Photographs are often helpful and biopsies are helpful but, again, it is lack of information that adds to uncertainty. GOODMAN: Let's go ahead with the vote. I am going to start with Dr. Bigby. BIGBY: So, is this a yes or no answer? GOODMAN: Or abstain. BIGBY: I would say yes, it is acceptably safe. GOODMAN: And explain your reason. BIGBY: You know, I think that this is an instance where we are being asked to make a decision on the basis of a single case that is probable but not definite. I mean, I have concern that when the drug is more widely used over a longer period of time you are going to see cases of SJS but you see that with lots of other drugs that are already marketed. GOODMAN: Before I go on with the vote, I actually expected a different response and I am assuming others did too. So, maybe there is room for further discussion, given the opinion you just rendered, before we go on with the vote. Does that change anybody's mind around the table? BRONSTEIN: I have one question of the investigator. It was my impression that you did not see this patient yourself until four weeks after the very final time the mom brought the child in. Is that correct? BELNOR: The mother refused to bring the child back in from the second visit until the last visit. BRONSTEIN: My question is when did you lay eyes on the patient. BELNOR: I saw the patient at the first visit. BRONSTEIN: Before the rash? BELNOR: Before the rash. BRONSTEIN: And did you see the patient on the last visit? BELNOR: Yes. BRONSTEIN: But not when the rash was in its fullest... BELNOR: No, none of the investigators saw the patient when the rash was present. We told the referring doctor to stop the medicine and send the patient to us for a biopsy. BRONSTEIN: And who did the write-up of the patient that was received? BELNOR: I did. BRONSTEIN: The first write-up that was received to the company? BELNOR: I did most of the write-ups. I don't know. There are a lot of errors in the history. BRONSTEIN: Thank you. GOODMAN: Do you have any further comments? BRONSTEIN: I am left with a lot of questions and a lot of lack of confidence, and I feel like erring on the side of conservatism, either longer testing or saying no but as the consumer representative I feel like the public needs to be protected and we have a lot of questions here. As a working mom, I really can relate to this mom not bringing the kid in; I did it myself. And, I don't know that you are going to get good anecdotal reporting. I also don't have a lot of confidence in non-dermatologists reading rashes. So, that is where I am with all this. GOODMAN: Dr. Wells? WELLS: While it may be true that the case for lack of safety has not been made, it is also true that the case for safety has not been sufficiently made, and I think that is what we have to have in order to make a statement that it is adequately safe and I am not there. GOODMAN: Dr. Pfeffer? PFEFFER: Am I voting or making a comment? GOODMAN: You are just making a comment. PFEFFER: I wanted to ask, I just began to remember, isn't it true, Dr. Bigby, that this problem, Stevens-Johnson for example, doesn't always appear on the entire body simultaneously? Isn't there a course that goes from head to foot? So, I was wondering about this case. How frequently did the pediatrician see the child once the rash occurred? BIGBY: So, Stevens-Johnson does normally evolve over a period of several days, and it is true that it is not full-blown at its onset. People can continue to get lesions over several days. I would say in the majority of cases you start getting new areas of involvement after about a week or so. GOODMAN: Dr. Robinson? ROBINSON: Well, I think it is very striking that the one case that we are debating about came in the context of somebody who was in a controlled trial. Even in a controlled trial, which wasn't designed to look at this issue, we are in the situation where experts can debate back and forth, and I think that says that if we approve the drug and say there is going to be postmarketing we would not get data that was really usable because even in a controlled trial we are debating. I think that argues for us getting a study design to look at this specifically so if somebody has a suspected case of it the proper information is obtained, like photographs and expert dermatologic consultation so that we can actually say what is an estimate. It is just striking that even in this sort of controlled trial we are not getting the information we need and I think that argues for a specific study. GOODMAN: Dr. Armenteros? ARMENTEROS: I also have a concern that I am not so sure that even a controlled trial moving forward from this point would still resolve our doubts. I am concerned about that. GOODMAN: Dr. Andreason? ANDREASON: I suppose for something that is as rare as Stevens- Johnson or, say, something like acute liver failure you don't even need a controlled because the historical control is so rare that if you pick up a case in an open-label trial of, say, 3000 patients that is significant. So, that would be an acceptable design to look at something like this. GOODMAN: Let's start with the vote again, and this time I will begin with myself. I am going to vote no. I have been persuaded by my colleagues around the table and my comfort level is not sufficient that this has been shown to be acceptably safe. I don't know what to make exactly of that one case and, frankly, I don't think we are ever going to be sure. It certainly raises a sufficient number of doubts about a serious adverse event that should not have occurred even at the rate of 1/1000 or less that we saw in this trial. Perhaps the other factor that has led to my decision is the absence of other strong, convincing reasons to consider this drug having advantages in other areas of safety or tolerability or efficacy so I am not willing to find the risk acceptable of going forward without additional data that would rest some of my concerns about the dermatological reactions. Now we can go back to Dr. Bigby. BIGBY: I voted. RAPPLEY: I do not think it is acceptably safe and I think you all have articulated my feelings. WANG: I think it is just unknown. Can I abstain until we have more information? I mean, it could be everything from this things shouldn't be approvable if this is a real signal to there is no warning needed at all if this isn't the case. We don't even know what to make of this case. There is no temporal or inter-rater reliability even within this meeting. GOODMAN: Dr. Laughren? LAUGHREN: Actually, I don't understand an abstention in this situation. I mean, we are asking you if you feel there is not enough information to make a judgment, then I think the answer would be no. WANG: No, OK. It is no, we don't have enough information. BRONSTEIN: My vote is no unless more information is obtained. PINE: I guess I will make two statements. I found Dr. Temple's statement about you will look into it and, the more doubtful this diagnosis becomes, everything changes, and I would agree with that. You know, just sitting here today it has to be obvious to anybody that knows nothing about Stevens-Johnson syndrome that there is a reasonable suspicion. I think everybody would agree with that, that there is a reasonable suspicion that this was a case of Stevens-Johnson syndrome related to the medication exposure. So, that is the first thing. The second thing is that I really don't think it is that big a deal to cap the risk at 1/1000. So, I am going to vote no and what I would recommend is a study of 3000 patients that is not an efficacy study, that is simply designed to make sure that there is not a single case of Stevens-Johnson syndrome, you know, treated for a month. LEON: I will vote no, based on the data we have seen that modafinil has not been shown to be acceptably safe for children and adolescents with ADHD. ROBINSON: I am voting no because I think that we do need a study specifically designed to at least get a good estimate of what the rate is, and especially in a therapeutic area where modafinil hasn't shown a specific efficacy that is greater than with the already available agents. PFEFFER: I am voting no also. I think that we need more information which I think will be extremely helpful in guiding not only the clinician but enhancing perhaps compliance of patients. My feeling is that if this were approved now, regardless of how the clinician might feel or try to explain it, I think the compliance of parents for the children would not be as good perhaps than if there were a clearer view of the risks where they could make a more informed decision. I think we need more data and I think that it is worth that wait. ARMENTEROS: Well, based on the confusion that I have been exposed to through the whole day, I am going to vote no and I am hoping that given this ADHD diagnosis we can identify readily and do studies to bring on the data. We are not talking about a condition that is rare so we should be able to move ahead at a later stage with much more clear information that in everyone's mind will be better at that stage. WELLS: Barbara Wells, and I will vote no. I don't believe the case for safety has been adequately made and, in addition, I don't believe we were convinced that it is more effective than available treatments and perhaps not as effective as available treatments. We also have reason to at least suspect that the incidence of even the common side effects is higher with this drug than with available treatments. DOKKEN: Deborah Dokken, I also vote no on the question of safety. I mean, the uncertainty about all of this today has been almost painful and on those grounds I think we do need more information before we can put it out for the public. MALONE: I vote no also. I think that the potential population who would get the drug is fairly big, especially considering the safety risks that we have been talking about today and the apparent lack of any safety advantages for this drug. MEHTA: I know I cannot vote but if I were to vote I feel like the California voter in the presidential elections where my vote doesn't count because it has already been decided. Anyway, let me make a couple of comments. One is that I am not convinced that this is a patient with Stevens-Johnson syndrome. I have heard enough discussions and I have been faced with and reviewed patients like that. I am not a dermatologist but still I do not believe that this is a case very clearly. Secondly, the case for the dose relationship, that a higher dose will lead to a higher incidence of Stevens-Johnson syndrome certainly has not been made. If that is the case, then one should use as a denominator something like 3 million patients. So, we have about four or five patients with Stevens-Johnson syndrome in an exposure of 3 million people, which is no different than anything else. So, from my point of view, if I had to vote I would have voted differently with a lot of strictures about how to get more data to make sure that the real incidence is not more than what we already see. GOODMAN: Could you give us the tally? REESE: Yes. There is one yes and 12 no. Going back to question one, it was 12 yes. Dr. Andreason? ANDREASON: Just for note-taking, I heard some discussion that a risk cap at 1/1000 would be something that you would like to know about. Did you want to talk about that or make a vote on that? PINE: Again, I would emphasize that really the question of efficacy is not on the table here, that we have been convinced of efficacy and I can imagine that a fair amount of time and energy and patients experiences have already been invested in doing that. I would not want to reinvent the wheel there. I think the main thing would be to know definitively what the risk is from a ballpark sampling. Again, just speaking for myself, if we were to see open-label treatment, treated by pediatricians who are seeing patients regularly, that there was not a single case that would raise any dermatological concerns about Stevens-Johnson syndrome in 1000 cases, then I would vote yes. REESE: Dr. Rappley? RAPPLEY: I would support that, and I think it is clear that the medication is efficacious and the comparison studies can be done postmarketing and I would be happy with that. GOODMAN: What I am about to say is not necessarily a criticism of this particular sponsor but I think there is a lesson in here about the need for better assessment of these dermatological adverse experiences, and I think a lot of these issues would have been settled and perhaps even the outcome would have been different if we had better documentation that would have allowed our dermatological colleagues to make a more definitive conclusion. So, I think we are dealing with some fuzzy information but, given that this wasn't a compelling enough story here, both on the efficacy side and on the safety side, to reach a comfort level by which this committee could endorse this compound moving forward to market. So, I think we did err on the side of consumer protection and I would hope sincerely that the company would find the means by which it could gather the additional data to collect the necessary safety data and the outcome could be different under those circumstances. I want to thank everybody for attending for the long day, and most of all for putting up with my scratchy voice. Thank you. LAUGHREN: And I want to thank the committee again for a heroic effort in helping us with our job. Thank you. END LOAD-DATE: August 16, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Other (Hearings) Copyright 2006 Data Licensing, LLC. ALL RIGHTS RESERVED 410 of 998 DOCUMENTS PR Newswire US March 23, 2006 Thursday 10:36 PM GMT FDA Advisory Committee Recommends Against Approval of SPARLON(TM) for Attention Deficit/Hyperactivity Disorder in Children and Adolescents; Cephalon 2006 Basic Adjusted Income Per Common Share Guidance Remains Unchanged LENGTH: 978 words DATELINE: FRAZER, Pa. March 23 FRAZER, Pa., March 23 /PRNewswire-FirstCall/ -- Cephalon, Inc. (NASDAQ:CEPH) today announced that the U.S. Food and Drug Administration's (FDA) Psychopharmacologic Drugs Advisory Committee voted not to recommend FDA approval of SPARLON(TM) (modafinil) Tablets [C-IV], the company's investigational medication for the treatment of attention- deficit/hyperactivity disorder (ADHD) in children and adolescents. The committee voted unanimously that SPARLON is effective for its intended use but recommended that the company collect additional data to support the safety of the drug in children and adolescents with ADHD. "We are obviously disappointed with the recommendation of the advisory committee. We will continue our discussions with the FDA to determine the next steps in the review of this drug application," said Dr. Paul Blake, Executive Vice President, Worldwide Medical and Regulatory Operations. The company's previously issued 2006 basic adjusted income per common share guidance of $3.80-$4.00 remains unchanged. In light of the advisory committee's recommendation, the company is reducing its 2006 sales guidance by $100 million to $1.45-1.50 billion; consistent with this reduction, guidance for CNS franchise sales also is reduced by $100 million to $665-715 million. The advisory committee's recommendation will be considered by the FDA in its review of the Supplemental New Drug Application that Cephalon submitted for SPARLON, a proprietary dosage form of modafinil, in December 2004. The FDA is not bound by the committee's recommendation, but takes its advice into consideration when reviewing investigational drugs seeking approval. Cephalon received an approvable letter from the FDA with respect to SPARLON in October 2005. Cephalon has scheduled a conference call with investors to discuss the outcome of the committee meeting at 6 p.m. EST on March 23, 2006. The conference call may be accessed by dialing 1-913-981-4901. The conference call ID number is 8645966. SPARLON SPARLON is a new formulation and proprietary dosage strength of modafinil, the active ingredient in PROVIGIL(R) (modafinil) Tablets [C-IV], which is approved for the treatment of adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome and shift work sleep disorder. SPARLON is chemically distinct from currently approved therapies and if approved, would provide a unique option for ADHD treatment. PROVIGIL is not approved to treat ADHD and is available only in 100 mg and 200 mg strengths. SPARLON should not be used in combination with PROVIGIL(R) or any other medications that contain modafinil. Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products in four core therapeutic areas: central nervous system, pain, oncology and addiction. Cephalon currently employs approximately 3,000 people in the United States and Europe. U.S. sites include the company's headquarters in Frazer, Pennsylvania, and offices, laboratories or manufacturing facilities in West Chester, Pennsylvania, Salt Lake City, Utah, and suburban Minneapolis, Minnesota. Cephalon's European headquarters are located in Maisons-Alfort, France. The company currently markets four proprietary products in the United States: PROVIGIL, GABITRIL(R) (tiagabine hydrochloride) Tablets, ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II], and TRISENOX(R) (arsenic trioxide) injection, and numerous products internationally. Full prescribing information on its U.S. products is available at http://www.cephalon.com/ or by calling 1-800-896-5855. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs; development of potential pharmaceutical products; interpretation of clinical results, including the results of the SPARLON clinical trials; prospects for final regulatory approval of SPARLON, including the impact of the advisory committee's recommendation on the FDA's decision whether to approve the sNDA for SPARLON; manufacturing development and capabilities; market prospects for its products, particularly with respect to SPARLON sales and earnings guidance; and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. CONTACT: Media: Jenifer Antonacci, +1-610-563-6018, jantonac@cephalon.com , or Investors: Robert (Chip) Merritt, +1-610-738-6376, cmerritt@cephalon.com , both of Cephalon Web site: http://www.cephalon.com/ Company News On-Call: http://www.prnewswire.com/comp/134563.html SOURCE Cephalon, Inc. URL: http://www.prnewswire.com LOAD-DATE: March 24, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 PR Newswire Association LLC. All Rights Reserved. 411 of 998 DOCUMENTS Associated Press Worldstream March 23, 2006 Thursday 11:25 PM GMT Narcolepsy drug needs more study as possible ADHD treatment, federal advisers say BYLINE: By ANDREW BRIDGES, Associated Press Writer SECTION: INTERNATIONAL NEWS LENGTH: 358 words DATELINE: WASHINGTON The narcolepsy drug modafinil should not be approved as a treatment for attention deficit hyperactivity disorder in children until more is learned about a possible link to a serious skin disease, federal advisers said Thursday. A Food and Drug Administration advisory committee voted 12-1 against recommending modafinil as safe for children with ADHD. Earlier Thursday, the psychopharmacologic drugs panel agreed unanimously that the modafinil works in treating ADHD. The FDA is not required to follow the recommendations of its advisory committees but usually does. The committee recommended that Cephalon Inc. undertake a 3,000-patient trial to determine what risk modafinil may pose for Stevens-Johnson Syndrome. Drug reactions cause nearly all cases of the sometimes fatal skin disease, which can produce widespread blistering and rashes, according to The Merck Manual. The FDA's drug chief, Dr. Robert Temple, said one out of roughly 900 children involved in earlier studies of the drug developed the disease. Temple and Cephalon spokeswoman Jenifer Antonacci said the agency and company would discuss the committee's recommendation. The company does not see a "clear link" between its drug and the skin disease, Antonacci said. In December 1998, the FDA originally approved modafinil, under the brand name Provigil, to treat adults with sleepiness associated with narcolepsy. The company has proposed calling a higher-dose version of the pill Sparlon when used to treat ADHD. Other drugs already approved by the FDA for ADHD include Ritalin, Strattera and Adderall. A different advisory committee recommended on Wednesday that the FDA add warnings to the labels of those and other ADHD drugs on the market alerting doctors and parents to the possible risk of hallucinations in the more than 3 million children receiving the popular medications. Narcolepsy is marked by recurring episodes of daytime sleep, lasting from a few seconds to an hour. The disease can be merely inconvenient to some people, but disabling and dangerous to others who may fall asleep while driving or operating machinery. On the Net: Food and Drug Administration: http://www.fda.gov LOAD-DATE: March 24, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 Associated Press All Rights Reserved 412 of 998 DOCUMENTS Theflyonthewall.com This content is provided to LexisNexis by Comtex News Network, Inc. March 22, 2006 Wednesday 9:32 AM Eastern Time CEPH: Hot Stocks LENGTH: 246 words 09:32 EDT Cephalon-CEPH gets brief on New Drug Application for Sparlon - Today the Psychopharmacologic Drugs Advisory Committee, or PDAC, posted on the FDA website a briefing document with respect to Cephalon's (CEPH) New Drug Application for Sparlon (modafinil) for the treatment of ADHD in children and adolescents. The briefing document, which will be reviewed by the PDAC at its meeting tomorrow, details the chronology of events leading up to the issuance by the FDA of an approvable letter for Sparlon. In September of 2006, the original clinical review of the NDA was completed by Glenn Mannheim, M.D., in the Division of Psychiatric Products of the FDA. In this review Dr. Mannheim concluded that modafinil should not be approved for ADHD. On October 12, 2005, Paul J. Andreason, M.D., the Acting Deputy Director of the DPP recommended an approvable action for modafinil for ADHD. On October 19, 2005, Thomas P. Laughren, M.D., the Director of the DPP recommended an approvable action for modafinil for ADHD. On October 20, 2005, the FDA issued an approvable letter to Cephalon for Sparlon, along with a proposal for labeling. Cephalon has a conference call scheduled for tomorrow at 6:00 p.m. EST to discuss the results of tomorrow's PDAC meeting. As of Saturday, 03-18-2006 23:59, the latest Comtex SmarTrend(SM) Alert, an automated pattern recognition system, indicated a DOWNTREND on 03-16-2006 for CEPH @ $74.59. (C) 2006 Comtex News Network, Inc. All rights reserved. LOAD-DATE: March 23, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Web Publication Copyright 2006 Comtex News Network, Inc. All Rights Reserved Copyright 2006 TheFlyOnTheWall.com 413 of 998 DOCUMENTS MarketWatch March 16, 2006 Thursday 11:53 AM EST Cephalon drops on FDA documents about new ADHD drug BYLINE: Val Brickates Kennedy LENGTH: 137 words BOSTON (MarketWatch) -- Shares of Cephalon (ceph) dropped 5% to $74.24 Thursday morning following reports that FDA briefing documents released earlier this week indicate its proposed drug to treat attention deficit hyperactivity disorder (ADHD), Sparlon, triggered suicidal and aggressive behavior in a small number of users during a clinical trial. Sparlon, also known as modafinil, is slated to be reviewed by an FDA advisory panel on March 23. Another FDA panel will be discussing the safety of several leading ADHD drugs on March 22. The FDA generally follows the recommendations of its advisory panels. Modafinil is already marketed for the treatment of narcolepsy under the name Provigil. ©1997-2002 MarketWatch.com, Inc. All rights reserved. See details at http://custom.marketwatch.com/custom/docs/useragreement.asp. LOAD-DATE: March 17, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Web Publication Copyright 2006 MarketWatch.com Inc. All Rights Reserved 414 of 998 DOCUMENTS The Sunday Times (London) March 12, 2006 Say goodbye to sleep BYLINE: Graham Lawton SECTION: FEATURES; Style; Pg. 44 LENGTH: 1511 words And hello to 24-hour living. Graham Lawton reports on a new wave of drugs that could help us stay awake for days and get a whole night's kip in just two hours Between a hectic work schedule and a thriving social life, Yves (not his real name), a 31-year-old software developer from Seattle, often doesn't have time for a full night's sleep, so he swallows something to make sure he doesn't need one. "If I take a dose just before I go to bed, I can wake up after 4 or 5 hours and feel refreshed," he says. Yves is talking about modafinil, a stimulant that, since its launch seven years ago, has acquired a near-mythical reputation for wiring you awake without the jitters, euphoria and eventual crash that come after caffeine or amphetamines. Yves has been popping modafinil on and off for three years, and says: "I'm more organised and more motivated, and it means I can go out partying on a Friday night and still go skiing early on Saturday morning." Modafinil is just the first in a wave of new drugs that will enable us to structure sleep to suit our lifestyles. "In 10 to 20 years, we'll be able to pharmacologically turn off sleep," says Professor Russell Foster, a circadian biologist at Imperial College London. Foster envisages a world where it is possible, or even routine, for people to be active 22 hours a day and sleep for two. If that sounds unlikely, think about what is already here. Modafinil has made it possible to have 48 hours of continuous wakefulness with few, if any, ill effects. New classes of sleeping pills are on the horizon that promise to deliver sleep that is deeper and more refreshing than the real thing. Further down the line are even more radical interventions: wakefulness promoters that can safely abolish sleep for several days at a stretch, and sleeping pills that deliver what feels like eight hours' sleep in half the time. To some degree, we are already adept at controlling sleep. Most people in full-time work deprive themselves of sleep during the week and catch up at the weekend. We often augment our sleep-suppressing powers with caffeine, nicotine or illegal stimulants such as cocaine and amphetamines. We are also dependent on substances that help us to sleep. The vast majority of sleeping pills known as hypnotics -are simply "knockout drops" that put you in a state almost like sleep, but without its full restorative properties. With their addictive nature, the drugs we use to keep us awake, such as coffee and amphetamines, are even worse. These sleeping and waking aids are driving ever more people into what Foster calls the "stimulant-sedative loop", where they need nightly help getting to sleep and daily help staying awake. Modafinil has changed the rules of the game. The drug is what is known as a eugeroic, meaning "good arousal" in Greek. It delivers natural-feeling alertness and wakefulness, without the powerful physical and mental jolt that earlier stimulants delivered. Perhaps the most remarkable thing about modafinil is that users don't seem to have to pay back any "sleep debt". Normally, if you stayed awake for 48 hours straight, you would have to sleep for about 16 hours to catch up. Modafinil somehow allows you to catch up with only eight hours or so. So how does modafinil work? Like other stimulant drugs, it prevents nerve cells from reabsorbing, and so reduces the effect of, the excitatory neurotransmitter dopamine once they release it into the brain. The difference is that it does so without producing the addictive highs and painful crashes associated with most stimulants. A number of independent studies suggest that this might be because it also interferes with the reuptake of another neurotransmitter, noradrenaline. However it works, modafinil is proving hugely successful. Sales in 2005 reached about $575m (£ 330m). Cephalon, its maker, insists that the drug is for treating "medical" sleepiness caused by diseases such as narcolepsy and sleep apnoea -it is prescription-only. But it is clear that modafinil is becoming a lifestyle drug for people such as Yves who want off-the-peg wakefulness. All the indications are that modafinil is safe. In fact, it is hard to find anyone with a bad word to say about it, except that there may be unseen problems down the line, as the drug becomes more widely used. In the long run, it is possible that casual users might have to keep upping their dose to get the same effect. Neil Stanley, head of sleep research at the Human Psychopharmacology Research Unit at the University of Surrey, has similar worries. "Is it a potential drug of abuse? Will it get street value?" he asks. "We'll see." Cephalon does not seem to be worried, and modafinil's success has spurred it to develop a successor, armodafinil. And the results of an experiment with a drug called CX717 suggest that Cephalon won't have the field to itself for ever. CX717 belongs to a class of drugs called ampakines, which ramp up brain activity by enhancing the action of its main excitatory neurotransmitter, glutamate. Cortex, the maker of CX717, originally saw the drug as a cognitive booster for people with Alzheimer's, but it is its potential to counter the effects of sleep deprivation that is attracting the most attention. Later this year, the Defense Advanced Research Projects Agency (Darpa), the research arm of the US Department of Defense, will put CX717 through its paces as a wakefulness promoter for combat. It hopes that the drug will counteract sleep deprivation. "The early signs are that people function better, their brain is a little more hyped. But we haven't tested sleepiness directly," says Roger Stoll, chief executive of Cortex. It is easy to see why Darpa is interested. Soldiers on special operations sometimes have to be awake, alert and active for 72 hours at a stretch, with only minimal rest. That is like starting work on Monday morning and not stopping until Thursday. The military isn't just interested in wakefulness. It also has a keen interest in the other side of the coin. John Caldwell of the US Air Force Research Laboratory has spent most of his career testing the effects of stimulants and sleep aids on pilots, and he has become aware that there is a quiet revolution going on in sleep medicine. "There's a new idea out there," he says. "Drugs that change sleep architecture (the different brain states that make up a full night's sleep)." In the past, says Caldwell, sleeping pills have generally suppressed the deepest and most restorative "slow-wave" sleep in favour of shallower sleep. Now, though, there are two new drugs in the offing (Merck's gaboxadol and Arena Pharmaceuticals' APD125) that significantly increase the amount of slow wave sleep. To Caldwell, these drugs hold out the promise of a power nap par excellence. "Maybe you can make a short period of sleep more restorative by filling it with slow-wave sleep," he says. Much like modafinil, gaboxadol and APD125 are the start of something bigger. For more than 35 years, sleeping pills have been a one-trick pony. If you wanted to send someone to the land of nod, there was only one way of doing so -targeting the neurotransmitter gamma-aminobutyric acid (gaba), which is the brain's all-purpose dimmer switch. Manipulating the gaba system is a sure-fire way of putting people to sleep, but it has its problems. The brain adapts to the drugs, which means that most cannot be taken for more than a few days without losing their potency, the groggy effects linger into the morning and many are addictive. Last year, the first non-gaba sleeping pill (rozerem, made by the Japanese firm Takeda) came onto the market, and there are at least three other new classes of hypnotic that don't go near the gaba system. According to Stanley, there is even more scope for improvement: "We are not that far away from having drugs that put you to sleep for a certain length of time." He predicts there could soon be tablets combining a hypnotic with an antidote or wakefulness promoter designed to give you a sleep that lasts for a precise number of hours. "A four-, five-or six-hour pill." We seem to be moving inescapably towards a society where sleep and wakefulness are available, if not on demand, then at least on request. Many sleep researchers have nagging worries about the long-term impact of millions of us using drugs to override the natural sleep-wake cycle. Stanley believes that drugs such as modafinil and CX717 will tempt people to overdose on wakefulness at the expense of sleep. Others point out that there are likely to be hidden health costs to overriding natural sleep-wake cycles. Still, even the doubters admit that we are too far down the road of the 24-hour society to turn back. For millions of people, good sleep and productive wakefulness are already elusive, night work or nightlife a reality, and the "stimulant-sedative" loop all too familiar. As Jeffrey Vaught, the president of research at Cephalon, says: "We're already there, so why not make it as clean and safe as possible?" 1 The full version of this article appeared in New Scientist magazine LOAD-DATE: March 24, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2006 Times Newspapers Limited All Rights Reserved 415 of 998 DOCUMENTS Pediatric News March 2006 Modafinil Offers New ADHD Option BYLINE: Heidi Splete SECTION: Pg. 32 Vol. 40 No. 3 ISSN: 0031-398X LENGTH: 355 words    Modafinil film-coated tablets significantly improved the clinical symptoms of attention-deficit hyperactivity disorder in children and adolescents aged 6-17 years, according to a new study by Dr. Joseph Biederman of Massachusetts General Hospital in Boston and his colleagues.    Modafinil, an agent generally prescribed to promote wakefulness in patients with narcolepsy, has been shown to activate the cortex alone. It lacks the widespread nervous system stimulation that occurs in medications typically prescribed for ADHD in children and adolescents.    In the randomized, double-blind trial conducted by Dr. Biederman and his colleagues, 164 children received a flexible dose of modafinil in tablet form, and 82 children received a placebo. The children began with one 85-mg tablet for the first 2 days; the dose was titrated to 170 mg on days 3-7, 255 mg on days 8-14, 340 mg on days 15-21, and 425 mg on day 22 (Pediatrics 2005;116:777-84).    The dose varied with the patient's tolerance, and the maximum daily dose was 425 mg. The children were evaluated at baseline and at 1, 2, 3, 5, 7, and 9 weeks after starting treatment.    After 9 weeks, 48% of patients in the modafinil group were deemed responders, compared with 17% of those in the placebo group. Overall, patients in the modafinil group demonstrated significant improvement in symptoms, including oppositional behavior, cognitive problems/inattention, hyperactivity, and the ADHD index on the Conners' Parent Rating Scale Revised, Short Form, compared with those in the placebo group.    Modafinil (Provigil) also was well tolerated. Only five of the patients in the treatment group (3%) and three in the placebo group (4%) discontinued the study because of adverse events. Most adverse events were mild to moderate, and the only reported severe events were insomnia in one modafinil patient, erythema multiforme in another modafinil patient, and headache in one placebo patient.    Given modafinil's safety profile and its low potential of abuse, the drug may offer clinicians a new option for treating ADHD in children and adolescents, the investigators said. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: PDNEWS Copyright 2006 Elsevier Inc., International Medical News Group All Rights Reserved 416 of 998 DOCUMENTS Reuters Health Medical News February 22, 2006 Wednesday 9:00 PM EST Modafinil safe and effective for attention-deficit/hyperactivity disorder SECTION: CLINICAL LENGTH: 329 words DATELINE: NEW YORK A new formulation of modafinil (film-coated tablets) improves symptoms of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents, and is well tolerated, according to a report in the January Journal of Clinical Psychiatry. Modafinil differs from central nervous system stimulants, the authors explain, and it may reduce the symptoms of ADHD in the same way that it improves wakefulness -- by selectively activating the cortex without generalized CNS effects. Dr. James M. Swanson from the University of California at Irvine and colleagues assessed the efficacy and tolerability of modafinil in a 7-week placebo-controlled study of 190 children and adolescents with ADHD, which was followed by a 2-week evaluation after abrupt discontinuation of modafinil. Modafinil-treated patients showed significant improvements in the ADHD Rating Scale-IV School Version and Home Version scores, the results indicate, and significantly more patients were rated by the investigators as "much improved" or "very much improved" on a clinical global impression scale. "These findings suggest consistent therapeutic effects of modafinil at school and home during weekdays, evenings, and weekends as evaluated by clinicians, teachers, and parents," the investigators write. After abrupt discontinuation of modafinil, there were no adverse physical or emotional effects, the researchers note, and there were no symptoms of withdrawal or rebound of symptoms of ADHD. Patients tolerated modafinil well, the report indicates, but insomnia and decreased appetite were reported significantly more often with modafinil than with placebo. "Treatment of children with ADHD with modafinil was effective across the full spectrum of symptoms of ADHD, including inattention, hyperactivity, and impulsivity," Dr. Swanson and colleagues conclude. "These findings suggest that modafinil may provide a novel therapeutic option for the management of ADHD in pediatric and adolescent patients." LOAD-DATE: March 4, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 Reuters Health All Rights Reserved 417 of 998 DOCUMENTS The Express February 18, 2006 Saturday U.K. 1st Edition Who needs eight hours a night? Sleeping is for wimps; LEADER BYLINE: David Robson SECTION: LEADER; 12 LENGTH: 1494 words THERE they were, tucked away just inside the entrance to my local London underground station, tensed, like greyhounds in the traps, just waiting for their moment. Click the digital clock hit 8.59.58 they edge their way out 8.59.59 they push their way through the crowd to the gates 9.00.00 they press their senior citizens' travel passes down hard on the electronic pad and the gates do not open. "Seek assistance, " the machine says. Seek assistance? Seek assistance! There were three of them, two men and a woman, all in their late 60s or 70s and they didn't want assistance, they wanted their rights; and they weren't seeking, they were screaming. "Look, it's 15 seconds past nine and the machine isn't letting us through it's disgusting." "Disgraceful!" "What's going on?" The "assistance", a bloke in royal blue uniform, was visibly shocked. He'd started to stammer some excuse when the machines kicked in and the three were let through, seething. It was 9.00.50. What had we seen? Was it just bog standard Age Rage, the new British disease that makes it unsafe for younger people to walk the streets during daylight hours, or something altogether more complicated? The travel passes Londoners can claim when they reach 60 give free travel on bus and Tube. They are called Freedom Passes but, as you might expect in Blair's Britain, freedom is far from unconfined. The passes do not work between 4.30 and 9am. Yes, you may think, Nanny Statism at its worst - it punishes law abiding over-60s who favour all-night hip hop clubs and 24-hour drinking joints. And then, you may think, older people aren't around much between 4.30 and 9am anyway - which would just show how little you know. NIGHT shift workers apart, I would wager that the majority of people awake in Britain in the small hours are either under 25 or over 60. Those in between spend lives of eight-hour-anight somnolence. But for many people, as they get older, all-night sleep becomes a thing of the past. A four o'clock wake-up is quite normal. "Gosh, " they think. "Four twenty. I'll just take a leak [as you do] and then I'll catch a night bus over to Jennifer's place for a drink oh, damn it all, my bus pass won't work." Come to think of it, perhaps it's part of the Government's campaign for lifelong learning. What can you do when you wake up in the middle of the night? Well you can read, or watch TV. What TV can you watch? Educational TV, that's what. True, in these digital days, there's always porn and programmes about the fabulous lifestyle of Paris Hilton to be had at any time of day or night but, late on, there's so much that is "improving". The BBC Learning Zone - chaps with beards, homeknitted sweaters and oldfashioned glasses explaining the rudiments of astrophysics; nice young women sauntering round shops in Madrid improving your language skills (en que planta estan los zapatos? - which floor are the shoes on? ; me resulta demasiado caro - it's too expensive for me). In the small hours, even football is educational: the Albanian second division, the Guatamalan junior cup. You see places and hear names you never even knew existed. Then at 7am, when UKTV History kicks in, you hear about the likes of Sir George Cayley, the Yorkshireman who may or may not have invented the aeroplane, or you can consider whether there was, or could have been, a roof on the Colosseum in Rome. It's only when you know what goes on in the small hours among ageing people of non-sleeping disposition that you understand how a 45second delay on getting your Freedom Pass to work might cause hyperventilation, or violence. That wasn't just Age Rage; that was an explosion from the OU - the Overeducated Undead. Apologies to those poor souls who feel their lives are blighted by insomnia but I reckon "a good night's sleep" is vastly overrated. "Three score years and 10 is such a stingy ration of time when there is so much time around, " said the great science fiction writer Brian Aldiss. "Perhaps that's why some of us are insomniacs; night is so precious that it would be pusillanimous to sleep all through it. A 'bad night' is not always a bad thing." Brian Aldiss has now passed four score years and I think he's right. As James Thurber wrote: "Early to rise and early to bed/Makes a man healthy, wealthy and dead." As far as I can see, there is only one real virtue in sleeping long - when you're sleeping you can't be eating. That apart, it's good to have more time to get on with things (needless to say it is nature's cruel joke that old age, when we may have fewer things to get on with, is the age when we are likely to sleep least). People who really have to "get on with things" develop different sleep strategies from the rest of us. Napoleon, reportedly, rarely got a good night's sleep and took naps during the day. He is believed to have suffered from apnoea (a condition that involves heavy snoring) which makes it seem likely that his "not tonight Josephine" was less frequent than her "not tonight Napoleon". LEONARDO da Vinci was said to be a polyphasic sleeper - in other words he catnapped 15 minutes at a time, every two hours. (Here is his hitherto unseen diary from 1505-6: woke up got on with painting Mona Lisa's nose had a nap moved on to the mouth had a nap started on her smile had a nap couldn't remember whether she was supposed to be smiling or not had a nap decided on a compromise had a nap finished her off had a nap slipped out for a cappuccino with Michelangelo). Ellen MacArthur obviously couldn't take extended kip during the 72 days of her roundthe-world race. She averaged 5.5 hours a day broken up into 10 naps. In the 1994 race, a French sailor fell asleep and ran aground on the south western coast of Australia. In 1990 Desmond Hampton allowed Sir Francis Chichester's Gypsy Moth V to smash into rocks while he slept. MacArthur had the assistance of Claudio Stampi of the Chronobiology Research Institute in Boston, Massachusetts, who monitored and designed her sleep patterns. The advantage of short polyphasic naps in her circumstances are pretty obvious. One is that it is the early stages of sleep that are most important in recuperation - so 10 early stages are the way to do it; the other is that lengthy slumbers are not appropriate when you've got a busy trimaran to run. Though we talk about "beauty sleep" it is not proven that shortage of sleep has any real physical effect on us. The brain needs rest but the body can get by without it. Recently there has been much talk, including in this week's New Scientist magazine, about the drug modafinil, which may well prove able to cut our need for sleep down to no more than a couple of hours a day. Millions have lived like that with amphetamines, which leave you a) wired and jittery, and b) addicted. Amphetamines may keep you awake but they don't do a lot for your judgment and disposition. MODAFINIL seems a quite different proposition. The American military took an interest in it early: American pilots flying bombladen B-2 stealth planes from Missouri to Afghanistan were prone to errors and slow response time. But not those using modafinil. In 2004 American woman sprinter Kelli White tested positive for modafinil, an illegal drug in athletics; she was stripped of her world 100m and 200m titles and banned for two years. Her training partner, British sprinter Dwain Chambers, also tested positive for the drug - his suspension from the sport has just ended. The excuse for using modafinil in White's case, and others, was "narcolepsy". "It is a little odd to find an epidemic of narcolepsy among top athletes, " said the head of the International Amateur Athletics Association's drugs commission. Modafinil was developed to combat narcolepsy, an affliction which makes people drift into sleep at random times but its broader role is giving users several extra hours a day of top performance, healthy wakeful time. Just as technologically-developed man strives to conquer the natural elements, he also dreams of taking control of time, so that he can choose how much or little time he sleeps and live to tell the tale (without babbling and dribbling). At the 2004 European Championships England, captained by David Beckham (who rarely dribbles), had a sleep consultant in the party. Their mattresses were modified to give better slumbers. That same year artist Sam Taylor Wood made a video of Beckham sleeping. He did it beautifully. It lasts 67 minutes - with modafinil that would be half a day's worth. But does that appeal to you - 22 hours of wakefulness and possible workfulness? Obviously sleep, if we can live happily without it, is nothing but a waste of time. On the other hand, with increasingly long lives we may have time to waste. Say what you will about sleep, it is at least environmentally friendly and it keeps death off the roads (unless you happen to be driving). And if every over-60 in Britain was awake 22 hours a day, I would not like to answer for the consequences. LOAD-DATE: February 19, 2006 LANGUAGE: ENGLISH GRAPHIC: WAKE UP CALL : But how much sleep do we need to feel refreshed in the morning? PUBLICATION-TYPE: Newspaper Copyright 2006 EXPRESS NEWSPAPERS All Rights Reserved 418 of 998 DOCUMENTS New Scientist February 18, 2006 Get up and go; A new wave of drugs will make it a breeze to go days without sleep, and give you a good night's shut-eye in two hours. Are you ready for 24-hour living, asks Graham Lawton BYLINE: Graham Lawton SECTION: FEATURES; Cover Story; Pg. 34 LENGTH: 3312 words SO MUCH to do, so little time. Between a hectic work schedule and a thriving social life, Yves (not his real name), a 31- year-old software developer from Seattle, often doesn't have time for a full night's sleep. So he swallows something to make sure he doesn't need one. "If I take a dose just before I go to bed, I can wake up after 4 or 5 hours and feel refreshed," he says. "The alarm goes off and I'm like, let's go!" Yves is talking about modafinil, a stimulant that since its launch seven years ago has acquired a near-mythical reputation for wiring you awake without the jitters, euphoria and eventual crash that come after caffeine or amphetamines. Yves has been popping modafinil on and off for the past three years and says it is "tremendously useful". "I find I can be very productive at work," he says. "I'm more organised and more motivated. And it means I can go out partying on a Friday night and still go skiing early on Saturday morning." Modafinil is just the first of a wave of new lifestyle drugs that promise to do for sleep what the contraceptive pill did for sex - unshackle it from nature. Since time immemorial, humans have structured their lives around sleep. In the near future, we will, for the first time, be able to significantly structure the way we sleep to suit our lifestyles. "The more we understand about the body's 24-hour clock the more we will be able to override it," says Russell Foster, a circadian biologist at Imperial College London. "In 10 to 20 years we'll be able to pharmacologically turn sleep off. Mimicking sleep will take longer, but I can see it happening." Foster envisages a world where it's possible, or even routine, for people to be active for 22 hours a day and sleep for two. It is not a world that everyone likes the sound of. "I think that would be the most hideous thing to happen to society," says Neil Stanley, head of sleep research at the Human Psychopharmacology Research Unit in the University of Surrey, UK. But most sleep researchers agree that it is inevitable. If that sounds unlikely, think about what is already here. Modafinil has made it possible to have 48 hours of continuous wakefulness with few, if any, ill effects. New classes of sleeping pills are on the horizon that promise to deliver sleep that is deeper and more refreshing than the real thing. Further down the line are even more radical interventions - wakefulness promoters that can safely abolish sleep for several days at a stretch, and sleeping pills that deliver what feels like 8 hours of sleep in half the time. Nor is it all about drugs: one research team even talks about developing a wearable electrical device that can wake your brain up at the flick of a switch. To some degree, we are already adept at controlling sleep. Most people in full-time work deprive themselves of sleep during the week, deliberately or otherwise, and catch up at the weekend. We often augment our sleep-suppressing powers with caffeine, nicotine or illegal stimulants such as cocaine and amphetamines. We are also highly dependent on substances that help us sleep. According to some estimates, 75 per cent of adults suffer at least one symptom of a sleep problem a few nights a week or more. In 1998, a team from the Henry Ford Health Sciences Research Institute in Detroit, Michigan, published a study revealing that 13 per cent of adult Americans had used alcohol to help them get to sleep in the previous year, and 18 per cent had used sleeping pills (Sleep , vol 21, p 178). Despite the enormous resources that we pour into getting good sleep and wakefulness when we want them, most of the drugs at our disposal are crude instruments at best. The vast majority of sleeping pills - known in the business as hypnotics - are simply "knockout drops" that put you in a state almost like sleep but without its full restorative properties. "Hypnotic-induced sleep is better than no sleep, but it isn't natural sleep," says Stanley. With their addictive nature, the drugs we use to keep us awake, such as coffee and amphetamines, are even worse. In combination with our clock-watching lifestyles, these sleep and wake aids are driving ever more people into what Foster calls the "stimulant-sedative loop" where they need nightly help getting to sleep and daily help staying awake. Modafinil has changed the rules of the game. The drug is what's known as a eugeroic, meaning "good arousal" in Greek. It delivers natural-feeling alertness and wakefulness without the powerful physical and mental jolt that earlier stimulants delivered. "There are no amphetamine-like feelings," says Yves. And as Yves' way of taking it shows, being on modafinil doesn't stop you from falling asleep if you want to. In fact, its effects are so subtle that many users say they don't notice anything at all - until they need to. "I wouldn't say it makes me feel more alert or less sleepy. It's just that thoughts of tiredness don't occur to me," says Yves. "If there's a job at hand that I should be doing, I'm focused, but if I'm watching a movie or something, there is no effect." People who take modafinil for medical reasons usually take just enough of the drug in the morning to see them through the day, but it also seems to be able to deliver sustained wakefulness - for a couple of days at least. "The military has tested sequential dosing," says Jeffrey Vaught, president of R&D at Cephalon, modafinil's Pennsylvania-based manufacturer. "It works for 48 hours or so, but eventually you need to sleep." Perhaps the most remarkable thing about modafinil is that users don't seem to have to pay back any "sleep debt". Normally, if you stayed awake for 48 hours straight you would have to sleep for about 16 hours to catch up. Modafinil somehow allows you to catch up with only 8 hours or so. Well before Cephalon took an interest in the drug, French researchers discovered this effect in cats back in the early 1990s (Brain Research , vol 591, p 319), and it has since been found to apply to humans too. So how does modafinil work? "No one really knows," admits Vaught. He says that Cephalon thinks it understands the drug, but is keeping the details under wraps. What is clear is that, like other stimulant drugs, modafinil prevents nerve cells from reabsorbing the excitatory neurotransmitter dopamine once they release it into the brain. The difference is that it somehow does so without producing the addictive highs and painful crashes associated with most stimulants. A number of independent studies suggest that this might be because it also interferes with the reuptake of another neurotransmitter, noradrenalin. However it works, modafinil is proving hugely successful. Since it hit the market in 1998, sales have been climbing steadily - from $25 million in 1999 to around $575 million in 2005. Cephalon insists that the drug is for treating "medical" sleepiness caused by diseases such as narcolepsy and sleep apnoea. Even so, it's clear that modafinil is becoming a lifestyle drug for people like Yves who want off-the-peg wakefulness. "At first I got it from a friend, and then I got diagnosed as a narcoleptic online," says Yves. All the indications are that modafinil is extremely safe. The drug can have side effects, most commonly headaches, but up to now there have been no severe reactions, says Vaught. In fact, it is hard to find anyone with a bad word to say about modafinil, except that there may be unseen problems down the line as the drug becomes more widely used. "I think it's unlikely that there can be an arousal drug with no consequences," says Foster. In the long run, it is possible that casual users might have to keep upping their dose to get the same effect. Stanley has similar worries. "Is it a potential drug of abuse?" he asks. "Will it get street value? We'll see." Cephalon does not seem to be worried. Modafinil's success has spurred it to develop a successor, armodafinil. The company is also developing other eugeroics - one experimental drug called CEP-16795 switches off the H3 histamine receptor, which appears to be one of the molecular switches that controls the sleep-wake cycle. However, Vaught claims that the original will be a tough act to follow. " Modafinil is very effective and very safe," he says. "How do you beat it?" There are ideas as to how. Last year, Sam Deadwyler of Wake Forest University in Winston-Salem, North Carolina, reported the results of an experiment with a drug called CX717. The findings suggest that modafinil won't have the field to itself forever. Deadwyler kept 11 rhesus monkeys awake for 36 hours, throughout which they performed short-term memory and general alertness tests (Public Library of Sciences Biology , vol 3, p 299). At that level of sleep deprivation, a monkey's performance would normally drop to the point where it could barely function at all, but Deadwyler found that CX717 had remarkable restorative powers. Monkeys on the drug were doing better after 36 hours of continual wakefulness than undrugged monkeys after normal sleep. When Deadwyler imaged their brains with functional magnetic resonance imaging, (fMRI), he found that the drug maintained normal activity even in severely sleep-deprived individuals. The results build on those of an earlier, small-scale trial on 16 men that found CX717 could largely reverse the cognitive decline that comes with 24 hours of sleep deprivation (New Scientist , 14 May 2005, p 6). Soldiers get high CX717 belongs to a class of drugs called ampakines, which subtly ramp up brain activity by enhancing the action of its main excitatory neurotransmitter, glutamate. Cortex Pharmaceuticals of Irvine, California, which developed CX717, originally saw the drug as a cognitive booster for people with Alzheimer's, but it is its potential to counter the effects of sleep deprivation that is attracting the most attention. Later this year, the Defense Advanced Research Projects Agency (DARPA), based in Arlington, Virginia, will put CX717 through its paces as a wakefulness promoter for combat. In an experiment designed to mimic the harsh demands of special ops, investigators will push 48 volunteers to the limit - four consecutive nights of hard work with only 4 hours of recovery sleep in between. "They'll go from being tired to exhausted to crashing," says Roger Stoll, Cortex's chief executive. For some of them, however, the ordeal will be softened by regular doses of CX717. DARPA hopes the drug will counteract the sleep deprivation. The trial should help answer some outstanding questions about CX717's potential. "We don't know yet if it eliminates feelings of sleepiness," says Stoll. "The early signs are that people function better, their brain is a little more hyped. But we haven't tested sleepiness directly." As with modafinil, the evidence suggests that people struggle to tell if they're on the drug or not, and that hasn't turned out to be much of a problem for modafinil. Whatever the outcome of the DARPA trial, CX717 won't be the last word on eugeroics. Stoll says Cortex has similar but more powerful molecules up its sleeve. Thought they are being developed mainly as memory enhancers, some may turn out to be powerful wakefulness promoters too. Industry giants GlaxoSmithKline and Eli Lilly have ampakine programmes of their own, and at least one other company, Arena Pharmaceuticals of San Diego, California, has declared an interest in wakefulness promoters, though it hasn't released any details of its research. When and if those drugs come through, the US military is sure to be interested. DARPA is one of the most active players in the drive to conquer sleep, setting up and funding much of the basic research on wakefulness. The army and air force have research programmes too. It's easy to see why DARPA is interested. "We make the assumption that soldiers are going to be sleep-deprived," says DARPA neuroscientist Amy Kruse, who runs the agency's sleep-deprivation research programme. "We want to know what we can do to bring them back up to the level they would be at if they had a good night's sleep." When DARPA talks about sleep deprivation, it really means it. Soldiers on special ops sometimes have to be awake, alert and active for 72 hours at a stretch with only minimal rest. That's like starting work on Monday morning and not stopping until Thursday. "Three days, that's when they really start hurting," says Kruse. The military has a long history of using caffeine and amphetamines to get its people through. It has now added modafinil to the list, and is clearly interested in CX717. And Kruse says she is confident that there is lots of room for further improvement. Last year, a DARPA-funded team led by Giulio Tononi at the University of Wisconsin Madison discovered a strain of fruit flies that gets by on just a third the normal amount of sleep. The "minisleep" mutant carries a change to a single gene, encoding a protein involved in potassium transport across cell membranes. Intriguingly, defects in potassium channels are associated with reduced sleep in humans, particularly in the autoimmune disease Morvan's syndrome, one symptom of which is chronic sleeplessness. What that suggests, says Kruse, is that new drugs designed to latch onto potassium channels in the brain could radically alter the need for sleep. There are also likely to be other molecular targets in the brain just waiting to be exploited, she says. DARPA is meanwhile pursuing other strategies to conquer sleep deprivation. At Yaakov Stern's lab at Columbia University in New York, DARPA-funded neuroscientists have used fMRI to image the brains of sleep-deprived people, to find out which regions are affected when you are very tired. Then they used a transcranial magnetic stimulation (TMS) machine - routinely used to switch localised brain regions on and off - to switch off those areas and see if that reversed the effects. "This is all proof of concept," says Stern. "It's hard to imagine a sleep deprived pilot using TMS," not least because the machines are too bulky to fit in a cockpit. "The next step is to apply TMS before or during sleep deprivation to see if it blunts the effect. That has more of a shot at a lasting effect." Stern says his team is also looking into a new technique called DC brain polarisation, which has similar brain-boosting effects to TMS but uses DC current instead of magnetism. The beauty of this "poor man's TMS" is that the equipment is significantly smaller and cheaper - it could even be incorporated into headgear that gives you a jolt of wakefulness at the flick of a switch. And then there's always neurofeedback - training people to activate the brain regions that get hit by sleep deprivation, effectively willing themselves awake. The military isn't just interested in wakefulness. It also has a keen interest in the other side of the coin. John Caldwell works at the US Air Force Research Laboratory in San Antonio, Texas. He has spent most of his career testing the effects of stimulants, including modafinil, on pilots. "I'm the guy who puts sleep-deprived pilots in a plane, gives them drugs and says, did it work?" he says. He has also done a handful of studies on sleep aids - testing the best way to help night pilots sleep well during the day, for example. In recent months Caldwell has become aware that there is a quiet revolution going on in sleep medicine. "There's a new idea out there," he says. "Drugs that change sleep architecture." Sleep researchers have known for over 50 years that sleep isn't merely a lengthy period of unconsciousness, but consists of several different brain states . How those states are put together to build a full night's sleep is called sleep architecture. Catching the slow waves In the past, says Caldwell, sleeping pills were designed not to mess with sleep architecture, although they generally do, suppressing the deepest and most restorative "slow-wave" sleep in favour of shallower stage 2 sleep. Now, though, modifying sleep architecture is seen as the way forward. There are two new drugs in the offing that significantly increase the amount of slow-wave sleep. One of them, gaboxadol, made by Merck, is in phase III clinical trials and could be on the market next year. To Caldwell these drugs hold out the promise of a power nap par excellence. "Maybe you can make a short period of sleep more restorative by filling it with up with slow-wave sleep," he says. Much like modafinil, gaboxadol and the other slow-wave sleep promoter - Arena Pharmaceuticals' APD125, currently in phase II - are the start of something bigger. For more than 35 years, sleeping pills have been a one-trick pony. If you wanted to send someone to the land of nod, there was only one way of doing so - targeting the neurotransmitter GABA, which is the brain's all-purpose dimmer switch. Old-fashioned hypnotics such as barbiturates and benzodiazepines work by making neurons more sensitive to the soporific effects of GABA. It's also why alcohol makes you sleepy. Even the newer, cleaner sleeping pills, such as the market leader Ambien, work through the GABA system. Manipulating the GABA system is a sure-fire way of putting people to sleep, but it has its problems. One is that the brain adapts to the drugs, which means that most cannot be taken for more than a few days without losing their potency. The effects often linger well into the morning, making people feel groggy and hung over. Many are also addictive. What's more, sleep quality has rarely been considered. "In the past we would take a hypnotic and say, does it put you to sleep?," says Stanley. "That's a pretty inexact way of dealing with it. In that respect, alcohol is a good hypnotic." Now, however, there is a recognition that there is much more to sleep than the GABA system. Last year the first non-GABA sleeping pill came onto the market - the first new class of hypnotic for 35 years. Rozerem, made by Japanese firm Takeda, mimics the effects of the sleep-promoting hormone melatonin. Nor is it the only one. There are at least three other new classes of hypnotic that don't go anywhere near the GABA system. And though gaboxadol works through GABA, it hits a type of receptor that has never been targeted by drugs before. According to Stanley, there is even more scope for improvement. "It is possible that pharmaceuticals will allow you a condensed dose of sleep," he says, "and we are not that far away from having drugs that put you to sleep for a certain length of time." He predicts you could soon have tablet combining a hypnotic with an antidote or wakefulness promoter designed to give you a precise number of hours' sleep. "A 4, 5 or 6-hour pill." We seem to be moving inescapably towards a society where sleep and wakefulness are available if not on demand then at least on request. It's not surprising, then, that many sleep researchers have nagging worries about the long-term impact of millions of us using drugs to override the natural sleep-wake cycle. Stanley believes that drugs like modafinil and CX717 will tempt people to overdose on wakefulness at the expense of sleep. "Being awake is seen to be attractive," he says. "It's not cool to be asleep." Foster has similar worries. "It seems like that technology will help us cope with 24/7, but is coping really living?" he asks. Others point out that there are likely to be hidden health costs to overriding our natural sleep-wake cycles. "Pharmaceuticals cannot substitute for normal sleep," says Vaught. Still, even the doubters admit that to all intents and purposes we are already too far down the road of the 24-hour society to turn back. For millions of people, good sleep and productive wakefulness are already elusive, night work or nightlife a reality, and the "stimulant-sedative" loop all too familiar. As Vaught puts it, "We're already there." So why not make it as clean and safe as possible? LOAD-DATE: February 18, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Magazine Copyright 2006 Reed Business Information, UK, a division of Reed Elsevier Inc. All Rights Reserved 419 of 998 DOCUMENTS The International Herald Tribune February 6, 2006 Monday Biker waits for a dream ruling; CYCLING BYLINE: Sam Abt SECTION: SPORT; Pg. 18 LENGTH: 700 words DATELINE: PARIS They say there's no rest for the weary, and the woeful proof of that is Franck Bouyer, so weary, so very weary, and so far from restful. Partly it's physical. Bouyer is the French bicycle racer who is as well known for a few small but sweet victories as for the fact that he has narcolepsy, a disorder that is marked by recurring, unpredictable episodes of sleep during normal waking hours and disturbed sleep at night. He was diagnosed with this genetic disease late in 2003. ''Still the same at night sleep a little, wake up, stay up, back to sleep a while, wake up,'' Bouyer, who will be 32 in March, said in a phone interview last week from the Etoile de Besseges race in the south of France. ''During the day, though, everything's fine,'' he added. During the day is when he takes his medicine. But the use of the medicine, called modafinil, is the reason he is weary psychologically. Because of modafinil, Bouyer has appeared in court lately as often as Perry Mason. His latest testimony was given in January, half a year after he thought he had been cleared to use the medicine while he competed in races. In August, the World Anti-Doping Agency ruled that modafinil did not enhance his performance illegally and that he could take it while competing. That decision was a reversal, since the agency had ruled five months earlier in a court case that the medication was banned. Pierre-Yves Mathe, the doctor for Bouyer's Bouygues Telecom team, was shocked by the first decision. He pointed out that a French doctor had refused to issue Bouyer's racing license unless he was using the drug. Without it, the doctor felt, the rider was too prone to falling asleep and causing crashes. ''We're caught between two contradictions,'' Mathe said. ''On the one hand, he won't get his license to race unless he takes the drug; on the other, he can't race if he takes the drug.'' Bouyer was puzzled, too. ''They're talking about enhanced performances,'' he said, ''but what they don't take into account is that, without my medicine, I wake up at 3 o'clock in the night because my sleep is so disturbed. What consequences does that have on my performance? ''They allow racers who have failed three drug tests to continue, but they shove aside somebody who's really sick.'' Then, on appeal, the World Anti-Doping Agency cleared him, and Bouyer began racing again. ''I didn't have any good results,'' he said on the phone, ''because it was so late in the season to begin. But I worked very hard this winter, did a lot of training and was ready to go this month except that it didn't turn out to be that simple.'' In what his lawyer, Philippe Senmartin, characterized as a turf war, the International Cycling Union, which governs the sport, took exception to the decision by the World Anti-Doping Agency and brought suit in the Court of Arbitration for Sport in Switzerland. Modafinil remains banned by the cycling union, which often chafes at the anti-doping agency's jurisdiction. Back onto the witness stand went Bouyer last month. Without his medication, he has testified, he can doze off at any moment, even on the open road amid a pack of other riders. Let that occur, and the result can be a mass crash. It has not happened that way yet, he says, but he has fallen asleep while training alone near his home in southwestern France. ''One time I found myself in the courtyard of a farm, woken up by a barking dog without knowing how I got there,'' Bouyer has said. Similarly, a photograph of him at the Bouygues Telecom team's presentation of its riders last year showed him sitting in a chair with his eyes closed, deep in the sandman's embrace while his praises were being sung onstage. He was having no such problems in the Etoile de Besseges, he noted on the phone, since he was back on his medication. ''With it,'' he said, ''I can continue my career. Without it ... '' He left the sentence incomplete. ''We expect a decision in four to six weeks,'' he continued. ''It's a long time to wait, but meanwhile I'm racing. ''All these court appearances, meetings with my lawyer, waiting for decisions they wear you out,'' he said, with a yawn. ''Both sides have experts, and they don't agree.'' Another yawn. ''It's exhausting.'' LOAD-DATE: February 6, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2006 International Herald Tribune All Rights Reserved 420 of 998 DOCUMENTS US Fed News February 6, 2006 Monday 7:00 AM EST French Inventors Develop Modafinil Polymorphic Forms BYLINE: US Fed News LENGTH: 188 words DATELINE: Alexandria, Va. ALEXANDRIA, Va., Feb. 6 -- Véronique Broquaire of Noisy le Onaud, France, Ludovic Broquaire of Bagnois en Foret, France, Laurent Courvoisier of Laigneville, France, Armand Frydman of Verrieres-le-Buisson, France, Gerard Coquerel of Boos, France, and Franck Mallet of Blangy sur Bresle, France, have developed modafinil polymorphic forms of modafinil racemate, methods of preparation thereof, pharmaceutical compositions and methods of therapeutic treatment involving modafinil polymorphic forms, the U.S. Patent & Trademark Office announced. The inventors were issued U.S. Patent No. 6,992,219 on Jan. 31. The patent has been assigned to Cephalon France, Maisons-Alfort, France. The original application was filed on Aug. 7, 2003, and is available at: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=/netahtml/se arch-adv.htm&r=1568&f=G&l=50&d=PTXT&s1=ISYMD-20060131&p=32&OS=ISD/01/31/2006&RS= ISD/01/31/2006. For more information about US Fed News federal patent awards please contact: Myron Struck, Managing Editor/US Bureau, US Fed News, Direct: 703/866-4708, Cell: 703/304-1897, Myron@targetednews.com. LOAD-DATE: February 7, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 HT Media Ltd. All Rights Reserved 421 of 998 DOCUMENTS Cancer Drug News Pharmaceuticals February 2, 2006 Barr/Cephalon enter agreements regarding settlement of Actiq and Provigil patent litigations LENGTH: 684 words Barr Laboratories has entered into agreements to settle its pending patent infringement disputes in the US related to Cephalon 's Actiq (oral transmucosal fentanyl citrate) [C-II] and Provigil ( modafinil ) Tablets [C-IV] products. The companies have entered into a supplemental licence agreement (SLA) related to Actiq, which supplements the licence Cephalon previously granted Barr, pursuant to an FTC Order, in mid-2004. The existing licence grants Barr a non-exclusive right to sell a generic version of Actiq, which is indicated for the management of breakthrough cancer pain in patients with malignancies who are already receiving and who are tolerant to opioid therapy for their underlying persistent cancer pain, effective on the earlier of final approval of Cephalon's fentanyl effervescent buccal tablet or 3rd February 2007, if Cephalon receives a paediatric extension for Actiq (or 5th September 2006, if Cephalon does not receive the extension). The SLA ensures that Barr will be allowed to enter the market no later than 6th December 2006, two months earlier than the 6th February 2007 date. The SLA will go into effect only if the existing licence is not otherwise effective on 6th December 2006, and will remain in effect until the existing licence becomes effective. During the term of the supplemental licence, Barr will have an exclusive royalty-bearing right to market and sell a generic version of Actiq in the US, and Cephalon will not market or sell, nor shall it license or authorise a third party to market or sell, a generic version of Actiq. The SLA will cease to be effective when the existing licence agreement becomes effective. After that date, Barr's rights will be controlled by the terms of the existing licence. In connection with the modafinil settlement, Cephalon will grant Barr a non-exclusive royalty-bearing right to market and sell a generic version of Provigil, which is indicated for the treatment of excessive sleepiness associated with shift-work sleep disorder, in the US. Barr's licence will become effective in October 2011, unless Cephalon obtains a paediatric extension for Provigil, which would permit entry by Barr in April 2012. An earlier entry by Barr may occur based upon the entry of another generic version of Provigil. Barr and Cephalon have also agreed to a series of business arrangements related to modafinil. Specifically, Barr has agreed to grant to Cephalon a non-exclusive licence, effective immediately, to certain of its worldwide intellectual property rights related to modafinil in exchange for an up-front payment. Cephalon has also agreed to purchase certain existing and in-process inventory of the active pharmaceutical ingredient, modafinil. The terms of the agreements are confidential and are subject to review by the FTC. Financial terms were not disclosed. The parties will promptly file a dismissal with the US District Courts for the Districts of New Jersey and Delaware that will conclude pending litigation between the parties regarding Provigil and Actiq, respectively. This settlement and the previously-announced settlements with Teva Pharmaceutical Industries and its affiliate, Ranbaxy Laboratories , and Mylan Pharmaceuticals resolve the Provigil litigation with all four firms that Cephalon understands were the first to submit ANDAs with Paragraph IV certifications to the FDA. As such, Teva, Ranbaxy, Mylan and Barr would be granted the 180-day exclusivity provided by the provisions of the Federal Food, Drug, and Cosmetic Act. The separate, ongoing Provigil patent litigation between Cephalon and Carlsbad Technology , pending in the US District Court in New Jersey, is unaffected by these settlements. The lawsuit against Carlsbad claims infringement of Cephalon's US Patent No. RE37,516, which covers pharmaceutical compositions and methods of treatment with the form of modafinil contained in Provigil. This patent expires on 6th October 2014 and may be extended by six months (to 6th April 2015), upon acceptance by the FDA of the paediatric study data that was submitted by the company on 21st December 2005. LOAD-DATE: February 2, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2006 ESPICOM Business Intelligence Ltd. All Rights Reserved 422 of 998 DOCUMENTS PR Newswire US February 2, 2006 Thursday 12:33 AM GMT Barr Announces Agreements with Cephalon, Inc. Regarding Settlement of ACTIQ(R) and PROVIGIL(R) Patent Litigations LENGTH: 1166 words DATELINE: WOODCLIFF LAKE, N.J. Feb. 1 WOODCLIFF LAKE, N.J., Feb. 1 /PRNewswire-FirstCall/ -- Barr Pharmaceuticals, Inc. (NYSE:BRL) today announced that its subsidiary, Barr Laboratories, Inc., and Cephalon, Inc. have entered into agreements to settle its pending patent infringement disputes in the United States related to Cephalon's ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II] and PROVIGIL(R) (modafinil) Tablets [C-IV] products. "We are pleased that these agreements allow both parties to resolve pending patent litigation in a way that ensures that Barr can launch generic fentanyl at least 90 days prior to the expiration of any pediatric exclusivity period Cephalon might obtain on ACTIQ and can launch generic modafinil prior to patent expiry," said Bruce L. Downey, Barr's Chairman and Chief Executive Officer. Barr and Cephalon have entered into a Supplemental License Agreement related to ACTIQ, which supplements the license Cephalon previously granted Barr, pursuant to a Federal Trade Commission Order, in mid-2004. The existing license grants Barr a non-exclusive right to sell a generic version of ACTIQ effective on the earlier of final approval of Cephalon's fentanyl effervescent buccal tablet (FEBT) or February 3, 2007, if Cephalon receives a pediatric extension for ACTIQ (or September 5, 2006, if Cephalon does not receive the extension). The Supplemental License Agreement ensures that Barr will be allowed to enter the market no later than December 6, 2006 - two months earlier than the February 6, 2007 date. The Supplemental License Agreement will go into effect only if the existing license is not otherwise effective on December 6, 2006 and will remain in effect until the existing license becomes effective. During the term of the Supplemental License, Barr will have an exclusive royalty-bearing right to market and sell a generic version of ACTIQ in the United States, and Cephalon will not market or sell, nor shall it license or authorize a third party to market or sell, a generic version of ACTIQ. The Supplemental License Agreement will cease to be effective when the existing license agreement becomes effective. After that date, Barr's rights will be controlled by the terms of the existing license. In connection with the modafinil settlement, Cephalon will grant Barr a non-exclusive royalty-bearing right to market and sell a generic version of PROVIGIL in the United States. Barr's license will become effective in October 2011, unless Cephalon obtains a pediatric extension for PROVIGIL which would permit entry by Barr in April 2012. An earlier entry by Barr may occur based upon the entry of another generic version of PROVIGIL. Barr and Cephalon also agreed to a series of business arrangements related to modafinil. Specifically, Barr has agreed to grant to Cephalon a non- exclusive license, effective immediately, to certain of its worldwide intellectual property rights related to modafinil in exchange for an upfront payment. The terms of the agreements are confidential, and are subject to review by the Federal Trade Commission. Financial terms were not disclosed. The parties will promptly file a dismissal with the United States District Courts for the Districts of New Jersey and Delaware that will conclude pending litigation between the parties regarding PROVIGIL and ACTIQ, respectively. About Barr Pharmaceuticals, Inc. Barr Pharmaceuticals, Inc. is a holding company whose principal subsidiaries, Barr Laboratories, Inc. and Duramed Pharmaceuticals, Inc., develop, manufacture and market generic and proprietary pharmaceuticals. Forward-Looking Statements Except for the historical information contained herein, the statements made in this press release constitute forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Forward-looking statements can be identified by their use of words such as "expects," "plans," "projects," "will," "may," "anticipates," "believes," "should," "intends," "estimates" and other words of similar meaning. Because such statements inherently involve risks and uncertainties that cannot be predicted or quantified, actual results may differ materially from those expressed or implied by such forward-looking statements depending upon a number of factors affecting the Company's business. These factors include, among others: the difficulty in predicting the timing and outcome of legal proceedings, including patent-related matters such as patent challenge settlements and patent infringement cases; the outcome of litigation arising from challenging the validity or non- infringement of patents covering our products; the difficulty of predicting the timing of FDA approvals; court and FDA decisions on exclusivity periods; the ability of competitors to extend exclusivity periods for their products; our ability to complete product development activities in the timeframes and for the costs we expect; market and customer acceptance and demand for our pharmaceutical products; our dependence on revenues from significant customers; reimbursement policies of third party payors; our dependence on revenues from significant products; the use of estimates in the preparation of our financial statements; the impact of competitive products and pricing on products, including the launch of authorized generics; the ability to launch new products in the timeframes we expect; the availability of raw materials; the availability of any product we purchase and sell as a distributor; the regulatory environment; our exposure to product liability and other lawsuits and contingencies; the increasing cost of insurance and the availability of product liability insurance coverage; our timely and successful completion of strategic initiatives, including integrating companies and products we acquire and implementing our new enterprise resource planning system; fluctuations in operating results, including the effects on such results from spending for research and development, sales and marketing activities and patent challenge activities; the inherent uncertainty associated with financial projections; changes in generally accepted accounting principles; and other risks detailed from time-to-time in our filings with the Securities and Exchange Commission, including in our Annual Report on Form 10-K for the fiscal year ended June 30, 2005. The forward-looking statements contained in this press release speak only as of the date the statement was made. The Company undertakes no obligation (nor does it intend) to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except to the extent required under applicable law. First Call Analyst: FCMN Contact: apeden@barrlabs.com CONTACT: Carol A. Cox, +1-201-930-3720, ccox@barrlabs.com Web site: http://www.barrlabs.com/ Company News On-Call: http://www.prnewswire.com/comp/089750.html SOURCE Barr Pharmaceuticals, Inc. URL: http://www.prnewswire.com LOAD-DATE: February 2, 2006 LANGUAGE: ENGLISH NOTES: NOTE TO EDITORS: Barr Pharmaceuticals, Inc. news releases are available free of charge through PR Newswire's News On-Call site at http://www.prnewswire.com/comp/089750.html. Barr news releases and corporate information are also available on Barr's website (www.barrlabs.com). For complete indications, warnings and contraindications, contact Barr Laboratories' Product Information Department at 1-800-Barr Lab. All trademarks referenced herein are the property of their respective owners. PUBLICATION-TYPE: Newswire Copyright 2006 PR Newswire Association LLC. All Rights Reserved. 423 of 998 DOCUMENTS Clinical Psychiatry News February 2006 Narcolepsy Drug Is Safe, Effective for ADHD BYLINE: Michele G. Sullivan, Mid-Atlantic Bureau SECTION: Pg. 34 Vol. 34 No. 2 ISSN: 0270-6644 LENGTH: 408 words    TORONTO - Modafinil is safe and effective in treating pediatric attention-deficit hyperactivity disorder, decreasing symptom scores twice as much as placebo, according to two posters presented at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.    The posters, sponsored by Cephalon Inc., concluded that children tolerated the film-coated tablets well in dosages of up to 425 mg/day. Insomnia, headache, and decreased appetite were the most commonly reported adverse events. Those adverse events typically occurred during the first 2 weeks of therapy and decreased thereafter, said Dr. Christopher Kratochvil of the University of Nebraska.    The posters analyzed three multicenter, double-blind studies that included a total of 633 children aged 6-17 years. Two of the studies were identical 9-week flexible-dosing trials. The third was a 7-week fixed-dose placebo-controlled study (340 or 425 mg/day), followed by a 2-week period in which half the modafinil group was switched to placebo without tapering while the other half continued modafinil treatment.    Adverse events were more common in the active group than the placebo group and included insomnia (27% vs. 4%), headache (20% vs. 13%), and decreased appetite (16% vs. 3%).    The adverse events were all classified as mild to moderate. They peaked in the first 2 weeks of treatment and subsequently subsided. No apparent association was found between adverse events and dosage.    There were no significant changes in heart rate or blood pressure between the groups, and the abrupt discontinuation of the drug did not lead to acute withdrawal symptoms or rebound effects.    The drug effectively reduced the symptoms of ADHD, especially hyperactivity and inattention, reported Dr. Joseph Biederman of Massachusetts General Hospital. The effects were consistent whether assessed by physician, parent, or teacher.    Physicians assessed almost 50% of the active groups as much improved at the end of treatment, compared with 20% of the placebo group.    Parents and teachers rated symptom improvement of those in the active group at about twice that of the placebo group in all areas: oppositional behavior, inattention, and hyperactivity.    Symptom improvement differed significantly from placebo at week 2 of treatment and continued to diverge throughout the course of all three studies. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: CPNEWS Copyright 2006 Elsevier Inc., International Medical News Group All Rights Reserved 424 of 998 DOCUMENTS PR Newswire US February 1, 2006 Wednesday 10:50 PM GMT Cephalon, Inc. Announces Agreements With Barr Laboratories, Inc. Regarding Settlement of PROVIGIL(R) and ACTIQ(R) Patent Litigations LENGTH: 1280 words DATELINE: FRAZER, Pa. Feb. 1 FRAZER, Pa., Feb. 1 /PRNewswire-FirstCall/ -- Cephalon, Inc. (NASDAQ:CEPH) announced today that it has entered into agreements with Barr Laboratories, Inc. to settle its pending patent infringement disputes in the United States related to PROVIGIL(R) (modafinil) Tablets [C-IV] and ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II]. "This is a transformational event for Cephalon," said Frank Baldino, Jr., Chairman and Chief Executive Officer. "Continued PROVIGIL sales provide a new foundation for further accelerating Cephalon's growth over the next several years." In connection with the settlements, Cephalon will grant Barr a non- exclusive royalty-bearing right to market and sell a generic version of PROVIGIL in the United States. Barr's license will become effective in October 2011, unless Cephalon obtains a pediatric extension for PROVIGIL which would permit entry by Barr in April 2012. An earlier entry by Barr may occur based upon the entry of another generic version of PROVIGIL. "While we remain confident in the strength of the PROVIGIL patent, we believe that with these settlements we have struck an appropriate balance between protecting our intellectual property rights and providing more certainty to our business through at least 2011," said John E. Osborn, Senior Vice President and General Counsel. Cephalon and Barr also agreed to a series of business arrangements related to modafinil. Specifically, Barr has agreed to grant to Cephalon a non- exclusive license, effective immediately, to certain of its worldwide intellectual property rights related to modafinil in exchange for an upfront payment. Cephalon also has agreed to purchase certain existing and in-process inventory of the active pharmaceutical ingredient modafinil. With respect to ACTIQ, Cephalon will grant Barr an exclusive royalty- bearing right to market and sell a generic version of ACTIQ in the United States, effective on December 6, 2006. Barr will pay specified royalties on net profits of its generic ACTIQ product for the period December 6, 2006 through February 3, 2007, subject to certain limitations. Under an agreement entered into with Barr in mid-2004 in connection with the company's acquisition of CIMA LABS and pursuant to a Federal Trade Commission order, Cephalon granted Barr a non-exclusive, royalty-free license to sell a generic version of ACTIQ effective on the earlier of final approval of Cephalon's fentanyl effervescent buccal tablet (FEBT) or February 3, 2007, if Cephalon receives a pediatric extension for ACTIQ (or September 5, 2006, if Cephalon does not receive the extension). The terms of the agreements are confidential, and are subject to review by the Federal Trade Commission. Financial terms were not disclosed. The parties will promptly file a dismissal with the United States District Courts for the Districts of New Jersey and Delaware that will conclude pending litigation between the parties regarding PROVIGIL and ACTIQ, respectively. This settlement and the previously announced settlements with Teva Pharmaceutical Industries Ltd. and its affiliate, Ranbaxy Laboratories Limited, and Mylan Pharmaceuticals Inc. resolve the PROVIGIL litigation with all four firms that Cephalon understands were the first to submit abbreviated new drug applications (ANDAs) with Paragraph IV certifications to the Food and Drug Administration. As such, Teva, Ranbaxy, Mylan and Barr would be granted the 180-day exclusivity provided by the provisions of the Federal Food, Drug, and Cosmetic Act. The separate, ongoing PROVIGIL patent litigation between Cephalon and Carlsbad Technology, Inc., pending in the U.S. District Court in New Jersey, is unaffected by these settlements. The lawsuit against Carlsbad claims infringement of Cephalon's U.S. Patent No. RE37,516, which covers pharmaceutical compositions and methods of treatment with the form of modafinil contained in PROVIGIL. This patent expires in October 6, 2014 and may be extended by six months (to April 6, 2015) upon acceptance by the FDA of the pediatric study data submitted by the company on December 21, 2005. As previously announced, Cephalon will reissue 2006 guidance when it releases its fourth quarter and full year 2005 financial results on February 14, 2006 to reflect the recent settlements of the PROVIGIL and ACTIQ patent infringement suits, the closing of the Zeneus acquisition, the current timeline for commercial launch of SPARLON, and the impact of the recent rise in the company's stock price on the number of shares included in the income per share calculation. The company expects to report a modest increase in 2006 guidance when issued. Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products to treat sleep and neurological disorders, cancer and pain. Cephalon currently employs approximately 2,600 people in the United States and Europe. U.S. sites include the company's headquarters in Frazer, Pennsylvania, and offices, laboratories or manufacturing facilities in West Chester, Pennsylvania, Salt Lake City, Utah, and suburban Minneapolis, Minnesota. The company currently markets four proprietary products in the United States: PROVIGIL, GABITRIL(R) (tiagabine hydrochloride), ACTIQ and TRISENOX(R) (arsenic trioxide) injection, and more than 20 products internationally. Full prescribing information for all U.S. products is available at http://www.cephalon.com/ or by calling 1-800-896-5855. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding the settlement of this litigation, including whether the Federal Trade Commission will approve the terms of such settlement; anticipated scientific progress on its research programs; development of potential pharmaceutical products; interpretation of clinical results; prospects for regulatory approval; manufacturing development and capabilities; market prospects for its products; sales and earnings guidance; and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. First Call Analyst: Robert S. Merritt FCMN Contact: CONTACT: Media, Robert Grupp, +1-610-738-6402, or rgrupp@cephalon.com , or Investors, Chip Merritt, +1-610-738-6376, or cmerritt@cephalon.com , both of Cephalon, Inc. Web site: http://www.cephalon.com/ Company News On-Call: http://www.prnewswire.com/comp/134563.html SOURCE Cephalon, Inc. URL: http://www.prnewswire.com LOAD-DATE: February 2, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 PR Newswire Association LLC. All Rights Reserved. 425 of 998 DOCUMENTS PR Newswire US February 1, 2006 Wednesday 10:28 PM GMT Cephalon, Inc. Provides Update on Regulatory Status of NUVIGIL(TM); Company Anticipates Launch of Product in Mid-2006 LENGTH: 848 words DATELINE: FRAZER, Pa. Feb. 1 FRAZER, Pa., Feb. 1 /PRNewswire-FirstCall/ -- Cephalon, Inc. (NASDAQ:CEPH) announced today that the United States Food and Drug Administration (FDA) has extended the action date for its review of the New Drug Application (NDA) for NUVIGIL(TM) (armodafinil) Tablets [C-IV] to improve wakefulness in patients suffering from excessive sleepiness associated with narcolepsy, shift work sleep disorder (SWSD) and obstructive sleep apnea/hypopnea syndrome (OSA/HS) to April 30, 2006. "We will continue to work closely with the FDA to assist them in completing their review of our application in a timely manner and do not anticipate any further delays beyond the April 30 action date," said Dr. Paul Blake, Executive Vice President, Worldwide Medical and Regulatory Operations. "As pioneers in the development of wake promoting agents, we are excited about the opportunity to bring NUVIGIL to market in the middle of this year." A NDA for NUVIGIL was filed with the FDA on March 31, 2005. The original action date under the Prescription Drug User Fee Act (PDUFA) for the NUVIGIL NDA was January 31, 2006. At the FDA's request, the company submitted additional information to FDA in October 2005. The FDA has informed the company that this submission has been classified as a major amendment to the NDA, which enables the FDA to extend the action date by 90 days to provide the agency time for a full review of the submission. About NUVIGIL NUVIGIL is a single-isomer formulation of modafinil, the active pharmaceutical ingredient contained in PROVIGIL(R) (modafinil) Tablets [C-IV]. The NDA is based on positive results of four double-blind, randomized, placebo-controlled studies in patients with excessive sleepiness associated with either narcolepsy, SWSD or OSA/HS. In these studies, NUVIGIL was generally well tolerated, with a safety profile consistent with that observed in studies of PROVIGIL. The most common adverse effects observed included headache, nausea, dizziness, insomnia and anxiety. About Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products to treat sleep and neurological disorders, cancer and pain. Cephalon currently employs approximately 2,600 people in the United States and Europe. U.S. sites include the company's headquarters in Frazer, Pennsylvania, and offices, laboratories or manufacturing facilities in West Chester, Pennsylvania, Salt Lake City, Utah, and suburban Minneapolis, Minnesota. The company currently markets four proprietary products in the United States: PROVIGIL, GABITRIL(R) (tiagabine hydrochloride), ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II] and TRISENOX(R) (arsenic trioxide) injection and more than 20 products internationally. Full prescribing information for all U.S. products is available at http://www.cephalon.com/ or by calling 1-800-896-5855. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs; development of potential pharmaceutical products; interpretation of clinical results, particularly with respect to the NUVIGIL Phase 3 trials; prospects for and timing of regulatory approval of NUVIGIL; anticipated product launch date and potential benefits of NUVIGIL; manufacturing development and capabilities; market prospects for its products; sales and earnings guidance; and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. First Call Analyst: Robert S. Merritt FCMN Contact: CONTACT: Media: Sheryl Williams, +1-610-738-6493, swilliam@cephalon.com , or Investors: Robert (Chip) Merritt, +1-610-738-6376, cmerritt@cephalon.com , both of Cephalon Web site: http://www.cephalon.com/ Company News On-Call: http://www.prnewswire.com/comp/134563.html SOURCE Cephalon, Inc. URL: http://www.prnewswire.com LOAD-DATE: February 2, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 PR Newswire Association LLC. All Rights Reserved. 426 of 998 DOCUMENTS CNS Drug News Pharmaceuticals January 26, 2006 Cephalon provides update on regulatory status of Sparlon LENGTH: 249 words Cephalon has reported that it does not expect final action from the FDA on its pending NDA for Sparlon ( modafinil ) Tablets [C-IV] for the treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents until after the completion of several FDA advisory committee meetings. The first two panels, scheduled for 9th February and 22nd March 2006, will consider safety and risk-management issues associated with products in the class of currently-approved ADHD treatments. Since Sparlon is not an approved drug, it will not be discussed at these meetings. A separate advisory panel to review Sparlon has been scheduled for 23rd March 2006. On 20th October 2005, the FDA issued an approvable letter with respect to Cephalon's NDA for Sparlon; the company now expects to launch the product during the second quarter of 2006. As a result of recent settlements of three patent infringement suits related to Provigil (modafinil) Tablets [C-IV], the closing of the acquisition of Zeneus Holdings, the parent company of Zeneus Pharma , the current timeline for commercial launch of Sparlon and the impact of the recent rise in the company's stock price on the number of shares included in the income per share calculation, Cephalon has determined that its previously-issued 2006 sales and diluted adjusted income per share guidance is outdated. The company will reissue 2006 guidance when it releases its fourth quarter and full-year 2005 financial results on 14th February 2006. LOAD-DATE: January 30, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2006 ESPICOM Business Intelligence Ltd. All Rights Reserved 427 of 998 DOCUMENTS World Generic Markets Pharmaceuticals January 16, 2006 Cephalon reaches modafinil litigation settlements with Teva, Ranbaxy and Mylan LENGTH: 390 words Cephalon has announced it has reached agreements with Teva Pharmaceutical Industries , Ranbaxy Laboratories and Mylan Pharmaceuticals to settle their respective pending patent infringement litigation cases over Cephalon's modafinil product, Provigil . In the case with Teva, the agreement settles disputes in both the United States and the United Kingdom. In the settlements with all three companies, Cephalon will grant the two non-exclusive royalty-bearing rights to market and sell generic modafinil in the United States. This will become effective for both companies in October 2011, assuming no paediatric exclusivity periods for Provigil, in which case the date would be set back by six months to April 2012. Interestingly, Provigil has two patents listed against it in the FDA's Orange Book, but neither expires in October 2011. The first expires on 22nd May 2007, and the second on 6th October 2014. However, earlier entry by either Ranbaxy, Mylan or Teva could occur if another generic version of the drug enters the market. In Teva's case, the two firms have agreed to comparable terms for the licence effective date, which would generally allow for entry in October 2012. Cephalon has also agreed a series of business arrangements related to modafinil with the two firms. Specifically, both Teva and Ranbaxy have agreed to grant Cephalon a non-exclusive licence, effective immediately, to certain of their worldwide intellectual property rights related to modafinil in exchange for milestone payments. Cephalon has also agreed to enter into arrangements related to the manufacture and supply of the modafinil active ingredient with the two companies. The specific terms of the agreements are confidential, but are subject to review by the Federal Trade Commission. In both cases, financial terms have not been disclosed. With the agreements, the parties will file dismissals with prejudice with the US District Court for the District of New Jersey which will conclude all pending litigation between the firms regarding modafinil. The lawsuits in both cases relate to Cephalon's patent which expires in 2014 and covers pharmaceutical compositions and methods of treatment with the form of modafinil contained in Provigil. With regard to Teva, the parties will also file a dismissal with the UK High Court of Justice, Chancery Division. LOAD-DATE: January 18, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2006 ESPICOM Business Intelligence Ltd. All Rights Reserved 428 of 998 DOCUMENTS Family Practice News January 15, 2006 Modafinil Safe and Effective for Pediatric ADHD BYLINE: Michele G. Sullivan, Mid-Atlantic Bureau SECTION: Pg. 57 Vol. 36 No. 2 ISSN: 0300-7073 LENGTH: 346 words    TORONTO - Modafinil is safe and effective in treating pediatric attention-deficit hyperactivity disorder. Symptom scores were twice as high as placebo, according to two posters presented at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.    The posters, sponsored by Cephalon Inc., concluded that children tolerated the film-coated tablets well in dosages of up to 425 mg/day. Insomnia, headache, and decreased appetite were the most commonly reported adverse events. Those adverse events typically occurred during the first 2 weeks of therapy and decreased thereafter, said Dr. Christopher Kratochvil of the University of Nebraska.    The posters analyzed three multicenter, double-blind studies that included a total of 633 children aged 6-17 years. Two studies were identical 9-week flexible-dosing trials. The third was a 7-week, fixed-dose, placebo-controlled study (340 or 425 mg/day), followed by a 2-week period in which half the modafinil group was switched to placebo without tapering while the other half continued modafinil treatment.    Adverse events were more common in the active group than the placebo group and included insomnia (27% vs. 4%), headache (20% vs. 13%), and decreased appetite (16% vs. 3%).    The adverse events were all classified as mild to moderate. They peaked in the first 2 weeks of treatment and subsequently subsided. No apparent association was found between adverse events and dosage.    There were no significant changes in heart rate or blood pressure between the groups, and the abrupt discontinuation of the drug did not lead to acute withdrawal symptoms or rebound effects.    The drug effectively reduced the symptoms of ADHD, especially hyperactivity and inattention, reported Dr. Joseph Biederman of Massachusetts General Hospital. Effects were consistent whether assessed by physician, parent, or teacher. Physicians assessed almost 50% of the active groups as much improved at the end of treatment, vs. 20% of the placebo group. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: FPNEWS Copyright 2006 Elsevier Inc., International Medical News Group All Rights Reserved 429 of 998 DOCUMENTS CNS Drug News Pharmaceuticals January 11, 2006 Cephalon/Mylan enter agreement to settle Provigil patent litigation LENGTH: 341 words Cephalon has entered into an agreement with Mylan Pharmaceuticals to settle its pending patent infringement dispute in the US related to Provigil ( modafinil ) Tablets [C-IV]. In connection with the settlement, Cephalon will grant Mylan a non-exclusive royalty-bearing right to market and sell a generic version of Provigil in the US. Mylan's licence will become effective in October 2011, unless Cephalon obtains a paediatric extension for Provigil, which would permit entry by Mylan in April 2012. An earlier entry by Mylan may occur based upon the entry of another generic version of Provigil. The terms of the agreement are confidential and are subject to review by the US FTC. Financial terms were not disclosed. The parties will promptly file a dismissal with prejudice with the US District Court for the District of New Jersey that will conclude all pending litigation between the parties regarding Provigil. This settlement and the previously-announced settlements with Teva Pharmaceutical Industries and its affiliate, and Ranbaxy Laboratories , do not affect the status of the ongoing Provigil patent litigations between Cephalon and certain other generic companies that are pending in the US District Court in New Jersey. These lawsuits claim infringement of Cephalon's US Patent No. RE37,516 (the '516 Patent), which covers pharmaceutical compositions and methods of treatment with the form of modafinil contained in Provigil. The '516 patent expires on 6th October 2014 and may be extended by six months (to 6th April 2015) upon submission of paediatric study data that are acceptable to the FDA. In January 2004, the FDA approved Provigil as the first and only medication to treat excessive sleepiness associated with shift-work sleep disorder. The medication is believed to work selectively through the sleep-wake centres to activate the cortex of the brain. The exact mechanism of action of Provigil is not known, however, it promotes wakefulness without causing the generalised stimulation of the brain associated with CNS stimulants. LOAD-DATE: January 12, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2006 ESPICOM Business Intelligence Ltd. All Rights Reserved 430 of 998 DOCUMENTS IPS-Inter Press Service January 9, 2006, Monday FRANCE: SOLDIERS SAY UNTESTED GULF WAR DRUG MADE THEM SICK BYLINE: By Julio Godoy LENGTH: 788 words DATELINE: PARIS, January 9 2006 The French army administered a drug to its soldiers during the first Gulf War in 1991 without informing them of the risks, according to evidence presented at a judicial inquiry. The drug, Modafinil, kept the soldiers awake for days, according to documents presented before a judicial inquiry into the Gulf War syndrome. The inquiry was launched by the public prosecution office in June 2002 to establish responsibility for illnesses suffered by French soldiers in Iraq. The drug was administered to some 1,000 French soldiers who participated in the war against Iraq. "I and many comrades were given the drug every eight hours under orders from our commanders," Yannick Morvan, a veteran of the 1991 Iraq campaign, told IPS. "I am ready to give my life defending France, but that does not mean that I am ready to be used as guinea pig against my will." Other veterans say the commanders never spelled out what kind of drug the soldiers were being given. The army decided to test Modafinil in Operation Dauphin in June 1990, two years before the drug was due for authorized distribution, according to evidence presented at the inquiry. In an internal note in January 1991, military authorities said the drug could only be used "outside national territory" and only with the "utmost discretion." The French army violated national and international rules on testing drugs that say that no test can be carried out without written consent of those taking the drugs, critics say. The drug contributed to several conditions that are seen as a part of Gulf War syndrome. Gulf War syndrome was first identified by the U.S. Centers for Disease Control and Prevention in 1994 after thousands of troops returning from Iraq complained of numerous unexplained symptoms. It is defined as having a set of symptoms that continue for more than six months, such as fatigue, mood and cognitive symptoms such as loss of sleep or memory, concentration disturbances, headaches and depression, and musculoskeletal pain. The French army denies any wrongdoing. The Defense Ministry says use of Modafinil could in no way be described as a test. Daniel Gautier, who served as head of the military medical department in the early 1990s, said at a hearing that "on the war field, military medical personnel wrongly believed that they were carrying out a therapeutic test." Maurice Schmitt, who was commander-in-chief of the armed forces between 1987 and 1991, told a parliamentary inquiry commission in November 2000 that he had not given specific authorization to test Modafinil. "I just left open the possibility to test it, if the need to do it became evident," he said. Both officers spoke of administration of the drug as a test. Several hundred French soldiers have lodged complaints against the army alleging they are suffering from Gulf War syndrome as a result of being given illegal drugs or due to exposure depleted uranium or to chemical weapons such as the nerve gas Sarin. The soldiers have created an association, Avigolfe (short for Association of the military and civilian victims of the Gulf War), which claims that at least 31 veterans of the Iraq campaign have died as a result of contamination from illegal drugs or weapons. The Avigolfe campaign led to the present judicial inquiry. A finding is expected in June, sources close to prosecutor Marie-Odille-Bertella Geoffroy told IPS. Guy Paris, legal counselor for Avigolfe, says soldiers still in service are reluctant to talk about their health difficulties for fear they could be expelled from the army. "Many soldiers wait until they have 15 years of service to get access to full pension before they present their pleas," Paris told IPS. Similar inquiries have been going on in the United States and in Britain for years. According to the U.S. Research Advisory Committee on Gulf War Veterans' Illnesses, an estimated 100,000 Gulf War veterans, or about one in seven soldiers who were deployed in Iraq in 1991, suffer war-related health problems. The committee was set up by the U.S. Congress in 1998 to "make recommendations to the (U.S.) Secretary of Veterans Affairs on government research relating to the health consequences of military service in the Southwest Asia theatre of operations" during the Gulf War of 1991. In a report released in October 2004, the committee concluded that "a substantial proportion of Gulf War veterans are ill with multi-symptom conditions probably linked to the exposure to chemical weapons and neurotoxins." The report said possible sources include Sarin from an Iraqi weapons depot blown up by U.S. forces in 1991, and also pyridostigmine bromide, a drug given to the troops to protect them against nerve gas. LOAD-DATE: January 19, 2006 LANGUAGE: ENGLISH Copyright 2006 IPS-Inter Press Service/Global Information Network 431 of 998 DOCUMENTS World Generic Markets Pharmaceuticals January 9, 2006 Cephalon reaches modafinil litigation settlements with Teva and Ranbaxy LENGTH: 385 words Cephalon has announced it has reached agreements with both Teva Pharmaceutical Industries and Ranbaxy Laboratories to settle their respective pending patent infringement litigation cases over Cephalon's modafinil product, Provigil . In the case with Teva, the agreement settles disputes in both the United States and the United Kingdom. In the settlements with both companies, Cephalon will grant the two non-exclusive royalty-bearing rights to market and sell generic modafinil in the United States. This will become effective for both companies in October 2011, assuming no paediatric exclusivity periods for Provigil, in which case the date would be set back by six months to April 2012. Interestingly, Provigil has two patents listed against it in the FDA's Orange Book, but neither expires in October 2011. The first expires on 22nd May 2007, and the second on 6th October 2014. However, earlier entry by either Ranbaxy or Teva could occur if another generic version of the drug enters the market. In Teva's case, the two firms have agreed to comparable terms for the licence effective date, which would generally allow for entry in October 2012. Cephalon has also agreed a series of business arrangements related to modafinil with the two firms. Specifically, both Teva and Ranbaxy have agreed to grant Cephalon a non-exclusive licence, effective immediately, to certain of their worldwide intellectual property rights related to modafinil in exchange for milestone payments. Cephalon has also agreed to enter into arrangements related to the manufacture and supply of the modafinil active ingredient with the two companies. The specific terms of the agreements are confidential, but are subject to review by the Federal Trade Commission. In both cases, financial terms have not been disclosed. With the agreements, the parties will file dismissals with prejudice with the US District Court for the District of New Jersey which will conclude all pending litigation between the firms regarding modafinil. The lawsuits in both cases relate to Cephalon's patent which expires in 2014 and covers pharmaceutical compositions and methods of treatment with the form of modafinil contained in Provigil. With regard to Teva, the parties will also file a dismissal with the UK High Court of Justice, Chancery Division. LOAD-DATE: January 12, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2006 ESPICOM Business Intelligence Ltd. All Rights Reserved 432 of 998 DOCUMENTS Reuters Health Medical News January 6, 2006 Friday 9:00 PM EST Modafinil unlikely to perk up Parkinson's patients during the day SECTION: CLINICAL LENGTH: 248 words DATELINE: NEW YORK Modafinil (Provigil), a wake-promoting agent approved for use in narcolepsy, does not appear to promote wakefulness in patients with Parkinson's disease-related excessive daytime somnolence, according to results of a 4-week double-blind, placebo-controlled study. The etiology of excessive daytime sleepiness, which often complicates PD, is "probably multifactorial but is probably exacerbated by dopaminergic medications," Houston-based researchers note in the December issue of the Journal of Neurology, Neurosurgery and Psychiatry. Dr. William G. Ondo from Baylor College of Medicine and colleagues tested the efficacy of modafinil (200 or 400 mg per day) against placebo in 40 PD patients with excessive daytime somnolence. According to the team, modafinil failed to significantly relieve daytime sleepiness on any of the tests used, including the Epworth Sleepiness Scale, the Multiple Sleep Latency Test, and the Fatigue Severity Scale. Hamilton Depression Scale scores were also unchanged with modafinil. "The drug, however, was very well tolerated and has an immediate effect, and individual patients did benefit from taking it," Dr. Ondo and colleagues note. "Since the etiology of excessive sleepiness is multifactorial, modafinil may be considered on an individual basis," they conclude. Dr. Ondo's group also points out in their report that modafinil was associated with significant improvement in PD-related daytime sleepiness in two smaller controlled trials of shorter duration. LOAD-DATE: March 4, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2006 Reuters Health All Rights Reserved 433 of 998 DOCUMENTS CNS Drug News Pharmaceuticals January 3, 2006 Ranbaxy enters agreement with Cephalon regarding settlement of Provigil patent litigation LENGTH: 420 words Ranbaxy Laboratories has entered into an agreement with Cephalon to settle the companies' pending patent infringement dispute in the US related to Provigil ( modafinil ) Tablets [C-IV]. In connection with the settlement, Cephalon will grant Ranbaxy a non-exclusive royalty-bearing right to market and sell a generic version of Provigil in the US. Ranbaxy's licence will become effective in October 2011, in the absence of a paediatric extension for Provigil, which would delay the entry date by six months (to April 2012). An earlier entry by Ranbaxy may occur based upon the entry of another generic version of Provigil. The companies have also agreed to a series of business arrangements related to modafinil. Specifically, Ranbaxy has agreed to grant to Cephalon a non-exclusive licence, effective immediately, to certain of its worldwide intellectual property rights related to modafinil in exchange for milestone payments. Cephalon has also agreed to enter into certain arrangements with Ranbaxy related to the latter's supply of the active pharmaceutical ingredient, modafinil. The terms of the agreement are confidential and are subject to review by the FTC. Financial terms were not disclosed. The parties will promptly file a dismissal with prejudice with the US District Court for the District of New Jersey that will conclude all pending litigation between the parties regarding Provigil. This settlement and the previously-announced settlements with Teva Pharmaceutical Industries and Teva Pharmaceuticals USA do not affect the status of the ongoing Provigil patent litigations between Cephalon and certain other generic companies that are pending in the US District Court in New Jersey. These lawsuits claim infringement of Cephalon's US Patent No. RE37, 516 (the '516 Patent), which covers pharmaceutical compositions and methods of treatment with the form of modafinil contained in Provigil. The '516 Patent expires on 6th October 2014, and may be extended by six months (to 6th April 2015) upon the submission of paediatric study data that are acceptable to the FDA. In January 2004, the FDA approved Provigil as the first and only medication to treat excessive sleepiness associated with shift-work sleep disorder. The medication is believed to work selectively through the sleep-wake centres to activate the cortex of the brain. The exact mechanism of action of Provigil is not known, however, it promotes wakefulness without causing the generalised stimulation of the brain associated with CNS stimulants. LOAD-DATE: January 9, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2006 ESPICOM Business Intelligence Ltd. All Rights Reserved 434 of 998 DOCUMENTS Clinical Psychiatry News January 2006 Clinical Capsules BYLINE: Heidi Splete SECTION: Pg. 44 Vol. 34 No. 1 ISSN: 0270-6644 LENGTH: 802 words Ethnicity and Depression in Teen Girls    Depression scores among white girls and young women decrease over time, but the scores tend to hold steady among their African American counterparts, reported Debra L. Franko, Ph.D., of Northeastern University, Boston, and her associates.    Depression scores among white girls and young women tend to start off higher, and that might play a role in the findings.    Previous comparisons of depression scores in African American and white girls have shown either mixed results or higher scores among white girls at younger ages.    The investigators conducted an age-matched study of 2,221 girls and young women aged 16-22 years, including 1,146 African Americans and 1,075 whites. The girls, participants in the 10-year longitudinal National Growth and Health Study, were asked to complete a packet of questionnaires, including the Center for Epidemiological Studies of Depression scale (CES-D) (J. Adolesc. Health 2005;37:526-9).    Adolescent depression was defined as a score of at least 24 on the CES-D.    Overall, as they got older, the percentage of white girls who met the criteria for depression fell, and the percentage of African American girls who met the criteria remained fairly steady. Specifically, 21% of 483 white 16-year-olds scored 24 or higher, compared with 14% of 332 white 22-year-olds. Among African Americans, 14% of 469 16-year-olds scored 24 or higher, compared with 15% of 452 22-year-olds.    The researchers noted that age-specific risk factors-such as body dissatisfaction subsequent to pubertal development-are more common among white girls and could partly account for the results. Other factors, such as access to and use of mental health care, also could explain some of the differences. Modafinil for ADHD    Modafinil film-coated tablets significantly improved clinical symptoms of attention-deficit hyperactivity disorder in children and adolescents aged 6-17 years, said Dr. Joseph Biederman of Massachusetts General Hospital in Boston and his colleagues.    Modafinil, an agent generally prescribed to promote wakefulness in patients with narcolepsy, has been shown to activate the cortex alone.    In the randomized, double-blind trial conducted by Dr. Biederman and his colleagues, 164 children received a flexible dose of modafinil in tablet form, and 82 children received a placebo. The children began with one 85-mg tablet for the first 2 days; the dose was titrated to 170 mg on days 3-7, 255 mg on days 8-14, 340 mg on days 15-21, and 425 mg on day 22 (Pediatrics 2005;116:777-84).    After 9 weeks, 48% of patients in the modafinil group were deemed responders, compared with 17% of those in the placebo group. Overall, patients in the modafinil group demonstrated significant improvement in symptoms, including oppositional behavior, cognitive problems/inattention, hyperactivity, and the ADHD index on the Conners' Parent Rating Scale Revised, Short Form, compared with those in the placebo group.    Modafinil (Provigil) also was well tolerated. Only five of the patients in the treatment group (3%) and three in the placebo group (4%) discontinued the study because of adverse events. Given modafinil's safety profile and its low potential of abuse, the drug may offer clinicians a new option for treating ADHD in children and adolescents, the investigators said. Teens' Perception of Body Weight    Many young teens from disadvantaged backgrounds do not perceive obesity as unacceptable, and despite common perceptions, not all of them are striving for thinness, reported Wendy Wills of the Centre for Research in Primary and Community Care, University of Hertfordshire, Hatfield, England.    In a qualitative study in eastern Scotland of 36 economically disadvantaged 13- to 14-year-olds, half of the subjects were either overweight (body mass index greater than 25 kg/m2) or obese (BMI greater than 30). The subjects were evenly split among boys and girls (Soc. Sci. Med. 2006;62:396-406).    The overweight and obese teens had complex views of their weight and body size. Three-quarters of them talked positively about their weight, body size, or parts of their bodies, or expressed comfort with their bodies. A minority who were comfortable with their bodies also reported dissatisfaction with some parts of their bodies, and about half of these subjects wanted to lose weight or had already tried.    Half of the overweight and obese teens had tried to lose weight (as had three in the normal-weight group). These teens experienced an "emotional high" when they lost weight, and a deterioration in well-being when they failed. Only a minority of the subjects cited the health benefits of weight loss, even after expressing a desire to lose weight. Most of the subjects said that family and friends did not need to lose weight and should not feel pressured to do so. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: CPNEWS Copyright 2006 Elsevier Inc., International Medical News Group All Rights Reserved 435 of 998 DOCUMENTS Clinical Psychiatry News January 2006 Sadness Alters Tx for Depression-Related Fatigue BYLINE: Sherry Boschert, San Francisco Bureau SECTION: Pg. 59 Vol. 34 No. 1 ISSN: 0270-6644 LENGTH: 649 words    SAN DIEGO - When choosing a therapy for physical fatigue in patients being treated for depression, it is important to consider the presence or absence of residual sadness, Dr. Stephen C. Ellen said at a psychopharmacology congress sponsored by the Neuroscience Education Institute.    Two strategies exist for treating patients on antidepressants who complain that activities make them feel more physically tired, winded, or older than they felt before depression set in, despite getting help for the depression. Both bupropion and stimulants will boost dopamine and norepinephrine in the cortex, striatum, and spinal cord. Modafinil will boost histamine in the cortex, he said.    Dr. Ellen is a speaker for GlaxoSmithKline, which makes Wellbutrin (bupropion). He also serves as a consultant and speaker for Cephalon Inc., which makes Provigil (modafinil).    If the patient's antidepressant therapy has virtually eliminated the sadness and mood issues, choose modafinil or methylphenidate (for example, Ritalin) or another stimulant to treat the residual physical fatigue. If some sadness still remains, however, bupropion may boost antidepressant effects and reduce fatigue, said Dr. Ellen of the University of Massachusetts, Worcester.    Modafinil or stimulants work much better at "waking somebody up" from residual symptoms of depression than does bupropion, he said. Bupropion "is brightening, but I don't think it is particularly wake promoting."    Physical fatigue is common in patients with depression or obstructive sleep apnea, and the two problems overlap. One in six depressed people has obstructive sleep apnea, and one in five people with obstructive sleep apnea is depressed, he noted. A 2003 study of 60 patients found that the more severe the depression in a patient with sleep apnea, the greater the level of fatigue.    In patients with both depression and obstructive sleep apnea, the fatigue usually derives from the depression. "So if you're still getting words that sound like fatigue" after treatment, consider switching to a stronger antidepressant or increasing the dose, Dr. Ellen advised.    Bupropion is widely used to treat fatigue in patients with depression but it "takes a while to kick in," typically 4-6 weeks, he said. Some reports suggest that bupropion may be less likely than other antidepressants to destabilize a patient with bipolar disorder, but other reports suggest that the risk is no different with bupropion.    A case series of 42 patients treated for depression with selective serotonin reuptake inhibitors found that energy levels stayed the same or improved in patients who received adjuvant bupropion but worsened in nearly half of patients who remained on monotherapy, Dr. Ellen said.    Stimulants are not commonly used to treat fatigue in depressed patients, but they can quickly provide a boost in alertness with short-term use. Most studies of stimulants for fatigue focus on patients with HIV or AIDS. There are no controlled trials of stimulants for fatigue associated with depression, "but that shouldn't throw you off, because there's not a single controlled study of [bupropion for this indication] either, and we use that like crazy," he said.    Stimulants, however, can cause cardiovascular or CNS side effects and have a high risk for abuse with long-term use. Patients may develop psychological or physical dependence on them, and tolerance to the drug develops rapidly, Dr. Ellen said.    Adding modafinil to antidepressant therapy appears to significantly reduce patients' fatigue scores if the drug is given in proper doses. The best effects are seen with 100-200 mg/day. Less benefit comes from a dosage of 300 mg/day, and a dosage of 400 mg/day can increase fatigue, he said.    Modafinil's effects on fatigue in depression appear to be independent of mood, and the onset of action usually is immediate, he noted. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: CPNEWS Copyright 2006 Elsevier Inc., International Medical News Group All Rights Reserved 436 of 998 DOCUMENTS Neurology Alert January 1, 2006 Does Modafinil Improve Daytime Somnolence in Parkinson's Disease? LENGTH: 828 words Does Modafinil Improve Daytime Somnolence in Parkinson's Disease? Abstracts & Commentary By Claire Henchcliffe, MD, DPhil, Assistant Professor, Department of Neurology, Weill Medical College, Cornell University. Dr. Henchcliffe is on the speaker's bureau for GlaxoSmithKline, Teva/Eisai, and Boehringer Ingelheim. Synopsis: Modafinil failed to significantly improve EDS in PD compared with placebo. Source: Ondo WG, et al. Modafinil for Daytime Somnolence in Parkinson's Disease: Double Blind, Placebo Controlled Parallel Trial. J Neurol Neurosurg Psychiatry. 2005;76:1636-1639. This 4-week, double blind, placebo controlled, parallel group trial randomized 40 subjects with Parkinson's disease (PD) and an Epworth Sleepiness Scale (ESS) score > 10, to either modafinil (200-400 mg daily, 20 patients) or placebo (20 patients). Patients with undefined serious medical conditions, as well as those diagnosed with sleep apnea and narcolepsy, were excluded. Of the 40 subjects, 37 completed the study (modafinil 19 patients, placebo 18 patients). ESS score provided the primary measure of efficacy, and secondary end points included the Fatigue Severity Scale, Hamilton Depression Scale, the multiple sleep latency test (MSLT), and the Unified Parkinson's Disease Rating Scale (UPDRS). Baseline mean ESS was 15.8 3.0 for modafinil and 15.9 3.5 for placebo treated patients, and the 2 groups were balanced for age (mean, 64.8 11.3 years), gender, duration of PD (mean, 6.8 5.0 years), daily dopaminergic dose, motor fluctuations, and UPDRS activities of daily living and motor scores. Subjects were given one tablet of modafinil (100 mg) or corresponding placebo upon waking and at lunch. After one week, modafinil was increased to 2 tables (200 mg) upon waking and at lunch. After another week, the ESS was administered by telephone. If patients experienced an adverse event at higher doses, they were allowed to decrease the total dose of modafinil to 200 mg daily. The final assessment was performed 4 weeks after the first visit. Modafinil was well tolerated, with only 1 patient electing to return to 200 mg daily because of anxiety and nausea. At 4 weeks, subjects on modafinil showed a non-significant improvement in ESS compared to controls (2.7 vs 1.5 points, P = 0.28). There was a non-significant decrease in MSLT (3.59 vs 3.28 minutes, P = 0.14), and no significant difference in any other secondary end point. Commentary Excessive daytime somnolence (EDS) affects up to approximately 50% of PD patients. It likely has multiple causes, and is associated with advanced PD, long disease duration, male gender, and the use of dopaminergic agents. Furthermore it has been linked to catechol-O-methyltransferase (COMT) genotype, as well as low levels of orexin-A/hypocretin-1 in ventricular cerebrospinal fluid. EDS interferes with social interactions and driving and, thus, may lead to social isolation. Polysomnographic testing is helpful in selected patients to exclude secondary causes of EDS. Treatment of EDS is difficult: use of stimulants, such as methylphenidate, has led to inconsistent results, and side effects are often limiting. Modafinil is a wake-promoting agent that is FDA-approved for narcolepsy, sleep apnea, and shift work sleep disorder. Its mechanism of action is not understood, and it is widely used off-label for a variety of conditions associated with impaired wakefulness or fatigue, including multiple sclerosis and traumatic brain injury. Results of this study by Ondo and colleagues failed to support the positive findings of 2 previous smaller randomized crossover studies.1,2 Should we therefore abandon modafinil in treating PD-associated EDS? In our practice, there are clearly PD patients with EDS who respond to modafinil. However, there are no established criteria as to which patient will respond to the drug, and response may depend upon etiology of EDS in each individual. Conflicting study results regarding modafinil use most likely reflect our poor understanding of variability in pathophysiology of PD-associated EDS, as well as small sample sizes, use of subjective measurement scales, and referral bias. Modafinil is currently not recommended in those with angina, left ventricular hypertrophy, and other cardiac conditions. However, all studies of modafinil in PD have found that in these selected patient groups derived from an elderly population, modafinil is well-tolerated. Until larger studies are completed in PD, similar to those performed for narcolepsy, modafinil is worth considering to alleviate the debilitating symptoms of EDS for selected PD patients. References 1. Hogl B, et al. Modafinil for the Treatment of Daytime Sleepiness in Parkinson's Disease: A Double-Blind, Randomized, Crossover, Placebo-Controlled Polygraphic Trial. Sleep. 2002;25:905-909. 2. Adler CH, et al. Randomized Trial of Modafinil for Treating Subjective Daytime Sleepiness in Patients with Parkinson's Disease. Mov Disord. 2003;18:287-293. LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2006 AHC Media LLC All Rights Reserved 437 of 998 DOCUMENTS BioWorld Insight December 26, 2005 Biotech - Big Pharma Collaborations: Modified And Terminated Agreements, Oct. 19-Dec. 22, 2005 LENGTH: 789 words I. MODIFIED AGREEMENTS Biotech Co.* Pharma Co. Change from Terms/Details (Country; Symbol) (Country) original agreement (Date) Actelion Ltd. UCB Pharma They replaced Actelion assumes (Switzerland; (Belgium) existing license full SWX:ATLN) deal covering the responsibility for Gaucher's disease the pre-UCB product Zavesca obligations on manufacturing and supply, and clinical development; UCB gets an up-front payment in return for a single- digit royalty rate on future sales (11/17) Cambridge Abbott They reached an CAT gets $255M, Antibody Laboratories agreement which it will pay Technology plc regarding to its licensors; (UK; CATG) royalties payable it also gets five to CAT under a annual payments of licence agreement up $9.375M; CAT's covering Humira royalty payments were reduced to 2.688% of sales from 5.1% (10/26) Cephalon Inc. Ranbaxy They settled Ranbaxy got a (CEPH) Laboratories Ltd. patent nonexclusive, (India) infringement royalty-bearing dispute in the right to market a U.S. related to generic version of Provigil ( the product modafinil) starting in 2011; they also entered a series of business arrangements related to modafinil (12/22) Cephalon Inc. Teva They settled Teva got a (CEPH) Pharmaceutical patent nonexclusive, Industries Ltd. infringement royalty-bearing (Israel) disputes in the right to market a U.S. and UK generic version of related to the product Provigil ( starting in 2011; modafinil) they also entered a series of business arrangements related to modafinil (12/9) CuraGen Corp. Bayer They revised terms CuraGen exercised (CRGN) Pharmaceuticals of deal in its right to Corp. metabolic revert to a tiered disorders relating royalty structure to development of on any sales and BAY 76-7171 no longer will (formerly CT052) contribute to development costs of the drug (12/20) Depomed Inc. Biovail Corp. They resolved a Under the new deal (DEPO) (Canada) dispute regarding Depomed has rights a license to the product in agreement on the the U.S.; Biovail metformin-based relinquished its diabetes product option to develop Glumetza metformin combination products; Depomed withdrew legal action following the agreement (12/13) Enzon Sanofi-Aventis They amended Enzon will pay a Pharmaceuticals Group (France) license agreement single-digit Inc. (ENZN) covering the royalty rate on leukemia drug annual sales that Oncospar exceed $25M; it had been paying 25% on all sales; Sanofi gets an up-front cash payment of $35M (10/31) Genetic Applera Corp. The companies Terms were not Technologies Ltd. settled a patent disclosed but do (Australia; GENE) dispute initiated include a license by Gene to the non-coding Technologies in patents from 2003 Genetic Technologies (12/12) Gilead Sciences F. Hoffmann-La They resolved a Gilead gets $62.5M Inc. (GILD) Roche Ltd. dispute related to in adjusted (Switzerland) their 1996 deal royalties, and covering the will get sales influenza drug royalties from 14% Tamiflu to 22%; Gilead also gets certain co-promotion options in the U.S.; the deal ends arbitration proceedings (11/16) Savient Barr They settled Barr paid Savient Pharmaceuticals Pharmaceuticals patent litigation $13.75M, of which Inc. (SVNTE) Inc. and NV regarding Barr's about $2.8M will Organon (the generic version of be passed on to Netherlands) Mircette, an oral the inventor contraceptive (12/2) product II. TERMINATED AGREEMENTS Aphton Corp. Sanofi Pasteur They ended a deal Aphton regained (APHT) (France) from 1997 to rights to the develop Aphton's G17DT immunogen, immunotherapy which is being compound Insegia developed for cancers, and intends to find a new partner (11/9) Avalon Sanofi-Aventis They ended The agreement Pharmaceuticals Group (France) December 2003 expired as a Inc. (AVRX) collaboration result of Sanofi's using molecular decision not to cytogenetics to advance targets identify and from the validate oncology collaboration targets (12/21) Arqule Inc. Pfizer Inc. Pfizer is ending The deal, started (ARQL) deal under which in 2001, will end Arqule has been May 22, 2006; producing Arqule expects to synthetic chemical receive $19.8M in compounds for connection with Pfizer the termination notification (12/6) Discovery Pfizer Inc. The companies Discovery has Partners terminated received about International discussions $92M from the Inc. (DPII) regarding a chemistry deal potential new deal from 2002 to 2005; to replace Discovery will existing one about reduce its to expire combinatorial chemistry operations as a result (11/29) Notes: # The information in the chart does not cover agreements between biotech companies or agricultural agreements. * Private companies are indicated with an asterisk. Unless otherwise noted, stock symbols listed are on the Nasdaq market. SWX = Swiss Stock Exchange. LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2005 AHC Media LLC All Rights Reserved 438 of 998 DOCUMENTS Hindustan Times December 23, 2005 Friday 8:25 AM EST RANBAXY ANNOUNCES AGREEMENT WITH CEPHALON REGARDING SETTLEMENT OF PROVIGIL PATENT LITIGATION BYLINE: Hindustan Times LENGTH: 343 words DATELINE: GURGAON, India GURGAON, India, Dec. 23 -- Ranbaxy Laboratories Limited issued the following press release: Ranbaxy Laboratories Limited (Ranbaxy) announced that it has entered into an agreement with Cephalon Inc., (Nasdaq: CEPH) to settle their pending patent infringement dispute in the United States related to PROVIGIL (modafinil) Tablets [C-IV]. In connection with the settlement, Cephalon will grant Ranbaxy a non-exclusive royalty-bearing right to market and sell a generic version of PROVIGIL in the United States. Ranbaxy's license will become effective in October 2011 absence of a pediatric extension for PROVIGIL, which would delay the entry date by six months (to April 2012). An earlier entry by Ranbaxy may occur based upon the entry of another generic version of PROVIGIL. The companies also agreed to a series of business arrangements related to modafinil. Specifically, Ranbaxy has agreed to grant to Cephalon a non-exclusive license, effective immediately, to certain of its worldwide intellectual property rights related to modafinil in exchange for milestone payments. Cephalon also has agreed to enter into certain arrangements with Ranbaxy related to Ranbaxy's supply of the active pharmaceutical ingredient modafinil. The terms of the agreement are confidential, and are subject to review by the US Federal Trade Commission. Financial terms were not disclosed. The parties promptly will file a dismissal with prejudice with the United States District Court for the District of New Jersey that will conclude all pending litigation between the parties regarding PROVIGIL. These lawsuits claim infringement of Cephalon's US Patent No. RE37, 516 ("the '516 Patent") which covers pharmaceutical compositions and methods of treatment with the form of modafinil contained in PROVIGIL. The '516 Patent expires in October 6, 2014 and may be extended by six months (to April 6, 2015) upon submission of pediatric study data that is acceptable to the US Food and Drug Administration. Edited press releases are provided through HT Syndication, New Delhi. LOAD-DATE: December 24, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2005 HT Media Ltd. All Rights Reserved 439 of 998 DOCUMENTS Indo-Asian News Service December 23, 2005 Friday 1:54 PM EST Cephalon, Ranbaxy settle patent suit BYLINE: Indo-Asian News Service LENGTH: 323 words DATELINE: New Delhi New Delhi, Dec 23 -- India's pharma major Ranbaxy Laboratories Limited has reached a settlement with Cephalon on its US patent covering the formulation of modafinil contained in Provigil, a treatment for daytime sleepiness associated with narcolepsy. Under the out of court settlement, Ranbaxy would be receiving a milestone payment or royalty on the intellectual property right beginning 2006. It would also supply active pharmaceutical ingredient (API) modafinil to Cephalon for an undisclosed amount. The new business arrangement worked out by the companies follows a similar settlement with Teva Pharamceuticals on the modafinil patent earlier this month. With this, Cephalon has arrived at a mutually beneficial business deal with two of four generic drug makers against which it had filed patent suits at the US District Court in New Jersey for alleged violation of its patent for modafinil. Cephalon claims its patent for Provigil does not expire until 2014. The other two generic drug companies are Mylan Pharmaceutical Inc and Barr Laboratories Inc. Cephalon has agreed to "grant Ranbaxy a non-exclusive royalty-bearing right to market and sell a generic version of Provigil in the US. Ranbaxy's license will become effective in October 2011 in the absence of a paediatric extension for Provigil, which would delay the entry date by six months (to April, 2012)", Ranbaxy said in a statement Friday. "An earlier entry by Ranbaxy may occur based upon the entry of another generic version of Provigil," the official statement said. "The terms of the agreement are confidential, and are subject to review by the US Federal Trade Commission." The financial terms were not disclosed. The parties will file a dismissal with prejudice with the US District Court in New Jersey to conclude all pending litigation between the parties regarding Provigil. Published by HT Syndication with permission from Indo-Asian News Service. LOAD-DATE: December 24, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2005 HT Media Ltd. All Rights Reserved 440 of 998 DOCUMENTS The Press Trust of India December 23, 2005 Friday Ranbaxy settles patent case with Cephalon for Provigil SECTION: NATIONWIDE INTERNATIONAL NEWS LENGTH: 237 words DATELINE: New Delhi Dec 23 Close on the heels of a US district court ruling against its patent challenge of Pfizer's Lipitor, Ranbaxy Laboratories Ltd today said it had entered into an out of court settlement with Cephalon Inc for the patent infringement dispute in the US related to psychostimulant Provigil (modafinil) tablets. As per the settlement, Cephalon will grant the Ranbaxy a non-exclusive royalty-bearing right to market and sell a generic version of Provigil in the US, a company statement said. The company's license will become effective in October 2011 in the absence of a pediatric extension for Provigil, which would delay the entry date by six months (to April, 2012), it added. Ranbaxy said an earlier entry might occur based upon the entry of another generic version of Provigil. The two companies have agreed to a series of business arrangements related to modafinil. Ranbaxy has a greed to grant to Cephalon an immediate non-exclusive license to certain of its worldwide intellectual property rights related to modafinil in exchange for milestone payments. Cephalon also has agreed to enter into certain arrangements with Ranbaxy regardign supply of the active pharmaceutical ingredient modafinil, it added. The two parties would promptly file for dismissal of their litigation in the US District Court of New Jersey, it said, adding, however, the out of court settlement would be subject to the approval of US Federal Trade Commission. LOAD-DATE: December 23, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2005 The Press Trust of India All Rights Reserved 441 of 998 DOCUMENTS MarketWatch December 22, 2005 Thursday 12:24 PM EST Cephalon inks deal w/ Ranbaxy Labs to settle patent dispute BYLINE: Katherine Hunt LENGTH: 194 words SAN FRANCISCO (MarketWatch) -- Cephalon Inc. (ceph) said Thursday it has entered into an agreement with Ranbaxy Laboratories Ltd. (rbxlf) to settle its patent infringement dispute related to modafinil, a wake-promoting agent marketed under the brand name Provigil. Financial terms weren't disclosed. Under the agreement, Cephalon will grant Ranbaxy a non-exclusive royalty-bearing right to market and sell a generic version of Provigil in the United States. Ranbaxy's license will become effective in October 2011 in the absence of a pediatric extension for Provigil, which would delay the entry date by six months, the Frazer, Pa.-based biopharmaceutical company said. Additionally, Ranbaxy has agreed to grant to Cephalon a non-exclusive license, effective immediately, to certain of its worldwide intellectual property rights related to modafinil in exchange for milestone payments. Cephalon also has agreed to enter into certain arrangements with Ranbaxy related to Ranbaxy's supply of the active pharmaceutical ingredient modafinil. ©1997-2002 MarketWatch.com, Inc. All rights reserved. See details at http://custom.marketwatch.com/custom/docs/useragreement.asp. LOAD-DATE: December 23, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: Web Publication Copyright 2005 MarketWatch.com Inc. All Rights Reserved 442 of 998 DOCUMENTS PR Newswire December 22, 2005 Thursday 5:01 PM GMT Ranbaxy Laboratories Limited Announces an Agreement With Cephalon Regarding Settlement of PROVIGIL(R) Patent Litigation; Parties Also Agree to Business Arrangements Related to Modafinil LENGTH: 504 words DATELINE: PRINCETON, N.J. Dec. 22 Ranbaxy Laboratories Limited (Ranbaxy) announced today that it has entered into an agreement with Cephalon, Inc.(NASDAQ:CEPH)to settle their pending patent infringement dispute in the United States related to PROVIGIL(R) (modafinil) Tablets [C-IV]. In connection with the settlement, Cephalon will grant Ranbaxy a non-exclusive royalty-bearing right to market and sell a generic version of PROVIGIL in the United States. Ranbaxy's license will become effective in October 2011 absence of a pediatric extension for PROVIGIL, which would delay the entry date by six months (to April, 2012). An earlier entry by Ranbaxy may occur based upon the entry of another generic version of PROVIGIL. The companies also agreed to a series of business arrangements related to modafinil. Specifically, Ranbaxy has agreed to grant to Cephalon a non-exclusive license, effective immediately, to certain of its worldwide intellectual property rights related to modafinil in exchange for milestone payments. Cephalon also has agreed to enter into certain arrangements with Ranbaxy related to Ranbaxy's supply of the active pharmaceutical ingredient modafinil. The terms of the agreement are confidential, and are subject to review by the U.S. Federal Trade Commission. Financial terms were not disclosed. The parties promptly will file a dismissal with prejudice with the United States District Court for the District of New Jersey that will conclude all pending litigation between the parties regarding PROVIGIL. These lawsuits claim infringement of Cephalon's U.S. Patent No. RE37, 516 ("the '516 Patent") which covers pharmaceutical compositions and methods of treatment with the form of modafinil contained in PROVIGIL. The '516 Patent expires in October 6, 2014 and may be extended by six months (to April 6, 2015) upon submission of pediatric study data that is acceptable to the U.S. Food and Drug Administration. Ranbaxy Laboratories Limited, headquartered in India, is an integrated, research based, international pharmaceutical company producing a wide range of quality, affordable generic medicines, trusted by healthcare professionals and patients across geographies. Ranbaxy's continued focus on R&D has resulted in several approvals in developed markets and significant progress in New Drug Discovery Research. The Company's foray into Novel Drug Delivery Systems has led to proprietary "platform technologies", resulting in a number of products under development. The Company is serving its customers in over 100 countries and has an expanding international portfolio of affiliates, joint ventures and alliances, ground operations in 46 countries and manufacturing operations in 7 countries. *PROVIGIL(R) is a registered trademark of Cephalon, Inc. CONTACT: Charles M. Caprariello, Vice President, CorporateCommunications, Ranbaxy Inc., +1-609-720-5615; or Edwige Buteau, +1-212-994-7517, or Anuj Baveja, +1-212-994-7552, both of RF Binder Partners Inc. forRanbaxy Inc. Web site: http://www.ranbaxy.com/ SOURCE Ranbaxy Laboratories Limited URL: http://www.prnewswire.com LOAD-DATE: November 29, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2005 PR Newswire Association LLC. All Rights Reserved. 443 of 998 DOCUMENTS PR Newswire December 22, 2005 Thursday 5:00 PM GMT Cephalon, Inc. Announces Agreement with Ranbaxy Laboratories Limited Regarding Settlement of PROVIGIL(R) Patent Litigation; Parties Also Agree to Business Arrangements Related to Modafinil LENGTH: 866 words DATELINE: FRAZER, Pa. Dec. 22 Cephalon, Inc.(NASDAQ:CEPH)announced today that it has entered into an agreement with Ranbaxy Laboratories Limited to settle its pending patent infringement dispute in the United States related to PROVIGIL(R) (modafinil) Tablets [C-IV]. In connection with the settlement, Cephalon will grant Ranbaxy a non- exclusive royalty-bearing right to market and sell a generic version of PROVIGIL in the United States. Ranbaxy's license will become effective in October 2011 in the absence of a pediatric extension for PROVIGIL, which would delay the entry date by six months (to April 2012). An earlier entry by Ranbaxy may occur based upon the entry of another generic version of PROVIGIL. The companies also agreed to a series of business arrangements related to modafinil. Specifically, Ranbaxy has agreed to grant to Cephalon a non- exclusive license, effective immediately, to certain of its worldwide intellectual property rights related to modafinil in exchange for milestone payments. Cephalon also has agreed to enter into certain arrangements with Ranbaxy related to Ranbaxy's supply of the active pharmaceutical ingredient modafinil. The terms of the agreement are confidential, and are subject to review by the U.S. Federal Trade Commission. Financial terms were not disclosed. The parties will promptly file a dismissal with prejudice with the United States District Court for the District of New Jersey that will conclude all pending litigation between the parties regarding PROVIGIL. This settlement and the previously announced settlements with Teva Pharmaceutical Industries Ltd. and Teva Pharmaceuticals USA, Inc. do not affect the status of the ongoing PROVIGIL patent litigations between Cephalon and certain other generic companies that are pending in the U.S. District Court in New Jersey. These lawsuits claim infringement of Cephalon's U.S. Patent No. RE37,516 ("the '516 Patent") which covers pharmaceutical compositions and methods of treatment with the form of modafinil contained in PROVIGIL. The '516 patent expires in October 6, 2014 and may be extended by six months (to April 6, 2015) upon submission of pediatric study data that is acceptable to the U.S. Food and Drug Administration. Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products to treat sleep and neurological disorders, cancer and pain. Cephalon currently employs approximately 2,600 people in the United States and Europe. U.S. sites include the company's headquarters in Frazer, Pennsylvania, and offices, laboratories or manufacturing facilities in West Chester, Pennsylvania, Salt Lake City, Utah, and suburban Minneapolis, Minnesota. The company currently markets four proprietary products in the United States: PROVIGIL, GABITRIL(R) (tiagabine hydrochloride), ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II] and TRISENOX(R) (arsenic trioxide) injection, and more than 20 products internationally. Full prescribing information for all U.S. products is available at http://www.cephalon.com/ or by calling 1-800-896-5855. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding the settlement of this litigation, including whether the Federal Trade Commission will approve the terms of such settlement, anticipated scientific progress on its research programs; development of potential pharmaceutical products; interpretation of clinical results; prospects for regulatory approval; manufacturing development and capabilities; market prospects for its products; sales and earnings guidance; and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. CONTACT: Media: Robert Grupp, +1-610-738-6402, rgrupp@cephalon.com ; orInvestors: Chip Merritt, +1-610-738-6376, cmerritt@cephalon.com , both ofCephalon Web site: http://www.cephalon.com/ Company News On-Call: http://www.prnewswire.com/comp/134563.html SOURCE Cephalon, Inc. URL: http://www.prnewswire.com LOAD-DATE: November 29, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2005 PR Newswire Association LLC. All Rights Reserved. 444 of 998 DOCUMENTS Internal Medicine News December 15, 2005 Data Back Broader Narcolepsy Indication for Sodium Oxybate BYLINE: Bruce Jancin, Denver Bureau SECTION: Pg. 23 Vol. 38 No. 24 ISSN: 1097-8690 LENGTH: 752 words    DENVER - Sodium oxybate (Xyrem) is effective not only for cataplexy-its only approved indication at present-but also for the other primary symptoms of narcolepsy, investigators reported at the annual meeting of the Associated Professional Sleep Societies.    Based on data from two randomized clinical trials presented at the meeting, the drug's manufacturer, Orphan Medical Inc., has submitted a supplemental New Drug Application to the Food and Drug Administration. If approval is granted, sodium oxybate's expanded indication would make it the first drug approved for treatment of all the primary symptoms of narcolepsy: excessive daytime sleepiness; fragmented sleep; and cataplexy, the sudden, brief loss of muscle tone frequently experienced by narcoleptics during periods of emotional intensity such as surprise, laughter, or anger.    Terri E. Weaver, Ph.D., noted that in the last few years, quality of life issues in patients with incurable chronic illnesses have drawn greater regulatory and clinical attention. And the quality of life impact of narcolepsy, she stressed, is profound: In one study, the impact was rated greater than living with Parkinson's disease.    "Individuals with narcolepsy are struggling to complete their activities of daily living," said Dr. Weaver of the University of Pennsylvania, Philadelphia. She presented the first-ever study of sodium oxybate's quality of life impact in narcoleptic patients. The double-blind, placebo-controlled, 8-week trial involved 228 patients randomized to receive either placebo or 4.5 g, 6 g, or 9 g sodium oxybate per night in two equally divided doses at bedtime and from 21/2 to 4 hours later.    Quality of life was assessed with the Functional Outcomes of Sleep Questionnaire administered at baseline, 4 weeks, and 8 weeks. Patients assigned to 4.5 g/night showed no quality of life gains. But those who received 6 g or 9 g had significant improvement in four of the five domains measured: general productivity, vigilance, social outcome, and activity level. The only domain in which they didn't fare significantly better than placebo was the intimacy/sexual relationships subscale.    The benefit was greater with the 9-g dose. "The effect size was clinically meaningful and quite large," she noted.    The potential for improved quality of life needs to be presented to patients in the context of the possible treatment disadvantages so they can make an informed decision. Patients on sodium oxybate experience a deep sleep and increased arousal threshold. They may not hear a smoke alarm, a late-night telephone call, or a child's cry.    "Individuals who have children at home have to weigh the benefit of having a good night's sleep and being able to function and take care of those children during the day. We all know daytime sleepiness and some of the other effects of narcolepsy can be hazardous, too, in terms of caring for young ones," Dr. Weaver said.    Jed E. Black, M.D., presented another phase III trial, this one designed to assess the relative efficacy of sodium oxybate when taken as monotherapy or with modafinil (Provigil), a widely used wakefulness-promoting agent approved for treatment of the excessive daytime sleepiness component of narcolepsy.    The double-blind, 230-patient trial began with all participants on 200-600 mg/day of modafinil. They were then randomized to receive modafinil plus placebo, modafinil plus sodium oxybate, placebo plus sodium oxybate, or double placebos. The sodium oxybate dose was 6 g/night for the first 4 weeks and 9 g thereafter. Monotherapy with either drug appeared equally effective for the primary study end point, reduction in excessive daytime sleepiness. The improvement was greater with the 9-g dose of sodium oxybate than with the 6-g dose.    But combination therapy was most effective of all, not only in terms of reduced daytime sleepiness but also consolidation of fragmented sleep and enhanced slow-wave sleep, said Dr. Black of Stanford (Calif.) University. Side effects that occurred more often with sodium oxybate than placebo included nausea, dizziness, headache, sleepiness, and bedwetting.    Prior to its 2002 approval as a tightly controlled schedule-III drug for cataplexy, sodium oxybate was available as [#x3b3]-hydroxybutyrate in health food stores. During that era it was abused as a recreational drug and implicated as a "date rape" drug.    Both randomized trials were sponsored by Orphan Medical. Dr. Weaver serves as a consultant to the company. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: IMNEWS Copyright 2005 Elsevier Inc., International Medical News Group All Rights Reserved 445 of 998 DOCUMENTS Generic Line December 14, 2005 Teva, Cephalon Reach Agreement to End Provigil Patent Dispute SECTION: Vol. 22, No. 24 LENGTH: 522 words Teva Pharmaceutical and Cephalon have agreed to settle patent infringement suits in the U.S. and the UK over Cephalon's narcolepsy drug Provigil. The settlement could remove one near-term generic threat to Provigil (modafinil) and its extended-release follow-on -- set to hit the market in early 2006 -- as well as removing a potential threat to another modafinil formulation Cephalon plans to market for pediatric attention-deficit/hyperactivity disorder (ADHD). However, three other generic firms -- Mylan Laboratories, Ranbaxy Laboratories and Barr Laboratories -- are still poised to market generic Provigil when Cephalon's orphan drug status expires, which will happen in late December or next June, depending on whether Cephalon receives a pediatric patent extension. "The opportunity presented itself and we pursued it," Cephalon spokesman Robert Grupp told Generic Line. "Investors don't like uncertainty. It made sense to settle this and remove one element of uncertainty." Under the agreement, Teva and biopharmaceutical firm Cephalon will file dismissals with prejudice with the U.S. District Court for the District of New Jersey as well as the Chancery Division of the UK's High Court of Justice. Teva will pay Cephalon a royalty for the non-exclusive right to market and sell a generic version of Provigil, and Teva will manufacture modafinil for Cephalon. Cephalon, meanwhile, will pay Teva a royalty on Provigil sales. Financial terms of the deal were not disclosed. Cephalon sued Teva and three other generic firms in March 2003 after they filed to market generic Provigil (Generic Line, April 9, 2003, Page 3). Teva will be able to start selling generic Provigil for the U.S. market in October 2011 and in Europe by October 2012 -- three years before Provigil's composition patents for those areas expire. However, Teva could launch generic Provigil earlier if another generic firm launches a version of the drug. Provigil was Cephalon's top-selling drug in 2004, generating sales of $439.7 million, and the FDA is poised to approve Nuvigil (armodafinil), an extended-release version of the drug, in January 2006. Provigil has also been shown to improve wakefulness, performance and attention level in patients with shift work sleep disorder. Meanwhile, Cephalon has also received an approvable letter from the FDA to market modafinil in a new formulation and dosage for pediatric ADHD in children ages 6 to 17. Cephalon will market Sparlon with the help of Johnson & Johnson's McNeil Consumer & Specialty Pharmaceuticals unit, which signed a co-promotion agreement with Cephalon in August. Once launched, Sparlon could see even greater commercial success since Eli Lilly in September warned that its ADHD drug Strattera may increase the risk of suicidal thoughts in adolescents and children. Grupp said Cephalon still plans to pursue litigation against Mylan, Ranbaxy and Barr. No trial date has been set yet for those cases, which have been consolidated in the New Jersey district court, Grupp said. -- Dar Haddix (mailto:dhaddix@fdanews.comtarget=_blank) Release date: Dec. 14, 2005 LOAD-DATE: December 13, 2005 LANGUAGE: ENGLISH Copyright 2005 Washington Business Information, Inc., All Rights Reserved 446 of 998 DOCUMENTS FDAnews Drug Daily Bulletin December 13, 2005 TEVA, CEPHALON REACH AGREEMENT TO END PATENT DISPUTE SECTION: Vol. 2, No. 242 LENGTH: 517 words Teva Pharmaceutical and Cephalon have agreed to settle patent infringement suits in the U.S. and the UK over Cephalon's narcolepsy drug Provigil. Under the agreement, Teva and biopharmaceutical firm Cephalon will file dismissals with prejudice with the U.S. District Court for the District of New Jersey as well as the Chancery Division of the UK's High Court of Justice. Cephalon sued Teva and three other generic firms in March 2003 after they filed to market generic Provigil. The settlement could remove one near-term generic threat to Provigil (modafinil) and its extended-release follow-on, set to hit the market in early 2006, as well as a potential threat to Cephalon's forthcoming modafinil-based drug intended as a treatment for pediatric attention-deficit/hyperactivity disorder (ADHD) in children ages 6 to 17. With its mild side effects, the ADHD drug now has even more commercial potential since Eli Lilly in September warned that its ADHD drug Strattera may increase the risk of suicidal thoughts in adolescents and children. "The opportunity presented itself and we pursued it," Cephalon spokesman Robert Grupp told FDAnews. "Investors don't like uncertainty. It made sense to settle this and remove one element of uncertainty." However, three other generic firms -- Mylan Laboratories, Ranbaxy Laboratories and Barr Laboratories -- are still poised to market generic Provigil when Cephalon's orphan drug status expires, which will happen in late December or next June, depending on whether Cephalon receives a pediatric patent extension. Under the agreement, Teva will be able to start selling generic Provigil for the U.S. market in October 2011 and in Europe by October 2012 -- three years before Provigil's composition patents for those areas expire. However, Teva could launch generic Provigil earlier if another generic firm launches a version of the drug. Provigil was Cephalon's top-selling drug in 2004, generating sales of $439.7 million, and the FDA is poised to approve Nuvigil (armodafinil), an extended-release version of the drug, in January 2006. Provigil has also been shown to improve wakefulness, performance and attention level in patients with shift work sleep disorder. Meanwhile, Cephalon has also received an approvable letter from the FDA to market modafinil in a new formulation and dosage for the treatment of pediatric ADHD. Cephalon will market Sparlon with the help of Johnson & Johnson's McNeil Consumer & Specialty Pharmaceuticals unit, which signed a co-promotion agreement with Cephalon in August. Under the settlement, Teva will pay Cephalon a royalty for the non-exclusive right to market and sell a generic version of Provigil, and Teva will manufacture modafinil for Cephalon. Cephalon meanwhile will pay Teva a royalty on Provigil sales. Financial terms of the deal were not disclosed. Grupp said Cephalon still plans to pursue litigation against Mylan, Ranbaxy and Barr. No trial date has been set yet for those cases, which have been consolidated in the New Jersey district court, Grupp said. Release date: Dec. 13, 2005 LOAD-DATE: December 12, 2005 LANGUAGE: ENGLISH Copyright 2005 Washington Business Information, Inc., All Rights Reserved 447 of 998 DOCUMENTS CNS Drug News Pharmaceuticals December 12, 2005 Teva and Cephalon settle pending Provigil patent infringement dispute LENGTH: 394 words Teva Pharmaceutical Industries has entered into an agreement with Cephalon to settle their pending patent infringement disputes in the US and the UK related to Provigil ( modafinil ) Tablets C-IV. Provigil is indicated for the treatment of excessive sleepiness associated with disorders of sleep and wakefulness in adults. In connection with the settlement, Cephalon will grant Teva a non-exclusive royalty-bearing right to market and sell a generic version of the drug. Teva's licence in the US will become effective in October 2011, without a paediatric extension for Provigil, which would delay the entry date by six months (to April 2012). Outside of the US, the parties agreed to comparable terms for the licence effective date, which generally allow for entry in October 2012. An earlier entry by Teva in any of the territories may occur based upon the entry of another generic version of the drug. The companies also agreed to a series of business arrangements related to modafinil. Specifically, Teva has agreed to grant to Cephalon a non-exclusive licence, effective immediately, to its worldwide intellectual property rights related to the manufacture, development and formulation of modafinil in exchange for royalty payments. Cephalon has also agreed to enter into certain arrangements with Teva related to the latter's manufacture and supply of the active pharmaceutical ingredient, modafinil. The terms of the agreement are confidential and are subject to review by the US Federal Trade Commission. Financial terms were not disclosed. The parties will promptly file dismissals with prejudice with the US District Court for the District of New Jersey and the UK High Court of Justice, Chancery Division, which will conclude all pending litigations between the parties regarding Provigil. Cephalon's US Patent No. RE37,516 expires on 6th October 2014 and may be extended by six months (to 6th April 2015) upon the submission of paediatric study data that are acceptable to the FDA. This settlement does not affect the status of the ongoing Provigil patent litigations between Cephalon and certain other generic companies that are pending in the US District Court in New Jersey. These lawsuits claim infringement of Cephalon's US '516 patent, which covers pharmaceutical compositions and methods of treatment with the form of modafinil contained in Provigil. LOAD-DATE: December 14, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2005 ESPICOM Business Intelligence Ltd. All Rights Reserved 448 of 998 DOCUMENTS Drug Industry Daily December 12, 2005 Teva, Cephalon Reach Agreement to End Provigil Patent Dispute SECTION: Vol. 4, No. 241 LENGTH: 527 words Teva Pharmaceutical and Cephalon have agreed to settle patent infringement suits in the U.S. and the UK over Cephalon's narcolepsy drug Provigil. Under the agreement, Teva and biopharmaceutical firm Cephalon will file dismissals with prejudice with the U.S. District Court for the District of New Jersey as well as the Chancery Division of the UK's High Court of Justice. Cephalon sued Teva and three other generic firms in March 2003 after they filed to market generic Provigil. The settlement could remove one near-term generic threat to Provigil (modafinil) and its extended-release follow-on, set to hit the market in early 2006, as well as a potential threat to Cephalon's forthcoming modafinil-based drug intended as a treatment for pediatric attention-deficit/hyperactivity disorder (ADHD) in children ages 6 to 17. With its mild side effects, the ADHD drug now has even more commercial potential since Eli Lilly in September warned that its ADHD drug Strattera may increase the risk of suicidal thoughts in adolescents and children. "The opportunity presented itself and we pursued it," Cephalon spokesman Robert Grupp told DID. "Investors don't like uncertainty. It made sense to settle this and remove one element of uncertainty." However, three other generic firms -- Mylan Laboratories, Ranbaxy Laboratories and Barr Laboratories -- are still poised to market generic Provigil when Cephalon's orphan drug status expires, which will happen in late December or next June, depending on whether Cephalon receives a pediatric patent extension. Under the agreement, Teva will be able to start selling generic Provigil for the U.S. market in October 2011 and in Europe by October 2012 -- three years before Provigil's composition patents for those areas expire. However, Teva could launch generic Provigil earlier if another generic firm launches a version of the drug. Provigil was Cephalon's top-selling drug in 2004, generating sales of $439.7 million, and the FDA is poised to approve Nuvigil (armodafinil), an extended-release version of the drug, in January 2006. Provigil has also been shown to improve wakefulness, performance and attention level in patients with shift work sleep disorder (DID, Aug. 8, Page 3). Meanwhile, Cephalon has also received an approvable letter from the FDA to market modafinil in a new formulation and dosage for the treatment of pediatric ADHD. Cephalon will market Sparlon with the help of Johnson & Johnson's McNeil Consumer & Specialty Pharmaceuticals unit, which signed a co-promotion agreement with Cephalon in August (DID, Oct. 24, Page 3). Under the settlement, Teva will pay Cephalon a royalty for the non-exclusive right to market and sell a generic version of Provigil, and Teva will manufacture modafinil for Cephalon. Cephalon meanwhile will pay Teva a royalty on Provigil sales. Financial terms of the deal were not disclosed. Grupp said Cephalon still plans to pursue litigation against Mylan, Ranbaxy and Barr. No trial date has been set yet for those cases, which have been consolidated in the New Jersey district court, Grupp said. -- Dar Haddix Release date: Dec. 12, 2005 LOAD-DATE: December 9, 2005 LANGUAGE: ENGLISH Copyright 2005 Washington Business Information, Inc., All Rights Reserved 449 of 998 DOCUMENTS Globes [online] - Israel's Business Arena December 11, 2005 Sunday Teva and Cephanol settle dispute over Provigil; Teva will be able to sell a generic version of wakefulness drug Provigil in October 2011. BYLINE: Globes correspondent LENGTH: 268 words Teva Pharmaceutical Industries Ltd. (Nasdaq: TEVA ; TASE: TEVA) and Teva Pharmaceuticals USA, Inc. have entered into an agreement with Cephalon, Inc. (Nasdaq: CEPH) to settle their pending patent infringement disputes in the US and the UK over Provigil (modafinil) tablets. Provigil is a mood-brightening and memory-enhancing psychostimulant which enhances wakefulness and vigilance. Cephalon will grant Teva a non-exclusive royalty-bearing right to market and sell a generic version of Provigil. Teva's license in the US will become effective in October 2011 absent a pediatric extension for Provigil, which would delay the entry date by six months (to April 2012). Outside the US, the parties agreed to comparable terms for the license effective date, which generally allow for entry in October 2012. An earlier entry by Teva in any of the territories may occur based upon the entry of another generic version of Provigil. The companies also agreed to a series of business arrangements related to modafinil. Teva has agreed to grant to Cephalon a non-exclusive license, effective immediately, to its worldwide intellectual property rights related to the manufacture, development and formulation of modafinil in exchange for royalty payments. Cephalon has also agreed to enter into certain arrangements with Teva related to Teva's manufacture and supply of the active pharmaceutical ingredient modafinil. The terms of the agreement are subject to review by the US Federal Trade Commission. Financial terms were not disclosed. Published by Globes [online], Israel business news - www.globes.co.il - on December 11, 2005 LOAD-DATE: December 11, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2005 Globes Publisher Itonut (1983) Ltd. All Rights Reserved 450 of 998 DOCUMENTS Business Wire December 9, 2005 Friday 1:45 PM GMT Teva Announces Agreement with Cephalon Regarding Settlement of PROVIGIL(R) Patent Litigation; Parties Also Agree to Business Arrangements Related to Modafinil LENGTH: 895 words DATELINE: JERUSALEM Dec. 9, 2005 Teva Pharmaceutical Industries Ltd. (Nasdaq: TEVA) and Teva Pharmaceuticals USA, Inc. announced today that they have entered into an agreement with Cephalon, Inc. (Nasdaq: CEPH) to settle their pending patent infringement disputes in the United States and the United Kingdom related to PROVIGIL(R) (modafinil) Tablets (C-IV). In connection with the settlement, Cephalon will grant Teva a non-exclusive royalty-bearing right to market and sell a generic version of PROVIGIL. Teva's license in the United States will become effective in October 2011 absent a pediatric extension for PROVIGIL, which would delay the entry date by six months (to April 2012). Outside the United States, the parties agreed to comparable terms for the license effective date, which generally allow for entry in October 2012. An earlier entry by Teva in any of the territories may occur based upon the entry of another generic version of PROVIGIL. The companies also agreed to a series of business arrangements related to modafinil. Specifically, Teva has agreed to grant to Cephalon a non-exclusive license, effective immediately, to its worldwide intellectual property rights related to the manufacture, development and formulation of modafinil in exchange for royalty payments. Cephalon has also agreed to enter into certain arrangements with Teva related to Teva's manufacture and supply of the active pharmaceutical ingredient modafinil. The terms of the agreement are confidential, and are subject to review by the U.S. Federal Trade Commission. Financial terms were not disclosed. The parties will promptly file dismissals with prejudice with the United States District Court for the District of New Jersey and United Kingdom High Court of Justice, Chancery Division, which will conclude all pending litigations between the parties regarding PROVIGIL. Cephalon's U.S. Patent No. RE37,516 expires in October 6, 2014 and may be extended by six months (to April 6, 2015) upon submission of pediatric study data that is acceptable to the U.S. Food and Drug Administration. Teva Pharmaceutical Industries Ltd., headquartered in Israel, is among the top 20 pharmaceutical companies and among the largest generic pharmaceutical companies in the world. The company develops, manufactures and markets generic and innovative human pharmaceuticals and active pharmaceutical ingredients. Close to 90% of Teva's sales are in North America and Europe. Safe Harbor Statement under the U. S. Private Securities Litigation Reform Act of 1995: This release contains forward-looking statements, which express the current beliefs and expectations of management. Such statements are based on management's current beliefs and expectations and involve a number of known and unknown risks and uncertainties that could cause Teva's future results, performance or achievements to differ significantly from the results, performance or achievements expressed or implied by such forward-looking statements. Important factors that could cause or contribute to such differences include whether and when the proposed acquisition of IVAX Corporation will be consummated and the terms of any conditions imposed in connection with such closing, the terms and conditions of the financing utilized by Teva for the IVAX acquisition, Teva's ability to rapidly integrate IVAX's operations and achieve expected synergies, Teva's ability to successfully develop and commercialize additional pharmaceutical products, the introduction of competitive generic products, the impact of competition from brand-name companies that sell or license their own generic products under generic trade dress and at generic prices (so called "authorized generics") or seek to delay the introduction of generic products, regulatory changes that may prevent Teva from exploiting exclusivity periods, potential liability for sales of generic products prior to a final court decision, including that relating to the generic versions of Neurontin(R) and Allegra(R), the effects of competition on Copaxone(R) sales, the impact of pharmaceutical industry regulation and pending legislation that could affect the pharmaceutical industry, the difficulty of predicting U.S. Food and Drug Administration, European Medicines Association and other regulatory authority approvals, the regulatory environment and changes in the health policies and structure of various countries, Teva's ability to successfully identify, consummate and integrate acquisitions, exposure to product liability claims, dependence on patent and other protections for innovative products, significant operations outside the United States that may be adversely affected by terrorism or major hostilities, fluctuations in currency, exchange and interest rates, operating results and other factors that are discussed in Teva's Annual Report on Form 20-F and its other filings with the U.S. Securities and Exchange Commission. Forward-looking statements speak only as of the date on which they are made and the Company undertakes no obligation to update publicly or revise any forward-looking statement, whether as a result of new information, future developments or otherwise. CONTACT: Teva Pharmaceutical Industries Ltd. Dan Suesskind, (011) 972-2-589-2840 or Teva North America George Barrett, (215) 591-3030 or Investor Relations: Liraz Kalif, (011) 972-3-926-7554 or Kevin Mannix, (215) 591-8912 URL: http://www.businesswire.com LOAD-DATE: December 10, 2005 LANGUAGE: ENGLISH DISTRIBUTION: Pharmaceutical Writers; Business Editors PUBLICATION-TYPE: Newswire Copyright 2005 Business Wire, Inc. 451 of 998 DOCUMENTS PR Newswire December 9, 2005 Friday 1:45 PM GMT Cephalon, Inc. Announces Agreement with Teva Pharmaceutical Industries Ltd. Regarding Settlement of PROVIGIL(R) Patent Litigation; Parties Also Agree to Business Arrangements Related to Modafinil LENGTH: 902 words DATELINE: FRAZER, Pa. Dec. 9 Cephalon, Inc.(NASDAQ:CEPH)announced today that it has entered into an agreement with Teva Pharmaceutical Industries Ltd.(NASDAQ:TEVA)and Teva Pharmaceuticals USA, Inc. to settle its pending patent infringement disputes in the United States and the United Kingdom related to PROVIGIL(R) (modafinil) Tablets [C-IV]. In connection with the settlement, Cephalon will grant Teva a non- exclusive royalty-bearing right to market and sell a generic version of PROVIGIL. Teva's license in the United States will become effective in October 2011 absent a pediatric extension for PROVIGIL, which would delay the entry date by six months (to April 2012). Outside the United States, the parties agreed to comparable terms for the license effective date, which generally allow for entry in October 2012. An earlier entry by Teva in any of the territories may occur based upon the entry of another generic version of PROVIGIL. The companies also agreed to a series of business arrangements related to modafinil. Specifically, Teva has agreed to grant to Cephalon a non-exclusive license, effective immediately, to its worldwide intellectual property rights related to the manufacture, development and formulation of modafinil in exchange for royalty payments. Cephalon has also agreed to enter into certain arrangements with Teva related to Teva's manufacture and supply of the active pharmaceutical ingredient modafinil. The terms of the agreement are confidential, and are subject to review by the U.S. Federal Trade Commission. Financial terms were not disclosed. The parties will promptly file dismissals with prejudice with the United States District Court for the District of New Jersey and United Kingdom High Court of Justice, Chancery Division, which will conclude all pending litigations between the parties regarding PROVIGIL. This settlement does not affect the status of the ongoing PROVIGIL patent litigations between Cephalon and certain other generic companies that are pending in the U.S. District Court in New Jersey. These lawsuits claim infringement of Cephalon's U.S. Patent No. RE37,516 ("the '516 Patent") which covers pharmaceutical compositions and methods of treatment with the form of modafinil contained in PROVIGIL. The '516 patent expires in October 6, 2014 and may be extended by six months (to April 6, 2015) upon submission of pediatric study data that is acceptable to the U.S. Food and Drug Administration. Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products to treat sleep and neurological disorders, cancer and pain. Cephalon currently employs approximately 2,500 people in the United States and Europe. U.S. sites include the company's headquarters in Frazer, Pennsylvania, and offices, laboratories or manufacturing facilities in West Chester, Pennsylvania, Salt Lake City, Utah, and suburban Minneapolis, Minnesota. The company currently markets four proprietary products in the United States: PROVIGIL, GABITRIL(R) (tiagabine hydrochloride), ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II] and TRISENOX(R) (arsenic trioxide) injection, and more than 20 products internationally. Full prescribing information for all U.S. products is available at http://www.cephalon.com/ or by calling 1-800-896-5855. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding the settlement of this litigation, including whether the Federal Trade Commission will approve the terms of such settlement, anticipated scientific progress on its research programs; development of potential pharmaceutical products; interpretation of clinical results; prospects for regulatory approval; manufacturing development and capabilities; market prospects for its products; sales and earnings guidance; and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. CONTACT: Media: Robert Grupp, +1-610-738-6402, rgrupp@cephalon.com , orInvestors: Chip Merritt, +1-610-738-6376, cmerritt@cephalon.com , both ofCephalon Web site: http://www.cephalon.com/ Company News On-Call: http://www.prnewswire.com/comp/134563.html SOURCE Cephalon, Inc. URL: http://www.prnewswire.com LOAD-DATE: November 29, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2005 PR Newswire Association LLC. All Rights Reserved. 452 of 998 DOCUMENTS CNS Drug News Pharmaceuticals December 6, 2005 Sparlon significantly improves ADHD symptoms in children and adolescents LENGTH: 394 words Results of a clinical study evaluating Sparlon ( modafinil ) Tablets (C-IV) for the treatment of attention-deficit hyperactivity disorder (ADHD) in children and adolescents have been published in the December issue of Pediatrics (2005;116:e777-e784). In the study, modafinil significantly improved the symptoms associated with ADHD as reported by physicians, parents and teachers, and was generally well tolerated. The published trial is one of three pivotal studies of Sparlon for the treatment of ADHD in children and adolescents. The nine-week, double-blind, flexible-dose study included 248 children and adolescents with ADHD (ages six to 17 years) who were randomised to either once-daily Sparlon or placebo. The primary endpoint was the teacher/physician-completed ADHD Rating Scale-IV (ADHD-RS-IV) School Version total score. Symptom improvement was also rated using a variety of other scales, including evaluations by parents. In the study, patients treated with Sparlon showed significantly greater improvement than with placebo in the core symptoms of ADHD at school and home (both p<0.0001). By the end of the study, 48 per cent of Sparlon-treated patients were rated by physicians as "much" or "very much" improved compared with 17 per cent of patients who received placebo (p<0.0001). In the study, the drug was generally well tolerated and discontinuation rates due to adverse events (AEs) were not significantly different from placebo. The most common AEs associated with Sparlon were generally mild-to-moderate in nature and included insomnia, headache and decreased appetite. Sparlon, marketed by Cephalon , is a new dosage form of modafinil, the active ingredient in the company's Provigil Tablets (C-IV), which is approved for the treatment of adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnoea/hypopnoea syndrome and shift work sleep disorder. Provigil is not approved to treat ADHD. In August 2005, Cephalon announced an agreement with McNeil Consumer & Specialty Pharmaceuticals Division of McNeil-PPC ( Johnson & Johnson ) to co-promote Sparlon. Cephalon has submitted data to the FDA requesting approval to market Sparlon for the treatment of ADHD in children and adolescents. The FDA has not yet determined that the drug is safe and effective. If approved, Sparlon is expected to be available in early 2006. LOAD-DATE: December 9, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2005 ESPICOM Business Intelligence Ltd. All Rights Reserved 453 of 998 DOCUMENTS PR Newswire December 5, 2005 Monday 12:15 PM GMT Pediatrics Publishes Pivotal Study Showing SPARLON(TM) Significantly Improves ADHD Symptoms in Children and Adolescents LENGTH: 1008 words DATELINE: FRAZER, Pa. Dec. 5 Cephalon, Inc.(NASDAQ:CEPH)today announced that results of a clinical study evaluating SPARLON(TM) (modafinil) Tablets [C-IV] for the treatment of attention- deficit/hyperactivity disorder (ADHD) in children and adolescents have been published in this month's issue of Pediatrics, the peer-reviewed journal of the American Academy of Pediatrics. In the study, SPARLON significantly improved the symptoms associated with ADHD as reported by physicians, parents and teachers, and was generally well tolerated. "In this study, children and adolescents treated with once-daily SPARLON showed improvement in ADHD symptoms, including inattention, impulsivity, and hyperactivity, both at school and at home," said Joseph Biederman, M.D., chief, Department of Pediatric Psychopharmacology, Massachusetts General Hospital, professor of Psychiatry at Harvard Medical School, and a lead investigator in the trial. "SPARLON also was associated with a favorable side effect profile." About the Study The published study is one of three pivotal studies of SPARLON for the treatment of ADHD in children and adolescents. The nine-week, double-blind, flexible-dose study included 248 children and adolescents with ADHD (ages six to 17 years) who were randomized to either once-daily SPARLON or placebo. The primary endpoint was the teacher/physician-completed ADHD Rating Scale-IV (ADHD-RS-IV) School Version total score. Symptom improvement also was rated using a variety of other scales, including evaluations by parents. In the study, patients treated with SPARLON showed significantly greater improvement than with placebo in the core symptoms of ADHD at school and home (both p<0.0001). By the end of the study, 48 percent of patients treated with SPARLON were rated by physicians as "much" or "very much" improved compared with 17 percent of patients who received placebo (p<0.0001). In the study, SPARLON was generally well tolerated and discontinuation rates due to adverse events were not significantly different from placebo. The most common adverse events associated with SPARLON were generally mild to moderate in nature and included insomnia, headache and decreased appetite. SPARLON SPARLON is a new dosage form of modafinil, the active ingredient in PROVIGIL(R) (modafinil) Tablets [C-IV], which is approved for the treatment of adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome and shift work sleep disorder. PROVIGIL is not approved to treat ADHD. Cephalon has submitted data to the FDA requesting approval to market SPARLON for the treatment of ADHD in children and adolescents. The FDA has not yet determined that SPARLON is safe and effective. If approved, SPARLON is expected to be available in early 2006. Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products to treat sleep and neurological disorders, cancer and pain. Cephalon currently employs approximately 2,500 people in the United States and Europe. U.S. sites include the company's headquarters in Frazer, Pennsylvania, and offices, laboratories or manufacturing facilities in West Chester, Pennsylvania, Salt Lake City, Utah, and suburban Minneapolis, Minnesota. Cephalon's European headquarters are located in Maisons-Alfort, France and other European offices are located in Guildford, England, and Martinsried, Germany. The company currently markets four proprietary products in the United States: PROVIGIL, GABITRIL(R) (tiagabine hydrochloride), ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II] and TRISENOX(R) (arsenic trioxide) injection and more than 20 products internationally. Full prescribing information for all U.S. products is available at http://www.cephalon.com/ or by calling 1-800-896-5855. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs, development of potential pharmaceutical products, interpretation of clinical results, including the results of the SPARLON clinical trials, prospects for final regulatory approval of SPARLON, including the anticipated timetable for the launch of the product, manufacturing development and capabilities, market prospects for its products, particularly with respect to SPARLON sales and earnings guidance, and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. CONTACT: Media, Jenifer Antonacci of Cephalon, +1-610-738-6674, jantonac@cephalon.com , or Kerry Dixon, +1-720-216-0011, or kdixon@gcigroup.com , for Cephalon, or Investors, Robert (Chip) Merritt ofCephalon, +1-610-738-6376, cmerritt@cephalon.com Web site: http://www.cephalon.com/ Company News On-Call: http://www.prnewswire.com/comp/134563.html SOURCE Cephalon, Inc. URL: http://www.prnewswire.com LOAD-DATE: November 29, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2005 PR Newswire Association LLC. All Rights Reserved. 454 of 998 DOCUMENTS The Evening Standard (London) November 28, 2005 Monday Spend money on buses, not Kiley SECTION: A MERGE; Pg. 43 LENGTH: 1151 words FURTHER to the outrage at Bob Kiley's "golden farewell", I support people being remunerated if they deserve it. The more pressing issue is that while TfL managers are being richly rewarded, the employees on whom commuters most rely are being given a rough deal (25 November). Bus travel requires good, dedicated drivers, yet increasingly passengers are complaining about poor service and bumpy rides. Little wonder as since privatisation, drivers have been denied access to the London Transport Superannuation Fund and have little incentive to stay put. Bus companies' pension policies are little better than savings schemes. Buses are the transport of the future, because they are an effective use of existing infrastructure. Yet the different bus companies in London have different internal layout and design; if you ask a Metroline employee when the next Stagecoach bus is coming they can't tell you and are not allowed to due to commercial confidentiality. In New York, Kiley famously came to an accommodation with the subway unions and in London he fought against Tube privatisation. Will his successor have more success in restoring some sense to our bus system? Nick Warner, N4. YOU report that there are 30,245 people who have applied for compensation for injuries sustained on London streets since 2000. The real figure may be significantly worse, depending on how many claims are still "in process", and the details provided seem to exclude Transport for London's highways, (24 November) My experience suggests the failure of transport contract management as much as the compensation culture may lie behind this situation. Since my retirement as Camden's chief engineer, it has become clear that no one from the council has been properly monitoring repairs that contractors are paid Pounds 1.2 million a year in advance to carry out. Over the past year, I have publicised 350 photographs of unfixed repairs but the council has still not apparently addressed these problems. This is also an issue in other boroughs - in Enfield, there is a pothole that has not been fixed for eight months. Meanwhile, Transport for London has told me that it has no specifications for controlling the storage of materials and equipment on its roads, which present major hazards, especially at night. Bob Kiley's successor should lead a campaign for "zero tolerance" of highway defects and the attitudes that allow them to pass. Dugald Gonsal, NW3. Don't mess with medicine FURTHER to your feature: The Genius Pill: would you be an idiot to take it? (22 November) in which the prescription-only drug modafinil was purchased over the internet and taken by three Evening Standard journalists, we wish to emphasise as licence holders of Provigil (modafinil) in the UK that the drug should only be used under the guidance of a doctor. Modafinil is indicated for the treatment of excessive sleepiness and is not a "cognitive-enhancing drug". Any attempts to demonstrate the medication is "memory-enhancing" or "mind-sharpening" are therefore ill-founded at best. We agree with Alice Hart-Davis's remark that "there's nothing clever about taking drugs without a prescription", and hope your readers take on board Dr Ebrahim's comment that "these medications shouldn't be used for purposes for which they are not licensed". Dr Alan McDougall, medical director, Cephalon UK Ltd. Kids are great sometimes I HAVE great sympathy for Liz Jones, who is dreading Christmas because of the contempt she is held in as a childless woman (22 November). I chose a partnership without children but have goddaughters and nephews to take on trips and buy presents for, and I can't understand the "me" generation who aren't happy unless you spoil their children as much as they do. Jones should practise tough love and inform any friends who tell her what their children "want" for Christmas that they'll get nothing at all. I pay my taxes, but do I get a handout or special treatment for not having children? I am sick of seeing family offers on posters and adverts, and yet when I choose to attend something I would consider an adult event I can guarantee my shins will be battered by a passing pram. Don't get me wrong - I love children, but I don't think they should take over everybody's life. Geoff Askey, Harrow. LIZ Jones's candid tales of her neuroses make me smile, but she really must try to understand the true concept of what it is to have children. What does she mean when she describes having kids as making a "lifestyle choice"? Does she think it's like deciding whether to buy another cat and give it a cashmere blanket for Christmas? I hope she shows more tolerance of other people's children when they're grown up and attending to her myriad needs. Ania Zawisza, W12. Clarkson's so rude, they'll love him in the US YOU speculate whether Jeremy Clarkson's nonappearance at the international Emmys in the US, at which he won an award, was to do with his track record of faux pas or because he had something better to do (21 November). Surely the reality is much more disturbing - that he is preparing to break into America and understands that this is the sort of uncouth and superior behaviour expected of a US star. Certainly his personality and the Top Gear programme would go down a storm there - without irony. Perhaps Clarkson sees a gap in the market for a man of his style, after the extent to which Graham Norton has been praised by American critics as a master of comedy. I trust that Clarkson's friend AA Gill will be able to take him down a peg. George Brooks, W12. Kids are great sometimes I HAVE great sympathy for Liz Jones, who is dreading Christmas because of the contempt she is held in as a childless woman (22 November). I chose a partnership without children but have goddaughters and nephews to take on trips and buy presents for, and I can't understand the "me" generation who aren't happy unless you spoil their children as much as they do. Jones should practise tough love and inform any friends who tell her what their children "want" for Christmas that they'll get nothing at all. I pay my taxes, but do I get a handout or special treatment for not having children? I am sick of seeing family offers on posters and adverts, and yet when I choose to attend something I would consider an adult event I can guarantee my shins will be battered by a passing pram. Don't get me wrong - I love children, but I don't think they should take over everybody's life. Geoff Askey, Harrow. LIZ Jones's candid tales of her neuroses make me smile, but she really must try to understand the true concept of what it is to have children. What does she mean when she describes having kids as making a "lifestyle choice"? Does she think it's like deciding whether to buy another cat and give it a cashmere blanket for Christmas? I hope she shows more tolerance of other people's children when they're grown up and attending to her myriad needs. Ania Zawisza, W12. LOAD-DATE: November 28, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2005 Associated Newspapers Ltd. All Rights Reserved 455 of 998 DOCUMENTS The Evening Standard (London) November 22, 2005 Tuesday The Genius Pill: would y you be an idiot to take it?; It's said to give you extra brainpower and is the smart new drug in the US. Now it's available on the internet. But does it work? BYLINE: ALICE HART-DAVIS SECTION: A SPR; Pg. 32 LENGTH: 862 words AT 2.45am, I send two emails then sit back and rub my eyes. They're burning with fatigue, which isn't surprising since I've been awake since 5.30am the previous day. What is astonishing, though, is that my brain feels as sharp as it did midmorning. I have achieved this spectacular lucidity by obtaining over the internet a prescription drug that might easily become a lifestyle aid among London's professional elite. Yet, as we all know, nothing is ever simple with drugs - and there are serious questions to be answered. There is no such thing as a free lunch. Modafinil is a "cognitive-enhancement" drug licensed in Britain and the US for the treatment of narcolepsy (a rare disorder in which patients fall asleep during the day) but is fast becoming the pep pill of choice for anyone who needs their brain to be working in overdrive or wants to stay up all night and still be functional the next day. Made by pharmaceutical company Cephalon and variously branded as Provigil or Modavigil, it can keep a person awake and alert for up to 90 hours without either the highs or jitters that amphetamines or caffeine would induce. It is huge in the States (American Vogue devoted four pages to it this month) with sales doubling from a million in 2002 to two million last year. Its properties are also highly regarded by the military; French soldiers use modafinil and the British MoD has bought more than 24,000 tablets since 1998. It is not precisely known how modafinil - otherwise known as 2-diphenylmethyl)sulfinyl]acetamide - works, though it appears to act on the central nervous system, slowing the release of GABA, a sleep-promoting amino acid, in the brain. It is a crystalline powder described as a "psychostimulant", but there is no "high", making it unlikely to become a street drug, and it's slow to act, taking a couple of hours to kick in. Dr Irshaad Ebrahim, medical director of the London Sleep Centre, describes the drug as highly effective in combating narcolepsy. He also uses it for other sleep disorders and knows it is used by US Air Force pilots in Iraq to raise alertness. "It has been proven not to be addictive in clinical trials, which differentiates it from amphetamines," he says. "But there are two problems associated with its use. A significant number of people who take it get headaches, though these usually disappear within a couple of weeks of daily use. There are also some cardiovascular effects, which are potentially dangerous in high doses (some narcoleptics need 10 100mg pills a day); raised blood pressure and abnormal heart rhythms." There are other listed side effects, too, including nausea, diarrhoea, dry mouth, loss of appetite, sore throat, dizziness and nervous feelings. So how do those willing to take the risk get hold of the drug? Some doctors, it is said, have been surprised at how many young professionals visiting their clinics claim to have previously undiagnosed narcolepsy, but no doctor of my acquaintanc e would contemplate prescribing a medicine I obviously didn't need. "I could be struck of f for doing that," said one. Finally, I order it off the internet, which is disturbingly easy. For Pounds 49.11, Inhousepharmacy. co. uk sent me 30 pills, no questions asked, which showed up eight days later, postmarked Vanuatu, an island in the South Pacific. Dr Ebrahim is appalled. "These medications shouldn't be used for purposes for which they are not licensed," he says. I take one 100mg pill, half the normal dose, first thing in the morning. After a while I feel anxious. The feeling gets worse and I can't settle at my desk. Gradually a sense of purpose comes on and I need to get on with my work. I make calls, work through the post, write emails. But I find I am frequently typing gibberish and have to edit the words carefully. My husband tells me I'm gabbling when I talk. And though I'm working hard, I'm not prioritising. By lunchtime, I haven't dispatched any of the three pieces waiting to be written, nor done my bit organising the school bazaar. Yet I feel keyed up and I know it's not caffeine or adrenaline doing it. At least there's no hint of the crushing fatigue that usually sets in for an hour after lunch and of all the possible side effects listed for the medication, I can only tick dry mouth, nervousness and loss of appetite. The afternoon is calmer. The anxiety goes, replaced with a clear, tense focus. I organise the children and cook dinner for friends. I daren't drink, worried about the effect of alcohol when combined with modafinil. I'm not hungry, either, and everything tastes a bit odd. When they go, I return to my desk. I normally work at night, but not past midnight. Tonight, however, it's easy. By 3am, I go to bed. One occasional modafinil user I spoke to warned me I might need sleeping pills, but I drop off instantly and am astonished to find, when my small son wakes me three hours later, that I feel fine. I feel awake and alert all day. It may be billed as a "clever pill", but I'm well aware that there's nothing clever about taking taking drugs without a prescription. The thing is, though, this pill worked for me. Would I take it again? I'm afraid it's only a question of when. LOAD-DATE: November 22, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2005 Associated Newspapers Ltd. All Rights Reserved 456 of 998 DOCUMENTS Family Practice News November 1, 2005 Caffeine, Medications Treat Excessive Sleepiness BYLINE: Sherry Boschert, San Francisco Bureau SECTION: Pg. 74 Vol. 35 No. 21 ISSN: 0300-7073 LENGTH: 641 words    SAN DIEGO - All three main treatments for problem sleepiness can perk patients up, but they differ in cost and side effects, Milton Erman, M.D., said at a psychopharmacology congress sponsored by the Neuroscience Education Institute.    Caffeine is the cheapest, most accessible, and most widely used stimulant. The two other treatment options are prescription medications, which are more expensive: modafinil or CNS stimulants (most commonly amphetamines or methylphenidate).    Tolerance to caffeine develops rapidly, however, and there's a moderate risk for dependence. Stopping a daily caffeine habit too quickly can trigger a "caffeine headache." Side effects from regularly drinking caffeine include nervousness, irritability, insomnia, and GI problems, said Dr. Erman of the University of California, San Diego.    "Many of my insomniac patients tell me proudly that they aren't using caffeine" to indicate that caffeine can't be blamed for their insomnia, he said. Ironically, a good cup of caffeine in the morning may be just what they need. "The problem with many of these insomniac patients is that they can't get going, get functioning in the morning," he explained. Limited use of caffeine in the morning may help them function better.    Use of CNS stimulants also leads to tolerance, and they have a high potential for dependence. Side effects from use include nervousness, headaches, insomnia, anorexia, GI problems, and mood changes. General CNS stimulants such as amphetamines have a high risk of abuse and hyperactivity because of their broad mechanism of action.    One experimental study of sleep deprivation that compared amphetamines with modafinil treatment to maintain wakefulness suggested that the two drugs are equally potent. In real life, however, "I think amphetamines are more potent," he said. Patients with narcolepsy who have used amphetamines in the past often aren't satisfied with the effects of modafinil.    Modafinil works more specifically on wakefulness circuits and has fewer side effects than other stimulants. Tolerance is not an issue-it maintains most of its efficacy over time-and use of the drug does not lead to dependence. Side effects include headache, nausea, dry mouth, insomnia, and hyperactivity.    The risk of headache relates to the dosing of modafinil. In early research on the drug, headache appeared primarily in patients who titrated up to a dose of 400 mg/day by the third day. In subsequent research that gave patients 7-9 days to titrate up to 400 mg/day, headache was much less of a problem, Dr. Erman said.    "Modafinil works quite well, particularly if we're not talking about the most severely hypersomnolent patients," such as narcoleptics who have become accustomed to taking stimulants, he said.    Dr. Erman is a speaker and consultant for, and has received research funding from, the company that makes modafinil, Cephalon Inc. Modafinil is approved to treat sleepiness from shift work, narcolepsy, and sleep apnea.    The most common cause of problem sleepiness is sleep apnea, which occurs in perhaps 10% of the population, he said. Restless leg syndrome can interrupt sleep and lead to daytime sleepiness. Narcolepsy is fairly uncommon. Insomnia can cause excessive sleepiness, but more often, insomniac patients are hypervigilant. "If anything, they are more alert" than they want to be, he said.    Secondary causes of sleepiness include chronic pain and any medical condition that causes pain or discomfort, which may interrupt sleep. Medications used to alleviate pain also can lead to daytime sleepiness because they affect breathing during sleep and increase the risk for sleep apnea.    Check to see if patients who complain of sleepiness are taking drugs that may cause sedation or that disrupt sleep, Dr. Erman added, and consider alternative therapies. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: FPNEWS Copyright 2005 Elsevier Inc., International Medical News Group All Rights Reserved 457 of 998 DOCUMENTS Internal Medicine News November 1, 2005 Treatments for Excess Sleepiness Compared BYLINE: Sherry Boschert, San Francisco Bureau SECTION: Pg. 36 Vol. 38 No. 21 ISSN: 1097-8690 LENGTH: 656 words    SAN DIEGO - All three main treatments for problem sleepiness-caffeine, modafinil, and central nervous system stimulants-can perk patients up, but they differ in cost and side effects, Milton Erman, M.D., said at a psychopharmacology congress sponsored by the Neuroscience Education Institute.    Caffeine is the cheapest, most accessible, and most widely used stimulant. The two other treatment options are prescription medications, which are more expensive: modafinil or CNS stimulants (most commonly amphetamines or methylphenidate).    Tolerance to caffeine develops rapidly, however, and there's a moderate risk for dependence. Stopping a daily caffeine habit too quickly can trigger a "caffeine headache." Side effects from regularly drinking caffeine include nervousness, irritability, insomnia, and GI problems, said Dr. Erman of the University of California, San Diego. "Many of my insomniac patients tell me proudly that they aren't using caffeine" to indicate that caffeine can't be blamed for their insomnia, he said.    Ironically, a good cup of caffeine in the morning may be just what they need. "The problem with many of these insomniac patients is that they can't get going, get functioning in the morning," he explained. Limited use of caffeine in the morning may help them function better.    Use of CNS stimulants also leads to tolerance, and they have a high potential for dependence. Side effects from use include nervousness, headaches, insomnia, anorexia, GI problems, and mood changes. General CNS stimulants such as amphetamines have a high risk of abuse and hyperactivity because of their broad mechanism of action.    One experimental study of sleep deprivation that compared amphetamines with modafinil treatment to maintain wakefulness suggested that the two drugs are equally potent. In real life, however, "I think amphetamines are more potent," he said.    Modafinil works more specifically on wakefulness circuits and has fewer side effects than other stimulants. Tolerance is not an issue, and use does not lead to dependence. Side effects include headache, nausea, dry mouth, insomnia, and hyperactivity.    The risk of headache relates to the dosing of modafinil. In early research on the drug, headache appeared primarily in patients who titrated up to a dose of 400 mg/day by the third day. In subsequent research that gave patients 7-9 days to titrate up to 400 mg/day, headache was much less of a problem, Dr. Erman said.    "Modafinil works quite well, particularly if we're not talking about the most severely hypersomnolent patients," such as narcoleptics who have become accustomed to taking stimulants, he said.    Dr. Erman is a speaker and consultant for, and has received research funding from, the company that makes modafinil, Cephalon Inc. Modafinil is approved to treat sleepiness from shift work, narcolepsy, and sleep apnea.    The most common cause of problem sleepiness is sleep apnea, which occurs in perhaps 10% of the population, he said. Restless leg syndrome can interrupt sleep and lead to daytime sleepiness. Narcolepsy is fairly uncommon. Insomnia can cause excessive sleepiness, but more often, insomniac patients are hypervigilant. "If anything, they are more alert" than they want to be, he said.    Secondary causes of sleepiness include any medical condition that causes pain or discomfort, which may interrupt sleep. Pain medications also can lead to daytime sleepiness as they affect breathing during sleep and increase the risk for sleep apnea.    Check to see if patients who complain of sleepiness are taking drugs that cause sedation or disrupt sleep, Dr. Erman added, and consider alternative therapies.    Lifestyle issues, such as graveyard shift work, also contribute to excessive sleepiness. The pace of U.S. culture commonly leads to chronic sleep deprivation that affects daytime function. "As a society, we really haven't dealt with this," he said. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: IMNEWS Copyright 2005 Elsevier Inc., International Medical News Group All Rights Reserved 458 of 998 DOCUMENTS CNS Drug News Pharmaceuticals October 24, 2005 Cephalon receives approvable letter for Sparlon LENGTH: 306 words Cephalon has received an approvable letter from the FDA to market Sparlon ( modafinil ) Tablets (C-IV) for the treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents ages six through 17 years. The company submitted an sNDA to the FDA in December 2004. Cephalon expects to launch Sparlon, a proprietary dosage form of modafinil, in early 2006, subject to final FDA approval. In August 2005, Cephalon announced an agreement with McNeil Consumer & Specialty Pharmaceuticals Division of McNeil-PPC ( Johnson & Johnson ) to co-promote Sparlon. Cephalon also presented, for the first time, results of integrated analyses of efficacy and safety data from its three pivotal trials evaluating Sparlon for the treatment of ADHD in children and adolescents at a major medical meeting of child and adolescent psychiatrists in Toronto, Canada. The three Phase III studies, in which more than 600 children and adolescents (ages six through 17 years) with ADHD were randomised to treatment with Sparlon or placebo, included two identically-designed, nine-week, flexible-dosage studies and one seven-week, fixed-dosage study. Patients treated with Sparlon experienced significant improvement compared to placebo as early as the first week, with continued improvement during titration and dose maintenance. In the trials, Sparlon was generally well tolerated and discontinuation rates due to adverse events were not significantly different from placebo. The most common adverse events associated with Sparlon were generally mild-to-moderate in nature and included insomnia, headache and decreased appetite. Insomnia and decreased appetite generally occurred upon initiation of treatment and often resolved with continued treatment. Data from these three trials were submitted to the FDA for evaluation as part of the sNDA. LOAD-DATE: November 4, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2005 ESPICOM Business Intelligence Ltd. All Rights Reserved 459 of 998 DOCUMENTS PR Newswire US October 21, 2005 Friday 11:30 AM GMT Cephalon Receives Approvable Letter for SPARLON(TM) for the Treatment of ADHD in Children and Adolescents; SPARLON Pivotal Data Presented at Major Child and Adolescent Psychiatry Meeting LENGTH: 1006 words DATELINE: FRAZER, Pa. Oct. 21 FRAZER, Pa., Oct. 21 /PRNewswire-FirstCall/ -- Cephalon, Inc. (NASDAQ:CEPH) today announced that it has received an approvable letter from the U.S. Food and Drug Administration (FDA) to market SPARLON(TM) (modafinil) Tablets [C-IV] for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents ages six through 17. The company submitted a supplemental new drug application (sNDA) to FDA in December 2004. "SPARLON is distinct from all currently available ADHD therapies," said Dr. Paul Blake, Executive Vice President, Worldwide Medical and Regulatory Operations. "We are excited to offer physicians and families a potential new option in the treatment of ADHD and are working closely with the FDA to obtain final approval." Cephalon expects to launch SPARLON, a proprietary dosage form of modafinil, in early 2006 subject to final FDA approval. In August 2005, Cephalon announced an agreement with McNeil Consumer & Specialty Pharmaceuticals Division of McNeil-PPC, Inc. to co-promote SPARLON. Cephalon also presented for the first time results of integrated analyses of efficacy and safety data from its three pivotal trials evaluating SPARLON Tablets [C-IV] for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents at a major medical meeting of child and adolescent psychiatrists in Toronto. The three Phase 3 studies in which more than 600 children and adolescents (ages six through 17) with ADHD were randomized to treatment with SPARLON or placebo included two identically designed nine-week, flexible-dosage studies and one seven-week, fixed-dosage study. Patients treated with SPARLON experienced significant improvement compared to placebo as early as the first week, with continued improvement during titration and dose maintenance. In the clinical trials, SPARLON was generally well tolerated and discontinuation rates due to adverse events were not significantly different from placebo. The most common adverse events associated with SPARLON were generally mild to moderate in nature and included insomnia, headache and decreased appetite. Insomnia and decreased appetite generally occurred upon initiation of treatment and often resolved with continued treatment. Data from these three trials were submitted to the FDA for evaluation as part of the sNDA. SPARLON SPARLON is a new formulation and proprietary dosage strength of modafinil, the active ingredient in PROVIGIL(R) (modafinil) Tablets [C-IV], which is approved for the treatment of adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome and shift work sleep disorder. PROVIGIL is not approved to treat ADHD and is available only in 100 mg and 200 mg strengths. If approved, SPARLON is expected to be available in early 2006. Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products to treat sleep and neurological disorders, cancer and pain. Cephalon currently employs approximately 2,300 people in the United States and Europe. U.S. sites include the company's headquarters in Frazer, Pennsylvania, and offices, laboratories or manufacturing facilities in West Chester, Pennsylvania, Salt Lake City, Utah, and suburban Minneapolis, Minnesota. Cephalon's European headquarters are located in Maisons-Alfort, France and other European offices are located in Guildford, England, and Martinsried, Germany. The company currently markets four proprietary products in the United States: PROVIGIL, GABITRIL(R) (tiagabine hydrochloride), ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II] and TRISENOX(R) (arsenic trioxide) injection and more than 20 products internationally. Full prescribing information for all U.S. products is available at http://www.cephalon.com/ or by calling 1-800-896-5855. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs, development of potential pharmaceutical products, interpretation of clinical results, including the results of the SPARLON clinical trials, prospects for final regulatory approval of SPARLON, including the anticipated timetable for the launch of the product, manufacturing development and capabilities, market prospects for its products, particularly with respect to SPARLON sales and earnings guidance, and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. CONTACT: Media: Jenifer Antonacci, +1-610-563-6018, jantonac@cephalon.com , or Investors: Robert (Chip) Merritt, +1-610-738-6376, cmerritt@cephalon.com , both of Cephalon Web site: http://www.cephalon.com/ Company News On-Call: http://www.prnewswire.com/comp/134563.html SOURCE Cephalon, Inc. URL: http://www.prnewswire.com LOAD-DATE: December 7, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2005 PR Newswire Association LLC. All Rights Reserved. 460 of 998 DOCUMENTS Clinical Psychiatry News October 2005 Data Back Broader Indication for Sodium Oxybate; Trial results lead Xyrem maker to seek approval of drug for narcolepsy symptoms beyond cataplexy. BYLINE: Bruce Jancin, Denver Bureau SECTION: Pg. 61 Vol. 33 No. 10 ISSN: 0270-6644 LENGTH: 781 words    DENVER - Sodium oxybate (Xyrem) is effective not only for cataplexy-its only approved indication at present-but also for the other primary symptoms of narcolepsy, investigators reported at the annual meeting of the Associated Professional Sleep Societies.    Based on data from two randomized clinical trials presented at the meeting, the drug's manufacturer, Orphan Medical Inc., has submitted a supplemental New Drug Application to the Food and Drug Administration. If approval is granted, sodium oxybate's expanded indication would make it the first drug approved for treatment of all the primary symptoms of narcolepsy: excessive daytime sleepiness; fragmented sleep; and cataplexy, the sudden, brief loss of muscle tone frequently experienced by narcoleptics during periods of emotional intensity such as surprise, laughter, or anger.    Terri E. Weaver, Ph.D., noted that in the last few years, quality of life issues in patients with incurable chronic illnesses have drawn greater regulatory and clinical attention. And the quality of life impact of narcolepsy, she stressed, is profound: In one study, the impact was rated greater than living with Parkinson's disease.    "Individuals with narcolepsy are struggling to complete their activities of daily living," said Dr. Weaver of the University of Pennsylvania, Philadelphia. She presented the first-ever study of sodium oxybate's quality of life impact in narcoleptic patients. The double-blind, placebo-controlled, 8-week trial involved 228 patients randomized to receive either placebo or 4.5 g, 6 g, or 9 g of sodium oxybate per night in two equally divided doses at bedtime and from 21/2 to 4 hours later.    Quality of life was assessed with the Functional Outcomes of Sleep Questionnaire administered at baseline, 4 weeks, and 8 weeks. Patients assigned to 4.5 g/night showed no quality of life gains. But those who received 6 g or 9 g experienced significant improvement in four of the five domains measured by this instrument: general productivity, vigilance, social outcome, and activity level. The only domain in which they didn't fare significantly better than placebo was the intimacy/sexual relationships subscale.    The benefit was greater with the 9-g dose. "The effect size was clinically meaningful and quite large," she noted.    The potential for improved quality of life needs to be presented to patients in the context of the possible treatment disadvantages so they can make an informed decision. Patients on sodium oxybate experience a deep sleep and increased arousal threshold. They may not hear a smoke alarm, a late-night telephone call, or a child's cry. "Individuals who have children at home have to weigh the benefit of having a good night's sleep and being able to function and take care of those children during the day. We all know daytime sleepiness and some of the other effects of narcolepsy can be hazardous, too, in terms of caring for young ones," Dr. Weaver said.    Jed E. Black, M.D., presented another phase III trial, this one designed to assess the relative efficacy of sodium oxybate when taken as monotherapy or with modafinil (Provigil), a widely used wakefulness-promoting agent approved for treatment of the excessive daytime sleepiness component of narcolepsy. The double-blind, 230-patient trial began with all participants on 200-600 mg/day of modafinil. They were then randomized to receive modafinil plus placebo, modafinil plus sodium oxybate, placebo plus sodium oxybate, or double placebos. The sodium oxybate dose was 6 g/night for the first 4 weeks and 9 g thereafter.    Monotherapy with sodium oxybate or modafinil appeared to be equally effective in terms of the primary study end point, reduction in excessive daytime sleepiness as measured by the Maintenance of Wakefulness Test, the Epworth Sleepiness Scale, and patient self-report. The improvement was greater with the 9-g dose of sodium oxybate than with the 6-g dose. But combination therapy was most effective of all, not only in terms of reduced daytime sleepiness but also consolidation of fragmented sleep and enhanced slow-wave sleep, said Dr. Black of Stanford (Calif.) University. Side effects that occurred more often with sodium oxybate than placebo in the trials included nausea, dizziness, headache, sleepiness, and bedwetting.    Prior to its 2002 approval as a tightly controlled schedule-III drug for cataplexy, sodium oxybate was available as [#x3b3]-hydroxybutyrate in health food stores. During that era it was abused as a recreational drug and implicated as a "date rape" drug.    Both randomized trials were sponsored by Orphan Medical. Dr. Weaver serves as a consultant to the company. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: CPNEWS Copyright 2005 Elsevier Inc., International Medical News Group All Rights Reserved 461 of 998 DOCUMENTS Family Practice News October 1, 2005 No Withdrawal Syndrome Seen With Modafinil for ADHD BYLINE: Damian Mcnamara, Miami Bureau SECTION: Pg. 61 Vol. 35 No. 19 ISSN: 0300-7073 LENGTH: 386 words    BOCA RATON, FLA. - Children and adolescents with attention-deficit hyperactivity disorder did not experience withdrawal or discontinuation syndrome after abrupt cessation of modafinil film-coated tablets in a phase III, double-blind, multicenter trial.    Researchers also found efficacy as early as 1 week in this 9-week study of 6- to 17-year-olds with attention-deficit hyperactivity disorder (ADHD). The Food and Drug Administration has approved modafinil (Provigil) for treatment of narcolepsy and is currently reviewing a special pediatric formulation for ADHD.    "This is not surprising. Modafinil is a medication that improves vigilance and alertness and could improve similar symptoms in ADHD," Joseph Biederman, M.D., said in an interview at his poster presentation during a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.    Dr. Biederman and his associates compared efficacy using the school and home versions of the ADHD Rating Scale-IV, the Clinical Global Impression of Improvement (CGI-I) scores, and adverse event reporting by 125 patients taking the pediatric formulation of modafinil and 64 taking a placebo.    The modafinil group had significantly improved school rating total scores, compared with those of the placebo group at 1 week, an effect that was maintained through week 7. The final 2 weeks of the study was a washout phase. Mean reduction from baseline was 17 points with modafinil versus 8 points with placebo. Significant reductions in home rating total scores also were observed with modafinil at all visits, according to Dr. Biederman, chief of the joint program in pediatric psychopharmacology, Massachusetts General Hospital, Boston.    A significantly greater percentage of modafinil patients was rated as "much" or "very much" improved on the CGI-I (49%) than were placebo patients (25%).    Modafinil was abruptly discontinued in 37 patients. Abrupt cessation was not associated with symptom rebound, and no evidence of withdrawal or discontinuation syndrome was seen.    This and other phase III study results were submitted to the FDA in December 2004. "I don't see any reason why they wouldn't approve it," said Dr. Biederman, who reported no affiliation with Cephalon Inc., the manufacturer and sponsor of the study. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: FPNEWS Copyright 2005 Elsevier Inc., International Medical News Group All Rights Reserved 462 of 998 DOCUMENTS NIDA Notes October 2005 Modafinil Improves Behavioral Therapy Results In Cocaine Addiction; Research Findings BYLINE: Patrick Zickler, NIDA NOTES Staff Writer SECTION: NIDA NOTES - Vol. 20, No. 3 LENGTH: 722 words NIDA-supported researchers evaluating modafinil's potential to enhance behavioral treatment for cocaine addiction have reported a second successful clinical efficacy trial. The new results affirm and extend the promising findings of the earlier, smaller, and less stringent "open label" trial, and they set the stage for large-scale multisite trials that could definitively establish the medication's usefulness. Dr. Charles Dackis and colleagues at the University of Pennsylvania Treatment Research Center recruited 62 individuals (44 male, 18 female; mean age, 44.5 years) for their double-blind study. All had come to the Center seeking treatment for cocaine addiction, had ingested at least $200 worth of cocaine in the 30 days prior to presenting for treatment, and met the cocaine-dependence criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV). The patients agreed to visit the clinic twice a week for individual sessions of cognitive-behavioral therapy (CBT) and provide urine samples 3 times a week for the 8-week course of the study. Once each week, the clinic staff dispensed a week's supply of pills, either modafinil in daily doses of four 100 mg pills (30 patients) or an equal number of identical-looking placebo pills (32 patients). [Table Omitted] Throughout the study, modafinil-treated patients gave fewer cocaine-positive urine samples than the placebo group. "More impressive, though, is the fact that more than twice as many modafinil patients as placebo patients (33 percent compared with 13 percent) were able to attain abstinence for 3 weeks or more, " Dr. Dackis says. "Maintaining abstinence for a prolonged period during treatment is an important clinical threshold. Cocaine is a binge drug, and it is common in outpatient treatment for a patient to go 4 or 5 days without using, relapse, then have another clean week. The long continuous abstinence we saw with modafinil is a strong and encouraging signal that this medication can help patients avoid relapse during the critical first weeks of treatment." Both groups of patients attended the same average number of CBT sessions, he adds, further supporting the likelihood that modafinil was the factor accounting for reduced cocaine abuse in those who received it. Modafinil, a medication currently used to treat narcolepsy, enhances levels of glutamate, a chemical that influences the activity of cells throughout the brain. Animal research has shown that repeated exposure to cocaine depletes glutamate levels in brain regions associated with development of dependence and addiction, and that increasing glutamate concentrations will block reinstatement of cocaine self-administration in rats--a model of relapse to drug abuse in humans (see ", " NIDA NOTES , Vol. 19, No. 3). Modafinil's modulation of glutamate transmission may account for a striking effect reported by patients: "The mechanism for this isn't clear, but some patients receiving modafinil told us that if they did use cocaine it did not produce the irresistible urge to use more, which they had always felt before, " Dr. Dackis says. "Some of the patients told me they had flushed cocaine away. In 25 years of treating addiction, no one ever told me they threw away cocaine." "The body of research suggesting that modafinil is effective in treating cocaine addiction is growing, " says Dr. Ivan Montoya of NIDA's Division of Pharmacotherapies and Medical Consequences of Drug Abuse. "Animal research supports the assumption that modafinil reverses the cocaine-induced neurochemical disruptions of glutamate and of dopamine-containing neurons in the brain's reward centers. Clinically, modafinil has effects that are opposite to the symptoms of cocaine withdrawal, which usually include oversleeping, depression, poor concentration, and craving." Dr. Dackis and his colleagues are now planning the next test for modafinil: a multisite clinical trial that will include more than 650 participants. The study will evaluate modafinil's efficacy in doses of 200 mg and 400 mg per day in combination with CBT, and results may be available by mid-2006, Dr. Montoya says. Source * Dackis, C.A., et al. A double-blind, placebo-controlled trial of modafinil for cocaine dependence. Neuropsychopharmacology 30(1): 205-211, 2005. [] Volume 20, Number 3 (October 2005) LOAD-DATE: January 2, 2006 LANGUAGE: ENGLISH PUBLICATION-TYPE: Report Copyright 2005 Federal Information and News Dispatch, Inc. 463 of 998 DOCUMENTS World Markets Analysis September 23, 2005 Cephalon's Modafinil Approved for New Indication in Germany BYLINE: Mitra Thompson SECTION: IN BRIEF LENGTH: 229 words U.S. pharmaceutical company Cephalon has seen its narcolepsy drug modafinil approved for a new indication by the Federal Institute for Drugs and Devices in Germany, where it will now be marketed for moderate-to-severe chronic shift-work sleep disorder in patients with excessive sleepiness who work night shifts. The company has not speculated on how much extra revenue it expects to earn via the extended indication - modafinil has been sold as a regular narcolepsy treatment in Germany since 1998 under the brand name Vigil - however, Germany is only the third European country to approve modafinil for this particular sleep disorder. Significance: Sales of modafinil, sold elsewhere as Provigil, leapt 51% year-on-year during 2004, amounting to US$439.7 million, or 43% of total company revenue. A new indication in Germany will be welcomed by Cephalon, despite the relatively limited market size of the indication. Generic competition for modafinil has been biting at Cephalon's heels over the past year, with Mylan, Barr (both U.S.), and Dr Reddy's (India) securing preliminary approval for their versions from the U.S. FDA, although Swiss generics firm Sandoz agreed in May to postpone its plans for a generic copy of Provigil until a key Cephalon patent expires in 2014 (see United States: 3 May 2005: Cephalon Relief as Sandoz Makes Provigil U-Turn). LOAD-DATE: September 23, 2005 LANGUAGE: ENGLISH Copyright 2005 World Markets Research Limited; All Rights Reserved 464 of 998 DOCUMENTS Internal Medicine Alert September 15, 2005 Pharmacology Watch LENGTH: 1423 words Beta-Blockers May Be Useful for Noncardiac Surgery Pharmacology Watch High risk patients benefit from perioperative beta-blockers when undergoing major noncardiac surgery according to new study. Researchers from Tufts University reviewed the records of 782,969 patients in 2000 and 2001 at 329 hospitals throughout the United States. Patients were graded with the Revised Cardiac Risk Index (RCRI), which takes into account high-risk surgery, ischemic heart disease, cerebrovascular disease, renal insufficiency, and diabetes. The RCRI is graded on a 0-5 point scale, with 5 representing the highest risk. High risk surgery included all intrathoracic, intraperitoneal, and superinguinal vascular procedures. Patients with contraindications to beta blocker therapy were excluded. Over 660,000 patients had no contraindications to beta-blockers, and 120,338 patients received beta-blocker treatment during the first 2 hospital days. The relationship between perioperative beta-blocker treatment and the risk of death varied directly with cardiac risk. Patients with an RCRI of 0 or 1 were found to have no benefit from beta-blocker treatment, whereas for patients with an RCRI of 2, 3, or 4, or more the adjusted odds ratio for death in the hospital, were 0.88 (95% CI, 0.80, 0.80-0.98), 0.71 (95% CI, 0.63 - 0.80) and 0.58 (95% CI, 0.50-0.67), respectively. The authors conclude that perioperative beta-blocker therapy is associated with a reduced risk of in-hospital death among high-risk patients undergoing major noncardiac surgery. They also noted that there was no benefit for low risk patients (Lindenauer PK, et al. Perioperative Beta-Blocker Therapy and Mortality After Major Noncardiac Surgery. N Engl J Med. 2005;353:349-361). An accompanying editorial points out that perioperative beta-blocker therapy has been somewhat controversial because of conflicting data in recent years. The current study shows an apparent benefit in high-risk patients, but they also look forward to the results of 2 ongoing randomized trials that will help clarify the role of beta-blockers for low-risk and intermediate-risk patients (Poldermans D, et al. Beta-Blocker Therapy in Noncardiac Surgery. N Engl J Med. 2005;353:412-414). Promising New Weight Loss Drug? More data shows that topiramate (Topamax) is associated with weight loss and, in this latest study, may also lower blood pressure in obese, hypertensive patients. In a study from Norway, 531 obese patients with hypertension were randomized to placebo, topiramate 96 mg/day, or topiramate 192 mg/day. All patients received the same diet, exercise, and behavioral modification advice. Patients were followed for 28 weeks. Mean weight loss was 1.9% for placebo and 5.9% and 6.5% for the 96 mg and 192 mg doses, respectively (P < 0.001 for each compared with placebo). Diastolic blood pressure was reduced 2.1, 5.5, and 6.3 mm Hg, respectively (P < 0.015 vs placebo). Systolic blood pressure was reduced 4.9, 8.6, and 9.7 mm Hg, respectively (P = NS). Paresthesia occurred in 33% of the active treatment group. The authors conclude that topiramate produced clinically relevant effects in reducing body weight and BP, with generally mild to moderate adverse effects (Tonstad S, et al. Efficacy and Safety of Topiramate in the Treatment of Obese Subjects with Essential Hypertension. Am J Cardiol. 2005;96:243-251). Treating Shift-Work Disorder Modafinil (Provigil) may be of some value for people with excessive sleepiness associated with shift-work sleep disorder. Researchers from Harvard randomized 209 patients with shift-work sleep disorder to receive either 200 mg of modafinil or placebo before the start of each shift. Modafinil resulted in modest improvement in nighttime sleep latency (1.7 + 0.4 vs 0.3 + 0.3 minutes, respectively; P = 0.002). More patients also had improvement in their clinical symptoms based on multiple objective tests and patients diaries (74% vs 36%, respectively; P < 0.001). Patients taking modafinil also had reduction in frequency and duration of lapses in attention during nighttime testing of performance, and proportionally fewer patients reported having had accidents or near accidents while commuting home (both P < 0.001). These benefits, however, were mild, and patients treated with modafinil continued to have excessive sleepiness and impaired performance at night. The authors conclude that modafinil 200 mg at the beginning of a shift may improve shift-worker's performance as compared to placebo, although the benefit is modest (Czeisler CA, et al. Modafinil for Excessive Sleepiness Associated with Shift-Work Disorder. N Engl J Med. 2005;353:476-486). An accompanying editorial urges caution when interpreting these results and suggests "the current study does not adequately assess the clinical value of this particular drug in shift-work sleep disorder, nor does it justify writing more prescriptions for modafinil." The authors do note that up to 20% of workers in industrialized nations are shift-workers and calls for "further scientific studies to address in a cohesive manner the serious health and safety issues that surround us by virtue of us having become, to a large extent, a shift-working society" (Basner RC. Shift-Work Sleep Disorder--The Glass is More Than Half Empty. N Engl J Med. 2005;353:519-521). Another Flu Vaccine Shortage? With the flu season looming, Chiron Corp. is again having difficulty with flu vaccine production. Last year the company found contamination at its Liverpool production plant, a situation that cause severe shortages of vaccine in the United States. This year, the company has discovered contamination at a German plant and is stating that it can only provide vaccine for the US market. The German plant was primarily the source of the Begrivac flu vaccine, which was sold on the world market. The company is making "substantial progress" in fixing problems at the Liverpool plant where the US vaccine is made. Meanwhile, Acambis plc is working on a universal flu vaccine that could offer permanent protection against all types of influenza. The company hopes to generate a universal vaccine that would not require annual changes in formulation and would protect against both influenza A and B including avian strains. The company, however, states that it may require years of clinical trials before earning approval. Fears of avian influenza pandemic have prompted the French company Sanofi-Aventis to work on a vaccine for the avian H5N1 strain that has killed millions of birds and 50 people in Asia. Preliminary results are promising, however, full-scale production could take months, according to Anthony Fauci, MD, Director of the National Institute of Allergy and Infectious Diseases. FDA Actions The FDA has approved the first of the new class of drugs for the treatment of insomnia characterized by difficulty with sleep onset. Takeda Pharmaceutical's ramelteon (Rozerem) is a selective agonist at 2 melatonin receptors in suprachiasmatic nucleus, receptors that are thought to regulate circadian rhythm and sleepiness. Recently marketed sleeping medications target GABA receptors (ambien, lunesta) and, although these drugs are associated with less addiction and sleep latency then benzodiazepines, they are still designated as Schedule IV drugs. Ramelteon has shown no evidence of abuse or dependence potential and will, therefore, be marketed as a unscheduled drug. It is also approved for long-term use and has not been associated with memory impairment or impairment of motor ability. The most common adverse events associated with ramelteon were somnolence, fatigue and dizziness (> 2% over placebo). Plan B, Barr Pharmaceutical's "morning-after pill" is being considered for over-the-counter approval by the FDA. The issue has become a political hot potato, and even briefly held up the Senate's confirmation of Lester Crawford, MD, as Commissioner of the FDA. It is expected that decision will be made by September. This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5416. E-mail: LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2005 AHC Media LLC All Rights Reserved 465 of 998 DOCUMENTS Clinical Cardiology Alert September 1, 2005 Pharmacology Watch: Beta-Blockers May Be Useful for Noncardiac Surgery LENGTH: 1420 words Beta-Blockers May Be Useful for Noncardiac Surgery Pharmacology Watch High-risk patients benefit from perioperative beta-blockers when undergoing major noncardiac surgery according to new study. Researchers from Tufts University reviewed the records of 782,969 patients in 2000 and 2001 at 329 hospitals throughout the United States. Patients were graded with the Revised Cardiac Risk Index (RCRI), which takes into account high-risk surgery, ischemic heart disease, cerebrovascular disease, renal insufficiency, and diabetes. The RCRI is graded on a 0-5 point scale, with 5 representing the highest risk. High risk surgery included all intrathoracic, intraperitoneal, and superinguinal vascular procedures. Patients with contraindications to beta blocker therapy were excluded. Over 660,000 patients had no contraindications to beta-blockers, and 120,338 patients received beta-blocker treatment during the first 2 hospital days. The relationship between perioperative beta-blocker treatment and the risk of death varied directly with cardiac risk. Patients with an RCRI of 0 or 1 were found to have no benefit from beta-blocker treatment, whereas for patients with an RCRI of 2, 3, or 4, or more the adjusted odds ratio for death in the hospital, were 0.88 (95% CI, 0.80, 0.80-0.98), 0.71 (95% CI, 0.63 - 0.80) and 0.58 (95% CI, 0.50-0.67), respectively. The authors conclude that perioperative beta-blocker therapy is associated with a reduced risk of in-hospital death among high-risk patients undergoing major noncardiac surgery. They also noted that there was no benefit for low risk patients (Lindenauer PK, et al. Perioperative Beta-Blocker Therapy and Mortality After Major Noncardiac Surgery. N Engl J Med. 2005;353:349-361). An accompanying editorial points out that perioperative beta-blocker therapy has been somewhat controversial because of conflicting data in recent years. The current study shows an apparent benefit in high-risk patients, but they also look forward to the results of 2 ongoing randomized trials that will help clarify the role of beta-blockers for low-risk and intermediate-risk patients (Poldermans D, et al. Beta-Blocker Therapy in Noncardiac Surgery. N Engl J Med. 2005;353:412-414). Promising New Weight Loss Drug? More data shows that topiramate (Topamax) is associated with weight loss and, in this latest study, may also lower blood pressure in obese, hypertensive patients. In a study from Norway, 531 obese patients with hypertension were randomized to placebo, topiramate 96 mg/day, or topiramate 192 mg/day. All patients received the same diet, exercise, and behavioral modification advice. Patients were followed for 28 weeks. Mean weight loss was 1.9% for placebo and 5.9% and 6.5% for the 96 mg and 192 mg doses, respectively (P < 0.001 for each compared with placebo). Diastolic blood pressure was reduced 2.1, 5.5, and 6.3 mm Hg, respectively (P < 0.015 vs placebo). Systolic blood pressure was reduced 4.9, 8.6, and 9.7 mm Hg, respectively (P = NS). Paresthesia occurred in 33% of the active treatment group. The authors conclude that topiramate produced clinically relevant effects in reducing body weight and BP, with generally mild to moderate adverse effects (Tonstad S, et al. Efficacy and Safety of Topiramate in the Treatment of Obese Subjects with Essential Hypertension. Am J Cardiol. 2005;96:243-251). Treating Shift-Work Disorder Modafinil (Provigil) may be of some value for people with excessive sleepiness associated with shift-work sleep disorder. Researchers from Harvard randomized 209 patients with shift-work sleep disorder to receive either 200 mg of modafinil or placebo before the start of each shift. Modafinil resulted in modest improvement in nighttime sleep latency (1.7 ~ 0.4 vs 0.3 ~ 0.3 minutes, respectively; P = 0.002). More patients also had improvement in their clinical symptoms based on multiple objective tests and patients diaries (74% vs 36%, respectively; P < 0.001). Patients taking modafinil also had reduction in frequency and duration of lapses in attention during nighttime testing of performance, and proportionally fewer patients reported having had accidents or near accidents while commuting home (both P < 0.001). These benefits, however, were mild, and patients treated with modafinil continued to have excessive sleepiness and impaired performance at night. The authors conclude that modafinil 200 mg at the beginning of a shift may improve shift-worker's performance as compared to placebo, although the benefit is modest (Czeisler CA, et al. Modafinil for Excessive Sleepiness Associated with Shift-Work Disorder. N Engl J Med. 2005;353:476-486). An accompanying editorial urges caution when interpreting these results and suggests "the current study does not adequately assess the clinical value of this particular drug in shift-work sleep disorder, nor does it justify writing more prescriptions for modafinil." The authors do note that up to 20% of workers in industrialized nations are shift-workers and calls for "further scientific studies to address in a cohesive manner the serious health and safety issues that surround us by virtue of us having become, to a large extent, a shift-working society" (Basner RC. Shift-Work Sleep Disorder--The Glass is More Than Half Empty. N Engl J Med. 2005;353:519-521). Another Flu Vaccine Shortage? With the flu season looming, Chiron Corp. is again having difficulty with flu vaccine production. Last year the company found contamination at its Liverpool production plant, a situation that cause severe shortages of vaccine in the United States. This year, the company has discovered contamination at a German plant and is stating that it can only provide vaccine for the US market. The German plant was primarily the source of the Begrivac flu vaccine, which was sold on the world market. The company is making "substantial progress" in fixing problems at the Liverpool plant where the US vaccine is made. Meanwhile, Acambis plc is working on a universal flu vaccine that could offer permanent protection against all types of influenza. The company hopes to generate a universal vaccine that would not require annual changes in formulation and would protect against both influenza A and B including avian strains. The company, however, states that it may require years of clinical trials before earning approval. Fears of avian influenza pandemic have prompted the French company Sanofi-Aventis to work on a vaccine for the avian H5N1 strain that has killed millions of birds and 50 people in Asia. Preliminary results are promising, however, full-scale production could take months, according to Anthony Fauci, MD, Director of the National Institute of Allergy and Infectious Diseases. FDA Actions The FDA has approved the first of the new class of drugs for the treatment of insomnia characterized by difficulty with sleep onset. Takeda Pharmaceutical's ramelteon (Rozerem) is a selective agonist at 2 melatonin receptors in suprachiasmatic nucleus, receptors that are thought to regulate circadian rhythm and sleepiness. Recently marketed sleeping medications target GABA receptors (ambien, lunesta) and, although these drugs are associated with less addiction and sleep latency then benzodiazepines, they are still designated as Schedule IV drugs. Ramelteon has shown no evidence of abuse or dependence potential and will, therefore, be marketed as a unscheduled drug. It is also approved for long-term use and has not been associated with memory impairment or impairment of motor ability. The most common adverse events associated with ramelteon were somnolence, fatigue and dizziness (> 2% over placebo). Plan B, Barr Pharmaceutical's "morning-after pill" is being considered for over-the-counter approval by the FDA. The issue has become a political hot potato, and even briefly held up the Senate's confirmation of Lester Crawford, MD, as Commissioner of the FDA. It is expected that decision will be made by September. This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5416. E-mail: LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2005 AHC Media LLC All Rights Reserved 466 of 998 DOCUMENTS Clinical Oncology Alert September 1, 2005 Pharmacology Watch LENGTH: 1420 words Beta-Blockers May Be Useful for Noncardiac Surgery Pharmacology Watch High risk patients benefit from perioperative beta-blockers when undergoing major noncardiac surgery according to new study. Researchers from Tufts University reviewed the records of 782,969 patients in 2000 and 2001 at 329 hospitals throughout the United States. Patients were graded with the Revised Cardiac Risk Index (RCRI), which takes into account high-risk surgery, ischemic heart disease, cerebrovascular disease, renal insufficiency, and diabetes. The RCRI is graded on a 0-5 point scale, with 5 representing the highest risk. High risk surgery included all intrathoracic, intraperitoneal, and superinguinal vascular procedures. Patients with contraindications to beta blocker therapy were excluded. Over 660,000 patients had no contraindications to beta-blockers, and 120,338 patients received beta-blocker treatment during the first 2 hospital days. The relationship between perioperative beta-blocker treatment and the risk of death varied directly with cardiac risk. Patients with an RCRI of 0 or 1 were found to have no benefit from beta-blocker treatment, whereas for patients with an RCRI of 2, 3, or 4, or more the adjusted odds ratio for death in the hospital, were 0.88 (95% CI, 0.80, 0.80-0.98), 0.71 (95% CI, 0.63 - 0.80) and 0.58 (95% CI, 0.50-0.67), respectively. The authors conclude that perioperative beta-blocker therapy is associated with a reduced risk of in-hospital death among high-risk patients undergoing major noncardiac surgery. They also noted that there was no benefit for low risk patients (Lindenauer PK, et al. Perioperative Beta-Blocker Therapy and Mortality After Major Noncardiac Surgery. N Engl J Med. 2005;353:349-361). An accompanying editorial points out that perioperative beta-blocker therapy has been somewhat controversial because of conflicting data in recent years. The current study shows an apparent benefit in high-risk patients, but they also look forward to the results of 2 ongoing randomized trials that will help clarify the role of beta-blockers for low-risk and intermediate-risk patients (Poldermans D, et al. Beta-Blocker Therapy in Noncardiac Surgery. N Engl J Med. 2005;353:412-414). Promising New Weight Loss Drug? More data shows that topiramate (Topamax) is associated with weight loss and, in this latest study, may also lower blood pressure in obese, hypertensive patients. In a study from Norway, 531 obese patients with hypertension were randomized to placebo, topiramate 96 mg/day, or topiramate 192 mg/day. All patients received the same diet, exercise, and behavioral modification advice. Patients were followed for 28 weeks. Mean weight loss was 1.9% for placebo and 5.9% and 6.5% for the 96 mg and 192 mg doses, respectively (P < 0.001 for each compared with placebo). Diastolic blood pressure was reduced 2.1, 5.5, and 6.3 mm Hg, respectively (P < 0.015 vs placebo). Systolic blood pressure was reduced 4.9, 8.6, and 9.7 mm Hg, respectively (P = NS). Paresthesia occurred in 33% of the active treatment group. The authors conclude that topiramate produced clinically relevant effects in reducing body weight and BP, with generally mild to moderate adverse effects (Tonstad S, et al. Efficacy and Safety of Topiramate in the Treatment of Obese Subjects with Essential Hypertension. Am J Cardiol. 2005;96:243-251). Treating Shift-Work Disorder Modafinil (Provigil) may be of some value for people with excessive sleepiness associated with shift-work sleep disorder. Researchers from Harvard randomized 209 patients with shift-work sleep disorder to receive either 200 mg of modafinil or placebo before the start of each shift. Modafinil resulted in modest improvement in nighttime sleep latency (1.7 ~ 0.4 vs 0.3 ~ 0.3 minutes, respectively; P = 0.002). More patients also had improvement in their clinical symptoms based on multiple objective tests and patients diaries (74% vs 36%, respectively; P < 0.001). Patients taking modafinil also had reduction in frequency and duration of lapses in attention during nighttime testing of performance, and proportionally fewer patients reported having had accidents or near accidents while commuting home (both P < 0.001). These benefits, however, were mild, and patients treated with modafinil continued to have excessive sleepiness and impaired performance at night. The authors conclude that modafinil 200 mg at the beginning of a shift may improve shift-worker's performance as compared to placebo, although the benefit is modest (Czeisler CA, et al. Modafinil for Excessive Sleepiness Associated with Shift-Work Disorder. N Engl J Med. 2005;353:476-486). An accompanying editorial urges caution when interpreting these results and suggests "the current study does not adequately assess the clinical value of this particular drug in shift-work sleep disorder, nor does it justify writing more prescriptions for modafinil." The authors do note that up to 20% of workers in industrialized nations are shift-workers and calls for "further scientific studies to address in a cohesive manner the serious health and safety issues that surround us by virtue of us having become, to a large extent, a shift-working society" (Basner RC. Shift-Work Sleep Disorder--The Glass is More Than Half Empty. N Engl J Med. 2005;353:519-521). Another Flu Vaccine Shortage? With the flu season looming, Chiron Corp. is again having difficulty with flu vaccine production. Last year the company found contamination at its Liverpool production plant, a situation that cause severe shortages of vaccine in the United States. This year, the company has discovered contamination at a German plant and is stating that it can only provide vaccine for the US market. The German plant was primarily the source of the Begrivac flu vaccine, which was sold on the world market. The company is making "substantial progress" in fixing problems at the Liverpool plant where the US vaccine is made. Meanwhile, Acambis plc is working on a universal flu vaccine that could offer permanent protection against all types of influenza. The company hopes to generate a universal vaccine that would not require annual changes in formulation and would protect against both influenza A and B including avian strains. The company, however, states that it may require years of clinical trials before earning approval. Fears of avian influenza pandemic have prompted the French company Sanofi-Aventis to work on a vaccine for the avian H5N1 strain that has killed millions of birds and 50 people in Asia. Preliminary results are promising, however, full-scale production could take months, according to Anthony Fauci, MD, Director of the National Institute of Allergy and Infectious Diseases. FDA Actions The FDA has approved the first of the new class of drugs for the treatment of insomnia characterized by difficulty with sleep onset. Takeda Pharmaceutical's ramelteon (Rozerem) is a selective agonist at 2 melatonin receptors in suprachiasmatic nucleus, receptors that are thought to regulate circadian rhythm and sleepiness. Recently marketed sleeping medications target GABA receptors (ambien, lunesta) and, although these drugs are associated with less addiction and sleep latency then benzodiazepines, they are still designated as Schedule IV drugs. Ramelteon has shown no evidence of abuse or dependence potential and will, therefore, be marketed as a unscheduled drug. It is also approved for long-term use and has not been associated with memory impairment or impairment of motor ability. The most common adverse events associated with ramelteon were somnolence, fatigue and dizziness (> 2% over placebo). Plan B, Barr Pharmaceutical's "morning-after pill" is being considered for over-the-counter approval by the FDA. The issue has become a political hot potato, and even briefly held up the Senate's confirmation of Lester Crawford, MD, as Commissioner of the FDA. It is expected that decision will be made by September. This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5416. E-mail: LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2005 AHC Media LLC All Rights Reserved 467 of 998 DOCUMENTS CNS Drug News Pharmaceuticals September 1, 2005 McNeil/Cephalon to co-promote modafinil for ADHD LENGTH: 327 words McNeil Consumer & Specialty Pharmaceuticals ( Johnson & Johnson ) has entered into an agreement with Cephalon to co-promote the attention-deficit hyperactivity disorder (ADHD) drug, modafinil . Under the terms agreed, McNeil will promote modafinil upon approval in the US primarily to paediatric specialists, whilst Cephalon will promote the product to psychiatrists, neurologists, primary care physicians and other appropriate healthcare professionals. The co-promotion agreement will run for up to three years following the date of commercial launch of modafinil. Cephalon will pay McNeil commission fees, calculated as a percentage of annual net sales of modafinil during the term of the agreement, retaining all responsibility for the development, manufacture, distribution and sale of the product. The companies also plan to form a joint commercial committee to manage the promotion of modafinil. The proprietary dosage form of modafinil, named Attenace by Cephalon, is awaiting FDA approval for the treatment of ADHD in children and adolescents. Cephalon submitted an sNDA in December 2004 and anticipates a response on the PDUFA date of 20th October 2005. Data from earlier trials in children and adolescents with ADHD led to the development of modafinil as small, film-coated tablets in unique dosage strengths. The new tablets will be available in 85, 170, 255, 340 and 425mg strengths, and will allow for tailored dosing with a single tablet for children and adolescents. The active ingredient in modafinil is currently available as Provigil Tablets [C-IV] in 100 and 200mg strengths. Provigil is indicated for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnoea/hypopnoea syndrome and shift work sleep disorder. The most frequently reported adverse events in clinical trials with Provigil were headache, nausea, nervousness, stuffy nose, diarrhoea, back pain, anxiety, trouble sleeping, dizziness and upset stomach. LOAD-DATE: September 1, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2005 ESPICOM Business Intelligence Ltd. All Rights Reserved 468 of 998 DOCUMENTS Critical Care Alert September 1, 2005 Pharmacology Watch: Beta-Blockers May Be Useful for Noncardiac Surgery LENGTH: 1420 words Beta-Blockers May Be Useful for Noncardiac Surgery Pharmacology Watch High risk patients benefit from perioperative beta-blockers when undergoing major noncardiac surgery according to new study. Researchers from Tufts University reviewed the records of 782,969 patients in 2000 and 2001 at 329 hospitals throughout the United States. Patients were graded with the Revised Cardiac Risk Index (RCRI), which takes into account high-risk surgery, ischemic heart disease, cerebrovascular disease, renal insufficiency, and diabetes. The RCRI is graded on a 0-5 point scale, with 5 representing the highest risk. High risk surgery included all intrathoracic, intraperitoneal, and superinguinal vascular procedures. Patients with contraindications to beta blocker therapy were excluded. Over 660,000 patients had no contraindications to beta-blockers, and 120,338 patients received beta-blocker treatment during the first 2 hospital days. The relationship between perioperative beta-blocker treatment and the risk of death varied directly with cardiac risk. Patients with an RCRI of 0 or 1 were found to have no benefit from beta-blocker treatment, whereas for patients with an RCRI of 2, 3, or 4, or more the adjusted odds ratio for death in the hospital, were 0.88 (95% CI, 0.80, 0.80-0.98), 0.71 (95% CI, 0.63 - 0.80) and 0.58 (95% CI, 0.50-0.67), respectively. The authors conclude that perioperative beta-blocker therapy is associated with a reduced risk of in-hospital death among high-risk patients undergoing major noncardiac surgery. They also noted that there was no benefit for low risk patients (Lindenauer PK, et al. Perioperative Beta-Blocker Therapy and Mortality After Major Noncardiac Surgery. N Engl J Med. 2005;353:349-361). An accompanying editorial points out that perioperative beta-blocker therapy has been somewhat controversial because of conflicting data in recent years. The current study shows an apparent benefit in high-risk patients, but they also look forward to the results of 2 ongoing randomized trials that will help clarify the role of beta-blockers for low-risk and intermediate-risk patients (Poldermans D, et al. Beta-Blocker Therapy in Noncardiac Surgery. N Engl J Med. 2005;353:412-414). Promising New Weight Loss Drug? More data shows that topiramate (Topamax) is associated with weight loss and, in this latest study, may also lower blood pressure in obese, hypertensive patients. In a study from Norway, 531 obese patients with hypertension were randomized to placebo, topiramate 96 mg/day, or topiramate 192 mg/day. All patients received the same diet, exercise, and behavioral modification advice. Patients were followed for 28 weeks. Mean weight loss was 1.9% for placebo and 5.9% and 6.5% for the 96 mg and 192 mg doses, respectively (P < 0.001 for each compared with placebo). Diastolic blood pressure was reduced 2.1, 5.5, and 6.3 mm Hg, respectively (P < 0.015 vs placebo). Systolic blood pressure was reduced 4.9, 8.6, and 9.7 mm Hg, respectively (P = NS). Paresthesia occurred in 33% of the active treatment group. The authors conclude that topiramate produced clinically relevant effects in reducing body weight and BP, with generally mild to moderate adverse effects (Tonstad S, et al. Efficacy and Safety of Topiramate in the Treatment of Obese Subjects with Essential Hypertension. Am J Cardiol. 2005;96:243-251). Treating Shift-Work Disorder Modafinil (Provigil) may be of some value for people with excessive sleepiness associated with shift-work sleep disorder. Researchers from Harvard randomized 209 patients with shift-work sleep disorder to receive either 200 mg of modafinil or placebo before the start of each shift. Modafinil resulted in modest improvement in nighttime sleep latency (1.7 ~ 0.4 vs 0.3 ~ 0.3 minutes, respectively; P = 0.002). More patients also had improvement in their clinical symptoms based on multiple objective tests and patients diaries (74% vs 36%, respectively; P < 0.001). Patients taking modafinil also had reduction in frequency and duration of lapses in attention during nighttime testing of performance, and proportionally fewer patients reported having had accidents or near accidents while commuting home (both P < 0.001). These benefits, however, were mild, and patients treated with modafinil continued to have excessive sleepiness and impaired performance at night. The authors conclude that modafinil 200 mg at the beginning of a shift may improve shift-worker's performance as compared to placebo, although the benefit is modest (Czeisler CA, et al. Modafinil for Excessive Sleepiness Associated with Shift-Work Disorder. N Engl J Med. 2005;353:476-486). An accompanying editorial urges caution when interpreting these results and suggests "the current study does not adequately assess the clinical value of this particular drug in shift-work sleep disorder, nor does it justify writing more prescriptions for modafinil." The authors do note that up to 20% of workers in industrialized nations are shift-workers and calls for "further scientific studies to address in a cohesive manner the serious health and safety issues that surround us by virtue of us having become, to a large extent, a shift-working society" (Basner RC. Shift-Work Sleep Disorder--The Glass is More Than Half Empty. N Engl J Med. 2005;353:519-521). Another Flu Vaccine Shortage? With the flu season looming, Chiron Corp. is again having difficulty with flu vaccine production. Last year the company found contamination at its Liverpool production plant, a situation that cause severe shortages of vaccine in the United States. This year, the company has discovered contamination at a German plant and is stating that it can only provide vaccine for the US market. The German plant was primarily the source of the Begrivac flu vaccine, which was sold on the world market. The company is making "substantial progress" in fixing problems at the Liverpool plant where the US vaccine is made. Meanwhile, Acambis plc is working on a universal flu vaccine that could offer permanent protection against all types of influenza. The company hopes to generate a universal vaccine that would not require annual changes in formulation and would protect against both influenza A and B including avian strains. The company, however, states that it may require years of clinical trials before earning approval. Fears of avian influenza pandemic have prompted the French company Sanofi-Aventis to work on a vaccine for the avian H5N1 strain that has killed millions of birds and 50 people in Asia. Preliminary results are promising, however, full-scale production could take months, according to Anthony Fauci, MD, Director of the National Institute of Allergy and Infectious Diseases. FDA Actions The FDA has approved the first of the new class of drugs for the treatment of insomnia characterized by difficulty with sleep onset. Takeda Pharmaceutical's ramelteon (Rozerem) is a selective agonist at 2 melatonin receptors in suprachiasmatic nucleus, receptors that are thought to regulate circadian rhythm and sleepiness. Recently marketed sleeping medications target GABA receptors (ambien, lunesta) and, although these drugs are associated with less addiction and sleep latency then benzodiazepines, they are still designated as Schedule IV drugs. Ramelteon has shown no evidence of abuse or dependence potential and will, therefore, be marketed as a unscheduled drug. It is also approved for long-term use and has not been associated with memory impairment or impairment of motor ability. The most common adverse events associated with ramelteon were somnolence, fatigue and dizziness (> 2% over placebo). Plan B, Barr Pharmaceutical's "morning-after pill" is being considered for over-the-counter approval by the FDA. The issue has become a political hot potato, and even briefly held up the Senate's confirmation of Lester Crawford, MD, as Commissioner of the FDA. It is expected that decision will be made by September. This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5416. E-mail: LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2005 AHC Media LLC All Rights Reserved 469 of 998 DOCUMENTS Infectious Disease Alert September 1, 2005 Pharmacology Watch: Beta-Blockers May Be Useful for Noncardiac Surgery LENGTH: 1420 words Beta-Blockers May Be Useful for Noncardiac Surgery Pharmacology Watch High risk patients benefit from perioperative beta-blockers when undergoing major noncardiac surgery according to new study. Researchers from Tufts University reviewed the records of 782,969 patients in 2000 and 2001 at 329 hospitals throughout the United States. Patients were graded with the Revised Cardiac Risk Index (RCRI), which takes into account high-risk surgery, ischemic heart disease, cerebrovascular disease, renal insufficiency, and diabetes. The RCRI is graded on a 0-5 point scale, with 5 representing the highest risk. High risk surgery included all intrathoracic, intraperitoneal, and superinguinal vascular procedures. Patients with contraindications to beta blocker therapy were excluded. Over 660,000 patients had no contraindications to beta-blockers, and 120,338 patients received beta-blocker treatment during the first 2 hospital days. The relationship between perioperative beta-blocker treatment and the risk of death varied directly with cardiac risk. Patients with an RCRI of 0 or 1 were found to have no benefit from beta-blocker treatment, whereas for patients with an RCRI of 2, 3, or 4, or more the adjusted odds ratio for death in the hospital, were 0.88 (95% CI, 0.80, 0.80-0.98), 0.71 (95% CI, 0.63 - 0.80) and 0.58 (95% CI, 0.50-0.67), respectively. The authors conclude that perioperative beta-blocker therapy is associated with a reduced risk of in-hospital death among high-risk patients undergoing major noncardiac surgery. They also noted that there was no benefit for low risk patients (Lindenauer PK, et al. Perioperative Beta-Blocker Therapy and Mortality After Major Noncardiac Surgery. N Engl J Med. 2005;353:349-361). An accompanying editorial points out that perioperative beta-blocker therapy has been somewhat controversial because of conflicting data in recent years. The current study shows an apparent benefit in high-risk patients, but they also look forward to the results of 2 ongoing randomized trials that will help clarify the role of beta-blockers for low-risk and intermediate-risk patients (Poldermans D, et al. Beta-Blocker Therapy in Noncardiac Surgery. N Engl J Med. 2005;353:412-414). Promising New Weight Loss Drug? More data shows that topiramate (Topamax) is associated with weight loss and, in this latest study, may also lower blood pressure in obese, hypertensive patients. In a study from Norway, 531 obese patients with hypertension were randomized to placebo, topiramate 96 mg/day, or topiramate 192 mg/day. All patients received the same diet, exercise, and behavioral modification advice. Patients were followed for 28 weeks. Mean weight loss was 1.9% for placebo and 5.9% and 6.5% for the 96 mg and 192 mg doses, respectively (P < 0.001 for each compared with placebo). Diastolic blood pressure was reduced 2.1, 5.5, and 6.3 mm Hg, respectively (P < 0.015 vs placebo). Systolic blood pressure was reduced 4.9, 8.6, and 9.7 mm Hg, respectively (P = NS). Paresthesia occurred in 33% of the active treatment group. The authors conclude that topiramate produced clinically relevant effects in reducing body weight and BP, with generally mild to moderate adverse effects (Tonstad S, et al. Efficacy and Safety of Topiramate in the Treatment of Obese Subjects with Essential Hypertension. Am J Cardiol. 2005;96:243-251). Treating Shift-Work Disorder Modafinil (Provigil) may be of some value for people with excessive sleepiness associated with shift-work sleep disorder. Researchers from Harvard randomized 209 patients with shift-work sleep disorder to receive either 200 mg of modafinil or placebo before the start of each shift. Modafinil resulted in modest improvement in nighttime sleep latency (1.7 ~ 0.4 vs 0.3 ~ 0.3 minutes, respectively; P = 0.002). More patients also had improvement in their clinical symptoms based on multiple objective tests and patients diaries (74% vs 36%, respectively; P < 0.001). Patients taking modafinil also had reduction in frequency and duration of lapses in attention during nighttime testing of performance, and proportionally fewer patients reported having had accidents or near accidents while commuting home (both P < 0.001). These benefits, however, were mild, and patients treated with modafinil continued to have excessive sleepiness and impaired performance at night. The authors conclude that modafinil 200 mg at the beginning of a shift may improve shift-worker's performance as compared to placebo, although the benefit is modest (Czeisler CA, et al. Modafinil for Excessive Sleepiness Associated with Shift-Work Disorder. N Engl J Med. 2005;353:476-486). An accompanying editorial urges caution when interpreting these results and suggests "the current study does not adequately assess the clinical value of this particular drug in shift-work sleep disorder, nor does it justify writing more prescriptions for modafinil." The authors do note that up to 20% of workers in industrialized nations are shift-workers and calls for "further scientific studies to address in a cohesive manner the serious health and safety issues that surround us by virtue of us having become, to a large extent, a shift-working society" (Basner RC. Shift-Work Sleep Disorder--The Glass is More Than Half Empty. N Engl J Med. 2005;353:519-521). Another Flu Vaccine Shortage? With the flu season looming, Chiron Corp. is again having difficulty with flu vaccine production. Last year the company found contamination at its Liverpool production plant, a situation that cause severe shortages of vaccine in the United States. This year, the company has discovered contamination at a German plant and is stating that it can only provide vaccine for the US market. The German plant was primarily the source of the Begrivac flu vaccine, which was sold on the world market. The company is making "substantial progress" in fixing problems at the Liverpool plant where the US vaccine is made. Meanwhile, Acambis plc is working on a universal flu vaccine that could offer permanent protection against all types of influenza. The company hopes to generate a universal vaccine that would not require annual changes in formulation and would protect against both influenza A and B including avian strains. The company, however, states that it may require years of clinical trials before earning approval. Fears of avian influenza pandemic have prompted the French company Sanofi-Aventis to work on a vaccine for the avian H5N1 strain that has killed millions of birds and 50 people in Asia. Preliminary results are promising, however, full-scale production could take months, according to Anthony Fauci, MD, Director of the National Institute of Allergy and Infectious Diseases. FDA Actions The FDA has approved the first of the new class of drugs for the treatment of insomnia characterized by difficulty with sleep onset. Takeda Pharmaceutical's ramelteon (Rozerem) is a selective agonist at 2 melatonin receptors in suprachiasmatic nucleus, receptors that are thought to regulate circadian rhythm and sleepiness. Recently marketed sleeping medications target GABA receptors (ambien, lunesta) and, although these drugs are associated with less addiction and sleep latency then benzodiazepines, they are still designated as Schedule IV drugs. Ramelteon has shown no evidence of abuse or dependence potential and will, therefore, be marketed as a unscheduled drug. It is also approved for long-term use and has not been associated with memory impairment or impairment of motor ability. The most common adverse events associated with ramelteon were somnolence, fatigue and dizziness (> 2% over placebo). Plan B, Barr Pharmaceutical's "morning-after pill" is being considered for over-the-counter approval by the FDA. The issue has become a political hot potato, and even briefly held up the Senate's confirmation of Lester Crawford, MD, as Commissioner of the FDA. It is expected that decision will be made by September. This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5416. E-mail: LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2005 AHC Media LLC All Rights Reserved 470 of 998 DOCUMENTS Neurology Alert September 1, 2005 Pharmacology Watch: Beta-Blockers May Be Useful for Noncardiac Surgery LENGTH: 1420 words Beta-Blockers May Be Useful for Noncardiac Surgery Pharmacology Watch High-risk patients benefit from perioperative beta-blockers when undergoing major noncardiac surgery according to new study. Researchers from Tufts University reviewed the records of 782,969 patients in 2000 and 2001 at 329 hospitals throughout the United States. Patients were graded with the Revised Cardiac Risk Index (RCRI), which takes into account high-risk surgery, ischemic heart disease, cerebrovascular disease, renal insufficiency, and diabetes. The RCRI is graded on a 0-5 point scale, with 5 representing the highest risk. High risk surgery included all intrathoracic, intraperitoneal, and superinguinal vascular procedures. Patients with contraindications to beta blocker therapy were excluded. Over 660,000 patients had no contraindications to beta-blockers, and 120,338 patients received beta-blocker treatment during the first 2 hospital days. The relationship between perioperative beta-blocker treatment and the risk of death varied directly with cardiac risk. Patients with an RCRI of 0 or 1 were found to have no benefit from beta-blocker treatment, whereas for patients with an RCRI of 2, 3, or 4, or more the adjusted odds ratio for death in the hospital, were 0.88 (95% CI, 0.80, 0.80-0.98), 0.71 (95% CI, 0.63 - 0.80) and 0.58 (95% CI, 0.50-0.67), respectively. The authors conclude that perioperative beta-blocker therapy is associated with a reduced risk of in-hospital death among high-risk patients undergoing major noncardiac surgery. They also noted that there was no benefit for low risk patients (Lindenauer PK, et al. Perioperative Beta-Blocker Therapy and Mortality After Major Noncardiac Surgery. N Engl J Med. 2005;353:349-361). An accompanying editorial points out that perioperative beta-blocker therapy has been somewhat controversial because of conflicting data in recent years. The current study shows an apparent benefit in high-risk patients, but they also look forward to the results of 2 ongoing randomized trials that will help clarify the role of beta-blockers for low-risk and intermediate-risk patients (Poldermans D, et al. Beta-Blocker Therapy in Noncardiac Surgery. N Engl J Med. 2005;353:412-414). Promising New Weight Loss Drug? More data shows that topiramate (Topamax) is associated with weight loss and, in this latest study, may also lower blood pressure in obese, hypertensive patients. In a study from Norway, 531 obese patients with hypertension were randomized to placebo, topiramate 96 mg/day, or topiramate 192 mg/day. All patients received the same diet, exercise, and behavioral modification advice. Patients were followed for 28 weeks. Mean weight loss was 1.9% for placebo and 5.9% and 6.5% for the 96 mg and 192 mg doses, respectively (P < 0.001 for each compared with placebo). Diastolic blood pressure was reduced 2.1, 5.5, and 6.3 mm Hg, respectively (P < 0.015 vs placebo). Systolic blood pressure was reduced 4.9, 8.6, and 9.7 mm Hg, respectively (P = NS). Paresthesia occurred in 33% of the active treatment group. The authors conclude that topiramate produced clinically relevant effects in reducing body weight and BP, with generally mild to moderate adverse effects (Tonstad S, et al. Efficacy and Safety of Topiramate in the Treatment of Obese Subjects with Essential Hypertension. Am J Cardiol. 2005;96:243-251). Treating Shift-Work Disorder Modafinil (Provigil) may be of some value for people with excessive sleepiness associated with shift-work sleep disorder. Researchers from Harvard randomized 209 patients with shift-work sleep disorder to receive either 200 mg of modafinil or placebo before the start of each shift. Modafinil resulted in modest improvement in nighttime sleep latency (1.7 ~ 0.4 vs 0.3 ~ 0.3 minutes, respectively; P = 0.002). More patients also had improvement in their clinical symptoms based on multiple objective tests and patients diaries (74% vs 36%, respectively; P < 0.001). Patients taking modafinil also had reduction in frequency and duration of lapses in attention during nighttime testing of performance, and proportionally fewer patients reported having had accidents or near accidents while commuting home (both P < 0.001). These benefits, however, were mild, and patients treated with modafinil continued to have excessive sleepiness and impaired performance at night. The authors conclude that modafinil 200 mg at the beginning of a shift may improve shift-worker's performance as compared to placebo, although the benefit is modest (Czeisler CA, et al. Modafinil for Excessive Sleepiness Associated with Shift-Work Disorder. N Engl J Med. 2005;353:476-486). An accompanying editorial urges caution when interpreting these results and suggests "the current study does not adequately assess the clinical value of this particular drug in shift-work sleep disorder, nor does it justify writing more prescriptions for modafinil." The authors do note that up to 20% of workers in industrialized nations are shift-workers and calls for "further scientific studies to address in a cohesive manner the serious health and safety issues that surround us by virtue of us having become, to a large extent, a shift-working society" (Basner RC. Shift-Work Sleep Disorder--The Glass is More Than Half Empty. N Engl J Med. 2005;353:519-521). Another Flu Vaccine Shortage? With the flu season looming, Chiron Corp. is again having difficulty with flu vaccine production. Last year the company found contamination at its Liverpool production plant, a situation that cause severe shortages of vaccine in the United States. This year, the company has discovered contamination at a German plant and is stating that it can only provide vaccine for the US market. The German plant was primarily the source of the Begrivac flu vaccine, which was sold on the world market. The company is making "substantial progress" in fixing problems at the Liverpool plant where the US vaccine is made. Meanwhile, Acambis plc is working on a universal flu vaccine that could offer permanent protection against all types of influenza. The company hopes to generate a universal vaccine that would not require annual changes in formulation and would protect against both influenza A and B including avian strains. The company, however, states that it may require years of clinical trials before earning approval. Fears of avian influenza pandemic have prompted the French company Sanofi-Aventis to work on a vaccine for the avian H5N1 strain that has killed millions of birds and 50 people in Asia. Preliminary results are promising, however, full-scale production could take months, according to Anthony Fauci, MD, Director of the National Institute of Allergy and Infectious Diseases. FDA Actions The FDA has approved the first of the new class of drugs for the treatment of insomnia characterized by difficulty with sleep onset. Takeda Pharmaceutical's ramelteon (Rozerem) is a selective agonist at 2 melatonin receptors in suprachiasmatic nucleus, receptors that are thought to regulate circadian rhythm and sleepiness. Recently marketed sleeping medications target GABA receptors (ambien, lunesta) and, although these drugs are associated with less addiction and sleep latency then benzodiazepines, they are still designated as Schedule IV drugs. Ramelteon has shown no evidence of abuse or dependence potential and will, therefore, be marketed as a unscheduled drug. It is also approved for long-term use and has not been associated with memory impairment or impairment of motor ability. The most common adverse events associated with ramelteon were somnolence, fatigue and dizziness (> 2% over placebo). Plan B, Barr Pharmaceutical's "morning-after pill" is being considered for over-the-counter approval by the FDA. The issue has become a political hot potato, and even briefly held up the Senate's confirmation of Lester Crawford, MD, as Commissioner of the FDA. It is expected that decision will be made by September. This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5416. E-mail: LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2005 AHC Media LLC All Rights Reserved 471 of 998 DOCUMENTS OB/GYN Clinical Alert September 1, 2005 Pharmacology Watch: Beta-Blockers May Be Useful for Noncardiac Surgery LENGTH: 1420 words Beta-Blockers May Be Useful for Noncardiac Surgery Pharmacology Watch High risk patients benefit from perioperative beta-blockers when undergoing major noncardiac surgery according to new study. Researchers from Tufts University reviewed the records of 782,969 patients in 2000 and 2001 at 329 hospitals throughout the United States. Patients were graded with the Revised Cardiac Risk Index (RCRI), which takes into account high-risk surgery, ischemic heart disease, cerebrovascular disease, renal insufficiency, and diabetes. The RCRI is graded on a 0-5 point scale, with 5 representing the highest risk. High risk surgery included all intrathoracic, intraperitoneal, and superinguinal vascular procedures. Patients with contraindications to beta blocker therapy were excluded. Over 660,000 patients had no contraindications to beta-blockers, and 120,338 patients received beta-blocker treatment during the first 2 hospital days. The relationship between perioperative beta-blocker treatment and the risk of death varied directly with cardiac risk. Patients with an RCRI of 0 or 1 were found to have no benefit from beta-blocker treatment, whereas for patients with an RCRI of 2, 3, or 4, or more the adjusted odds ratio for death in the hospital, were 0.88 (95% CI, 0.80, 0.80-0.98), 0.71 (95% CI, 0.63 - 0.80) and 0.58 (95% CI, 0.50-0.67), respectively. The authors conclude that perioperative beta-blocker therapy is associated with a reduced risk of in-hospital death among high-risk patients undergoing major noncardiac surgery. They also noted that there was no benefit for low risk patients (Lindenauer PK, et al. Perioperative Beta-Blocker Therapy and Mortality After Major Noncardiac Surgery. N Engl J Med. 2005;353:349-361). An accompanying editorial points out that perioperative beta-blocker therapy has been somewhat controversial because of conflicting data in recent years. The current study shows an apparent benefit in high-risk patients, but they also look forward to the results of 2 ongoing randomized trials that will help clarify the role of beta-blockers for low-risk and intermediate-risk patients (Poldermans D, et al. Beta-Blocker Therapy in Noncardiac Surgery. N Engl J Med. 2005;353:412-414). Promising New Weight Loss Drug? More data shows that topiramate (Topamax) is associated with weight loss and, in this latest study, may also lower blood pressure in obese, hypertensive patients. In a study from Norway, 531 obese patients with hypertension were randomized to placebo, topiramate 96 mg/day, or topiramate 192 mg/day. All patients received the same diet, exercise, and behavioral modification advice. Patients were followed for 28 weeks. Mean weight loss was 1.9% for placebo and 5.9% and 6.5% for the 96 mg and 192 mg doses, respectively (P < 0.001 for each compared with placebo). Diastolic blood pressure was reduced 2.1, 5.5, and 6.3 mm Hg, respectively (P < 0.015 vs placebo). Systolic blood pressure was reduced 4.9, 8.6, and 9.7 mm Hg, respectively (P = NS). Paresthesia occurred in 33% of the active treatment group. The authors conclude that topiramate produced clinically relevant effects in reducing body weight and BP, with generally mild to moderate adverse effects (Tonstad S, et al. Efficacy and Safety of Topiramate in the Treatment of Obese Subjects with Essential Hypertension. Am J Cardiol. 2005;96:243-251). Treating Shift-Work Disorder Modafinil (Provigil) may be of some value for people with excessive sleepiness associated with shift-work sleep disorder. Researchers from Harvard randomized 209 patients with shift-work sleep disorder to receive either 200 mg of modafinil or placebo before the start of each shift. Modafinil resulted in modest improvement in nighttime sleep latency (1.7 ~ 0.4 vs 0.3 ~ 0.3 minutes, respectively; P = 0.002). More patients also had improvement in their clinical symptoms based on multiple objective tests and patients diaries (74% vs 36%, respectively; P < 0.001). Patients taking modafinil also had reduction in frequency and duration of lapses in attention during nighttime testing of performance, and proportionally fewer patients reported having had accidents or near accidents while commuting home (both P < 0.001). These benefits, however, were mild, and patients treated with modafinil continued to have excessive sleepiness and impaired performance at night. The authors conclude that modafinil 200 mg at the beginning of a shift may improve shift-worker's performance as compared to placebo, although the benefit is modest (Czeisler CA, et al. Modafinil for Excessive Sleepiness Associated with Shift-Work Disorder. N Engl J Med. 2005;353:476-486). An accompanying editorial urges caution when interpreting these results and suggests "the current study does not adequately assess the clinical value of this particular drug in shift-work sleep disorder, nor does it justify writing more prescriptions for modafinil." The authors do note that up to 20% of workers in industrialized nations are shift-workers and calls for "further scientific studies to address in a cohesive manner the serious health and safety issues that surround us by virtue of us having become, to a large extent, a shift-working society" (Basner RC. Shift-Work Sleep Disorder--The Glass is More Than Half Empty. N Engl J Med. 2005;353:519-521). Another Flu Vaccine Shortage? With the flu season looming, Chiron Corp. is again having difficulty with flu vaccine production. Last year the company found contamination at its Liverpool production plant, a situation that cause severe shortages of vaccine in the United States. This year, the company has discovered contamination at a German plant and is stating that it can only provide vaccine for the US market. The German plant was primarily the source of the Begrivac flu vaccine, which was sold on the world market. The company is making "substantial progress" in fixing problems at the Liverpool plant where the US vaccine is made. Meanwhile, Acambis plc is working on a universal flu vaccine that could offer permanent protection against all types of influenza. The company hopes to generate a universal vaccine that would not require annual changes in formulation and would protect against both influenza A and B including avian strains. The company, however, states that it may require years of clinical trials before earning approval. Fears of avian influenza pandemic have prompted the French company Sanofi-Aventis to work on a vaccine for the avian H5N1 strain that has killed millions of birds and 50 people in Asia. Preliminary results are promising, however, full-scale production could take months, according to Anthony Fauci, MD, Director of the National Institute of Allergy and Infectious Diseases. FDA Actions The FDA has approved the first of the new class of drugs for the treatment of insomnia characterized by difficulty with sleep onset. Takeda Pharmaceutical's ramelteon (Rozerem) is a selective agonist at 2 melatonin receptors in suprachiasmatic nucleus, receptors that are thought to regulate circadian rhythm and sleepiness. Recently marketed sleeping medications target GABA receptors (ambien, lunesta) and, although these drugs are associated with less addiction and sleep latency then benzodiazepines, they are still designated as Schedule IV drugs. Ramelteon has shown no evidence of abuse or dependence potential and will, therefore, be marketed as a unscheduled drug. It is also approved for long-term use and has not been associated with memory impairment or impairment of motor ability. The most common adverse events associated with ramelteon were somnolence, fatigue and dizziness (> 2% over placebo). Plan B, Barr Pharmaceutical's "morning-after pill" is being considered for over-the-counter approval by the FDA. The issue has become a political hot potato, and even briefly held up the Senate's confirmation of Lester Crawford, MD, as Commissioner of the FDA. It is expected that decision will be made by September. This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5416. E-mail: LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2005 AHC Media LLC All Rights Reserved 472 of 998 DOCUMENTS Pharma Marketletter September 1, 2005 McNeil to co-promote modafinil for ADHD with Cephalon LENGTH: 159 words McNeil Consumer & Specialty Pharmaceuticals, a subsidiary of Johnson & Johnson, has entered into an agreement with Cephalon to co-promote modafinil. This proprietary dosage form of modafinil is awaiting US Food and Drug Administration approval for the treatment of attention-deficit hyperactivity disorder in children and adolescents. Cephalon submitted a supplemental New Drug Application for the compound to the FDA in December 2004 and anticipates a response on October 20. Upon approval in the USA, more than 300 McNeil sales representatives who currently sell the ADHD product Concerta (methylphenidate HCl) C-II extended-release tablets will promote modafinil, primarily to pediatric specialists. Cephalon will use its existing central nervous system specialty sales force of approximately 400 detailmen to promote modafinil to psychiatrists, neurologists, primary care physicians and other appropriate health care professionals. LOAD-DATE: September 1, 2005 LANGUAGE: ENGLISH Copyright 2005 Marketletter Publications Ltd. 473 of 998 DOCUMENTS Primary Care Reports September 1, 2005 Pharmacology Watch: Beta-Blockers May Be Useful for Noncardiac Surgery LENGTH: 1422 words Beta-Blockers May Be Useful for Noncardiac Surgery Pharmacology Watch High-risk patients benefit from perioperative beta-blockers when undergoing major noncardiac surgery according to new study. Researchers from Tufts University reviewed the records of 782,969 patients in 2000 and 2001 at 329 hospitals throughout the United States. Patients were graded with the Revised Cardiac Risk Index (RCRI), which takes into account high-risk surgery, ischemic heart disease, cerebrovascular disease, renal insufficiency, and diabetes. The RCRI is graded on a 0-5 point scale, with 5 representing the highest risk. High risk surgery included all intrathoracic, intraperitoneal, and superinguinal vascular procedures. Patients with contraindications to beta blocker therapy were excluded. Over 660,000 patients had no contraindications to beta-blockers, and 120,338 patients received beta-blocker treatment during the first 2 hospital days. The relationship between perioperative beta-blocker treatment and the risk of death varied directly with cardiac risk. Patients with an RCRI of 0 or 1 were found to have no benefit from beta-blocker treatment, whereas for patients with an RCRI of 2, 3, or 4, or more the adjusted odds ratio for death in the hospital, were 0.88 (95% CI, 0.80, 0.80-0.98), 0.71 (95% CI, 0.63 - 0.80) and 0.58 (95% CI, 0.50-0.67), respectively. The authors conclude that perioperative beta-blocker therapy is associated with a reduced risk of in-hospital death among high-risk patients undergoing major noncardiac surgery. They also noted that there was no benefit for low risk patients (Lindenauer PK, et al. Perioperative Beta-Blocker Therapy and Mortality After Major Noncardiac Surgery. N Engl J Med. 2005;353:349-361). An accompanying editorial points out that perioperative beta-blocker therapy has been somewhat controversial because of conflicting data in recent years. The current study shows an apparent benefit in high-risk patients, but they also look forward to the results of 2 ongoing randomized trials that will help clarify the role of beta-blockers for low-risk and intermediate-risk patients (Poldermans D, et al. Beta-Blocker Therapy in Noncardiac Surgery. N Engl J Med. 2005;353:412-414). Promising New Weight Loss Drug? More data shows that topiramate (Topamax) is associated with weight loss and, in this latest study, may also lower blood pressure in obese, hypertensive patients. In a study from Norway, 531 obese patients with hypertension were randomized to placebo, topiramate 96 mg/day, or topiramate 192 mg/day. All patients received the same diet, exercise, and behavioral modification advice. Patients were followed for 28 weeks. Mean weight loss was 1.9% for placebo and 5.9% and 6.5% for the 96 mg and 192 mg doses, respectively (P < 0.001 for each compared with placebo). Diastolic blood pressure was reduced 2.1, 5.5, and 6.3 mm Hg, respectively (P < 0.015 vs placebo). Systolic blood pressure was reduced 4.9, 8.6, and 9.7 mm Hg, respectively (P = NS). Paresthesia occurred in 33% of the active treatment group. The authors conclude that topiramate produced clinically relevant effects in reducing body weight and BP, with generally mild to moderate adverse effects (Tonstad S, et al. Efficacy and Safety of Topiramate in the Treatment of Obese Subjects with Essential Hypertension. Am J Cardiol. 2005;96:243-251). Treating Shift-Work Disorder Modafinil (Provigil) may be of some value for people with excessive sleepiness associated with shift-work sleep disorder. Researchers from Harvard randomized 209 patients with shift-work sleep disorder to receive either 200 mg of modafinil or placebo before the start of each shift. Modafinil resulted in modest improvement in nighttime sleep latency (1.7 + 0.4 vs 0.3 + 0.3 minutes, respectively; P = 0.002). More patients also had improvement in their clinical symptoms based on multiple objective tests and patients diaries (74% vs 36%, respectively; P < 0.001). Patients taking modafinil also had reduction in frequency and duration of lapses in attention during nighttime testing of performance, and proportionally fewer patients reported having had accidents or near accidents while commuting home (both P < 0.001). These benefits, however, were mild, and patients treated with modafinil continued to have excessive sleepiness and impaired performance at night. The authors conclude that modafinil 200 mg at the beginning of a shift may improve shift-worker's performance as compared to placebo, although the benefit is modest (Czeisler CA, et al. Modafinil for Excessive Sleepiness Associated with Shift-Work Disorder. N Engl J Med. 2005;353:476-486). An accompanying editorial urges caution when interpreting these results and suggests "the current study does not adequately assess the clinical value of this particular drug in shift-work sleep disorder, nor does it justify writing more prescriptions for modafinil." The authors do note that up to 20% of workers in industrialized nations are shift-workers and calls for "further scientific studies to address in a cohesive manner the serious health and safety issues that surround us by virtue of us having become, to a large extent, a shift-working society" (Basner RC. Shift-Work Sleep Disorder--The Glass is More Than Half Empty. N Engl J Med. 2005;353:519-521). Another Flu Vaccine Shortage? With the flu season looming, Chiron Corp. is again having difficulty with flu vaccine production. Last year the company found contamination at its Liverpool production plant, a situation that cause severe shortages of vaccine in the United States. This year, the company has discovered contamination at a German plant and is stating that it can only provide vaccine for the US market. The German plant was primarily the source of the Begrivac flu vaccine, which was sold on the world market. The company is making "substantial progress" in fixing problems at the Liverpool plant where the US vaccine is made. Meanwhile, Acambis plc is working on a universal flu vaccine that could offer permanent protection against all types of influenza. The company hopes to generate a universal vaccine that would not require annual changes in formulation and would protect against both influenza A and B including avian strains. The company, however, states that it may require years of clinical trials before earning approval. Fears of avian influenza pandemic have prompted the French company Sanofi-Aventis to work on a vaccine for the avian H5N1 strain that has killed millions of birds and 50 people in Asia. Preliminary results are promising, however, full-scale production could take months, according to Anthony Fauci, MD, Director of the National Institute of Allergy and Infectious Diseases. FDA Actions The FDA has approved the first of the new class of drugs for the treatment of insomnia characterized by difficulty with sleep onset. Takeda Pharmaceutical's ramelteon (Rozerem) is a selective agonist at 2 melatonin receptors in suprachiasmatic nucleus, receptors that are thought to regulate circadian rhythm and sleepiness. Recently marketed sleeping medications target GABA receptors (ambien, lunesta) and, although these drugs are associated with less addiction and sleep latency then benzodiazepines, they are still designated as Schedule IV drugs. Ramelteon has shown no evidence of abuse or dependence potential and will, therefore, be marketed as a unscheduled drug. It is also approved for long-term use and has not been associated with memory impairment or impairment of motor ability. The most common adverse events associated with ramelteon were somnolence, fatigue and dizziness (> 2% over placebo). Plan B, Barr Pharmaceutical's "morning-after pill" is being considered for over-the-counter approval by the FDA. The issue has become a political hot potato, and even briefly held up the Senate's confirmation of Lester Crawford, MD, as Commissioner of the FDA. It is expected that decision will be made by September. This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5416. E-mail: LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2005 AHC Media LLC All Rights Reserved 474 of 998 DOCUMENTS Travel Medicine Advisor September 1, 2005 Pharmacology Watch: Beta-Blockers May Be Useful for Noncardiac Surgery LENGTH: 1420 words Beta-Blockers May Be Useful for Noncardiac Surgery Pharmacology Watch High risk patients benefit from perioperative beta-blockers when undergoing major noncardiac surgery according to new study. Researchers from Tufts University reviewed the records of 782,969 patients in 2000 and 2001 at 329 hospitals throughout the United States. Patients were graded with the Revised Cardiac Risk Index (RCRI), which takes into account high-risk surgery, ischemic heart disease, cerebrovascular disease, renal insufficiency, and diabetes. The RCRI is graded on a 0-5 point scale, with 5 representing the highest risk. High risk surgery included all intrathoracic, intraperitoneal, and superinguinal vascular procedures. Patients with contraindications to beta blocker therapy were excluded. Over 660,000 patients had no contraindications to beta-blockers, and 120,338 patients received beta-blocker treatment during the first 2 hospital days. The relationship between perioperative beta-blocker treatment and the risk of death varied directly with cardiac risk. Patients with an RCRI of 0 or 1 were found to have no benefit from beta-blocker treatment, whereas for patients with an RCRI of 2, 3, or 4, or more the adjusted odds ratio for death in the hospital, were 0.88 (95% CI, 0.80, 0.80-0.98), 0.71 (95% CI, 0.63 - 0.80) and 0.58 (95% CI, 0.50-0.67), respectively. The authors conclude that perioperative beta-blocker therapy is associated with a reduced risk of in-hospital death among high-risk patients undergoing major noncardiac surgery. They also noted that there was no benefit for low risk patients (Lindenauer PK, et al. Perioperative Beta-Blocker Therapy and Mortality After Major Noncardiac Surgery. N Engl J Med. 2005;353:349-361). An accompanying editorial points out that perioperative beta-blocker therapy has been somewhat controversial because of conflicting data in recent years. The current study shows an apparent benefit in high-risk patients, but they also look forward to the results of 2 ongoing randomized trials that will help clarify the role of beta-blockers for low-risk and intermediate-risk patients (Poldermans D, et al. Beta-Blocker Therapy in Noncardiac Surgery. N Engl J Med. 2005;353:412-414). Promising New Weight Loss Drug? More data shows that topiramate (Topamax) is associated with weight loss and, in this latest study, may also lower blood pressure in obese, hypertensive patients. In a study from Norway, 531 obese patients with hypertension were randomized to placebo, topiramate 96 mg/day, or topiramate 192 mg/day. All patients received the same diet, exercise, and behavioral modification advice. Patients were followed for 28 weeks. Mean weight loss was 1.9% for placebo and 5.9% and 6.5% for the 96 mg and 192 mg doses, respectively (P < 0.001 for each compared with placebo). Diastolic blood pressure was reduced 2.1, 5.5, and 6.3 mm Hg, respectively (P < 0.015 vs placebo). Systolic blood pressure was reduced 4.9, 8.6, and 9.7 mm Hg, respectively (P = NS). Paresthesia occurred in 33% of the active treatment group. The authors conclude that topiramate produced clinically relevant effects in reducing body weight and BP, with generally mild to moderate adverse effects (Tonstad S, et al. Efficacy and Safety of Topiramate in the Treatment of Obese Subjects with Essential Hypertension. Am J Cardiol. 2005;96:243-251). Treating Shift-Work Disorder Modafinil (Provigil) may be of some value for people with excessive sleepiness associated with shift-work sleep disorder. Researchers from Harvard randomized 209 patients with shift-work sleep disorder to receive either 200 mg of modafinil or placebo before the start of each shift. Modafinil resulted in modest improvement in nighttime sleep latency (1.7 ± 0.4 vs 0.3 ± 0.3 minutes, respectively; P = 0.002). More patients also had improvement in their clinical symptoms based on multiple objective tests and patients diaries (74% vs 36%, respectively; P < 0.001). Patients taking modafinil also had reduction in frequency and duration of lapses in attention during nighttime testing of performance, and proportionally fewer patients reported having had accidents or near accidents while commuting home (both P < 0.001). These benefits, however, were mild, and patients treated with modafinil continued to have excessive sleepiness and impaired performance at night. The authors conclude that modafinil 200 mg at the beginning of a shift may improve shift-worker's performance as compared to placebo, although the benefit is modest (Czeisler CA, et al. Modafinil for Excessive Sleepiness Associated with Shift-Work Disorder. N Engl J Med. 2005;353:476-486). An accompanying editorial urges caution when interpreting these results and suggests "the current study does not adequately assess the clinical value of this particular drug in shift-work sleep disorder, nor does it justify writing more prescriptions for modafinil." The authors do note that up to 20% of workers in industrialized nations are shift-workers and calls for "further scientific studies to address in a cohesive manner the serious health and safety issues that surround us by virtue of us having become, to a large extent, a shift-working society" (Basner RC. Shift-Work Sleep Disorder--The Glass is More Than Half Empty. N Engl J Med. 2005;353:519-521). Another Flu Vaccine Shortage? With the flu season looming, Chiron Corp. is again having difficulty with flu vaccine production. Last year the company found contamination at its Liverpool production plant, a situation that cause severe shortages of vaccine in the United States. This year, the company has discovered contamination at a German plant and is stating that it can only provide vaccine for the US market. The German plant was primarily the source of the Begrivac flu vaccine, which was sold on the world market. The company is making "substantial progress" in fixing problems at the Liverpool plant where the US vaccine is made. Meanwhile, Acambis plc is working on a universal flu vaccine that could offer permanent protection against all types of influenza. The company hopes to generate a universal vaccine that would not require annual changes in formulation and would protect against both influenza A and B including avian strains. The company, however, states that it may require years of clinical trials before earning approval. Fears of avian influenza pandemic have prompted the French company Sanofi-Aventis to work on a vaccine for the avian H5N1 strain that has killed millions of birds and 50 people in Asia. Preliminary results are promising, however, full-scale production could take months, according to Anthony Fauci, MD, Director of the National Institute of Allergy and Infectious Diseases. FDA Actions The FDA has approved the first of the new class of drugs for the treatment of insomnia characterized by difficulty with sleep onset. Takeda Pharmaceutical's ramelteon (Rozerem) is a selective agonist at 2 melatonin receptors in suprachiasmatic nucleus, receptors that are thought to regulate circadian rhythm and sleepiness. Recently marketed sleeping medications target GABA receptors (ambien, lunesta) and, although these drugs are associated with less addiction and sleep latency then benzodiazepines, they are still designated as Schedule IV drugs. Ramelteon has shown no evidence of abuse or dependence potential and will, therefore, be marketed as a unscheduled drug. It is also approved for long-term use and has not been associated with memory impairment or impairment of motor ability. The most common adverse events associated with ramelteon were somnolence, fatigue and dizziness (> 2% over placebo). Plan B, Barr Pharmaceutical's "morning-after pill" is being considered for over-the-counter approval by the FDA. The issue has become a political hot potato, and even briefly held up the Senate's confirmation of Lester Crawford, MD, as Commissioner of the FDA. It is expected that decision will be made by September. This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5416. E-mail: LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2005 AHC Media LLC All Rights Reserved 475 of 998 DOCUMENTS CNS Drug News Pharmaceuticals August 31, 2005 Cephalon receives approval to market modafinil for SWSD in Germany LENGTH: 161 words Cephalon has received authorisation from the Federal Institute for Drugs and Devices (BfArM) to market modafinil tablets in Germany for the treatment of moderate-to-severe chronic shift work sleep disorder (SWSD) with excessive sleepiness in patients working night shifts, if measures of sleep hygiene have not led to a satisfactory improvement. Marketed under the tradename Vigil , modafinil has been available in Germany since 1998. Modafinil is the first and only medication in a new class of wake-promoting agents believed to work selectively through the sleep/wake centres to activate the cortex of the brain. The medication is currently approved in more than 20 countries and available under several brandnames, including Provigil , Alertec , Modiodal , Modasomil and Modavigil . In 2004, the FDA approved Provigil C-IV Tablets for improving wakefulness in patients with excessive sleepiness associated with obstructive sleep apnoea/hypopnoea syndrome and SWSD. LOAD-DATE: August 31, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2005 ESPICOM Business Intelligence Ltd. All Rights Reserved 476 of 998 DOCUMENTS Midnight Trader This content is provided to LexisNexis by Comtex News Network, Inc. August 30, 2005 Tuesday Cephalon Gets German OK to Market Modafinil for Sleep Disorder LENGTH: 199 words DATELINE: Boston Cephalon (CEPH) said tonight that it has received authorization from the Federal Institute for Drugs and Devices to market modafinil tablets in Germany for the treatment of moderate to severe chronic shift work sleep disorder with excessive sleepiness in patients working night shifts, if measures of sleep hygiene have not led to a satisfactory improvement. Marketed under the trade name VIGIL, modafinil has been available in Germany since 1998. GET MIDNIGHTTRADER IN REALTIME: This report is delayed. The full MidnightTrader extended-hours trading analysis and news service is available in real-time through COMTEX. For more information and to signup for a FREE TRIAL visit http://www.MidnightTrader.com/free_trial.html . ABOUT MIDNIGHTTRADER: MidnightTrader is the premier source of extended-hours US equity trading analysis, news and forecasting for the retail and institutional investment community. MidnightTrader's extended-hours analytical trading service empowers both retail and institutional equity traders by providing the information necessary to make the most informed and opportunistic investment decisions. http://www.midnighttrader.com LOAD-DATE: August 31, 2005 LANGUAGE: ENGLISH Copyright 2005 Comtex News Network, Inc. All Rights Reserved Copyright 2005 MidnightTrader.com. All rights reserved. Unauthorized reproduction is strictly prohibited. 477 of 998 DOCUMENTS PR Newswire US August 30, 2005 Tuesday 8:30 PM GMT Cephalon Receives Approval to Market Modafinil for Shift Work Sleep Disorder in Germany LENGTH: 848 words DATELINE: FRAZER, Pa. Aug. 30 FRAZER, Pa., Aug. 30 /PRNewswire-FirstCall/ -- Cephalon, Inc. (NASDAQ:CEPH) announced today that the company has received authorization from the Federal Institute for Drugs and Devices (BfArM) to market modafinil tablets in Germany for the treatment of moderate to severe chronic shift work sleep disorder with excessive sleepiness in patients working night shifts, if measures of sleep hygiene have not led to a satisfactory improvement. Marketed under the trade name VIGIL(R), modafinil has been available in Germany since 1998. "Germany is the third European country to approve modafinil for the treatment of shift work sleep disorder and to recognize the need to treat it. This new indication capitalizes on the strong clinical data surrounding this medication and allows us to improve the quality of life of the people suffering from this debilitating disorder," said Alain Aragues, President, Cephalon Europe. Modafinil Modafinil is the first and only medication in a new class of wake- promoting agents believed to work selectively through the sleep/wake centers to activate the cortex of the brain. The medication is currently approved in more than 20 countries and available under several brand names (PROVIGIL(R), ALERTEC(R), MODIODAL(R), MODASOMIL(R), MODAVIGIL(R) VIGIL). In 2004, the United States Food and Drug Administration approved PROVIGIL(R) (modafinil) [C-IV] Tablets for improving wakefulness in patients with excessive sleepiness associated with obstructive sleep apnea/hypopnea syndrome and shift work sleep disorder (SWSD). PROVIGIL was originally approved in 1998 for improving wakefulness in patients with excessive sleepiness associated with narcolepsy. About Cephalon Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products to treat sleep and neurological disorders, cancer and pain. Cephalon currently employs approximately 2,300 people in the United States and Europe. U.S. sites include the company's headquarters in Frazer, Pennsylvania, and offices, laboratories or manufacturing facilities in Salt Lake City, Utah, and suburban Minneapolis, Minnesota. The company currently markets four proprietary products in the United States: PROVIGIL(R), GABITRIL(R) (tiagabine hydrochloride), ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II] and TRISENOX(R) (arsenic trioxide) injection and more than 20 products internationally. Full prescribing information for all U.S. products is available at http://www.cephalon.com/ or by calling 1-800-896-5855 (PROVIGIL, GABITRIL, and ACTIQ) or 1-800-715-0944 (TRISENOX). Cephalon Europe Cephalon Europe has headquarters in Maisons-Alfort France and offices in the United Kingdom, Germany and Switzerland employing more than 600 people. European operations market more than 20 pharmaceutical products such as ACTIQ(R) for cancer pain; GABITRIL(R) for seizures associated with epilepsy; modafinil under the brand names PROVIGIL(R), MODIODAL(R) and VIGIL(R) for excessive sleepiness associated with multiple disorders; and SPASFON(R), an antispasmodic. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs, development of potential pharmaceutical products, interpretation of clinical results, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, sales and earnings guidance, and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. CONTACT: Media: Sheryl Williams, +1-610-738-6493, swilliam@cephalon.com , or Investors: Robert (Chip) Merritt, +1-610-738-6376, cmerritt@cephalon.com , both of Cephalon Web site: http://www.cephalon.com/ Company News On-Call: http://www.prnewswire.com/comp/134563.html SOURCE Cephalon, Inc. URL: http://www.prnewswire.com LOAD-DATE: August 31, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2005 PR Newswire Association LLC. All Rights Reserved. 478 of 998 DOCUMENTS Hamilton Spectator (Ontario, Canada) August 23, 2005 Tuesday Final Edition It's often tough to pick up zzzzzzzs after a night's work SOURCE: The Hamilton Spectator SECTION: WELL-BEING; Pg. G06 LENGTH: 237 words When people work all night and try to sleep during the day, some adjust but others never do. They're chronically sleepy on the job and experience daytime insomnia, a condition known as shift work sleep disorder. A study assigned 204 adults who worked night shifts and had been diagnosed with shift work sleep disorder to take modafinil (Provigil) or a placebo 30 to 60 minutes before starting work each night. After three months, 74 per cent of the modafinil group reported at least minimal improvements, compared with 36 per cent of the placebo group. They also had fewer attention lapses during their normal working hours, whereas the placebo group experienced more, and they reported having fewer accidents or near-accidents while commuting home than the others. However, the modafinil group continued to be excessively sleepy and exhibited nighttime performance weaknesses. Neither the drug nor the placebo worsened daytime insomnia. Caveats: Long-term safety and effectiveness of the drug were not tested. The study was funded by Cephalon, which makes Provigil. Four of the 10 primary authors work for the pharmaceutical company; the others have received consultants' fees from it. Find the study in the New England Journal of Medicine; abstract available online at www.nejm.org. Learn more about shift work and sleep problems at www.sleepfoundation.org/sleeptionary and www.mayoclinic.com. LOAD-DATE: August 23, 2005 LANGUAGE: ENGLISH GRAPHIC: Photo: TYPE: News Copyright 2005 Metroland Media Group Ltd 479 of 998 DOCUMENTS The Houston Chronicle August 14, 2005, Sunday 2 STAR EDITION Drug helping night workers stay alert, researchers find; Study indicates medication for shift-work sleep disorder is the first in its field SOURCE: Newsday BYLINE: DELTHIA RICKS SECTION: A; Pg. 15 LENGTH: 474 words In the first study of medicating people who work graveyard shifts, researchers have found that an alertness drug can spur wakefulness and prevent accidents on the drive home. The drug, modafinil, sold as Provigil, originally was approved to treat the uncontrollable sleepiness of narcolepsy. The study, reported in the New England Journal of Medicine by Boston researchers, marks the first time that it has been tested in people who must remain awake all night. "One out of 10 people have difficulty adapting to night-shift work," said Dr. Charles Czeisler, chief of Brigham and Women's Sleep Medicine division. He said not just anyone who yawns on an overnight shift meets criteria for shift-work sleep disorder, which he defines as most prevalent among people who can't stay awake past midnight. Czeisler said those with the condition are more likely to doze incessantly on the job but remain awake during the day. They also are more likely to be depressed, have cardiovascular problems and ulcers. Czeisler also defines the group as being more prone to "accidents and near-accidents" in their commute home. "We live in a society in which a number of critical services are offered at night," Czeisler said, "so it is important for some people to be awake. This isn't exactly new to the modern world; even shepherds had to guard their flocks because of nocturnal predators." In the study of 209 patients, 74 percent of roughly half who got modafinil were less likely to be sleepy at work, compared with 36 percent of those who got a dummy pill. Manufactured by Cephalon Inc., modafinil was approved by the Food and Drug Administration in 1998. Cephalon also sponsored the study, which was conducted at 28 medical centers throughout the United States. Czeisler acknowledged that no one knows how the drug induces wakefulness, though he adds that the medication is safe. The drug is being studied by the Department of Defense to maintain alertness in pilots and troops in Iraq. Dr. Robert Basner, a sleep expert at Columbia University's College of Physicians and Surgeons in Manhattan, said the study is not definitive. "This is very contentious, and a lot is at stake here," he said. "I am not taking out my pad to write more prescriptions for modafinil based on this study." Basner said while shift-work sleep disorder is a genuine medical condition, doctors should not assume Czeisler's study has proven that the drug is safe for patients with the condition. "They've taken this one drug and given it to shift workers to determine if it would make them less sleepy - and it did, compared to nothing, which was the placebo. There are other stimulants that can be studied in a similar protocol." He suggested caffeine probably would produce similar results if studied the same way. LOAD-DATE: August 14, 2005 LANGUAGE: ENGLISH Copyright 2005 The Houston Chronicle Publishing Company 480 of 998 DOCUMENTS Sunday Age (Melbourne, Australia) August 7, 2005 Sunday First Edition The science of never celling yourself short BYLINE: MARK RUSSELL SECTION: EXTRA; Pg. 17 LENGTH: 800 words Whether it's listening to Mozart or popping Modafinil, there are ways to retrain your brain and enjoy greater wellbeing, writes Mark Russell. EATING beans on toast for breakfast, an omelet and salad for lunch with a yoghurt dessert, and fish for dinner followed by strawberries and blueberries, is a good way to boost brain power, according to the New Scientist's list of 11 Steps to a Better Brain. The list suggests that a high-protein diet helps to stimulate and improve the brain, as does listening to Mozart, taking smart drugs, getting a decent night's sleep, walking for half an hour three times a week, doing the crossword, knitting, paying attention, memorising such things as a series of dots on a grid, and using the power of thought to boost creativity and alter personality traits. Leading Australian brain experts believe this new list of ways to improve the brain is an example of the public's increasing fascination with the science of wellbeing. The 11 Steps to a Better Brain involves the use of smart drugs (including Modafinil, which keeps the brain alert for up to 90 hours); music (Mozart makes listeners feel better); bionics (electrodes to send small currents to the brain); mental workouts (such as mathematics tests); memory tricks; hobbies; sleep; physical exercise; food; concentration; and neurofeedback (thought control). Dr Evian Gordon, founding director of the Brain Dynamics Centre at Sydney's Westmead Hospital and chief executive of the Brain Resource Company, said it was remarkable how many people wanted to know more about what he terms positive psychology to increase brain power. "Theoretically if you do activate your brain neurones in a very targeted way to, say, improve your memory, there's no reason that your memory shouldn't improve to some extent," Dr Gordon told The Sunday Age. "It's a very interesting area, this notion of retraining the brain. "When people actually see evidence that they can genuinely improve their own brain function, it has a very significant impact on them. "We all know we should do exercise and eat better, but when you actually see it having an effect (on the brain), it's like lowering your own heart rate. It really is a concrete way in which people can see they are more masters of their own destinies than they imagined." But while applauding efforts to improve the brain, Dr Gordon cautioned against the use of so-called smart drugs. He said the brain was a highly interconnected system which was susceptible to side-effects when using smart drugs. New Scientist claims research shows the drug Modafinil helps to keep people awake without the side-effects that amphetamines or coffee produce while Ritalin helps to improve concentration during exams or important negotiations. Dr Gordon said: "There's that broad kind of concern in tinkering with the brain . . . that we're tinkering with a system that we don't fully understand. "The issue to me is how much is the variance explained. In other words, if I'm going to take a drug to improve my memory, how much of a benefit is there and how enduring is that benefit? "It's all very well to say this is a drug that shows improvement (to the brain), but is there a better way to do it, is there a less invasive way to do it?" 11 STEPS TO A BETTER BRAIN - Food for thought: you are what you eat. - Gainful employment: put your mind to work in the right way and it could bring an impressive bonus. - Body and mind: physical exercise can boost brain as well as brawn. - Memory marvels: mind like a sieve? Don't worry. The difference between mere mortals and memory champs is more method than mental capacity. - Bionic brains: if training and tricks seem too much like hard work, some technological short cuts can boost brain function. - Attention-seeking: you can be smart, well-read, creative and knowledgeable, but none of it is any use if your mind isn't on the job. - Positive feedback: Thought control is easier than you might imagine. - The Mozart effect: Mozart has been shown to improve mathematical and spatial reasoning but the impact of music lessons is even more impressive. The IQ scores of six-year-old music students were 2 to 3 points higher than their peers. - Sleep on it: never underestimate the power of a good night's rest. - Smart drugs: 'cognitive enhancement' drugs are already on the market. - Nuns on a run: a study of the School Sisters of Notre Dame in Minnesota found many of its 75- to 107-year-old inhabitants have avoided any kind of dementia or senility. Their secrets included: the right amount of vitamin folate; verbal ability early in life; positive emotions early in life; activities, crosswords, knitting and exercising. Source: New Scientist magazine, May 28, 2005, Kate Douglas, Alison George, Bob Holmes, Graham Lawton, John McCrone, Alison Motluk, Helen Phillips. LOAD-DATE: July 19, 2007 LANGUAGE: ENGLISH GRAPHIC: EIGHT PHOTOS PUBLICATION-TYPE: Newspaper Copyright 2005 The Age Company Limited All Rights Reserved 481 of 998 DOCUMENTS The Pharmaceutical Journal August 5, 2005 Modafinil for sleep disorder BYLINE: Old_manager LENGTH: 59 words Modafinil is of some value in treating shift-work sleep disorder but does not restore sleepiness to normal levels (New England Journal of Medicine 2005;353:476). In 209 patients modafinil 200mg taken before a night shift improved symptoms of sleepiness as well as objective measures of sleep propensity and performance compared with placebo. LOAD-DATE: November 10, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Journal Copyright 2005 PJ Online All Rights Reserved 482 of 998 DOCUMENTS UPI August 5, 2005 Friday 1:33 PM EST Drug may help night-shift workers BYLINE: EVA A. SYLWESTER LENGTH: 1145 words DATELINE: WASHINGTON, Aug. 5 Working at night and sleeping during the day is not natural for any human body, but some people have trouble adapting to such arrangements to the point where their distress qualifies as a medical disorder. Now, this underdiagnosed and difficult-to-treat condition is the subject of the first-ever clinical trial of the promising medication modafinil. Shift-work sleep disorder is marked by sleepiness during night-time working hours, insomnia while trying to sleep during the day and instances of fatigue-induced accidents and errors on the job in people whose work shifts include more than six hours between 10 p.m. and 8 a.m. Effects include higher rates of accidents, absenteeism, depression, ulcers and frequently missing family and social activities. Charles Czeisler, lead author of the study -- which appears in the Aug. 4 issue of the New England Journal of Medicine -- told United Press International the condition affects 5 percent to 10 percent of night-shift workers. It also is often underdiagnosed because it is mistaken for ordinary fatigue. Czeisler compared the difference between normal tiredness and the disorder to the scene at tourist destinations, where some travelers walk around examining landmarks and others slump on benches due to the effects of jet lag. "Some people are more affected than others," he said. David Dinges, chief of the Division of Sleep and Chronobiology at the University of Pennsylvania in Philadelphia and a co-author of the paper, told UPI he has been conducting another study. This one, sponsored by the National Institutes of Health, is examining healthy people not on shift-work schedules who have spent non-consecutive nights without sleep. He said he found that participants who have experienced great difficulty during their first night without sleep also had difficulty on subsequent nights without sleep -- regardless of how much they slept in the interim. At the same time, participants who remained relatively functional after their first sleepless night retained that ability on other nights when they stayed up. "This is a trait-like characteristic of people," Dinges said. Czeisler, who is chief of sleep medicine at Brigham and Women's Hospital in Boston and a professor of medicine at Harvard Medical School, said that in addition to revealing a possible treatment, another notable aspect of the study was its findings on the effects of shift-work sleep disorder. "It revealed how sleepy this group of patients is," Czeisler said. "They're just as sleepy as patients with narcolepsy or sleep apnea." In the study, researchers assigned 209 shift-work sleep-disorder patients to receive 200 milligrams of either modafinil or a placebo before the start of each work shift. Modafinil is sold under the trade name Provigil and is manufactured by Cephalon Inc., which provided research funds to Czeisler. The drug also is used for narcolepsy and sleep apnea. The study measured sleep latency and lapses of attention. Sleep latency is the amount of time it takes a person to fall asleep given the opportunity. Czeisler said that in the daytime, falling asleep in less than five minutes signifies excessive sleepiness. No standards have been developed for healthy sleep latency at night, so the sleep-latency figures collected in his study simply served as a measure of change. The average decrease in sleep latency for patients receiving modafinil was 1.7 minutes, compared to 0.3 minutes for the placebo group. The difference in sleep latency was most pronounced early in the night, around 2 a.m., and decreased toward 6 a.m. The Psychomotor Vigilance Test was used to monitor lapses of attention. Patients in the modafinil group experienced a median rate of 2.63 fewer lapses of attention per 20-minute test, while patients in the placebo group experienced 3.75 more lapses of attention than they had before receiving the placebo. Patients in Czeisler's study worked a wide variety of occupations, including manufacturing, investment banking, police work and hospital nursing. "Something that was common to all of them was actual or near-miss motor-vehicle accidents driving home from work," Czeisler said. Among the study's placebo group, 54 percent reported accidents or near accidents during their commute home, while only 29 percent of patients receiving modafinil reported such incidents. Czeisler acknowledged that although modafinil is helpful, it does not enable perfect functioning. "It brings (patients) about a third of the way to what's normal during the daytime, but we don't know what's normal during the night," he said. Also, patients in the modafinil group experienced daytime insomnia at a 6-percent higher rate than the placebo group. Czeisler said the brain sends out a strong drive for sleep at night, and that it is contrary to the body's circadian rhythms to work at night and sleep in the daytime, but modern life sometimes demands the suppression of biological directives. "There are many essential services provided by people who do work at night, and we live in a society that requires many round-the-clock operations," Czeisler said. Dinges said that with the number of U.S. shift workers at 6 million and growing, it would be economically unfeasible to bar even people with innate difficulties from night-shift work, even though numerous government and scientific studies point to dangerous consequences from such activities, such as industrial accidents and highway collisions. "I don't know how realistic it is to suggest that people who are vulnerable shouldn't work night shift," he said. Other doctors suggest that more possibilities may be found for managing the disorder. Robert Basner, associate professor of clinical medicine at Columbia University, wrote in the NEJM article that other researchers' findings show 600 mg doses of caffeine can produce similar effects to modafinil in improved performance for people who have been awake more than 40 hours, and according to Czeisler's study, modafinil does not affect the underlying circadian rhythm. "Neither these data nor any other published studies provide evidence to indicate that modafinil is uniquely suited to be used as an enhancer of wakefulness and vigilance in humans subjected to nighttime shift work," Basner wrote. Czeisler said he did not test -- nor would he personally advocate -- the drug's potential to keep people awake for indefinite periods of time, such as all-night studying. Dinges said caffeine and bright lights have been used to treat shift-work sleep disorder for years, but they have not been tried in many experiments. "In the experiments where they have been tried, they have limited utility," he said. He agreed that more research needs to be done on the disorder and in establishing standards for normal levels of nighttime alertness. Eva Sylwester is an intern for UPI Science News. E-mail: sciencemail@upi.com LOAD-DATE: August 6, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2005 U.P.I. All Rights Reserved 483 of 998 DOCUMENTS CNS Drug News Pharmaceuticals August 4, 2005 Modafinil demonstrates reduced excessive sleepiness in SWSD patients LENGTH: 401 words The results of Cephalon 's pivotal Phase III study of Provigil ( modafinil ) in patients with shift-work sleep disorder (SWSD) have been published in the 4th August issue of the NEJM (2005;353:476-486). In the first ever clinical study of SWSD, patients taking modafinil showed improvements in their wakefulness, performance and level of attention. Cephalon has also completed a larger Phase III study in SWSD with its second wake-promoting agent, Nuvigil ( armodafinil ), which is currently being reviewed as part of a request for marketing approval by the FDA. The three-month, randomised, double-blind, placebo-controlled study was conducted at 28 centres in the US between December 2001 and September 2002. All 204 patients treated in the study were prescreened for SWSD and received modafinil 200mg or placebo. Key results of the study showed that: modafinil significantly improved patients' level of alertness when measured objectively, as compared to patients treated with placebo; modafinil significantly reduced patients' level of sleepiness when measured subjectively, as compared to patients treated with placebo; patients treated with modafinil had a significant reduction in the number and duration of lapses of attention during 20-minute computerised tests conducted in a sleep laboratory, as compared to patients treated with placebo; and a higher percentage of patients treated with modafinil (74 per cent) were rated as improved using the physician-rated Clinical Global Impression of Change scale, as compared to patients treated with placebo (36 per cent). The study concluded that treatment with modafinil 200mg reduced the extreme sleepiness that is observed in patients with SWSD and resulted in a small but significant improvement in performance as compared with placebo. However, according to the study authors, the residual sleepiness that was observed in the treated patients underscores the need for the development of interventions that are even more effective. In January 2004, the FDA approved Provigil as the first and only medication to treat excessive sleepiness associated with SWSD. The medication is believed to work selectively through the sleep-wake centres to activate the cortex of the brain. The exact mechanism of action of Provigil is not known, however, it promotes wakefulness without causing the generalised stimulation of the brain associated with CNS stimulants. LOAD-DATE: August 4, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2005 ESPICOM Business Intelligence Ltd. All Rights Reserved 484 of 998 DOCUMENTS The Vancouver Province (British Columbia) August 4, 2005 Thursday Final Edition Pill helps night-shift workers stay awake, research shows: Increases vigilance, wakefulness: study BYLINE: Scripps Howard SECTION: NEWS; Pg. A26 LENGTH: 302 words In a 24-7 world, tens of thousands of North Americans fall victim to shift-work sleep disorder -- they're sleepy during their night of work, but suffer from insomnia when they try to sleep in the daytime. A study published today shows that a drug first prescribed for narcolepsy sufferers also offers some relief to night-shift workers. The drug, called modafinil and sold under the brand name Provigil, extended the length of time it took shift workers between the ages of 18 and 60 to nod off at night from an average of about two minutes to nearly four minutes. It improved the workers' self-reported wakefulness and vigilance in tests. Researchers say nearly 6.5 million North Americans work at night on a permanent or rotating basis, and some five per cent to 10 per cent suffer from the shift-work disorder. "Shift-work sleep disorder . . . can compromise personal safety and significantly impact quality of life," said Dr. Charles Czeisler, chief of the sleep-medicine division at Brigham and Women's Hospital in Boston and leader of the study presented in The New England Journal of Medicine. "This study demonstrates that while modafinil can significantly improve symptoms and reduce sleep tendency during night-work hours, patients remain excessively sleepy even after treatment for this sleep-wake disturbance," Czeisler said. Originally intended to treat narcoleptics -- people with a rare brain disorder that causes them to uncontrollably fall asleep -- the drug is now approved in the U.S. for people with shift-work disorder as well as those suffering from sleep apnea. The drug's manufacturer, Cephalon, sponsored the new research and Czeisler is a paid consultant to the firm. The pills generally keep people awake with less of the jitteriness and other side-effects seen from using caffeine or amphetamines. LOAD-DATE: August 4, 2005 LANGUAGE: ENGLISH DOCUMENT-TYPE: News PUBLICATION-TYPE: Newspaper Copyright 2005 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 485 of 998 DOCUMENTS Internal Medicine News August 1, 2005 Antinarcolepsy Drug May Improve ADHD BYLINE: Mary Ellen Schneider, Senior Writer SECTION: Pg. 46 Vol. 38 No. 15 ISSN: 1097-8690 LENGTH: 857 words    ATLANTA - Results from two new studies highlight a possible alternative to stimulants for the treatment of attention-deficit hyperactivity disorder in children and adolescents.    Two phase III studies presented at the annual meeting of the American Psychiatric Association show that a once-daily pediatric formulation of modafinil is well tolerated and improves attention-deficit hyperactivity disorder (ADHD) symptoms in children and adolescents.    Modafinil is currently marketed by Cephalon under the brand name Provigil in 100-mg and 200-mg strengths. Provigil is indicated for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea, hypopnea syndrome, and shift work sleep disorder.    The company, which funded the phase II trials, is seeking approval from the Food and Drug Administration to market modafinil in 85-mg, 170-mg, 255-mg, 340-mg, and 425-mg strengths. If approved, the drug would be indicated for treatment of ADHD in children and adolescents aged 6-17 years.    The company is planning to launch the drug under the brand name Attenace by early 2006.    In one study, 189 patients with ADHD aged 6-17 years were randomized to a 7-week double-blind, fixed-dose treatment with either modafinil or placebo. This regimen was followed by a 2-week withdrawal period in which half of the modafinil-treated patients were placed on placebo without tapering, and half were continued on the drug, said Joseph Biederman, M.D., the lead investigator in the study and professor of psychiatry at Harvard University in Boston.    Modafinil was administered once daily, starting at 85 mg/day, and was rapidly titrated over 7-9 days to dosages of either 340 mg/day for patients who weighed less than 30 kg or 425 mg/day for patients who weighed 30 kg or more.    The results of the study were assessed using the school and home ADHD Rating Scale-IV total score change from baseline to last treatment visit.    After 1 week, the 125 modafinil-treated patients had significantly greater improvements in school scores, compared with the 64 placebo patients, and those results were maintained through week 7.    On the school scale, patients on modafinil experienced a 17.2-point drop in symptoms, compared with an 8.2-point drop for patients on placebo. Modafinil also significantly improved total scores from parents, compared with placebo.    The side effects included insomnia and appetite decrease. Overall, the side effects were generally mild and occurred at initiation of the treatment. There were two serious adverse events not associated with the trial, said Dr. Biederman, who is an advisory board member for Cephalon and receives research/grant support from the company.    The researchers also assessed ADHD symptoms and physical/emotional response after rapid discontinuation. During the 2-week withdrawal phase, there were no reported symptom rebounds, no adverse events related to withdrawal, and no physical or emotional responses.    Modafinil appears to work like a gentler stimulant, Dr. Biederman said in an interview. The findings present possible new treatment options, he said. Although stimulants are effective, they are not universally effective. About 30%-40% of patients are nonresponsive to stimulants, he said, and some patients also have tolerability problems.    Stimulants also have the potential for acute deterioration and symptom rebound if treatment is interrupted or discontinued without tapering, Dr. Biederman said.    In the second study, researchers considered the effect of a flexible dose of modafinil in children and adolescents.    The study included 198 patients aged 6-17 years who were started on a dose of 85 mg/day of modafinil, which was titrated over 22 days based on clinical effectiveness. The maximum dose was 425 mg/day with once-daily dosing, said James Swanson, Ph.D., of the University of California at Irvine Child Development Center, who was the lead investigator.    The results were assessed using the school and home ADHD Rating Scale-IV, the Clinical Global Impression of Improvement (CGI-I), and the Test of Variables of Attention (TOVA).    The home score showed a mean drop of 17.6 points in symptoms for the 131 patients receiving modafinil at a mean stable dose of 361 mg/day, compared with a 7.5-point drop in symptoms for the 67 patients on placebo. The improvement in the total school score was also significantly greater for modafinil patients, Dr. Swanson reported.    Modafinil was shown to significantly improve inattention and hyperactivity/impulsivity, and there was an improvement in overall clinical condition and in the TOVA measurements of ADHD.    The researchers focused not only on decreasing symptoms of ADHD, but on increasing positive interaction and social skills, and they saw an increase in positive behaviors, he said.    The side effects included insomnia, headache, and appetite problems, which are similar to the side effects for stimulants, said Dr. Swanson, who is an advisory board member with Cephalon, receives research/grant support from the company, and is a member of the company's speakers' bureau. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: IMNEWS Copyright 2005 Elsevier Inc., International Medical News Group All Rights Reserved 486 of 998 DOCUMENTS Pediatric News August 2005 Trial Finds No Withdrawal Syndrome With Modafinil BYLINE: Damian Mcnamara, Miami Bureau SECTION: Pg. 28 Vol. 39 No. 8 ISSN: 0031-398X LENGTH: 388 words    BOCA RATON, FLA. - Children and adolescents with attention-deficit hyperactivity disorder did not experience withdrawal or discontinuation syndrome after abrupt cessation of modafinil film-coated tablets in a phase III, double-blind, multicenter trial.    Researchers also found efficacy as early as 1 week in this 9-week study of 6- to 17-year-olds with attention-deficit hyperactivity disorder (ADHD). The Food and Drug Administration has approved modafinil (Provigil) for treatment of narcolepsy and is currently reviewing a special pediatric formulation for ADHD.    "This is not surprising. Modafinil is a medication that improves vigilance and alertness and could improve similar symptoms in ADHD," Joseph Biederman, M.D., said in an interview at his poster presentation during a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.    Dr. Biederman and his associates compared efficacy using the school and home versions of the ADHD Rating Scale-IV, the Clinical Global Impression of Improvement (CGI-I) scores, and adverse event reporting by 125 patients taking the pediatric formulation of modafinil and 64 taking a placebo.    The modafinil group had significantly improved school rating total scores, compared with those of the placebo group at 1 week, an effect that was maintained through week 7. The final 2 weeks of the study was a washout phase. Mean reduction from baseline was 17 points with modafinil versus 8 points with placebo. Significant reductions in home rating total scores also were observed with modafinil at all visits, according to Dr. Biederman, chief of the joint program in pediatric psychopharmacology, Massachusetts General Hospital, Boston.    A significantly greater percentage of patients, 49%, was rated as "much" or "very much" improved on the CGI-I in the modafinil group vs. 25% in the placebo group.    Modafinil was abruptly discontinued in 37 patients. Abrupt cessation was not associated with symptom rebound, and no evidence of withdrawal or discontinuation syndrome was seen.    This and other phase III study results were submitted to the FDA in December 2004. "I don't see any reason why they wouldn't approve it," said Dr. Biederman, who reported no affiliation with Cephalon Inc., the manufacturer and sponsor of the study. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: PDNEWS Copyright 2005 Elsevier Inc., International Medical News Group All Rights Reserved 487 of 998 DOCUMENTS Family Practice News July 15, 2005 Pediatric Modafinil Eased ADHD Symptoms BYLINE: Mary Ellen Schneider, Senior Writer SECTION: Pg. 41 Vol. 35 No. 14 ISSN: 0300-7073 LENGTH: 850 words    ATLANTA - Results from new research point to a possible alternative to stimulants for the treatment of attention-deficit hyperactivity disorder in children and adolescents.    Two phase III studies presented at the annual meeting of the American Psychiatric Association show that a once-daily pediatric formulation of modafinil is well tolerated and improves attention-deficit hyperactivity disorder (ADHD) symptoms in children and adolescents.    Modafinil is currently marketed by Cephalon under the brand name Provigil in 100-mg and 200-mg strengths. Provigil is indicated for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea, hypopnea syndrome, and shift work sleep disorder.    The company, which funded the phase II trials, is seeking approval from the Food and Drug Administration to market modafinil in 85-mg, 170-mg, 255-mg, 340-mg, and 425-mg strengths. If approved, the drug would be indicated for treatment of ADHD in children and adolescents aged 6-17 years. The company is planning to launch the drug under the brand name Attenace by early 2006.    In one study, 189 patients with ADHD aged 6-17 years were randomized to a 7-week double-blind, fixed-dose treatment with either modafinil or placebo. This regimen was followed by a 2-week withdrawal period in which half of the modafinil-treated patients were placed on placebo without tapering, and half were continued on the drug, said Joseph Biederman, M.D., the lead investigator in the study and professor of psychiatry at Harvard University in Boston.    Modafinil was administered once daily, starting at 85 mg/day, and was rapidly titrated over 7-9 days to dosages of either 340 mg/day for patients who weighed less than 30 kg or 425 mg/day for patients who weighed 30 kg or more.    The results of the study were assessed using the school and home ADHD Rating Scale-IV total score change from baseline to last treatment visit.    After 1 week, the 125 modafinil-treated patients had significantly greater improvements in school scores, compared with the 64 placebo patients, and those results were maintained through week 7.    On the school scale, patients on modafinil experienced a 17.2-point drop in symptoms, compared with an 8.2-point drop for patients on placebo. Modafinil also significantly improved total scores from parents, compared with placebo.    The side effects included insomnia and appetite decrease. Overall, the side effects were generally mild and occurred at initiation of the treatment. There were two serious adverse events not associated with the trial, said Dr. Biederman, who is an advisory board member for Cephalon and receives research/grant support from the company.    The researchers also assessed ADHD symptoms and physical/emotional response after rapid discontinuation. During the 2-week withdrawal phase, there were no reported symptom rebounds, no adverse events related to withdrawal, and no physical or emotional responses.    Modafinil appears to work like a gentler stimulant, Dr. Biederman told this newspaper. The findings present possible new treatment options, he said. Although stimulants are effective, they are not universally effective. About 30%-40% of patients are nonresponsive to stimulants, and some patients also have tolerability problems.    Stimulants have the potential for acute deterioration and symptom rebound if treatment is interrupted or discontinued without tapering, he said.    In the second study, researchers considered the effect of a flexible dose of modafinil in children and adolescents.    The study included 198 patients aged 6-17 years who were started on a dose of 85 mg/day of modafinil, which was titrated over 22 days based on clinical effectiveness. The maximum dose was 425 mg/day with once-daily dosing, said James Swanson, Ph.D., of the University of California at Irvine Child Development Center, who was the lead investigator.    The results were assessed using the school and home ADHD Rating Scale-IV, the Clinical Global Impression of Improvement (CGI-I), and Test Variables of Attention (TOVA).    The home score showed a mean drop of 17.6 points in symptoms for the 131 patients receiving modafinil at a mean stable dose of 361 mg/day, compared with a 7.5-point drop in symptoms for the 67 patients on placebo. The improvement in the total school score was also significantly greater for modafinil patients, Dr. Swanson said.    Modafinil was shown to significantly improve inattention and hyperactivity/impulsivity, and there was an improvement in overall clinical condition and in the TOVA measurements of ADHD.    The researchers focused not only on decreasing symptoms of ADHD, but on increasing positive interaction and social skills, and they saw an increase in positive behaviors, he said.    The side effects included insomnia, headache, and appetite problems, which are similar to the side effects for stimulants, said Dr. Swanson, who is an advisory board member with Cephalon, receives research/grant support from the company, and is a member of the company's speakers' bureau. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: FPNEWS Copyright 2005 Elsevier Inc., International Medical News Group All Rights Reserved 488 of 998 DOCUMENTS RELIGION & ETHICS NEWSWEEKLY Prepared by Burrelle's Information Services, which takes sole responsibility for accuracy of transcription. July 15, 2005 Friday SHOW: Religion & Ethics NewsWeekly 6:00 PM EST PBS Neuroscience and brain gain ANCHORS: BOB ABERNETHY REPORTERS: LUCKY SEVERSON LENGTH: 1555 words BOB ABERNETHY, anchor: We have a story today about some of the ways drugmakers and neuroscientists are enhancing what human brains can do and what the implications of these developments are. For instance, what if brain researchers someday learn to find out what a patient is thinking? Or to predict a disabling disease? Or, right now, what about so-called "smart pills" that improve a college student's performance on an exam? Is it fair that only the well-off can afford them? Lucky Severson reports from Austin, Texas. LUCKY SEVERSON reporting: There's no way of knowing how many college students are popping "cognitive performance enhancers." But health-care professionals say the use of so-called "smart pills" has been increasing dramatically over the past five years. It comes as no surprise to Charles Brieden, an economics major at the University of Texas in Austin. Mr. CHARLIE BRIEDEN (University of Texas Student): I would definitely say that most of the kids who use it at least on a, you know, semifrequent basis don't have a prescription. You know, it--it's fairly easy to get a hold of. SEVERSON: Unlike most students, Charlie has a prescription for the drug he takes, called Adderall. Charlie has attention deficit disorder or ADD. Adderall and another drug, Ritalin, are often prescribed to treat ADD, but a lot of students use the drugs to enhance performance--that is, to help them concentrate and focus and face the stress and tests of modern college life. Mr. BRIEDEN: They're in demand and you know, kids--kids pay for them, you know, from--from their friends--buy them from their friends all the time. SEVERSON: Is it very popular amongst the students? Mr. ALEX MALDONADO (University of Texas Student): It is very popular, very expensive. SEVERSON: Alex Maldonado is another University of Texas student, a freshman, who bought one pill of Adderall to cram for an exam. Mr. MALDONADO: I aced the test so--I mean, I was happy about it. If it wasn't that expensive, maybe I would take it more often. SEVERSON: There's now a relatively new memory-boosting drug known as modafinil or Provigil that appears, so far, to be an even more effective enhancer with virtually no side effects. But it can cost as much as $200 for 30 pills. Dr. JUDY ILLES (Stanford University): What does it mean to have a college student who can't even afford an expensive drug like modafinil--for example, to stay up all night--and vs. somebody who is able to have as much modafinil as they wish? SEVERSON: Judy Illes is a neuroethicist at Stanford University, and she worries that these powerful new drugs could create an unfair advantage for kids who can afford them. Dr. ILLES: What does that mean for opportunities to individuals and disenfranchised populations and so forth? So there's a host of very complex issues that come into play there. SEVERSON: This new science that allows us to enhance, even to alter who we are, promises advances that seemed decades away only a few years ago. Now it's here. Problem is, for every advance, there will be a trade-off. Dr. Paul Root Wolpe is a professor of psychiatry at the University of Pennsylvania. Dr. PAUL ROOT WOLPE (University of Pennsylvania): There's an enormous amount of talk about genetics right now. But, in fact, I really think that it's neuroscience that's the cutting edge of the ethical issues that we have in our society. The challenges of neuroscience are happening right now. We can do things now that were science fiction just a short time ago. Unidentified Man: Those signals go out through the chip. SEVERSON: For instance, this FDA-approved, privately funded clinical trial that could give Matthew Nagel's brain the means to move objects. Mr. MATTHEW NAGEL: I am going to open the first e-mail, which has congrats. It says, `You are doing a great job.' SEVERSON: Matthew has been a paraplegic since a car accident four years ago. The object here is to enable him to operate a computer by his thoughts, with the aid of a tiny electrode chip implanted in his brain. Mr. NAGEL: Now I am going to close the hand. SEVERSON: John Donoghue is chairman of neuroscience at Brown University and founder of Cyberkinetics, Inc. Dr. JOHN DONOGHUE (Cyberkinetics, Inc.): These kinds of devices kick off a whole new age of neurotechnology developments in which we can create medical devices that can cure a whole host of diseases. Mr. NAGEL: I can't put it into words. It's just, I--I use my brain. I just thought it. I said, `Cursor go up to the top right.' And it did, and now I can control it all over the screen. It will give me a sense of independence. SEVERSON: Stanford law Professor Hank Greely says the chip adds something to the human dimension that wasn't there before. Professor HANK GREELY (Stanford University): When we get into people talking about various implants to either put new sensory--you give humans new senses or allow humans by thinking to control devices externally, that becomes a little more troubling. To a lot of people, the idea that somehow we're transcending what we're supposed to be as humans. SEVERSON: In the popular thriller "The Manchurian Candidate," a brain implant prompts a man to become an assassin. That scenario is no longer science fiction. Scientists say the technology to modify our personality or memory is barely around the bend. Mr. MICHAEL GAZZANIGA (Dartmouth College): There are things happening with incredible speed. SEVERSON: Michael Gazzaniga is director of neuroscience at Dartmouth College. Mr. GAZZANIGA: Two years ago--I would say, three years ago, no one would imagine that in a brain-imaging environment, you could begin to understand how people go about doing moral reasoning. And that is now happening. SEVERSON: Gazzaniga is author of "The Ethical Brain." He thinks our brains are all wired with similar moral circuitry--at least those of us considered normal. Mr. GAZZANIGA: We don't kill. We don't like incest. We don't like cheaters. The guess is that there's something, probably some moral spark, that's in us. Some moral compass is guiding us through all this social behavior. SEVERSON: That would mean that a secular person may have the same moral values as a religious one. It's a controversial conclusion. Mr. GAZZANIGA: I'm not antireligious in any way, shape or form. It's none of my business how you got to your--your set of moral values. I think what's happening is, though, we're going to find out that everybody in the room basically has their brain built in such a way that they tend to respond in a particular moral way, because of the way their brain is built. SEVERSON: It's all possible because of magnetic resonance imaging, MRI, that is becoming so sophisticated neuroscientists are able to identify what kinds of thoughts and emotions stimulate certain parts of the brain. Dr. ROOT WOLPE: We can do things now, such as looking at brain images, and predict what a person had just been looking at or what they had just been thinking about. SEVERSON: Professor Greely says a potential negative side of the neuroscience revolution is the ability to predict someone's physical or mental illness. Prof. GREELY: If your insurer can figure out well in advance that you're going to have Parkinson's disease or Alzheimer's disease, then that could be pretty significant in terms of whether you can get long-term care insurance. SEVERSON: And there's more. Until now, our thoughts were our own. Dr. ROOT WOLPE: We may actually be able to breach that barrier and ex--extract directly from your brain information that before we could only get by you choosing to tell it to us. That's very, very new. And it raises profound questions about privacy. SEVERSON: There are many troubling questions that have profound implications, some ethical, some physical. The smart pills, for example, so popular on campus, it's too early to tell if they have dangerous side effects. Mr. GAZZANIGA: The safety and efficacy of these drugs is simply not known. The possible side effects, in terms of real damage to the nervous system, hasn't even begun to be worked out. Mr. BRIEDEN: I had my first, you know, bout with depression. Like, last--last semester I actually, like, started freaking out. Because I was taking it, I was taking it too frequently, and it was, you know, you can start to get, you know, schized out. SEVERSON: Ultimately, the bigger question, in the view of Professor Wolpe, is the question of values. Dr. ROOT WOLPE: Do we want to say that some path to self-improvement is ennobled by the struggle? Or are we OK with the idea that there's a quicker path to enlightenment? SEVERSON: The answer is not entirely clear. Take Fiorella Vargas, a George Washington University graduate. She survived college without the help of cognitive enhancers. Ms. FIORELLA VARGAS: It is very--it's very stressful. So, but you deal with it. And you get beyond it. And then you are proud once graduation day comes. SEVERSON: Charlie, on the other hand, wouldn't think twice. Mr. BRIEDEN: Any way you can get a leg up in life, you know, any way you can get an advantage, you know, whatever it may be, you know, I'd say go for it. SEVERSON: The question that can't be answered yet is whether smart pills and brain technology actually enhance us or prevent us from discovering and developing who we really are. For RELIGION & ETHICS NEWSWEEKLY, I'm Lucky Severson in Washington. LOAD-DATE: July 18, 2005 LANGUAGE: ENGLISH DOCUMENT-TYPE: Profile PUBLICATION-TYPE: Transcript Copyright 2005 WNET-TV. All Rights Reserved 489 of 998 DOCUMENTS Clinical Psychiatry News July 2005 Antinarcolepsy Drug May Improve ADHD; Modafinil could prove an alternative to stimulants for addressing symptoms, phase III studies show. BYLINE: Mary Ellen Schneider, Senior Writer SECTION: Pg. 38 Vol. 33 No. 7 ISSN: 0270-6644 LENGTH: 856 words    ATLANTA - Results from new research point to a possible alternative to stimulants for the treatment of attention-deficit hyperactivity disorder in children and adolescents.    Two phase III studies presented at the annual meeting of the American Psychiatric Association show that a once-daily pediatric formulation of modafinil is well tolerated and improves attention-deficit hyperactivity disorder (ADHD) symptoms in children and adolescents.    Modafinil is currently marketed by Cephalon under the brand name Provigil in 100-mg and 200-mg strengths. Provigil is indicated for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea, hypopnea syndrome, and shift work sleep disorder.    The company, which funded the phase II trials, is seeking approval from the Food and Drug Administration to market modafinil in 85-mg, 170-mg, 255-mg, 340-mg, and 425-mg strengths. If approved, the drug would be indicated for treatment of ADHD in children and adolescents aged 6-17 years.    The company is planning to launch the drug under the brand name Attenace by early 2006.    In one study, 189 patients with ADHD aged 6-17 years were randomized to a 7-week double-blind, fixed-dose treatment with either modafinil or placebo. This protocol was followed by a 2-week withdrawal period in which half of the modafinil-treated patients were placed on placebo without tapering, and half were continued on the drug, said Joseph Biederman, M.D., the lead investigator in the study and professor of psychiatry at Harvard University in Boston.    Modafinil was administered once daily, starting at 85 mg/day, and was rapidly titrated over 7-9 days to dosages of either 340 mg/day for patients who weighed less than 30 kg or 425 mg/day for patients who weighed 30 kg or more.    The results of the study were assessed using the school and home ADHD Rating Scale-IV total score change from baseline to last treatment visit.    After 1 week, the 125 modafinil-treated patients had significantly greater improvements in school scores, compared with the 64 placebo patients, and those results were maintained through week 7.    On the school scale, patients on modafinil experienced a 17.2-point drop in symptoms, compared with an 8.2-point drop for patients on placebo. Modafinil also significantly improved total scores from parents, compared with placebo.    The side effects included insomnia and appetite decrease. Overall, the side effects were generally mild and occurred at initiation of the treatment. There were two serious adverse events not associated with the trial, said Dr. Biederman, who is an advisory board member for Cephalon and receives research/grant support from the company.    The researchers also assessed ADHD symptoms and physical/emotional response after rapid discontinuation. During the 2-week withdrawal phase there were no reported symptom rebounds, no adverse events related to withdrawal, and no physical or emotional responses.    Modafinil appears to work like a gentler stimulant, Dr. Biederman said in an interview.    The findings present possible new treatment options, he said. Although stimulants are effective, they are not universally effective. About 30%-40% of patients are nonresponsive to stimulants, he said, and some patients also have tolerability problems.    Stimulants also have the potential for acute deterioration and symptom rebound if treatment is interrupted or discontinued without tapering, Dr. Biederman said.    In the second study, researchers considered the effect of a flexible dose of modafinil in children and adolescents.    The study included 198 patients aged 6-17 years who were started on a dose of 85 mg/day of modafinil, which was titrated over 22 days based on clinical effectiveness. The maximum dose was 425 mg/day with once-daily dosing, said James Swanson, Ph.D., of the University of California at Irvine Child Development Center, who was the lead investigator.    The results were assessed using the school and home ADHD Rating Scale-IV, the Clinical Global Impression of Improvement (CGI-I), and Test Variables of Attention (TOVA).    The home score showed a mean drop of 17.6 points in symptoms for the 131 patients receiving modafinil at a mean stable dose of 361 mg/day, compared with a 7.5-point drop in symptoms for the 67 patients on placebo. The improvement in the total school score was also significantly greater for modafinil patients, Dr. Swanson reported.    Modafinil was shown to significantly improve inattention and hyperactivity/impulsivity, and there was an improvement in overall clinical condition and in the TOVA measurements of ADHD.    The researchers focused not only on decreasing symptoms of ADHD, but on increasing positive interaction and social skills, and they saw an increase in positive behaviors, he said.    The side effects included insomnia, headache, and appetite problems, which are similar to the side effects for stimulants, said Dr. Swanson, who is an advisory board member with Cephalon, receives research/grant support from the company, and is a member of the company's speakers' bureau. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: CPNEWS Copyright 2005 Elsevier Inc., International Medical News Group All Rights Reserved 490 of 998 DOCUMENTS Pediatric News July 2005 Pediatric Modafinil Shows Results in ADHD BYLINE: Mary Ellen Schneider, Senior Writer SECTION: Pgs. 28-29 Vol. 39 No. 7 ISSN: 0031-398X LENGTH: 864 words    ATLANTA - Results from new research point to a possible alternative to stimulants for the treatment of attention-deficit hyperactivity disorder in children and adolescents.    Two phase III studies presented at the annual meeting of the American Psychiatric Association show that a once-daily pediatric formulation of modafinil is well tolerated and improves attention-deficit hyperactivity disorder (ADHD) symptoms in children and adolescents.    Modafinil is currently marketed by Cephalon under the brand name Provigil in 100-mg and 200-mg strengths.    Provigil is indicated for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea, hypopnea syndrome, and shift work sleep disorder.    The company, which funded the phase II trials, is seeking approval from the Food and Drug Administration to market modafinil in 85-mg, 170-mg, 255-mg, 340-mg, and 425-mg strengths. If approved, the drug would be indicated for treatment of ADHD in children and adolescents aged 6-17 years.    The company is planning to launch the drug under the brand name Attenace by early 2006.    In one study, 189 patients with ADHD aged 6-17 years were randomized to a 7-week double-blind, fixed-dose treatment with either modafinil or placebo. This regime was followed by a 2-week withdrawal period in which half of the modafinil -treated patients were placed on placebo without tapering, and half were continued on the drug, said Joseph Biederman, M.D., the lead investigator in the study and professor of psychiatry at Harvard University in Boston.    Modafinil was administered once daily, starting at 85 mg/day, and was rapidly titrated over 7-9 days to dosages of either 340 mg/day for patients who weighed less than 30 kg or 425 mg/day for patients who weighed 30 kg or more.    The results of the study were assessed using the school and home ADHD Rating Scale-IV total score change from baseline to last treatment visit.    After 1 week, the 125 modafinil-treated patients had significantly greater improvements in school scores, compared with the 64 placebo patients, and those results were maintained through week 7.    On the school scale, patients on modafinil experienced a 17.2-point drop in symptoms, compared with an 8.2-point drop for patients who were on placebo. Modafinil also significantly improved total scores from parents, compared with placebo.    The side effects included insomnia and appetite decrease. Overall, the side effects were generally mild and occurred at initiation of the treatment. There were two serious adverse events not associated with the trial, said Dr. Biederman, who is an advisory board member for Cephalon and receives research/grant support from the company.    The researchers also assessed ADHD symptoms and physical/emotional response after rapid discontinuation. During the 2-week withdrawal phase, there were no reported symptom rebounds, no adverse events related to withdrawal, and no physical or emotional responses.    Modafinil appears to work like a gentler stimulant, Dr. Biederman said in an interview. The findings present possible new treatment options, he said. Although stimulants are effective, they are not universally effective.    About 30%-40% of patients are nonresponsive to stimulants, he said, and some patients also have tolerability problems.    Stimulants also have the potential for acute deterioration and symptom rebound if treatment is interrupted or discontinued without tapering, Dr. Biederman said.    In the second study, the researchers considered the effect of a flexible dose of modafinil in children and adolescents.    The study included 198 patients aged 6-17 years who were started on a dose of 85 mg/day of modafinil, which was titrated over 22 days based on clinical effectiveness. The maximum dose was 425 mg/day with once-daily dosing, said James Swanson, Ph.D., of the University of California at Irvine Child Development Center, who was the lead investigator.    The results were assessed using the school and home ADHD Rating Scale-IV, the Clinical Global Impression of Improvement (CGI-I), and the Test of Variables of Attention (TOVA).    The home score showed a mean drop of 17.6 points in symptoms for the 131 patients receiving modafinil at a mean stable dose of 361 mg/day, compared with a 7.5-point drop in symptoms for the 67 patients on placebo.    The improvement in the total school score was also significantly greater for modafinil patients, Dr. Swanson reported.    The researchers said Modafinil was shown to significantly improve inattention and hyperactivity/impulsivity, and there was an improvement in overall clinical condition and in the TOVA measurements of ADHD.    The researchers focused not only on decreasing symptoms of ADHD, but on increasing positive interaction and social skills, and they saw an increase in positive behaviors, he said.    The side effects included insomnia, headache, and appetite problems, which are similar to the side effects for stimulants, said Dr. Swanson, who is an advisory board member with Cephalon, receives research/grant support from the company, and is a member of the company's speakers' bureau. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: PDNEWS Copyright 2005 Elsevier Inc., International Medical News Group All Rights Reserved 491 of 998 DOCUMENTS The Herald (Glasgow) June 14, 2005 Doping drug rejected by NHS over cost BYLINE: CALUM MacDONALD SECTION: NEWS; Pg. 4 LENGTH: 168 words A DRUG which has been at the centre of a number of doping scandals involving athletes has been rejected for use by the NHS in Scotland because it is not cost-effective. The Scottish Medicines Consortium (SMC) has advised NHS boards not to prescribe Provigil, a brand name for the generic modafinil drug, to patients suffering from excessive sleepiness associated with shift work sleep disorder or obstructive sleep apnoea, the complete absence of breathing for more than 10 seconds during sleep. Despite trials showing that modafinil did bring about a modest improvement in sleepiness and quality of life, the SMC decided the therapy was not cost-effective. Modafinil is a moodbrightening and memoryenhancing psychostimulant which enhances wakefulness and vigilance. Kelli White, the American sprinter, received a two-year ban for using modafinil and was stripped of her 100m and 200m gold medals won in Paris in 2003. It was claimed at the time that she used the drug for treating narcolepsy, the sleeping disorder. LOAD-DATE: June 17, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: NEWSPAPER JOURNAL-CODE: GHERLD Copyright 2005 Newsquest Media Group All rights reserved 492 of 998 DOCUMENTS New Scientist May 28, 2005 11 steps to a better brain; It doesn't matter how brainy you are or how much education you've had - you can still improve and expand your mind. Boosting your mental faculties doesn't have to mean studying hard or becoming a reclusive bookworm. There are lots of tricks, techniques and habits as well as changes to your lifestyle, diet and behaviour that can help you flex your grey matter and get the best out of your brain cells. Follow New Scientist's guide to getting smarter, and maximise your brain's potential BYLINE: Kate Douglas, Alison George, Bob Holmes, Graham Lawton, John McCrone, Alison Motluk, Helen Phillips SECTION: FEATURES; Pg. 28 LENGTH: 4542 words Smart drugs Does getting old have to mean worsening memory, slower reactions and fuzzy thinking? AROUND the age of 40, honest folks may already admit to noticing changes in their mental abilities. This is the beginning of a gradual decline that in all too many of us will culminate in full-blown dementia. If it were possible somehow to reverse it, slow it or mask it, wouldn't you? A few drugs that might do the job, known as "cognitive enhancement", are already on the market, and a few dozen others are on the way. Perhaps the best-known is modafinil. Licensed to treat narcolepsy, the condition that causes people to suddenly fall asleep, it has notable effects in healthy people too. Modafinil can keep a person awake and alert for 90 hours straight, with none of the jitteriness and bad concentration that amphetamines or even coffee seem to produce. In fact, with the help of modafinil, sleep-deprived people can perform even better than their well-rested, unmedicated selves. The forfeited rest doesn't even need to be made good. Military research is finding that people can stay awake for 40 hours, sleep the normal 8 hours, and then pull a few more all-nighters with no ill effects. It's an open secret that many, perhaps most, prescriptions for modafinil are written not for people who suffer from narcolepsy, but for those who simply want to stay awake. Similarly, many people are using Ritalin not because they suffer from attention deficit or any other disorder, but because they want superior concentration during exams or heavy-duty negotiations. The pharmaceutical pipeline is clogged with promising compounds - drugs that act on the nicotinic receptors that smokers have long exploited, drugs that work on the cannabinoid system to block pot-smoking-type effects. Some drugs have also been specially designed to augment memory. Many of these look genuinely plausible: they seem to work, and without any major side effects. So why aren't we all on cognitive enhancers already? "We need to be careful what we wish for," says Daniele Piomelli at the University of California at Irvine. He is studying the body's cannabinoid system with a view to making memories less emotionally charged in people suffering from post-traumatic stress disorder. Tinkering with memory may have unwanted effects, he warns. "Ultimately we may end up remembering things we don't want to." Gary Lynch, also at UC Irvine, voices a similar concern. He is the inventor of ampakines, a class of drugs that changes the rules about how a memory is encoded and how strong a memory trace is - the essence of learning (see New Scientist , 14 May, p 6). But maybe the rules have already been optimised by evolution, he suggests. What looks to be an improvement could have hidden downsides. Still, the opportunity may be too tempting to pass up. The drug acts only in the brain, claims Lynch. It has a short half-life of hours. Ampakines have been shown to restore function to severely sleep-deprived monkeys that would otherwise perform poorly. Preliminary studies in humans are just as exciting. You could make an elderly person perform like a much younger person, he says. And who doesn't wish for that? Food for thought You are what you eat, and that includes your brain. So what is the ultimate mastermind diet? YOUR brain is the greediest organ in your body, with some quite specific dietary requirements. So it is hardly surprising that what you eat can affect how you think. If you believe the dietary supplement industry, you could become the next Einstein just by popping the right combination of pills. Look closer, however, and it isn't that simple. The savvy consumer should take talk of brain-boosting diets with a pinch of low-sodium salt. But if it is possible to eat your way to genius, it must surely be worth a try. First, go to the top of the class by eating breakfast. The brain is best fuelled by a steady supply of glucose, and many studies have shown that skipping breakfast reduces people's performance at school and at work. But it isn't simply a matter of getting some calories down. According to research published in 2003, kids breakfasting on fizzy drinks and sugary snacks performed at the level of an average 70-year-old in tests of memory and attention. Beans on toast is a far better combination, as Barbara Stewart from the University of Ulster, UK, discovered. Toast alone boosted children's scores on a variety of cognitive tests, but when the tests got tougher, the breakfast with the high-protein beans worked best. Beans are also a good source of fibre, and other research has shown a link between a high-fibre diet and improved cognition. If you can't stomach beans before midday, wholemeal toast with Marmite makes a great alternative. The yeast extract is packed with B vitamins, whose brain-boosting powers have been demonstrated in many studies. A smart choice for lunch is omelette and salad. Eggs are rich in choline, which your body uses to produce the neurotransmitter acetylcholine. Researchers at Boston University found that when healthy young adults were given the drug scopolamine, which blocks acetylcholine receptors in the brain, it significantly reduced their ability to remember word pairs. Low levels of acetylcholine are also associated with Alzheimer's disease, and some studies suggest that boosting dietary intake may slow age-related memory loss. A salad packed full of antioxidants, including beta-carotene and vitamins C and E, should also help keep an ageing brain in tip-top condition by helping to mop up damaging free radicals. Dwight Tapp and colleagues from the University of California at Irvine found that a diet high in antioxidants improved the cognitive skills of 39 ageing beagles - proving that you can teach an old dog new tricks. Round off lunch with a yogurt dessert, and you should be alert and ready to face the stresses of the afternoon. That's because yogurt contains the amino acid tyrosine, needed for the production of the neurotransmitters dopamine and noradrenalin, among others. Studies by the US military indicate that tyrosine becomes depleted when we are under stress and that supplementing your intake can improve alertness and memory. Don't forget to snaffle a snack mid-afternoon, to maintain your glucose levels. Just make sure you avoid junk food, and especially highly processed goodies such as cakes, pastries and biscuits, which contain trans-fatty acids. These not only pile on the pounds, but are implicated in a slew of serious mental disorders, from dyslexia and ADHD (attention deficit hyperactivity disorder) to autism. Hard evidence for this is still thin on the ground, but last year researchers at the annual Society for Neuroscience meeting in San Diego, California, reported that rats and mice raised on the rodent equivalent of junk food struggled to find their way around a maze, and took longer to remember solutions to problems they had already solved. It seems that some of the damage may be mediated through triglyceride, a cholesterol-like substance found at high levels in rodents fed on trans-fats. When the researchers gave these rats a drug to bring triglyceride levels down again, the animals' performance on the memory tasks improved. Brains are around 60 per cent fat, so if trans-fats clog up the system, what should you eat to keep it well oiled? Evidence is mounting in favour of omega-3 fatty acids, in particular docosahexaenoic acid or DHA. In other words, your granny was right: fish is the best brain food. Not only will it feed and lubricate a developing brain, DHA also seems to help stave off dementia. Studies published last year reveal that older mice from a strain genetically altered to develop Alzheimer's had 70 per cent less of the amyloid plaques associated with the disease when fed on a high-DHA diet. Finally, you could do worse than finish off your evening meal with strawberries and blueberries. Rats fed on these fruits have shown improved coordination, concentration and short-term memory. And even if they don't work such wonders in people, they still taste fantastic. So what have you got to lose? The Mozart effect Music may tune up your thinking, but you can't just crank up the volume and expect to become a genius A DECADE ago Frances Rauscher, a psychologist now at the University of Wisconsin at Oshkosh, and her colleagues made waves with the discovery that listening to Mozart improved people's mathematical and spatial reasoning. Even rats ran mazes faster and more accurately after hearing Mozart than after white noise or music by the minimalist composer Philip Glass. Last year, Rauscher reported that, for rats at least, a Mozart piano sonata seems to stimulate activity in three genes involved in nerve-cell signalling in the brain. This sounds like the most harmonious way to tune up your mental faculties. But before you grab the CDs, hear this note of caution. Not everyone who has looked for the Mozart effect has found it. What's more, even its proponents tend to think that music boosts brain power simply because it makes listeners feel better - relaxed and stimulated at the same time - and that a comparable stimulus might do just as well. In fact, one study found that listening to a story gave a similar performance boost. There is, however, one way in which music really does make you smarter, though unfortunately it requires a bit more effort than just selecting something mellow on your iPod. Music lessons are the key. Six-year-old children who were given music lessons, as opposed to drama lessons or no extra instruction, got a 2 to 3-point boost in IQ scores compared with the others. Similarly, Rauscher found that after two years of music lessons, pre-school children scored better on spatial reasoning tests than those who took computer lessons. Maybe music lessons exercise a range of mental skills, with their requirement for delicate and precise finger movements, and listening for pitch and rhythm, all combined with an emotional dimension. Nobody knows for sure. Neither do they know whether adults can get the same mental boost as young children. But, surely, it can't hurt to try. Bionic brains If training and tricks seem too much like hard work, some technological short cuts can boost brain function Gainful employment Put your mind to work in the right way and it could repay you with an impressive bonus UNTIL recently, a person's IQ - a measure of all kinds of mental problem-solving abilities, including spatial skills, memory and verbal reasoning - was thought to be a fixed commodity largely determined by genetics. But recent hints suggest that a very basic brain function called working memory might underlie our general intelligence, opening up the intriguing possibility that if you improve your working memory, you could boost your IQ too. Working memory is the brain's short-term information storage system. It's a workbench for solving mental problems. For example if you calculate 73 ? 6 + 7, your working memory will store the intermediate steps necessary to work out the answer. And the amount of information that the working memory can hold is strongly related to general intelligence. A team led by Torkel Klingberg at the Karolinska Institute in Stockholm, Sweden, has found signs that the neural systems that underlie working memory may grow in response to training. Using functional magnetic resonance imaging (fMRI) brain scans, they measured the brain activity of adults before and after a working-memory training programme, which involved tasks such as memorising the positions of a series of dots on a grid. After five weeks of training, their brain activity had increased in the regions associated with this type of memory (Nature Neuroscience , vol 7, p 75). Perhaps more significantly, when the group studied children who had completed these types of mental workouts, they saw improvement in a range of cognitive abilities not related to the training, and a leap in IQ test scores of 8 per cent (Journal of the American Academy of Child and Adolescent Psychiatry , vol 44, p 177). It's early days yet, but Klingberg thinks working-memory training could be a key to unlocking brain power. "Genetics determines a lot and so does the early gestation period," he says. "On top of that, there is a few per cent - we don't know how much - that can be improved by training." Memory marvels Mind like a sieve? Don't worry. The difference between mere mortals and memory champs is more method than mental capacity AN AUDITORIUM is filled with 600 people. As they file out, they each tell you their name. An hour later, you are asked to recall them all. Can you do it? Most of us would balk at the idea. But in truth we're probably all up to the task. It just needs a little technique and dedication. First, learn a trick from the "mnemonists" who routinely memorise strings of thousands of digits, entire epic poems, or hundreds of unrelated words. When Eleanor Maguire from University College London and her colleagues studied eight front runners in the annual World Memory Championships they did not find any evidence that these people have particularly high IQs or differently configured brains. But, while memorising, these people did show activity in three brain regions that become active during movements and navigation tasks but are not normally active during simple memory tests. This may be connected to the fact that seven of them used a strategy in which they place items to be remembered along a visualised route (Nature Neuroscience , vol 6, p 90). To remember the sequence of an entire pack of playing cards for example, the champions assign each card an identity, perhaps an object or person, and as they flick through the cards they can make up a story based on a sequence of interactions between these characters and objects at sites along a well-trodden route. Actors use a related technique: they attach emotional meaning to what they say. We always remember highly emotional moments better than less emotionally loaded ones. Professional actors also seem to link words with movement, remembering action-accompanied lines significantly better than those delivered while static, even months after a show has closed. Helga Noice, a psychologist from Elmhurst College in Illinois, and Tony Noice, an actor, who together discovered this effect, found that non-thesps can benefit by adopting a similar technique. Students who paired their words with previously learned actions could reproduce 38 per cent of them after just 5 minutes, whereas rote learners only managed 14 per cent. The Noices believe that having two mental representations gives you a better shot at remembering what you are supposed to say. Strategy is important in everyday life too, says Barry Gordon from Johns Hopkins University in Baltimore, Maryland. Simple things like always putting your car keys in the same place, writing things down to get them off your mind, or just deciding to pay attention, can make a big difference to how much information you retain. And if names are your downfall, try making some mental associations. Just remember to keep the derogatory ones to yourself. Sleep on it Never underestimate the power of a good night's rest SKIMPING on sleep does awful things to your brain. Planning, problem-solving, learning, concentration,working memory and alertness all take a hit. IQ scores tumble. "If you have been awake for 21 hours straight, your abilities are equivalent to someone who is legally drunk," says Sean Drummond from the University of California, San Diego. And you don't need to pull an all-nighter to suffer the effects: two or three late nights and early mornings on the trot have the same effect. Luckily, it's reversible - and more. If you let someone who isn't sleep-deprived have an extra hour or two of shut-eye, they perform much better than normal on tasks requiring sustained attention, such taking an exam. And being able to concentrate harder has knock-on benefits for overall mental performance. "Attention is the base of a mental pyramid," says Drummond. "If you boost that, you can't help boosting everything above it." These are not the only benefits of a decent night's sleep. Sleep is when your brain processes new memories, practises and hones new skills - and even solves problems. Say you're trying to master a new video game. Instead of grinding away into the small hours, you would be better off playing for a couple of hours, then going to bed. While you are asleep your brain will reactivate the circuits it was using as you learned the game, rehearse them, and then shunt the new memories into long-term storage. When you wake up, hey presto! You will be a better player. The same applies to other skills such as playing the piano, driving a car and, some researchers claim, memorising facts and figures. Even taking a nap after training can help, says Carlyle Smith of Trent University in Peterborough, Ontario. There is also some evidence that sleep can help produce moments of problem-solving insight. The famous story about the Russian chemist Dmitri Mendeleev suddenly "getting" the periodic table in a dream after a day spent struggling with the problem is probably true. It seems that sleep somehow allows the brain to juggle new memories to produce flashes of creative insight. So if you want to have a eureka moment, stop racking your brains and get your head down. Body and mind Physical exercise can boost brain as well as brawn IT'S a dream come true for those who hate studying. Simply walking sedately for half an hour three times a week can improve abilities such as learning, concentration and abstract reasoning by 15 per cent. The effects are particularly noticeable in older people. Senior citizens who walk regularly perform better on memory tests than their sedentary peers. What's more, over several years their scores on a variety of cognitive tests show far less decline than those of non-walkers. Every extra mile a week has measurable benefits. It's not only oldies who benefit, however. Angela Balding from the University of Exeter, UK, has found that schoolchildren who exercise three or four times a week get higher than average exam grades at age 10 or 11. The effect is strongest in boys, and while Balding admits that the link may not be causal, she suggests that aerobic exercise may boost mental powers by getting extra oxygen to your energy-guzzling brain. There's another reason why your brain loves physical exercise: it promotes the growth of new brain cells. Until recently, received wisdom had it that we are born with a full complement of neurons and produce no new ones during our lifetime. Fred Gage from the Salk Institute in La Jolla, California, busted that myth in 2000 when he showed that even adults can grow new brain cells. He also found that exercise is one of the best ways to achieve this. In mice, at least, the brain-building effects of exercise are strongest in the hippocampus, which is involved with learning and memory. This also happens to be the brain region that is damaged by elevated levels of the stress hormone cortisol. So if you are feeling frazzled, do your brain a favour and go for a run. Even more gentle exercise, such as yoga, can do wonders for your brain. Last year, researchers at the University of California, Los Angeles, reported results from a pilot study in which they considered the mood-altering ability of different yoga poses. Comparing back bends, forward bends and standing poses, they concluded that the best way to get a mental lift is to bend over backwards. And the effect works both ways. Just as physical exercise can boost the brain, mental exercise can boost the body. In 2001, researchers at the Cleveland Clinic Foundation in Ohio asked volunteers to spend just 15 minutes a day thinking about exercising their biceps. After 12 weeks, their arms were 13 per cent stronger. Nuns on a run If you don't want senility to interfere with your old age, perhaps you should seek some sisterly guidance THE convent of the School Sisters of Notre Dame on Good Counsel Hill in Mankato, Minnesota, might seem an unusual place for a pioneering brain-science experiment. But a study of its 75 to 107-year-old inhabitants is revealing more about keeping the brain alive and healthy than perhaps any other to date. The "Nun study" is a unique collaboration between 678 Catholic sisters recruited in 1991 and Alzheimer's expert David Snowdon of the Sanders-Brown Center on Aging and the University of Kentucky in Lexington. The sisters' miraculous longevity - the group boasts seven centenarians and many others well on their way - is surely in no small part attributable to their impeccable lifestyle. They do not drink or smoke, they live quietly and communally, they are spiritual and calm and they eat healthily and in moderation. Nevertheless, small differences between individual nuns could reveal the key to a healthy mind in later life. Some of the nuns have suffered from Alzheimer's disease, but many have avoided any kind of dementia or senility. They include Sister Matthia, who was mentally fit and active from her birth in 1894 to the day she died peacefully in her sleep, aged 104. She was happy and productive, knitting mittens for the poor every day until the end of her life. A post-mortem of Sister Matthia's brain revealed no signs of excessive ageing. But in some other, remarkable cases, Snowdon has found sisters who showed no outwards signs of senility in life, yet had brains that looked as if they were ravaged by dementia. How did Sister Matthia and the others cheat time? Snowdon's study, which includes an annual barrage of mental agility tests and detailed medical exams, has found several common denominators. The right amount of vitamin folate is one. Verbal ability early in life is another, as are positive emotions early in life, which were revealed by Snowdon's analysis of the personal autobiographical essays each woman wrote in her 20s as she took her vows. Activities, crosswords, knitting and exercising also helped to prevent senility, showing that the old adage "use it or lose it" is pertinent. And spirituality, or the positive attitude that comes from it, can't be overlooked. But individual differences also matter. To avoid dementia, your general health may be vital: metabolic problems, small strokes and head injuries seem to be common triggers of Alzheimer's dementia. Obviously, you don't have to become a nun to stay mentally agile. We can all aspire to these kinds of improvements. As one of the sisters put it, "Think no evil, do no evil, hear no evil, and you will never write a best-selling novel." Attention seeking You can be smart, well-read, creative and knowledgeable, but none of it is any use if your mind isn't on the job PAYING attention is a complex mental process, an interplay of zooming in on detail and stepping back to survey the big picture. So unfortunately there is no single remedy to enhance your concentration. But there are a few ways to improve it. The first is to raise your arousal levels. The brain's attentional state is controlled by the neurotransmitters dopamine and noradrenalin. Dopamine encourages a persistent, goal-centred state of mind whereas noradrenalin produces an outward-looking, vigilant state. So not surprisingly, anything that raises dopamine levels can boost your powers of concentration. One way to do this is with drugs such as amphetamines and the ADHD drug methylphenidate, better known as Ritalin. Caffeine also works. But if you prefer the drug-free approach, the best strategy is to sleep well, eat foods packed with slow-release sugars, and take lots of exercise. It also helps if you are trying to focus on something that you find interesting. The second step is to cut down on distractions. Workplace studies have found that it takes up to 15 minutes to regain a deep state of concentration after a distraction such as a phone call. Just a few such interruptions and half the day is wasted. Music can help as long as you listen to something familiar and soothing that serves primarily to drown out background noise. Psychologists also recommend that you avoid working near potential diversions, such as the fridge. There are mental drills to deal with distractions. College counsellors routinely teach students to recognise when their thoughts are wandering, and catch themselves by saying "Stop! Be here now!" It sounds corny but can develop into a valuable habit. As any Zen meditator will tell you, concentration is as much a skill to be lovingly cultivated as it is a physiochemical state of the brain. Positive feedback Thought control is easier than you might imagine IT SOUNDS a bit New Age, but there is a mysterious method of thought control you can learn that seems to boost brain power. No one quite knows how it works, and it is hard to describe exactly how to do it: it's not relaxation or concentration as such, more a state of mind. It's called neurofeedback. And it is slowly gaining scientific credibility. Neurofeedback grew out of biofeedback therapy, popular in the 1960s. It works by showing people a real-time measure of some seemingly uncontrollable aspect of their physiology - heart rate, say - and encouraging them to try and change it. Astonishingly, many patients found that they could, though only rarely could they describe how they did it. More recently, this technique has been applied to the brain - specifically to brain wave activity measured by an electroencephalogram, or EEG. The first attempts were aimed at boosting the size of the alpha wave, which crescendos when we are calm and focused. In one experiment, researchers linked the speed of a car in a computer game to the size of the alpha wave. They then asked subjects to make the car go faster using only their minds. Many managed to do so, and seemed to become more alert and focused as a result. This early success encouraged others, and neurofeedback soon became a popular alternative therapy for ADHD. There is now good scientific evidence that it works, as well as some success in treating epilepsy, depression, tinnitus, anxiety, stroke and brain injuries. And to keep up with the times, some experimenters have used brain scanners in place of EEGs. Scanners can allow people to see and control activity of specific parts of the brain. A team at Stanford University in California showed that people could learn to control pain by watching the activity of their pain centres (New Scientist , 1 May 2004, p 9). But what about outside the clinic? Will neuro feedback ever allow ordinary people to boost their brain function? Possibly. John Gruzelier of Imperial College London has shown that it can improve medical students' memory and make them feel calmer before exams. He has also shown that it can improve musicians' and dancers' technique, and is testing it out on opera singers and surgeons. Neils Birbaumer from the University of Tübingen in Germany wants to see whether neurofeedback can help psychopathic criminals control their impulsiveness. And there are hints that the method could boost creativity, enhance our orgasms, give shy people more confidence, lift low moods, alter the balance between left and right brain activity, and alter personality traits. All this by the power of thought. LOAD-DATE: May 31, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: Magazine Copyright 2005 Reed Business Information, UK, a division of Reed Elsevier Inc. All Rights Reserved 493 of 998 DOCUMENTS The Guardian (London) - Final Edition May 19, 2005 Drugs in sport: I was like a drugs guinea pig, says banned sprinter BYLINE: Duncan Mackay SECTION: Guardian Sport Pages, Pg. 32 LENGTH: 553 words Kelli White, the former training partner of Britain's banned sprinter Dwain Chambers, has claimed she was treated like a "guinea pig" as she experimented with a cocktail of banned substances. The American told the World Anti-Doping Agency at a hearing in Montreal that she was asked to try out a range of performance-enhancing drugs, including the designer anabolic steroid tetrahydrogestrinone (THG), the blood-boosting hormone erythropoietin (EPO) and the stimulant modafinil, without ever being warned of the potential side effects. "I was offered a lot of things and asked to test them to see if I responded better to certain products," she said. "I was like a guinea pig. I tried a lot of stimulants and modafinil suited me perfectly. The same for THG, which helped put on muscle very quickly." White tested positive for modafinil at the 2003 world championships in Paris and was stripped of the gold medals she had won in the 100 and 200 metres. She was later implicated in the steroid investigation into the Bay Area Laboratory Co-Operative and was banned for two years after she admitted using banned drugs. Her former coach, the Ukrainian-born Remi Korchemny who also trained Chambers, is among four men facing federal charges in the Balco case. After her positive test, White claimed she had used modafinil to treat the sleeping disorder narcolepsy. She told Wada that was a cover story devised by Balco's founder and owner Victor Conte and a doctor, Brian Goldman. "I never suffered from narcolepsy," she said. "I never even knew the word existed until a few hours after the announcement of my positive test." White passed 17 drugs tests after starting the programme in March 2003 but suffered physically. "My menstrual cycle was completely disturbed. I had acne and my voice changed incredibly. And probably the worst thing was my blood pressure shot up. It took a long time to stabilise." Meanwhile, revelations by some of Australia's top sportsmen that they have been using caffeine tablets to boost their performance has led Wada to threaten to put the substance back on its banned list. Caffeine in high dosages was removed from its list in January 2004 because there was no scientific evidence that it helped athletes. The Australian men's hockey team experimented with caffeine tablets during the Olympics in Athens and after winning the gold medal for the first time reported that their endurance had improved. Wada issued its warning yesterday after Australia's rugby union captain George Gregan became the latest figure to admit he had taken caffeine pills, which are said to contain the equivalent of 12 cups of coffee. The undisputed world super-lightweight boxing champion Kostya Tszyu, who is due to fight Manchester's Ricky Hatton, is another Australian who has admitted experimenting with caffeine tablets. "The interesting thing," said Dick Pound, the chairman of Wada, "is that the (Australian Institute of Sport) says it is performance-enhancing, has research to back up its claims and recommends how it should be taken. Having heard this, (we) will take another look at it." A recent UK Sport survey revealed that 36% of sportsmen and women in the UK have used supplements that contain caffeine. That rose to 50% among rugby league players. LOAD-DATE: May 19, 2005 LANGUAGE: ENGLISH Copyright 2005 Guardian Newspapers Limited 494 of 998 DOCUMENTS The Record (Kitchener-Waterloo, Ontario) May 19, 2005 Thursday Final Edition 'Treated me like guinea pig'; After admitting she used banned substances, sprinter says she was asked to try other enhancers SOURCE: Associated Press SECTION: SPORTS; Pg. C7 LENGTH: 453 words DATELINE: PARIS American sprinter Kelli White, serving a two-year suspension after admitting she used banned substances, says she was treated like a "guinea pig" to try out doping products. White testified about her drug use to the World Anti-Doping Agency executive committee in Montreal on Monday. The French sports daily L'Equipe, which said it was the only news organization inside the hearing, published a transcript yesterday. White said she was asked to try out various performance-enhancing drugs, including the designer steroid THG, endurance-boosting hormone EPO and stimulant modafinil. She said she was never warned of potential side effects. "I was offered a lot of things and asked to test them to see if I responded better to certain products," she was quoted as saying. "I was like a guinea pig. I tried a lot of stimulants and modafinil suited me perfectly. The same for THG, which helped put on muscle very quickly." White tested positive for modafinil at the 2003 world championships in Paris and was stripped of her gold medals in the 100 and 200 metres. White was later implicated in the steroid investigation into the Bay Area Laboratory Co-Operative. She acknowledged her use of the drugs when the U.S. Anti-Doping Agency confronted her with evidence it had gathered against her. White was suspended for two years in 2004 and is cooperating with the U.S. agency. Her former coach, Remi Korchemny, is among four men indicted on federal charges in the Bay Area Laboratory case. After testing positive at the worlds, White claimed she had used modafinil to treat the sleeping disorder narcolepsy. She told the world agency that was a cover story devised by Bay Area Laboratory founder Victor Conte and a doctor, Brian Goldman. "I never suffered from narcolepsy," she said. "I never even knew the word existed until a few hours after the announcement of my positive test." White's allegation about the cover story was reported in February by the San Francisco Chronicle. Goldman, who was an associate of Conte, hasn't been charged in the Bay Area Laboratory case. White told the world agency panel that she took a cocktail of drugs -- including THG, EPO, a masking agent and a mix of stimulants -- starting in March 2003 for at least four months, and said the results were "incredible." White said she passed 17 doping tests in 2003 before the world championships. "The tests didn't worry me," she said. "I was calm." But White said she suffered physical effects from the drugs. "My menstrual cycle was completely disturbed," she said. "I had acne and my voice changed incredibly. And probably the worst thing was my blood pressure shot up. It took a long time to stabilize." LOAD-DATE: May 24, 2005 LANGUAGE: ENGLISH GRAPHIC: Photo: ASSOCIATED PRESS; Kelli White suffered many side effects from doping products, including high blood pressure that "took a long time to stabilize." TYPE: NEWS Copyright 2005 Metroland Media Group Ltd 495 of 998 DOCUMENTS Associated Press Worldstream May 18, 2005 Wednesday White treated like a 'guinea pig' as she tested doping products SECTION: SPORTS LENGTH: 520 words DATELINE: PARIS American sprinter Kelli White, serving a two-year suspension after admitting she used banned substances, says she was treated like a "guinea pig" to try out doping products. White testified about her drug use to the World Anti-Doping Agency executive committee in Montreal on Monday. The French sports daily L'Equipe, which said it was the only news organization inside the hearing, published a transcript Wednesday. White said she was asked to try out various performance-enhancing drugs, including the designer steroid THG, endurance-boosting hormone EPO and stimulant modafinil. She said she was never warned of potential side effects. "I was offered a lot of things and asked to test them to see if I responded better to certain products," she was quoted as saying. "I was like a guinea pig. I tried a lot of stimulants and modafinil suited me perfectly. The same for THG, which helped put on muscle very quickly." White tested positive for modafinil at the 2003 world championships in Paris and was stripped of her gold medals in the 100 and 200 meters. White was later implicated in the steroid investigation into the Bay Area Laboratory Co-Operative. She acknowledged her use of the drugs when the U.S. Anti-Doping Agency confronted her with evidence it had gathered against her. White was suspended for two years in 2004 and is cooperating with USADA. Her former coach, Remi Korchemny, is among four men indicted on federal charges in the BALCO case. After testing positive at the worlds, White claimed she had used modafinil to treat the sleeping disorder narcolepsy. She told WADA that was a cover story devised by BALCO founder Victor Conte and a doctor, Brian Goldman. "I never suffered from narcolepsy," she said. "I never even knew the word existed until a few hours after the announcement of my positive test." White's allegation about the cover story was reported in February by the San Francisco Chronicle. Goldman, who was an associate of Conte, hasn't been charged in the BALCO case. White told the WADA panel that she took a cocktail of drugs - including THG, EPO, a masking agent and a mix of stimulants - starting in March 2003 for at least four months, and said the results were "incredible." White said she passed 17 doping tests in 2003 before the world championships. "The tests didn't worry me," she said. "I was calm." But White said she suffered physical effects from the drugs. "My menstrual cycle was completely disturbed," she said. "I had acne and my voice changed incredibly. And probably the worst thing was my blood pressure shot up. It took a long time to stabilize." White said she's concerned that other athletes are still looking for an illegal edge. "The worst thing is that many athletes continue to talk to me about doping and want to know how to acquire these substances," she said. "It's troubling. "The fight against doping must be increased and the angles of attack must be increased," White added. "Other athletes are ready to talk and a lot of things are still going on today. Let's not forget the trainers, because they advise the athletes." LOAD-DATE: May 19, 2005 LANGUAGE: ENGLISH Copyright 2005 Associated Press All Rights Reserved 496 of 998 DOCUMENTS Generic Line May 18, 2005 Sandoz Drops Patent Challenge Against Cephalon's Provigil SECTION: Vol. 22, No. 10 LENGTH: 165 words Cephalon has dodged a patent challenge against its top-selling drug Provigil, which was recently targeted by an abbreviated new drug application (ANDA) filed by Sandoz. Cephalon said May 2 that Sandoz, the generic division of Novartis Pharmaceuticals, no longer intends to challenge Cephalon's U.S. particle-size Provigil (modafinil) patent. Instead, Sandoz plans to convert its ANDA for modafinil from a Paragraph IV certification to a Paragraph III certification, Cephalon said. The effect of this conversion is that Sandoz will certify to the FDA that it does not intend to market a generic form of modafinil until Cephalon's patent on the drug expires in 2014, Cephalon said. In turn, Cephalon has agreed to drop its patent infringement lawsuit against Sandoz. Sandoz officials were not available to comment before press time. Provigil, a treatment for narcolepsy, was Cephalon's top-selling drug in 2004, generating sales of $439.7 million. Release date: May 18, 2005 LOAD-DATE: May 17, 2005 LANGUAGE: ENGLISH Copyright 2005 Washington Business Information, Inc., All Rights Reserved 497 of 998 DOCUMENTS FDAnews Drug Daily Bulletin May 12, 2005 Cephalon's Provigil Avoids Patent Challenge From Sandoz SECTION: Vol. 2, No. 94 LENGTH: 153 words Cephalon has dodged a patent challenge against its top-selling drug Provigil, which was recently targeted by an abbreviated new drug application (ANDA) filed by Sandoz. Cephalon said that Sandoz, the generic division of Novartis Pharmaceuticals, no longer intends to challenge Cephalon's U.S. particle-size Provigil (modafinil) patent. Instead, Sandoz plans to convert its ANDA for modafinil from a Paragraph IV certification to a Paragraph III certification, Cephalon said. The effect of this conversion is that Sandoz will certify to the FDA that it does not intend to market a generic form of modafinil until Cephalon's patent on the drug expires in 2014, Cephalon said. In turn, Cephalon has agreed to drop its patent infringement lawsuit against Sandoz. Provigil, a treatment for narcolepsy, was Cephalon's top-selling drug in 2004, generating sales of $439.7 million. Release date: May 12, 2005 LOAD-DATE: May 11, 2005 LANGUAGE: ENGLISH Copyright 2005 Washington Business Information, Inc., All Rights Reserved 498 of 998 DOCUMENTS World Generic Markets Pharmaceuticals May 10, 2005 Cephalon reports modafinil and tiagabine challenge updates LENGTH: 237 words Cephalon has been notified that Sandoz will no longer challenge Cephalon's US particle-size modafinil patent; modafinil is the generic form of Cephalon's Provigil tables. Instead, Sandoz will convert its ANDA for the drug from a Paragraph IV certification to a Paragraph III certification; this will mean Sandoz will not intend to market a generic version of the drug until the applicable patent listed in the Orange Book has expired. This will happen on 6th October 2014. Consequently, Cephalon noted it will no longer be necessary for it to continue to pursue its patent infringement litigation against Sandoz. Separately, Cephalon reported that the ANDA filing for a generic version of its tiagabine hydrochloride product, Gabitril , that was posted on the FDA's website in April does not challenge the composition of matter patent covering the drug. Cephalon added that Gabitril is protected by four patents listed in the Orange Book, including a composition of matter patent. The four patents expire on 30th September 2011, 24th March 2012, 29th April 2016 and 10th June 2017. Cephalon also noted that Sun Pharmaceutical Industries has filed an ANDA which targets the other three patents. However, this ANDA also does not contain a Paragraph IV certification for the composition of matter patent. Consequently, Cephalon noted Sun is not seeking to market a generic version of the drug until after this patent expires in 2011. LOAD-DATE: May 11, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2005 ESPICOM Business Intelligence Ltd. All Rights Reserved 499 of 998 DOCUMENTS CNS Drug News Pharmaceuticals May 3, 2005 Cephalon updates on patent litigation for Provigil and Gabitril LENGTH: 278 words Sandoz ( Novartis ) has notified Cephalon that it will no longer challenge Cephalon's US particle-size modafinil patent. Instead, Sandoz intends to convert its ANDA for approval of a generic equivalent of modafinil, the active ingredient in Provigil Tablets C-IV, from a Paragraph IV certification to a Paragraph III certification. Provigil is indicated for the treatment of excessive sleepiness associated with disorders of sleep and wakefulness in adults. The effect of this conversion is that Sandoz will certify to the FDA that it does not intend to market a generic form of modafinil until the applicable patent for the drug (listed in the Orange Book) has expired in 2014. Therefore, it will no longer be necessary for Cephalon to continue to pursue its patent infringement litigation against Sandoz. Separately, Cephalon has learned that the ANDA filing against Gabitril ( tiagabine ) Tablets that was posted last month on the FDA website does not challenge the composition of matter patent covering the currently approved product. Gabitril is indicated as adjunctive therapy for partial seizures in adults and children 12 years and older. The product is protected by four Orange Book-listed patents, including a composition of matter patent claiming the active drug substance. Cephalon recently received notification from Sun Pharmaceutical Industries that its ANDA is targeting the three other Cephalon patents covering Gabitril. However, the filing does not include a Paragraph IV certification with respect to the composition of matter patent. As such, Sun is not seeking to market a generic form of Gabitril until after the expiration of this patent in 2011. LOAD-DATE: May 5, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2005 ESPICOM Business Intelligence Ltd. All Rights Reserved 500 of 998 DOCUMENTS Drug Industry Daily May 3, 2005 Sandoz Drops Patent Challenge Against Cephalon's Provigil SECTION: Vol. 4, No. 87 LENGTH: 166 words Cephalon has dodged a patent challenge against its top-selling drug Provigil, which was recently targeted by an abbreviated new drug application (ANDA) filed by Sandoz. Cephalon said May 2 that Sandoz, the generic division of Novartis Pharmaceuticals, no longer intends to challenge Cephalon's U.S. particle-size Provigil (modafinil) patent. Instead, Sandoz plans to convert its ANDA for modafinil from a Paragraph IV certification to a Paragraph III certification, Cephalon said. The effect of this conversion is that Sandoz will certify to the FDA that it does not intend to market a generic form of modafinil until Cephalon's patent on the drug expires in 2014, Cephalon said. In turn, Cephalon has agreed to drop its patent infringement lawsuit against Sandoz. Sandoz officials were not available to comment before press time. Provigil, a treatment for narcolepsy, was Cephalon's top-selling drug in 2004, generating sales of $439.7 million. -- MN Release date: May 3, 2005 LOAD-DATE: May 2, 2005 LANGUAGE: ENGLISH Copyright 2005 Washington Business Information, Inc., All Rights Reserved  501 of 998 DOCUMENTS World Markets Analysis May 03, 2005 Cephalon Relief as Sandoz Makes Provigil U-Turn BYLINE: Simon King SECTION: IN BRIEF LENGTH: 207 words Executives at US pharma company Cephalon have breathed a collective sigh of relief after Swiss-based Novartis's unit Sandoz confirmed it would not be launching a generic version of the narcolepsy drug Provigil (modafinil). Sandoz announced that it would end its bid to challenge Cephalon's patent on Provigil and does not intend to market a generic version of modafinil until at least 2014, when a key patent on the compound expires. Significance: In response, Cephalon has announced that legal action against Sandoz has been dropped. Generics-driven loss for Provigil sales would be a major setback for Cephalon, given the recent performance of the drug (see United States: 16 February 2005: Sleeping Disorder Drug Drives Revenue Surge for Cephalon). The US company is not out of the woods yet, however, with three generic versions of modafinil manufactured by Mylan, Barr (both US) and Dr Reddy's (India) having already secured preliminary approval with the FDA (see United States: 11 February 2005: FDA Tentatively Clears Mylan's Generic Modafinil). The impact of Sandoz's U-turn is therefore somewhat limited, although it does perhaps suggest that patent protection for Provigil will be hard to overcome in the legal arena. LOAD-DATE: May 03, 2005 LANGUAGE: ENGLISH Copyright 2005 World Markets Research Limited; All Rights Reserved 502 of 998 DOCUMENTS Knobias.com This content is provided to LexisNexis by Comtex News Network, Inc. May 2, 2005 Monday CEPH: Provides Update on Patent Litigation Matters LENGTH: 131 words DATELINE: Ridgeland, MS Cephalon, Inc. (CEPH) reported that Sandoz, Inc. has notified Cephalon that it will no longer challenge Cephalon's U.S. particle-size modafinil patent. Instead, Sandoz said it intends to convert its abbreviated new drug application (ANDA) for approval of a generic equivalent of modafinil, the active ingredient contained in PROVIGIL(R) Tablets [C-IV], from a paragraph IV certification to a paragraph III certification. The effect of this conversion is that Sandoz will certify to the FDA that it does not intend to market a generic form of modafinil until the applicable patent for modafinil listed in the Orange Book has expired in 2014. Therefore, it will no longer be necessary for Cephalon to continue to pursue its patent infringement litigation against Sandoz. LOAD-DATE: May 3, 2005 LANGUAGE: ENGLISH Copyright 2005 Comtex News Network, Inc. All Rights Reserved Copyright 2005 Knobias.com, LLC, All rights reserved 503 of 998 DOCUMENTS MarketWatch May 2, 2005 Monday Cephalon: Sandoz will not challenge modafinil patent BYLINE: Heather Wilson LENGTH: 69 words SAN FRANCISCO (MarketWatch) -- Cephalon Inc. (ceph) said Monday that Sandoz Inc. has notified the company that it will not challenge Cephalon's patent on modafinil. Sandoz will convert its abbreviated new drug application for a generic version of modafinil to a paragraph III certification, thereby ending the patent dispute between the two companies, Cephalon said. Modafinil is the active ingredient in Provigil. LOAD-DATE: May 3, 2005 LANGUAGE: ENGLISH Copyright 2005 MarketWatch.com Inc., All Rights Reserved 504 of 998 DOCUMENTS PR Newswire US May 2, 2005 Monday 02:10 PM GMT Cephalon, Inc. Provides Update on Patent Litigation Matters; Sandoz, Inc. to Drop Challenge to PROVIGIL(R) Patent; GABITRIL(R) Composition of Matter Patent Not Targeted by Recent Filing LENGTH: 826 words DATELINE: FRAZER, Pa. May 2 FRAZER, Pa., May 2 /PRNewswire-FirstCall/ -- Cephalon, Inc. (NASDAQ:CEPH) reported today that Sandoz, Inc. has notified Cephalon that it will no longer challenge Cephalon's U.S. particle-size modafinil patent. Instead, Sandoz said it intends to convert its abbreviated new drug application (ANDA) for approval of a generic equivalent of modafinil, the active ingredient contained in PROVIGIL(R) Tablets [C-IV], from a paragraph IV certification to a paragraph III certification. The effect of this conversion is that Sandoz will certify to the U.S. Food and Drug Administration (FDA) that it does not intend to market a generic form of modafinil until the applicable patent for modafinil listed in the Orange Book has expired in 2014. Therefore, it will no longer be necessary for Cephalon to continue to pursue its patent infringement litigation against Sandoz. Separately, Cephalon has learned that the ANDA filing against GABITRIL(R) (tiagabine hydrochloride) Tablets that was posted last month on the FDA website does not challenge the composition of matter patent covering the currently approved product. GABITRIL is protected by four Orange Book-listed patents, including a composition of matter patent claiming the active drug substance contained in GABITRIL. Cephalon recently received notification from SUN Pharmaceutical Industries Limited that its ANDA is targeting the three other Cephalon patents covering GABITRIL. However, the filing does not include a paragraph IV certification with respect to the composition of matter patent. As such, SUN is not seeking to market a generic form of GABITRIL until after the expiration of this patent in 2011. Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products to treat sleep and neurological disorders, cancer and pain. Cephalon currently employs approximately 2,400 people in the United States and Europe. U.S. sites include the company's headquarters in Frazer, PA, and offices, laboratories or manufacturing facilities in West Chester, PA, Salt Lake City, UT, and suburban Minneapolis, MN. Cephalon's major European offices are located in Guildford, England, Martinsried, Germany, and Maisons-Alfort, France. The company currently markets three proprietary products in the United States: PROVIGIL, GABITRIL and ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II] and more than 20 products internationally. Further information about Cephalon and full prescribing information on its U.S. products is available at http://www.cephalon.com/ or by calling 1-800-896-5855. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding Sandoz's intent to convert its ANDA filing to a Paragraph III filing and the need to continue the patent infringement lawsuit against Sandoz, SUN Pharmaceuticals Paragraph IV certification with respect to three of the four GABITRIL patents and any decision by them to not seek to market a generic form of GABITRIL prior to 2011, anticipated scientific progress on its research programs, development of potential pharmaceutical products, interpretation of clinical results, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, sales and earnings guidance, and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. CONTACT: Investor Contact: Chip Merritt, +1-610-738-6376 or cmerritt@cephalon.com , or Media Contact: Robert W. Grupp, +1-610-738-6402 or rgrupp@cephalon.com , both of Cephalon Web site: http://www.cephalon.com/ Company News On-Call: http://www.prnewswire.com/comp/134563.html SOURCE Cephalon, Inc. URL: http://www.prnewswire.com LOAD-DATE: May 3, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2005 PR Newswire Association LLC. All Rights Reserved. 505 of 998 DOCUMENTS The Pharmaceutical Journal April 29, 2005 Modafinil fails to improve fatigue BYLINE: Old_manager LENGTH: 308 words Modafinil, a drug used to treat daytime sleepiness, does not appear to improve fatigue in patients with multiple sclerosis, a trial has revealed. Aspirin, on the other hand, may reduce the severity of this symptom. French researchers examined the effects of modafinil in 115 patients with relapsing remitting or progressive MS who were also suffering from chronic fatigue. They found that the drug was no better than placebo at relieving self-reported fatigue symptoms. After 35 days of treatment, both had improved mean scores on a modified fatigue impact scale (63.1±9.3 to 52.3±18.5 for modafinil vs 63.3±10 to 49.2±16.6 for placebo). Although the researchers conclude that no benefit was detected for modafinil, they say that an unpublished post hoc analysis did reveal an effect related to sleepiness. "Among patients with excessive daytime sleepiness, modafinil tended to provide more benefit than placebo on the physical component of fatigue," they say (Neurology2005;64:1139). In a second study (ibid, p1267), researchers observed an improvement in patient scores during treatment with aspirin (1,300mg daily) compared with placebo (P=0.043). Patients were treated with both aspirin and placebo in the cross-over trial. Among the 26 patients who completed both phases, 10 (38.5 per cent) preferred aspirin whereas only one (3.9 per cent) preferred placebo (P=0.012). An accompanying editorial warns that the apparent benefit of aspirin and the lack of benefit of modafinil may be related to their effects on other MS symptoms. "It is not clear that patients adequately distinguish effects of fatigue from motor impairment, cognitive impairment and other symptoms," the authors argue (ibid, p1111). LOAD-DATE: November 10, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Journal Copyright 2005 PJ Online All Rights Reserved 506 of 998 DOCUMENTS Reuters Health Medical News April 22, 2005 Friday 9:00 PM EST Modafinil ineffective in treating MS fatigue, but aspirin might help SECTION: CLINICAL LENGTH: 361 words DATELINE: NEW YORK The narcolepsy drug modafinil (Provigil, Cephalon) does not affect fatigue experienced by patients with multiple sclerosis (MS), results of a double-blind controlled trial suggest. However, a separate study found that aspirin may be of some benefit. Both studies appeared in the April 12th issue of Neurology. In the first study, Dr. Bruno Stankoff, at Hopital de la Salpetriere in Paris and members of the French Modafinil Study Group note that two small pilot studies recently showed a positive impact of modafinil on MS fatigue. To further investigate, the group randomly assigned 56 patients scoring 45 or more on the Modified Fatigue Impact Scale (MFIS) to modafinil, maximum 400 mg/day, and 59 to placebo. Both groups experienced decreased fatigue during the 35-day trial, but change in scores on the MFIS, Fatigue Impact Scale, and Epworth Sleepiness Scale did not differ significantly between groups. In the second paper, Dr. Dean M. Wingerchuk and colleagues point out that some MS patients using aspirin for other purposes report reduced fatigue. In the randomized crossover trial, 30 patients with MS and fatigue took either aspirin 650 mg twice daily or placebo for 6 weeks, separated by a 2-week washout period. Mean score on the MFIS was lower during aspirin treatment (38.1 versus 42.5, p = 0.043), and there was a trend toward aspirin benefit on a 10-point visual analog scale (5.9 versus 5.4, p = 0.076). However, response did not differ significantly on the Fatigue Severity Scale or MS-Specific Fatigue Scale. The researchers suggest that aspirin's ability to inhibit cyclooxygenase and block prostaglandin E2 production "could modulate hypothalamic output, thereby affecting neuroendocrine and autonomic responses important in fatigue perception." Commenting on such trials in a related editorial, Drs. Steven R. Schwid of the University of Rochester, New York and T. Jock Murray of Dalhousie University in Halifax, Nova Scotia observe that "until we make progress in distinguishing fatigue from other MS symptoms, in identifying its mechanisms and in measuring it accurately, we will not make substantial progress in treating this disabling symptom." LOAD-DATE: March 4, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2005 Reuters Health All Rights Reserved 507 of 998 DOCUMENTS CNS Drug News Pharmaceuticals April 19, 2005 Alfresa files for approval to manufacture modafinil in Japan LENGTH: 111 words Alfresa Pharma ( Alfresa Holdings ) has filed an application for approval to manufacture modafinil for the treatment of narcolepsy with the Japanese Ministry of Health, Labour and Welfare. In June 1998, the company obtained an exclusive right to develop, manufacture and market modafinil in Japan from Cephalon . Since January 2000, when modafinil was designated as an orphan drug by the Ministry, Alfresa has conducted clinical trials and observed positive results. The company aims to expand indications for modafinil not only for narcolepsy, but also for childhood attention deficit hyperactivity disorder. Currently, modafinil is approved in 33 countries worldwide. LOAD-DATE: April 21, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2005 ESPICOM Business Intelligence Ltd. All Rights Reserved 508 of 998 DOCUMENTS JCNN April 18, 2005 Monday Alfresa Pharma Files Manufacturing Approval for Modafinil for Narcolepsy BYLINE: Aki Tsukioka; Staff Writer, newsroom@japancorp.net LENGTH: 118 words DATELINE: Tokyo, Japan Alfresa Holdings [TSE: 2784] announced on April 15 that its wholly owned subsidiary Alfresa Pharma has filed an application for approval to manufacture modafinil for the treatment of to the Ministry of Health, Labor and Welfare. In June 1998, the company obtained an exclusive right to develop, manufacture and market modafinil in Japan from US pharmaceutical Cephalon. Since January 2000 when modafinil was designated as an orphan drug by the ministry, Alfresa Pharma has conducted clinical trials and seen positive results. The company aims to expand indications for modafinil not only for narcolepsy but also for childhood ADHD. Currently, Modafinil is approved in 33 countries worldwide. LOAD-DATE: April 19, 2005 LANGUAGE: ENGLISH Copyright 2005 Japan Corporate News Network. All Rights Reserved. 509 of 998 DOCUMENTS M2 Presswire April 1, 2005 US Financial Network: Sanofi Pasteur's new polio vaccine licensed and Cephalon files new drug application for NUVIGIL LENGTH: 509 words M2 PRESSWIRE-APRIL 1, 2005-US Financial Network: Sanofi Pasteur's new polio vaccine licensed and Cephalon files new drug application for NUVIGIL ©1994-2005 M2 COMMUNICATIONS LTD City of Industry, CA - Biotechnology industry news provided by Financial News USA (OTC: FNWU). Sanofi Pasteur (NYSE:SNY), the vaccines business of the sanofi-aventis group, has received a license from the Agence Francaise de Securite Sanitaire des Produits de Sante (AFSSAPS) for a new polio vaccine, which is the first new vaccine developed to fight that disease in decades. The new vaccine - Monovalent Oral Polio Vaccine 1 or MOPV1 - will be used first in Egypt as a critical part of a new World Health Organization's strategy to end polio transmission by the end of this year. StemCells, Inc. (NASDAQ: STEM) announced recent, positive progress towards its goal of initiating Phase I clinical testing of its proprietary neural cell therapy product - HuCNS-SC - in Batten disease. Cephalon, Inc. (Nasdaq: CEPH) announced Thursday that it has filed a New Drug Application (NDA) with the U.S. Food and Drug Administration seeking approval to market NUVIGIL(TM) (armodafinil) Tablets [C-IV] to improve wakefulness in patients suffering from excessive sleepiness associated with narcolepsy, shift work sleep disorder (SWSD) and obstructive sleep apnea/hypopnea syndrome (OSA/HS). NUVIGIL is a single-isomer formulation of modafinil, the active pharmaceutical ingredient contained in PROVIGIL (modafinil) Tablets [C-IV]. U.S. BioDefense (OTCBB: UBDEE) Files for Stem Cell Research Center of Excellence with National Institutes of Health with Research Collaborators from Los Alamos, CHOC, UCLA, and UCI and Liver Regeneration Technology from UCL Biomedica University College London. About Financial News USA Financial News USA is a Next Generation Financial Communications firm focused on the distribution of market moving news. Financial News USA has developed leading edge e-publishing tools including programming proprietary RSS feeds and enabling open source press release publishing across its network. Financial News USA has been aggressively expanding its news distribution network by targeting direct feeds to financial news and data providers such as FinancialContent, Yahoo (Nasdaq: YHOO), among others. 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LOAD-DATE: April 1, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: NEWSWIRE Copyright 2005 M2 Communications Ltd All rights reserved 510 of 998 DOCUMENTS Xinhua General News Service March 19, 2005 Saturday 10:00 PM EST CAS rejects cyclist's appeal to use banned drug SECTION: WORLD NEWS; Sports LENGTH: 157 words DATELINE: GENEVA The Court of Arbitration for Sport has refused French cyclist Franck Bouyer to use banned drug treating his sleep disorder, the court decided Friday. Bouyer suffers from narcolepsy which causes bouts of sudden sleep and has not cycled competitively since last May. But the Bouygues Telecom rider had not received clearance by the sport's world governing body International Cycling Union (UCI) or the World Anti-Doping Agency to use the medicine which contains Modafinil. Bouyer then decided to take up the issue with CAS but CAS said he had not managed to prove the use of the medicine would not improve his performance and it was up to him to show that. CAS added in their statement that Bouyer did have the possibility of making a new request to the UCI to use the drug by which time more information on its effect on sports performance might have been obtained. Modafinil is on cycling's banned list of drugs. LOAD-DATE: March 19, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2005 Xinhua News Agency 511 of 998 DOCUMENTS Agence France Presse -- English March 18, 2005 Friday 4:33 PM GMT CAS refuse cyclist's request to use drug against sleep disorder LENGTH: 165 words DATELINE: GENEVA March 18 French cyclist Franck Bouyer, who suffers from narcolepsy where the sufferer falls asleep suddenly, had his request to take a drug to treat it turned down by the Court of Arbitration for Sport here on Friday. As Bouyer had not received clearance by the sport's world governing body UCI (International Cycling Union) or the World Anti-Doping Agency to use the medicine which contains Modafinil, he decided to take up the issue with CAS. However CAS said the Bouygues Telecom rider had not managed to prove the use of the medicine would not improve his performance and it was up to him to show that. CAS added in their statement that Bouyer did have the possibility of making a new request to the UCI to use the drug by which time more information on its effect on sports performance might have been obtained. Bouyer, who has not cycled competitively since last May, suffers from bouts of sudden sleep and Modafinil is needed to treat it but it is on cycling's banned list of drugs. avz/mo/jd05 LOAD-DATE: March 19, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2005 Agence France Presse All Rights Reserved 512 of 998 DOCUMENTS Associated Press Worldstream March 18, 2005 Friday Court rejects French cyclist's appeal to use banned stimulant SECTION: SPORTS LENGTH: 350 words DATELINE: LAUSANNE, Switzerland The Court of Arbitration for Sport turned down French cyclist Franck Bouyer's request to be allowed the therapeutic use of banned stimulant modafinil. The court backed the International Cycling Union and the World Anti-Doping Agency, who had already denied Bouyer's request. Bouyer, who has not raced since the end of May 2004, wanted to be allowed modafinil to alleviate a condition that causes sudden faintness and uncontrollable drowsiness. He said it can occur when he is riding. He turned to the court after his case was rejected by the other bodies. The case was handed to a panel of three experts and the hearing held March 4 in Lausanne, with Bouyer, his council, and representatives from the UCI and WADA attending. The court noted that, according to WADA and UCI rules, one of the conditions in awarding permission to use a banned substance for therapeutic use is that it does not enhance performance outside that of the athlete returning to normal health following treatment of a proven pathological condition. The jury concluded that Bouyer had failed to prove that modafinil would not enhance his performance. The panel told Bouyer that he could renew his request to UCI for special dispensation if he came up with any new evidence. Witness testimony said it was difficult to regulate modafinil dosage to prevent performance enhancement, and that there is no reliable method to do so. U.S. sprinter Kelli White, who won two gold medals at the world championships in 2003, tested positive for the drug later the same year. She claimed she took the prescription stimulant because she suffered from narcolepsy, but later admitted to taking illegal performance-enhancing drugs after the USADA confronted her with evidence that she used undetectable steroids. She was banned for two years - missing the Athens Olympics - and was stripped of every medal she'd won the past four years. The United States was also stripped of its 1,600-meter relay gold medal from the 2003 worlds after Calvin Harrison was found guilty of using modafinil at the June 2003 U.S. championships. LOAD-DATE: March 19, 2005 LANGUAGE: ENGLISH Copyright 2005 Associated Press All Rights Reserved 513 of 998 DOCUMENTS Scotland on Sunday February 27, 2005, Sunday MOD'S SECRET PEP PILL TO KEEP FORCES AWAKE BYLINE: Brian Brady Westminster Editor SECTION: Pg. 13 LENGTH: 712 words SOLDIERS and aircrews will be dosed up with "pep pills" to help them stay alert for longer under controversial plans being developed by the Ministry of Defence, confidential papers have revealed. A secret MoD report obtained by Scotland on Sunday has laid bare the project to test whether the drug modafinil could be used to reduce the amount of sleep needed by servicemen and women on active duty. The covert supply of stimulants to fighting forces has become a controversial subject in recent years, particularly after it emerged that two United States F-16 pilots - Major Harry Schmidt and Major William Umbach - who killed four Canadians in a "friendly fire" incident in Afghanistan in April 2003, had taken an amphetamine issued by their superiors. Defence chiefs have spent more than GBP 50,000 on modafinil allegedly to treat conditions including the sleep disorder narcolepsy. However, the secret report, obtained by Scotland on Sunday under the Freedom of Information Act, shows that the MoD has ploughed hundreds of thousands of pounds into researching whether they should follow the lead of forces including the French Foreign Legion and start using the drug to keep military personnel vigilant for up to 60 hours at a time. A GBP 300,000 investigation completed last year has effectively given the green light to start using the drug, marketed as 'Provigil', after it found a single dose helped people stay alert for more than 18 hours with limited side -effects. Following problems with the amphetamine Dexedrine, attention has switched to modafinil, which has vastly improved alertness in patients with narcolepsy, shift-work sleep disorder and sleep apnoea, and with few apparent side -effects. But it has already been banned as a performance-enhancing drug by athletics governing bodies, and been implicated in the BALCO doping scandal in which Kelli White is one of a number of top US athletes accused of using modafinil to propel her to championship-winning performances. The report into stimulant drugs, presented to MoD chiefs by the Defence Evaluation Research Agency (Dera) six years ago, said the Canadians and the French had found that "during a period of 64 hours' continuous work, modafinil improved performance in a manner similar to amphetamine, and led to fewer side -effects". However, later studies warned that the drug could lead to "over-confidence", cause motion-sickness, vertigo and dizziness in air-crews, and therefore the Americans preferred to stick to amphetamine-based stimulants. Nevertheless, the MoD agreed to spend almost GBP 300,000 on research into the use of "hypnotics and stimulants", including modafinil. Key documents relating to the lengthy research programme explicitly state that its purpose was to test the drug for use in combat situations. One of the reports focusing on air operations, compiled by the defence agency QinetiQ, states: "In recent years there has been much interest in the stimulant modafinil, which is reported to have beneficial effects on performance during prolonged periods of wakefulness extending from 24 to 60 hours." The findings, presented to the MoD last summer and delivered to a high-level conference in the autumn, suggest that the side-effects can be manageable as long as the dose is restricted. Defence chiefs and ministers are now discussing whether to issue the drug on a routine basis to service personnel on operational duty. When it emerged last summer that the department had bought 24,000 Provigil pills since 1998, with a particularly large order delivered before the campaign in Iraq, the MoD maintained that the drug was purely for medical purposes. MoD surgeon-general, Vice Admiral Ian Jenkins, said: "The MoD does not use Provigil for performance-enhancing purposes or to alleviate the effects of sleep deprivation on operations or in training. "Provigil may only be prescribed by medical officers within the Defence Medical Services for legitimate clinical reasons, in the same manner as it would be used by the NHS." An MoD spokeswoman insisted that the armed forces did not issue stimulants to servicemen and women. She said: "Our current policy is that we don't provide stimulants." LOAD-DATE: February 28, 2005 LANGUAGE: ENGLISH PUB-TYPE: PAPER Copyright 2005 The Scotsman Publications Ltd. 514 of 998 DOCUMENTS Generic Line February 23, 2005 Briefs SECTION: Vol. 22, No. 4 LENGTH: 639 words FDA Approves Mylan's Generic Celexa The FDA has granted final approval for Mylan Laboratories' abbreviated new drug application for citalopram hydrobromide tablets, the generic version of Forest Laboratories' antidepressant Celexa. The product will be available in 10-, 20- and 40-mg doses. Sanofi-Aventis to Market Eloxatin The FDA has granted marketing approval to sanofi-aventis' aqueous solution formulation of its colorectal cancer drug Eloxatin. Eloxatin injection is expected to be more convenient for doctors and nurses than the original Eloxatin, as it takes fewer steps to administer, sanofi-aventis said. Eloxatin in combination with infusional 5-FU/LV has been approved in the U.S. for treatment of advanced carcinoma of the colon or rectum since January 9, 2004. Eloxatin first received European approval in France for second-line treatment of metastatic colorectal cancer in April 1996. Tentative Approval for Mylan's Modafinil The FDA had granted tentative approval to Mylan Laboratories' abbreviated new drug application for 100- and 200-mg modafinil tablets. Modafinil tablets are the generic version of Cephalon's Provigil tablets, indicated to treat excessive tiredness associated with sleep disorders resulting from narcolepsy, shift work sleep disorder or obstructive sleep apnea/hypopnea syndrome. The agency issued Mylan tentative approval for its product because Provigil is covered by patents that do not expire until 2007 and 2014. Cephalon said it expects Provigil sales of up to $450 million in 2004 and up to $600 million in 2005. FDA Approves Chewable Amoxicillin The FDA has granted final approval to Teva Pharmaceutical's abbreviated new drug application for amoxicillin/clavulante potassium chewable tablets USP in 200 mg/28.5 mg and 400 mg/57 mg doses. The company is expecting to ship the product, which is the generic equivalent of GlaxoSmithKline's antibiotic Augmentin chewable tablets, immediately. Augmentin is used to treat bacterial infections of the ears, lungs, sinuses, skin and urinary tract. Total annual brand and generic sales of the product are approximately $21 million. Teva Moving Ahead on Levofloxacin Teva Pharmaceutical has received tentative approval from the FDA for its abbreviated new drug application for levofloxacin injection 5 mg/mL in 250 mg/bag and 500 mg/bag doses and levofloxacin injection 25 mg/mL in 20 mL and 30 mL vials. Levofloxacin injection is the generic equivalent of Ortho McNeil's antibacterial agent Levaquin. Final approval for the product will depend on resolution of ongoing patent litigation, Teva said. Total annual sales of the brand product are approximately $220 million. Dr. Reddy's Starts Ireland Trial Indian drugmaker Dr. Reddy's has initiated a Phase I clinical trial in Belfast, Ireland, to test its cardiovascular drug candidate, RUS 3108, in humans. The company is developing the drug to treat atherosclerosis, a major cause of heart attacks and strokes. Currently there is no treatment on the market to directly treat this disorder. The drug uses a protein called perlecan to affect multiple pathways involved in the disease such as inflammation, proliferation and thrombosis. The study marks the first time Dr. Reddy's has conducted a trial in Europe. Spectrum Challenging Imitrex Patent Spectrum Pharmaceuticals is challenging GlaxoSmithKline's (GSK) patent on Imitrex injection 6mg/0.5mL. Spectrum said it believes GSK' s patent on Imitrex (sumatriptan succinate), which is set to expire Feb. 6, 2009, is invalid. Spectrum submitted an abbreviated new drug application containing a Paragraph IV certification for a generic Imitrex injection product with the FDA in October 2004, and received notification of acceptance with Paragraph IV certification in January 2005. Release date: Feb. 23, 2005 LOAD-DATE: February 22, 2005 LANGUAGE: ENGLISH Copyright 2005 Washington Business Information, Inc., All Rights Reserved 515 of 998 DOCUMENTS The San Francisco Chronicle FEBRUARY 21, 2005, MONDAY, FINAL EDITION Sprinters say doctor helped get their drugs; Bay Area psychiatrist says he did sporadic consulting for Conte SOURCE: Chronicle Staff Writer BYLINE: Seth Rosenfeld SECTION: NEWS; Pg. A1 LENGTH: 1522 words Two champion athletes who have admitted obtaining illegal steroids from BALCO, the Bay Area firm at the center of the nation's largest sports-doping case, have claimed a local doctor played a role in their use of banned performance-enhancing substances. In an interview with The Chronicle, world class sprinter Kelli White said Dr. Brian Goldman publicly stated he had diagnosed her with a sleeping disorder in an effort to justify her use of a banned stimulant that he made available to her. White said that she had no sleeping disorder, and that Goldman's statements were part of a false story devised by BALCO head Victor Conte. In sworn testimony, world champion sprinter Tim Montgomery said Goldman wrote a prescription for him under a false name so it would not be traceable. Both athletes said they had never met Goldman at the time. During several telephone conversations with The Chronicle, Goldman declined to discuss White. He denied Montgomery's account. "There's just no story here," said Goldman. "I don't have anything to hide at all." Goldman, 50, was an associate of Conte, who ran the Bay Area Laboratory Co-Operative, or BALCO. Conte and three other men were indicted in U.S. District Court in San Francisco on steroid conspiracy charges. They have pleaded not guilty. Goldman, a psychiatrist, has not been charged. He has said he was medical director of BALCO in 1984, when the firm focused on holistic health, but since then has done only on-and-off consulting with Conte. Goldman specializes in treating adults and children with autistic-spectrum disorders and other behavioral problems. He works at the Amen Clinic in Fairfield and at Diablo Behavioral Healthcare center in Danville, where clinical director William Shryer called him a "top-flight" doctor. The U.S. attorney's office declined to comment on Goldman in regard to the BALCO case. Robert Holley, Conte's lawyer, also declined to comment. The case of Kelli White, the Union City sprinter, began to unfold in August 2003, when she tested positive for modafinil after winning gold medals in the 100- and 200-meter sprints during the World Track and Field Championships in Paris. At a news conference the night her test result became public, she said she took the drug for a sleeping disorder called narcolepsy. "I have never taken any substance to enhance my performance," she said on Aug. 30, 2003. "Close members of my family have been under doctor's care for the condition of narcolepsy for years. I, too, have been diagnosed with this condition by my physician, Dr. Brian Goldman. He prescribed the drug Provigil (which contains modafinil) for this condition ...." In a "To whom it may concern" letter dated the same day, Goldman said White "has been consulting with our clinic since the beginning of the year. "Kelli has had excessive daytime somnolence, particularly in the afternoon and worsening toward the late afternoon and evening. Kelli has complained of falling asleep while talking on the telephone ... . "Per my instruction, Kelli was provided with one or two sample bottles of modafinil (Provigil), by my staff," Goldman said in the letter. "I have recommended that her nutritional regime include the prescription medication, modafinil (Provigil) ...." He said he did not believe modafinil had been banned in her sport. The same day, Goldman told the Washington Post that he gave her two sample bottles of the drug after diagnosing her as suffering from narcolepsy during a consultation in the Bay Area. In a Sept. 3, 2003, letter to the International Association of Athletics Federations, the governing body for world track and field, Goldman said: "Modafinil was prescribed for her and I believe was taken by her in the spirit of allowing her to feel as normal as the other athletes, who do not have a sleep disorder, to level the playing field, and not to seek any untoward advantage." Goldman later gave copies of his letters to The Chronicle, and told the newspaper that Conte had referred White to him because he is a "local narcolepsy expert." But White's story about narcolepsy began to unravel. In late 2003, she testified before the federal grand jury investigating BALCO, and some of the evidence from that case was turned over to the U.S. Anti-Doping Agency. She then admitted to USADA officials that she did not have narcolepsy and had taken modafinil and other banned drugs to gain a competitive advantage. USADA in May 2004 suspended White from competition for two years. She received the minimum punishment after acknowledging her mistakes and agreeing to help USADA fight doping. In a December interview with several reporters, which USADA helped arrange, White took responsibility for her doping and said she deeply regretted cheating. White confirmed that she did not have a sleeping disorder and admitted that modafinil helped her compete. In response to questions from a Chronicle reporter, White said Goldman's statements were part of a story concocted by Conte. According to White, within hours of testing positive for modafinil in Paris, she phoned Conte, who told her to issue the false statement saying she took the drug for narcolepsy. "It sounded good. It was a story that Victor (Conte) told me to use," she said. Soon after that, she said, Goldman called and helped make up the story for the press conference. "I was contacted by Dr. Goldman, and that's how the story came about," she said. "And that was my first time ever meeting, or speaking, to Dr. Goldman." But though White said Goldman helped her with the cover story, she added that she was unsure how much he knew about her situation. "I'm not sure exactly what Victor told Dr. Goldman," she said. "But I don't think he fully knew what was going on... I think he was really oblivious. I don't think he knew." White's New Jersey lawyer, Jerrold Colton, who was present at the interview, emphasized that White took responsibility for her drug use, and commented about Goldman in response to reporters' questions. Contacted last month, Goldman declined to comment on White's account and his prior statements about her. He referred The Chronicle to a former assistant who said White had been seen by Goldman at the Amen Clinic, but could not recall whether it was before or after she tested positive for modafinil. Montgomery, who holds the world record for the 100-meter sprint, testified about Goldman during his Nov. 6, 2003, appearance before the grand jury investigating BALCO. The sprinter said that Conte had given him a steroid called "the clear," and that Goldman wrote him a prescription under a false name for Clomid, which helped boost testosterone production. Assistant U.S. Attorney Jeff Nedrow later asked: "Who was the person he (Conte) got to get prescriptions -- what did Mr. Conte tell you about that?" Montgomery: "Dr. Goldman." Nedrow asked: "To your knowledge, did Dr. Goldman actually legitimately consult with athletes in developing treatments for them for diseases and stuff like that?" Montgomery said that "Dr. Goldman was a guy that he (Conte) would talk to on the telephone and (Conte would) tell him what was going on with the athlete. And he (Goldman) would -- he would give a suggestion on what they should do, what they should not do. And if it was a prescription that needed to be written out, he would make it out." Montgomery said he knew of these activities because in March 2001 he visited Conte at BALCO and Conte "told me how the whole operation was running." Montgomery said he was present when Conte spoke with Goldman on the phone. "Yes, I was. That's how I got the Clomid." In a June 25, 2004, interview, Goldman disputed Montgomery's testimony. "Everything is a lie," he told The Chronicle. "I don't think I've ever prescribed Clomid. The fact is, I've never spoken to him, never spoken to anyone about him, have nothing to do with his treatment, and I would not OK any non-physician to write prescriptions." Montgomery's lawyers declined to comment. In October 2003, Prentice Steffen, a San Francisco physician and bicycle racing coach, asked the California Medical Board to examine Goldman's conduct after reading news reports that he had been medical director of BALCO. The board told Steffen in a letter that it had closed the case on Jan. 9, 2004, for lack of evidence. "The Medical Board of California ... has concluded its review of your complaint alleging that Dr. Goldman is involved in the BALCO doping case," the letter said. "It was determined that the board does not have sufficient evidence to proceed." In a separate inquiry, the state Department of Health Services last month decided not to fine Goldman for BALCO's alleged violations of laboratory regulations. The department agreed with Goldman's assertion that his name had been forged on records listing him as medical director of BALCO between 1989 and 2003. Chronicle staff writers Gwen Knapp, Mark Fainaru-Wada and Lance Williams contributed to this report.E-mail Seth Rosenfeld at srosenfeld@sfchronicle.com. LOAD-DATE: February 21, 2005 LANGUAGE: ENGLISH GRAPHIC: PHOTO (3), (1) Sprinters Kelli White (left) / Paul Sakuma / Associated Press 2003, (2) and Tim Montgomery say Dr. Brian Goldman helped them obtain performance-enhancing substances. White says Goldman provided her with modafinil, while Montgomery says Goldman wrote a prescription for a drug that boosts testosterone. / Michel Euler / Associated Press 2002, (3)Victor Conte Copyright 2005 The Chronicle Publishing Co. 516 of 998 DOCUMENTS World Markets Analysis February 11, 2005 FDA Tentatively Clears Mylan's Generic Modafinil BYLINE: Henry Dummett SECTION: IN BRIEF LENGTH: 185 words The US FDA has granted tentative approval for a generic version of modafinil in 100mg and 200mg tablet form, submitted by US drug-maker Mylan Pharmaceuticals. Modafinil is marketed by Cephalon (US), under the Provigil brand, and is used to treat narcolepsy; it is the only FDA approved drug for excessive sleepiness associated with obstructive sleep apnea/hypopnea syndrome and shift-work sleep disorder. The efficacy of Cephalon against attention deficit hyperactivity disorder (ADHD) is currently being assessed.. Significance: The onset of generic competition would cause greater damage to Cephalon's top line than it would benefit the marketer of a generic version. Provigil is one of only three products marketed by Cephalon, and is a major growth-driver for the company. During the first nine months of 2004, the drug garnered US$276.1m on the US market, an year-on-year increase of 48%. Mylan will find itself in a competitive market when formal FDA approval is issued, with Barr (US) and Ranbaxy (India) having already secured preliminary FDA clearance for generic versions of the drug. LOAD-DATE: February 11, 2005 LANGUAGE: ENGLISH Copyright 2005 World Markets Research Limited; All Rights Reserved 517 of 998 DOCUMENTS MarketWatch February 10, 2005 Thursday CORRECT: Mylan modafinil tablets get tentative FDA OK BYLINE: Heather Wilson LENGTH: 71 words SAN FRANCISCO (MarketWatch) -- Mylan Laboratories (myl) said Thursday that its modafinil tablets have received tentative approval from the U.S. Food and Drug Administration. Modafinil is used to treat sleep disorders such as narcolepsy and sleep apnea/hypopnea syndrome. The Pittsburgh-based pharmaceutical company said the drug is a generic version of Cephalon's (ceph) Provigil. (Corrects spelling of Cephalon and Provigil.) LOAD-DATE: February 11, 2005 LANGUAGE: ENGLISH Copyright 2005 MarketWatch.com Inc., All Rights Reserved 518 of 998 DOCUMENTS PR Newswire US February 10, 2005 Thursday Mylan Receives Tentative Approval for Modafinil Tablets LENGTH: 153 words DATELINE: PITTSBURGH Feb. 10 PITTSBURGH, Feb. 10 /PRNewswire-FirstCall/ -- Mylan Laboratories Inc. (NYSE:MYL) today announced that the U.S. Food and Drug Administration has granted tentative approval for Mylan Pharmaceuticals Inc.'s Abbreviated New Drug Application for Modafinil Tablets, 100 mg and 200 mg. Modafinil Tablets are the generic version of Cephalon Inc.'s Provigil(R) Tablets. Mylan Laboratories Inc. is a leading pharmaceutical company with four subsidiaries, Mylan Pharmaceuticals Inc., Mylan Technologies Inc., UDL Laboratories Inc. and Mylan Bertek Pharmaceuticals Inc., that develop, license, manufacture, market and distribute an extensive line of generic and proprietary products. For more information about Mylan, visit http://www.mylan.com/ . CONTACT: Media, Heather Bresch, +1-724-514-1800, or Investors, Kris King, +1-724-514-1800, both of Mylan Laboratories Inc. Web site: http://www.mylan.com/ SOURCE Mylan Laboratories Inc. URL: http://www.prnewswire.com LOAD-DATE: February 11, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2005 PR Newswire Association LLC. All Rights Reserved. 519 of 998 DOCUMENTS Clinical Psychiatry News February 2005 Modafinil Still Effective for Sleep Apnea After 17 Weeks of Therapy BYLINE: Nicholas Mulcahy, Contributing Writer SECTION: Pg. 60 Vol. 33 No. 2 ISSN: 0270-6644 LENGTH: 440 words    PHILADELPHIA - Modafinil in patients with obstructive sleep apnea and excessive daytime sleepiness despite positive airway pressure therapy was effective in improving wakefulness for at least 17 weeks in a small study presented at the annual meeting of the Associated Professional Sleep Societies.    Previous studies of the wakefulness drug and obstructive sleep apnea (OSA) had been limited to 12 weeks, Juan Moralejo, M.D., reported.    "In our study population, modafinil was more likely to be effective in the elderly and those with high Epworth Sleepiness Scale scores at the time of diagnosis" of daytime sleepiness, said Dr. Moralejo, a pulmonary medicine fellow at Graduate Hospital, Philadelphia.    The study sample consisted of 22 patients (13 males and 9 females), mean age 53.9 years. Of the 18 patients receiving "conventional treatment," 9 were using continuous positive airway pressure, 8 were using bilevel positive airway pressure, and 1 was using a dental device. At the time of the survey, four patients were not using any conventional treatment for OSA.    The mean Epworth Sleepiness Scale score was 15.9 at diagnosis, 13.6 after treatment with conventional modalities, and 8.9 after treatment with modafinil (Provigil). A lower Epworth score is indicative of improved wakefulness, and reduction of 4 points is considered a response to treatment. No statistical difference was found between the Epworth scores before and after conventional treatment, but the change after modafinil treatment was significant, Dr. Moralejo said.    The improvement in Epworth Sleepiness Scale score was similar whether patients were on modafinil for more than or less than 12 weeks. The average duration of treatment was 17 weeks (range 1-40).    On univariate analysis, factors associated with response to modafinil were higher Epworth Sleepiness Scale score at diagnosis, higher Epworth score while on conventional therapy, and male gender, said Dr. Moralejo, who has no affiliation with Cephalon, maker of Provigil. But on multivariate analysis, a high Epworth score at diagnosis of OSA and increasing age correlated best with response to modafinil.    The average dosage of modafinil was 227.3 mg once daily (range 100-800). No significant side effects were documented.    Epworth Sleepiness Scale scores at the diagnosis of OSA and after treatment with conventional modalities were obtained from the patients' records. A telephone survey was conducted and included questions about patients' demographics, modafinil treatment, and type of ongoing conventional treatment for OSA as well as patient compliance with this treatment. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: CPNEWS Copyright 2005 Elsevier Inc., International Medical News Group All Rights Reserved 520 of 998 DOCUMENTS Pharma Company Insight Pharmaceuticals January 19, 2005 Orphan Medical submits Xyrem sNDA LENGTH: 703 words Orphan Medical has submitted an sNDA to the FDA for Xyrem ( sodium oxybate ) oral solution. Xyrem is currently marketed as the only approved treatment for cataplexy, a sudden loss of muscle tone that is a debilitating symptom of narcolepsy. The sNDA is expected to expand the product's label to encompass improvement in the other primary symptoms of narcolepsy, specifically the reduction of excessive daytime sleepiness (EDS) and the improvement in fragmented night-time sleep. There is no medication currently approved to treat all of the primary symptoms of narcolepsy. EDS has been treated with stimulant medications and disrupted night-time sleep by sedative-hypnotic medications. The sNDA includes two Phase IIIb trials with EDS as the primary efficacy measure, as well as positive data relating to the treatment of other components of narcolepsy. The FDA user fee (PDUFA) deadline is ten months from the date the FDA receives the sNDA submission. The first Phase IIIb trial, SXB-15, generated strong positive data across both primary and secondary endpoints. The trial evaluated improvement in the EDS of patients with narcolepsy when a dose of 4.5, 6.0 or 9.0g of Xyrem was added to unchanged stimulant therapy. The trial results demonstrated dose-related improvement in the Epworth Sleepiness Scale (ESS) scores, statistically significant at the 6 and 9g daily doses. At the 9g dose, Xyrem produced statistically significant improvement in the Maintenance of Wakefulness Test (MWT), an established objective measure of EDS. Treatment of sleep continuity and structure was significantly improved at the 6 and 9g doses, with reductions in subjectively and objectively measured awakenings after sleep onset, and a marked increase in delta sleep, thought to be the restorative period of sleep. Daytime functionality was assessed using the validated Functional Outcome of Sleep Questionnaire (FOSQ). The FOSQ outcomes demonstrated dose-related improvements in four of the five factorial assessments, as well as significant improvement in the global score at the 6 and 9g dose levels. This double-blind, placebo-controlled, randomised trial assessed 228 patients over an eight-week treatment period in 40 sleep centres in North America and eight in Europe. The second trial, EXCEEDS (Evaluation of Xyrem to Check Efficacy in Excessive Daytime Sleepiness), was designed to evaluate the improvement of EDS associated with narcolepsy when Xyrem is used alone or with Cephalon 's Provigil ( modafinil ), a wakefulness-promoting agent approved for the treatment of EDS. The primary endpoint of the trial was EDS as measured by the objective MWT. The secondary endpoint also measured EDS using the ESS. The trial demonstrated that Xyrem monotherapy is effective in the treatment of EDS associated with narcolepsy using both measures. The combined use of Xyrem and modafinil showed a greater response than either agent alone. EXCEEDS was a double-blind, double-dummy, placebo-controlled, parallel-group, multi-centre randomised study. In both trials, the safety profile is consistent with that of previous Xyrem trials and commercial use. The most commonly-reported dose-related adverse events (AEs) occurring in more than 5 per cent of patients across all controlled trials were nausea, dizziness, headache, vomiting, somnolence and enuresis. No significant new or unexpected AEs were seen in the SXB-15 trial. Occurring infrequently, but more often at the 9g dose, were disorientation, sleepwalking and enuresis. These side effects occurred at reduced rates in the expanded safety dataset of the sNDA. The safety profile of Xyrem in the EXCEEDS trial was consistent with other previous controlled clinical trials. The side effect of nausea occurred more often for groups receiving Xyrem and both Xyrem and modafinil together, as did vomiting which had a markedly lower incidence. Headache was a common symptom in the EXCEEDS trial, including placebo, but dizziness and tremor were more common in the group on both drugs, as was anxiety. The incidence of sleep walking and enuresis, previously reported as associated with Xyrem, showed a very low incidence in this study that was not significantly different between groups. LOAD-DATE: January 19, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2005 ESPICOM Business Intelligence Ltd. All Rights Reserved 521 of 998 DOCUMENTS The Independent (London) January 18, 2005, Tuesday HEALTH: MESSING WITH OUR MINDS;  WANT TO IMPROVE YOUR MENTAL ABILITY, BOOST CONCENTRATION AND EVEN BYLINE: JEREMY LAURANCE SECTION: First Edition; FEATURES; Pg. 8 LENGTH: 1481 words HIGHLIGHT: Science fiction or future fact? Jim Carrey erases unhappy memories in Eternal Sunshine of the Spotless Mind' To err is human. But for the pilot of a commercial airliner, it is unacceptable. As holidaymakers jet off on winter breaks or plan next summer's long-haul adventure, the one thing that they will demand above all is safety. Airlines have spent millions devising elaborate systems to guarantee maximum safety. Pilot error can never be ruled out, but researchers now believe that it might be reduced - by careful tweaking of brain chemistry. Drugs are becoming available that increase alertness and improve concentration. Should all pilots take them? This question has begun to tax scientists in the US involved in the development of so-called "smart" drugs - chemical enhancements for the mind. A range of compounds are being tested - some are already available and being traded over the internet - that may change not only the way we perform, but what we think of as "normal" performance. The drugs being examined have applications far beyond air travel. Three areas that are attracting attention are movement and endurance, attention and learning, and moods. Medicines such as anabolic steroids can already make people stronger, swifter and more enduring. Though life-giving to victims of muscle disorders, they are widely abused in sport. Long- distance lorry drivers and Air Force pilots have used amphetamines to ward off drowsiness. Generations of students have sustained themselves through exams with over-the-counter caffeine tablets. But the new "cognitive enhancers" may offer more powerful, better targeted and longer lasting improvements in mental acuity. And some are already being tested on human volunteers. One such drug is donepezil, a cholinesterase inhibitor developed for the treatment of dementia. This drug slows the progress of Alzheimer's disease and is being used as a treatment for age-associated memory impairment. But what is causing excitement among researchers is the possibility that donepezil may boost highly skilled performance, where concentration and alertness are prerequisites. A study published in the journal Neurology found that commercial pilots who took 5mg of donepezil for one month performed better than pilots on a placebo when asked to fly a Cessna 172 on a flight simulator. There was a marked difference between the groups when dealing with emergencies. Modafinil, a drug used to treat the sleep disorder narcolepsy, has also been tested on pilots. A trial reported in the Psychopharmacology journal found that it boosted the performance of helicopter pilots flying on simulators who had been deprived of sleep. Anyone who has gone two nights without sleep will know what it is like to suffer from extreme tiredness. Nothing can defeat the desire to sleep. Nothing except, apparently, modafinil. While commercial pilots have strict rules governing flying time and rest periods, fighter pilots may be called to action at a moment's notice. Modafinil is under investigation by the military for its ability to keep pilots and other members of the armed forces awake for long periods without the "rebound" effect associated with stimulants such as amphetamines. Barbara Sahakian, Professor of Neuropsychology at the University of Cambridge, who tested modafinil in a series of experiments on volunteers found that they showed greater concentration, faster learning and increased mental agility. "It may be the first real smart drug," she says. "A lot of people will probably take modafinil. I suspect they do already." "If people can gain a millimetre, they'll want to take it," says Jerome Yesavage, director of Stanford University's Ageing Clinical Research Center, and an author of the donepezil study. That view was backed by Judy Illes, a psychologist at Stanford's Centre for Biomedical Ethics. Mind-enhancing medicine could become as "ordinary as a cup of coffee", she says. If drugs such as donepezil and modafinil were proved to raise performance, and hence safety, the implications could be far-reaching. Airline executives might require pilots to take the drugs, or offer financial incentives for doing so. They might market their airline as the one whose pilots took the safety-enhancing drug. Would people pay more to fly on such an airline? The question is raised in a review of the new science, dubbed "cosmetic neurology", by Dr Anjan Chatterjee, a neurologist at the University of Pennsylvania. As the rich turn to cosmetic surgery to refine what nature gave them, cosmetic neurology offers a different kind of personal improvement. It is the "nip and tuck" for the mind. The conventional aids of caffeine, alcohol and tobacco are already used to boost mood and performance, and neurologists argue that the use of other drugs is a logical extension of this self-medication. Writing in Annals of Neurology, Dr Chatterjee says that amphetamine drugs that help stroke patients who have suffered partial paralysis to relearn motor skills might assist healthy individuals to learn to swim or play the piano. A new class of drugs called ampakines are being investigated as memory enhancers, and have already been shown to boost recall in early studies in humans. Trials of the heart drug propranolol, a beta-blocker, have shown that it can neutralise emotionally charged memories so that they do not cause distress when recalled. In one experiment, reported in Biological Psychiatry, patients injured in accidents were given propranolol in the A&E department and were found to suffer fewer post-traumatic stress disorder symptoms when assessed one month later. The new science is creating problems for neurologists, who are used to treating the sick, not enhancing the healthy. Dr Chatterjee writes: "One plausible scenario is that neurologists will become quality-of-life consultants. Following the model of financial consultants, we could offer a menu of options with the likely outcomes and risks." The advent of cosmetic neurology is inevitable, he says, and warns: "Prospecting for better brains may be the new gold rush." Signs that it has already arrived can be seen on college campuses in the US. Faced with the pressure of exams and essay deadlines, students have been abandoning the traditional crutches of coffee and cigarettes for Ritalin, a stimulant best known as a treatment for hyperactive children. It has found a ready black market among students who are desperate to succeed. Users say that it helps them to concentrate. Anecdotal reports from drug agencies in Britain suggest that the problem is just emerging here. It has already spread to Canada and Australia, and university authorities have been warned to be vigilant. The search for a short cut in learning has worried teachers. But doctors have confirmed the potential benefits of the drugs, unwittingly encouraging the trend. For example, Eric Heiligenstein, the director of clinical psychiatry at Wisconsin University, says: "Caffeine is fine. This Ritalin is better. Students are able to accumulate more information in a shorter time. They minimise fatigue and help maintain a high performance level." A study of 2,200 students at an unnamed university in North America, published in Pharmacotherapy last year, found that 66 of them (3 per cent) admitted abusing Ritalin in the previous year. "Illicit use of prescription-only stimulants on college campuses is a potentially serious public health issue," it said. If "natural" performance or responses can be boosted in these areas, it may challenge our concept of what it is to be human. In one view, medicine should be about healing the sick, not turning people into gods. But the boundary between therapy and enhancement can be hard to define. Short people can be treated with growth hormone - but is that cosmetic or therapeutic? In an ageing society, treatments to boost attention, learning and memory will be increasingly relevant - but should they be applied to people who are healthy but merely old? In the field of athletics, drug use is rife but it is referred to disparagingly as "doping". The underlying assumption is that boosting performance without doing the work is cheating and undermines human endeavour. Yet no one feels the same way about putting up with a headache or indigestion. We reach for tablets without hesitation. The ethical dilemma may prove to be academic, however, if the drugs now being tested fail to deliver on performance, or their side-effects prove to be troublesome. A memory drug might cause subjects to remember too much detail, cluttering the mind, for example. Martha Farah, a psychologist at the University of Pennsylvania, says: "The brain was designed by evolution over millennia to be well adapted because of the lives we lead. We are better served by being able to focus on the essential information than being able to remember every little detail. We meddle with these designs at our peril." LOAD-DATE: January 18, 2005 LANGUAGE: ENGLISH Copyright 2005 Independent Print Ltd 522 of 998 DOCUMENTS Philadelphia Inquirer January 12, 2005, Wednesday Drug may help addicts kick cocaine BYLINE: By Stacey Burling SECTION: DOMESTIC NEWS LENGTH: 654 words PHILADELPHIA _ After decades of failed attempts to find a drug that helps addicts kick cocaine, researchers at the University of Pennsylvania say they have finally found a medication that looks promising _ a drug currently approved to treat sleepiness. Addicts who took modafinil _ used to treat narcolepsy and help pilots and night-shift workers stay alert _ were about twice as likely to avoid cocaine in a given week as those who received a placebo pill, according to a small Penn study published this month in the Journal of Neuropsychopharmacology. Patients taking the medicine, marketed as Provigil, were also nearly three times as likely as unmedicated counterparts to stay off cocaine for a three-week stretch _ 33 percent vs. 13 percent, said Charles Dackis, chief of psychiatry at Penn's Medical Center-Presbyterian and lead investigator of the 62-patient study. The National Institute on Drug Abuse funded the Penn study and is paying for three longer, larger studies as well. The institute is also funding similar studies of three other medicines: baclofen, which is used to treat spastic disorders; topiramate, an anti-convulsant; and disulfiram or Antabuse. Ultimately, the medicines may be targeted at specific subgroups within the nation's 1.5 million cocaine users, said Frank Vocci, director of the division of pharmacotherapies and medical consequences of drug abuse. Modafinil, he said, has qualities that could "propel it to the top." Addicts don't mind its side effects and like its "alerting effect." It may also reduce impulsiveness, a key factor in addiction. Given the high percentage of addicts in the study who still used cocaine, the drug clearly is not a cure for cocaine addiction, which is notoriously difficult to treat. But it may be an important, early step toward better drug therapies, said Robert Malcolm, a Medical University of South Carolina psychiatrist who heads another of the modafinil studies. "Is this drug a home run?" he asked. "No. Maybe it's a single or at best a double." Nonetheless, he and Dackis said modafinil is the most promising drug they have seen for cocaine addiction in 20 years. Dackis said researchers had tried as many as a 100 drugs against cocaine during that time with no success. Modafinil, made by Cephalon Inc. of West Chester, Pa., earned $300 million in 2003 and has projected sales of $410 million for 2004. The company is awaiting word on its request to market the drug for attention deficit hyperactivity disorder. Dackis believes that modafinil helps restore function to the brain's pleasure center, which is thrown chemically off balance by long-term cocaine use. Addicts often say they don't "feel right" without cocaine. "You're craving something that will make you feel better," he said. Modafinil, he added, "does promote a sense of well being but not euphoria and certainly not the rush of euphoria you experience with cocaine." One of his previous studies showed that the drug blunted the cocaine euphoria. The government lists modafinil as having mild potential for abuse. Dackis said he saw no evidence that modafanil is addictive. A middle-aged man who participated in the Penn study believes the drug helped him go 14 weeks without cocaine, an unusually long time for him during 15 years of addiction. "I had more energy to stay focused on things I had to do on my job, things I had to do at home, at church," he said. "I didn't have time to sneak off into North Philly and get lost." The man, a professional with a college degree who asked that his name not be used, said he stopped taking the medicine when the study ended. He used cocaine again last week. Now, he has asked his primary-care doctor to prescribe modafinil for him. He also plans to go back into therapy. "I guess I need that crutch," he said. ___ Visit Philadelphia Online, the Inquirer's World Wide Web site, at http://www.philly.com/ LOAD-DATE: January 12, 2005 LANGUAGE: ENGLISH KR-ACC-NO: K3682 JOURNAL-CODE: PH Copyright 2005 Knight Ridder/Tribune News Service Knight Ridder/Tribune News Service Copyright 2005 The Philadelphia Inquirer 523 of 998 DOCUMENTS UPI January 12, 2005 Wednesday 12:01 AM EST Drug shows promise for cocaine addiction LENGTH: 188 words DATELINE: PHILADELPHIA, Jan. 12 U.S. researchers said a medication used to treat the sleep disorder narcolepsy also has shown promise for treating cocaine addiction. Cocaine addicts who were given the drug, known as Modafinil, were more likely to abstain from using cocaine than addicts who received an inactive placebo, said researchers from the University of Pennsylvania Medical Center, who reported the finding in the January issue of Journal of Neuropsychopharmacology. If the finding is confirmed, Modafinil could become the first medication for treating cocaine addiction, they said. Cocaine addiction affects thousands of people around the globe and can disrupt the lives of not only addicts but also their loved ones. In the study, researchers treated 30 cocaine addicts with Modafinil and gave 32 others a placebo for eight weeks. The Modafinil-treated addicts were more likely to go for long periods without using cocaine, as confirmed by cocaine-negative urine samples. The researchers also noted Modafinil did not appear to cause any serious side effects and none of the addicts dropped out of the study due to adverse reactions to the medication. LOAD-DATE: January 12, 2005 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2005 U.P.I. All Rights Reserved 524 of 998 DOCUMENTS The Philadelphia Inquirer JANUARY 11, 2005 Tuesday CITY-D EDITION Drug offers cocaine addicts hope; Modafinil boosts alertness and may curb impulsiveness, a Penn study shows. BYLINE: Stacey Burling INQUIRER STAFF WRITER SECTION: NATIONAL; Pg. A04 LENGTH: 651 words After decades of failed attempts to find a drug that helps addicts kick cocaine, researchers at the University of Pennsylvania say they have finally found a medication that looks promising - a drug currently approved to treat sleepiness. Addicts who took modafinil - used to treat narcolepsy and help pilots and night-shift workers stay alert - were about twice as likely to avoid cocaine in a given week as those who received a placebo pill, according to a small Penn study published this month in the Journal of Neuropsychopharmacology. Patients taking the medicine, marketed as Provigil, were also nearly three times as likely as unmedicated counterparts to stay off cocaine for a three-week stretch - 33 percent vs. 13 percent, said Charles Dackis, chief of psychiatry at Penn's Medical Center-Presbyterian and lead investigator of the 62-patient study. The National Institute on Drug Abuse funded the Penn study and is paying for three longer, larger studies as well. The institute is also funding similar studies of three other medicines: baclofen, which is used to treat spastic disorders; topiramate, an anti-convulsant; and disulfiram or Antabuse. Ultimately, the medicines may be targeted at specific subgroups within the nation's 1.5 million cocaine users, said Frank Vocci, director of the division of pharmacotherapies and medical consequences of drug abuse. Modafinil, he said, has qualities that could "propel it to the top." Addicts don't mind its side effects and like its "alerting effect." It may also reduce impulsiveness, a key factor in addiction. Given the high percentage of addicts in the study who still used cocaine, the drug clearly is not a cure for cocaine addiction, which is notoriously difficult to treat. But it may be an important, early step toward better drug therapies, said Robert Malcolm, a Medical University of South Carolina psychiatrist who heads another of the modafinil studies. "Is this drug a home run?" he asked. "No. Maybe it's a single or at best a double." Nonetheless, he and Dackis said modafinil is the most promising drug they have seen for cocaine addiction in 20 years. Dackis said researchers had tried as many as a 100 drugs against cocaine during that time with no success. Modafinil, made by Cephalon Inc. of West Chester, earned $300 million in 2003 and has projected sales of $410 million for 2004. The company is awaiting word on its request to market the drug for attention deficit hyperactivity disorder. Dackis believes that modafinil helps restore function to the brain's pleasure center, which is thrown chemically off balance by long-term cocaine use. Addicts often say they don't "feel right" without cocaine. "You're craving something that will make you feel better," he said. Modafinil, he added, "does promote a sense of well being but not euphoria and certainly not the rush of euphoria you experience with cocaine." One of his previous studies showed that the drug blunted the cocaine euphoria. The government lists modafinil as having mild potential for abuse. Dackis said he saw no evidence that modafanil is addictive. A middle-aged man who participated in the Penn study believes the drug helped him go 14 weeks without cocaine, an unusually long time for him during 15 years of addiction. "I had more energy to stay focused on things I had to do on my job, things I had to do at home, at church," he said. "I didn't have time to sneak off into North Philly and get lost." The man, a professional with a college degree who asked that his name not be used, said he stopped taking the medicine when the study ended. He used cocaine again last week. Now, he has asked his primary-care doctor to prescribe modafinil for him. He also plans to go back into therapy. "I guess I need that crutch," he said. Contact staff writer Stacey Burling at 215-854-4944 or sburling@phillynews.com. LOAD-DATE: September 6, 2005 LANGUAGE: ENGLISH Copyright 2005 Philadelphia Newspapers, LLC All Rights Reserved 525 of 998 DOCUMENTS Clinical Psychiatry News January 2005 Modafinil Dose Higher in Narcolepsy Than Apnea BYLINE: Nicholas Mulcahy, Contributing Writer SECTION: Pg. 65 Vol. 33 No. 1 ISSN: 0270-6644 LENGTH: 617 words    PHILADELPHIA - The median dose of modafinil was 300 mg for patients with obstructive sleep apnea and 400 mg for patients with narcolepsy in long-term open-label extensions of placebo-controlled trials, , Jonathan Schwartz, M.D., said at the annual meeting of the Associated Professional Sleep Societies.    The labeling for modafinil (Provigil) calls for a dosage of 200 mg/day to improve wakefulness in patients with excessive sleepiness associated with either condition.    "Modafinil dosing was flexible-between 200 and 400 mg/day-based on the investigators' impressions of clinical efficacy and tolerability [during the open-label extensions]. The dose was slightly higher in patients with narcolepsy, which may be attributable to the underlying differences in severity of excessive sleepiness between the two conditions," said Dr. Schwartz, a pulmonologist in Oklahoma City.    The open-label extensions involved two double-blind, placebo-controlled trials of modafinil in patients with narcolepsy and one in patients with nasal continuous positive airway pressure (nCPAP)-treated obstructive sleep apnea (OSA).    In the narcolepsy studies, 84% of 478 patients were titrated to a modafinil dose greater than 200 mg, with 50% at 400 mg, 34% at 300 mg, and 16% at 200 mg. In the OSA study, 76% of the 266 patients were titrated to a modafinil dose greater than 200 mg, with 43% at 300 mg, 33% at 400 mg, and 24% at 200 mg.    Modafinil was well tolerated in both populations at all doses, Dr. Schwartz said. Adverse events were similar in the two patient populations.    Treatment duration was 40 weeks for both narcolepsy studies and 12 months for the OSA study.    Baseline excessive sleepiness was assessed by mean score on the Epworth Sleepiness Scale (ESS); the score was significantly higher in the narcolepsy patients than in the OSA population (17.4 vs. 14.5, respectively; P< .001).    "Narcolepsy and obstructive sleep apnea are both frequently associated with excessive sleepiness, but patients with narcolepsy are usually sleepier than nCPAP-treated patients with OSA," said Dr. Schwartz.    In OSA, modafinil is indicated as an adjunct to standard treatments for the underlying obstruction in patients who continue to experience residual excessive sleepiness, despite treatment of the underlying obstruction, he added.    At least 20% of OSA patients are still sleepy despite nCPAP therapy, he said.    The mean change in ESS scores from baseline to final clinic visit in the study populations was virtually identical-about 4.25 points-for the narcolepsy and OSA patients, said Dr. Schwartz. In other words, there was a similar efficacy (mean reduction in sleepiness), despite the difference in the mean dose.    The mean body mass index was significantly lower in the narcolepsy group (28.8 kg/m2) than in the OSA patients (36.2 kg/m2). Despite having significantly lower body mass indexes than OSA patients, patients with narcolepsy were titrated to higher modafinil doses to achieve clinical improvement, Dr. Schwartz observed.    The mean age for the narcolepsy patients was 42 years; the OSA patients' mean age was 50 years. Of the narcolepsy patients, 46% were male, as were 77% of the OSA patients.    Overall, 84% of patients in the studies completed the specified treatment period, but completion rates were higher in the 40-week narcolepsy studies (95%) than in the single 12-month OSA study (66%).    Clinic visits for both narcolepsy studies were scheduled at baseline and after 1, 2, 6, 8, 16, 24, and 40 weeks.    Clinic visits for the OSA study were scheduled at baseline and at 3, 6, 9, and 12 months.    The study was funded by Cephalon Inc., the maker of modafinil. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: CPNEWS Copyright 2005 Elsevier Inc., International Medical News Group All Rights Reserved 526 of 998 DOCUMENTS Clinical Neurology News January 2005 Narcolepsy Requires Higher Modafinil Dose BYLINE: Nicholas Mulcahy, Contributing Writer SECTION: Pg. 24 Vol. 1 No. 1 ISSN: 1553-3212 LENGTH: 637 words    PHILADELPHIA - The median therapeutic dose of modafinil was 300 mg for patients with obstructive sleep apnea and 400 mg for patients with narcolepsy in long-term open-label extensions of placebo-controlled trials, Dr. , Jonathan Schwartz said at the annual meeting of the Associated Professional Sleep Societies.    The labeling for modafinil (Provigil) calls for a dosage of 200 mg/day to improve wakefulness in patients with excessive sleepiness associated with either condition. "Modafinil dosing was flexible-between 200 and 400 mg/day-based on the investigators' impressions of clinical efficacy and tolerability [during the open-label extensions]. The dose was slightly higher in patients with narcolepsy, which may be attributable to the underlying differences in severity of excessive sleepiness between the two conditions," said Dr. Schwartz, a pulmonologist in Oklahoma City.    The open-label extensions involved two double-blind, placebo-controlled trials of modafinil in patients with narcolepsy and one in patients with nasal continuous positive airway pressure (nCPAP)-treated obstructive sleep apnea (OSA).    In the narcolepsy studies, 84% of 478 patients were titrated to a modafinil dose greater than 200 mg, with 50% at 400 mg, 34% at 300 mg, and 16% at 200 mg. In the OSA study, 76% of the 266 patients were titrated to a modafinil dose greater than 200 mg, with 43% at 300 mg, 33% at 400 mg, and 24% at 200 mg.    Modafinil was well tolerated in both populations at all doses, Dr. Schwartz said. Adverse events were similar in the two patient populations. Treatment duration was 40 weeks for both narcolepsy studies and 12 months for the OSA study.    Baseline excessive sleepiness was assessed by mean score on the Epworth Sleepiness Scale (ESS); the score was significantly higher in the narcolepsy patients than in the OSA population (17.4 vs. 14.5, respectively; P < .001).    "Narcolepsy and obstructive sleep apnea are both frequently associated with excessive sleepiness, but patients with narcolepsy are usually sleepier than nCPAP-treated patients with OSA," said Dr. Schwartz.    In OSA, modafinil is indicated as an adjunct to standard treatments for the underlying obstruction in patients who continue to experience residual excessive sleepiness, despite treatment of the underlying obstruction, he added.    At least 20% of OSA patients are still sleepy despite nCPAP therapy, he said.    The mean change in ESS scores from baseline to final clinic visit in the study populations was virtually identical-about 4.25 points-for the narcolepsy and OSA patients, said Dr. Schwartz. In other words, there was a similar efficacy (mean reduction in sleepiness), despite the difference in the mean dose.    The mean body mass index was significantly lower in the narcolepsy group (28.8 kg/m2) than in the OSA patients (36.2 kg/m2). Despite having significantly lower body mass index than OSA patients, patients with narcolepsy were titrated to higher modafinil doses to achieve clinical improvement, Dr. Schwartz observed.    The mean age for the narcolepsy patients was 42 years; the OSA patients' mean age was 50 years. Of the narcolepsy patients, 46% were male, as were 77% of the OSA patients.    Overall, 84% of patients in the studies completed the specified treatment period, but completion rates were higher in the 40-week narcolepsy studies (95%) than in the single 12-month OSA study (66%).    Clinic visits for both narcolepsy studies were scheduled at baseline and after 1, 2, 6, 8, 16, 24, and 40 weeks.    Clinic visits for the OSA study were scheduled at baseline and at 3, 6, 9, and 12 months.    The study included patients who withdrew after two evaluations if their withdrawal was not due to adverse events.    The study was funded by Cephalon Inc., the maker of modafinil. LOAD-DATE: July 31, 2009 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper JOURNAL-CODE: CNNEWS Copyright 2005 Elsevier Inc., International Medical News Group All Rights Reserved 527 of 998 DOCUMENTS PR Newswire US December 21, 2004 Tuesday Cephalon Files Application for Marketing Approval of New Modafinil Formulation for the Treatment of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder; Accelerated Submission Date Based on Highly Significant Results From Three Studies of New Once-Daily Doses LENGTH: 1284 words DATELINE: WEST CHESTER, Pa. Dec. 21 WEST CHESTER, Pa., Dec. 21 /PRNewswire-FirstCall/ -- Cephalon, Inc. (NASDAQ:CEPH) today announced that it has filed a supplemental new drug application (sNDA) with the U.S. Food and Drug Administration (FDA) requesting marketing approval of ATTENACE(TM) (modafinil) Tablets [C-IV], a new proprietary dosage form of modafinil for the treatment of attention- deficit/hyperactivity disorder (ADHD) in children and adolescents between the ages of six and 17. In August 2004, Cephalon announced results from three multi-center clinical trials that showed that ATTENACE 340 mg and 425 mg tablets significantly improve symptoms of ADHD in children and adolescents. Based upon the strength of the study results, the company accelerated the filing of its application with the FDA from the first quarter of 2005 to the fourth quarter of 2004. The company is targeting a launch of ATTENACE by early 2006. "Physicians and parents continue to seek treatment for children and adolescents with ADHD that provides a balanced efficacy and tolerability profile. In our phase 3 trials, we were encouraged that ATTENACE improved the symptoms of many children and adolescents with ADHD to levels within the range considered normal for those without ADHD, as measured by the ADHD rating scales used in our studies. There was a low discontinuation rate due to adverse events in these studies as well," said Paul Blake, MB, FRCP, Senior Vice President of Clinical Research and Regulatory Affairs. "The consistency of the effectiveness of ATTENACE to treat the full range of ADHD symptoms uniformly across the three studies allows us to present what we believe is a strong submission package to FDA," Dr. Blake added. Frank Baldino Jr., Ph.D., Chairman and CEO, said, "We are enthusiastic about the data from our clinical trials and the potential for ATTENACE, once approved, to capture a substantial portion of the ADHD market. We expect that ATTENACE will provide another exceptional growth opportunity for Cephalon." About the Clinical Trials In three nine-week, double-blind, placebo-controlled studies, more than 600 children and adolescents between the ages of six and 17 with ADHD were randomized to either placebo or ATTENACE. The primary endpoint in all studies was the teacher-completed school version of the ADHD Rating Scale IV. All of the ATTENACE-treated groups showed a highly statistically significant improvement on the ADHD rating scale compared to placebo (p<0.0001). ATTENACE was generally well tolerated, with a safety profile consistent with that observed in other studies of modafinil. The most common adverse events observed in the phase 3 trials with children and adolescents with ADHD included mild transient insomnia, headache and loss of appetite. The complete Phase 3 study data are expected to be presented at major medical meetings in 2005. ATTENACE Data from earlier clinical trials in children and adolescents with ADHD led to the development of ATTENACE as small, film-coated tablets in unique dosage strengths. The new tablets will be available in 85 mg, 170 mg, 255 mg, 340 mg, and 425 mg strengths and will allow for tailored dosing with a single tablet for children and adolescents with ADHD. The active ingredient in ATTENACE, modafinil , is currently available as PROVIGIL(R) (modafinil) Tablets [C-IV] in 100 mg and 200 mg strengths. PROVIGIL is indicated for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome (OSAHS) and shift work sleep disorder. The most frequently reported adverse events in clinical trials with PROVIGIL were headache, nausea, nervousness, stuffy nose, diarrhea, back pain, anxiety, trouble sleeping, dizziness and upset stomach. Attention-Deficit/Hyperactivity Disorder According to the National Institutes of Mental Health, ADHD is one of the most common psychiatric disorders among children, affecting three to five percent of American children. The most common ADHD behaviors fall into three categories: inattention, hyperactivity, and impulsivity. A diagnosis of ADHD is generally made when these behaviors become excessive, long-term, and pervasive. Studies have shown that children with ADHD have higher medical costs than children without ADHD due to the risk of accidents and injury resulting from inattention, impulsivity and hyperactivity. Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products to treat sleep and neurological disorders, cancer and pain. Cephalon currently employs approximately 2,100 people in the United States and Europe. U.S. sites include the company's headquarters in West Chester, Pennsylvania, and offices and manufacturing facilities in Salt Lake City, Utah, and suburban Minneapolis, Minnesota. Cephalon's European offices are located in Guildford, England, Martinsried, Germany, and Maisons-Alfort, France. The company currently markets three proprietary products in the United States: PROVIGIL, GABITRIL(R) (tiagabine hydrochloride) and ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II] and more than 20 products internationally. Further information about Cephalon and full prescribing information on its U.S. products is available at http://www.cephalon.com/ or by calling 1-800-896-5855. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs, development of potential pharmaceutical products, interpretation of clinical results, including the results of the three multi-center clinical trials of ATTENACE, prospects for regulatory approval of ATTENACE, including the strength of the Company's submission package to FDA and the anticipated timetable for the launch of the product, manufacturing development and capabilities, market prospects for its products, particularly with respect to the potential for the Company to capture a substantial portion of the ADHD marketplace with ATTENACE and the growth opportunity provided by the product, sales and earnings guidance, and other statements regarding matters that are not historical facts. You may identify some of these forward- looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. CONTACT: Media: Jenifer Antonacci, +1-610-738-6674, jantonac@cephalon.com ; or Investors: Robert (Chip) Merritt, +1-610-738-6376, cmerritt@cephalon.com , both of Cephalon Web site: http://www.cephalon.com/ Company News On-Call: http://www.prnewswire.com/comp/134563.html SOURCE Cephalon, Inc. URL: http://www.prnewswire.com LOAD-DATE: December 22, 2004 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2004 PR Newswire Association LLC. All Rights Reserved. 528 of 998 DOCUMENTS The San Francisco Chronicle DECEMBER 11, 2004, SATURDAY, FINAL EDITION Collins slapped with 8-year ban; Sprinter, 33, faces end of her career SOURCE: Chronicle Staff Writer BYLINE: John Crumpacker SECTION: SPORTS; Pg. D1 LENGTH: 834 words If Michelle Collins were a Major League Baseball player, she would have received a slap on the wrist for using banned performance-enhancing drugs. Instead, she's a track and field athlete. She was clobbered by the iron fist of her sport's anti-doping organization. Collins, a sprinter from Raleigh, N.C., became the first athlete from the BALCO investigation to be suspended based on non-analytical evidence, meaning a lack of a positive drug test, when the U.S. Anti-Doping Agency on Friday banned her from competition for eight years. Collins is the 13th track and field athlete with BALCO ties to receive sanctions for doping offenses. USADA has also charged sprinters Chryste Gaines and Tim Montgomery with doping offenses based on non-analytical evidence. Their arbitration hearings are scheduled for next year. At 33, the suspension is tantamount to a lifetime ban for Collins, once a training partner of Marion Jones. She has one avenue of appeal left, should she decide to take it, with the international Court of Arbitration for Sport. "I've never heard of anyone getting eight years," said Collins' attorney, Brian Getz of San Francisco. "We are disappointed with the (decision) and are studying it as we consider our options." A three-person panel of the American Arbitration Association/North American CAS ruled that "USADA has proved, beyond a reasonable doubt, that Collins took EPO, the testosterone/epitestosterone cream, and THG." The panel, comprised of two lawyers and a judge, concluded that because Collins used a variety of illegal drugs for several years and attempted to cover up her doping through substances designed to avoid detection in urine tests, her ban should be double what other BALCO athletes received. "I think they (the panelists) said she never admitted to her guilt, didn't agree to cooperate and because of that it amounted to a cover-up," said Travis Tygart, legal counsel for USADA. "(It) will keep her out of coaching until she's 41." Sprinter Alvin Harrison admitted to using a variety of illegal drugs and was banned for four years. Middle-distance runner Regina Jacobs tested positive for THG ("the clear") and received four years. Neither athlete agreed to cooperate with USADA's investigation, thus the four years. Sprinter Kelli White, conversely, admitted to using a regimen of banned drugs from BALCO, agreed to cooperate with investigators and was given a two-year sanction. White, in fact, was one of four witnesses called by USADA to provide testimony in Collins' hearing, which was held Nov. 17-18 in San Francisco, based on her involvement with BALCO and subsequent admission of guilt to doping charges. "Kelli White, when she was first confronted with the evidence, denied everything," Getz said. "She's doing it to benefit herself because she wants to race again." The other witnesses were Dr. Larry Bowers, USADA's managing director; Dr. Michael Sawka, an expert on blood doping; and Dr. Richard Clark, a pharmacology expert with the company GlaxoSmithKline. Sawka examined several of Collins' blood tests and concluded her elevated red blood cell levels could only be the result of the endurance-boosting agent EPO. Even when fortified by transfusions of their own red blood cells, U.S. military personnel training at high altitude did not have as high a percentage as Collins, Sawka testified. Clark testified that Collins' extreme fluctuations in testosterone levels could be explained by her use of BALCO's testosterone cream -- which she admitted to in e-mail exchanges with Conte. All of Collins' competitive results since Feb. 1, 2002, are nullified as a result of the ban. Her biggest accomplishments were winning U.S. and World Indoor championships at 200 meters in 2003. Allyson Felix is thus the U.S. indoor champ for 2003 while Muriel Hurtis of France claims the retroactive World Indoor title for that year. ------------------------------------------------------ The BALCO bunch Here are the track and field athletes affiliated with BALCO who have received sanctions for doping offenses, with their events, suspensions and the substances they were penalized for using: Dwain Chambers* (100) -- Life (THG); Michelle Collins (200, 400) -- 8 years (EPO, THG, testosterone cream); Alvin Harrison (400) -- 4 years (EPO, THG, testosterone cream, insulin, modafinil); Regina Jacobs (1,500) -- 4 years (THG) Calvin Harrison (400) -- 2 years (modafinil); John McEwen (hammer) -- 2 years (THG, modafinil); Melissa Price (hammer) -- 2 years (THG); Kevin Toth (shot put) -- 2 years (THG); Kelli White (100, 200) -- 2 years (EPO, THG, modafinil) All received public warnings for use of modafinil: Chryste Gaines (100, 200); Sandra Glover (400 hurdles); Chris Phillips (110 hurdles); Eric Thomas (400 hurdles) Note: Further doping cases pending -- Gaines, Tim Montgomery *British citizen. Banned for life from Olympics by his federationE-mail John Crumpacker at jcrumpacker@sfchronicle.com. LOAD-DATE: December 11, 2004 LANGUAGE: ENGLISH GRAPHIC: PHOTO, Michelle Collins never tested positive for banned substances. / Thomas Kienzle / Associated Press TYPE: RELATED STORY ATTACHED Copyright 2004 The Chronicle Publishing Co. 529 of 998 DOCUMENTS Pittsburgh Post-Gazette (Pennsylvania) November 29, 2004 Monday SOONER EDITION U.S. STRIPPED OF GOLD MEDAL BYLINE: From local and wire dispatches SECTION: SPORTS; MORNING BRIEFING; Pg. E-7 LENGTH: 616 words The United States was stripped of its 1,600-meter relay gold medal from the 2003 world championships because of Calvin Harrison's second doping violation. The gold instead goes to France, with Jamaica getting the silver and the Bahamas the bronze, the world governing body of track and field said. Harrison was found guilty of using the stimulant modafinil at the U.S. championships in June 2003. He had contended that modafinil wasn't specifically mentioned on the official list of banned substances at the time. Ten years earlier, Harrison tested positive for the stimulant pseudoephedrine during the 1993 U.S. junior indoor championships and served a three-month ban. More running Gunder Hagg, who set the mile world record in 1945 and held it until Roger Bannister broke the four-minute barrier, died at 85 after a long illness. Hagg died Saturday at a nursing home and spent his last years in a wheelchair, sports writer and friend Ulf R. Johansson said. Hagg broke 15 world marks in middle distance running and set no less than 10 world marks during three months in 1942. That year, the Swede also was the first to run 5,000 meters in under 14 minutes. He is survived by wife, Daisy, and son Gunder Hagg, Jr. Tennis This week's U.S.-Spain Davis Cup final in Seville, Spain, is expected to break the attendance record for a sanctioned tennis match. The temporary clay court set up in Seville's Olympic Stadium has been configured to seat 26,600. The existing mark was set in 1954 in Sydney, Australia, when 25,578 watched the United States defeat Australia in the Davis Cup final. Volleyball The Penn State women's team has been selected to the NCAA tournament field for the 24th year in a row. The fourth-ranked and second-seeded Lions (27-2) will face American University (24-6) Friday in the first round. Pitt (21-10) also made the 64-team field and will take on Ohio (28-2) Friday in Columbus. Skiing Bode Miller became the first man to open a World Cup season with three victories in three disciplines, winning a super-giant slalom in Lake Louise, Alberta, ahead of Hermann Maier. Miller's first career Super G win came one day after his first World Cup downhill victory. He also won the season-opening giant slalom in Soelden, Austria, and is just the fourth skier to win World Cup races in all five disciplines in his career (slalom and combined are the others). * Finland's Tanja Poutiainen won for the second time in three races at Aspen Mountain, beating Italy's Manuela Moelgg by more than a second in a World Cup slalom in Aspen, Colo. American Kristina Koznick was third. * Finland's Janne Ahonen won his second consecutive World Cup ski jump on a large hill before his home fans in Kuusamo. Austria's Thomas Morgenstern was second and the Czech Republic's Jakub Janda third. Swimming South Africa's Ryk Neethling and Australia's Libby Lenton each won a fifth event at a World Cup short-course swim meet in Melbourne, Australia. Lenton took the 200 freestyle in 1 minute, 56.98 seconds to edge countrywoman Shayne Reese. Lenton won the 50- and 100-meter freestyle and 50 and 100 butterfly events on the opening two nights. Neethling added the 50-meter freestyle to the 100 and 200 freestyle, 50 butterfly and 100 individual medley. Neethling and Lenton shared swimmer of the meet honors. Speed skating Apolo Anton Ohno won two races and teamed with Hyo-Jung Kim to give the United States a sweep in the 1,000-meter event at the World Cup short-track tournament in Madison, Wis. Ohno won the 1,000 meters in 1:26.914 then captured the 3,000-meter event in 5:13.504. Ohno increased his World Cup medal count this season to 13. He also took gold in the 1,500 meters and silver in the 500 meters this weekend. LOAD-DATE: October 20, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2004 P.G. Publishing Co. 530 of 998 DOCUMENTS Edmonton Journal (Alberta) October 20, 2004 Wednesday Final Edition U.S. runner accepts ban for steroid use: Alvin Harrison was BALCO client BYLINE: San Jose Mercury News SECTION: SPORTS; Pg. D5 LENGTH: 369 words DATELINE: SAN JOSE, Calif. SAN JOSE, Calif. - In another victory for the U.S. Anti-Doping Agency's effort to clean up track and field, Olympic runner Alvin Harrison accepted a four-year suspension Tuesday for drug violations stemming from the BALCO Laboratories case. Harrison, 30, became the second athlete connected to BALCO to admit to using performance-enhancing drugs after being presented with evidence from the criminal case. Sprinter Kelli White accepted a two-year ban in May. "It was time for him to speak out," said Harrison's lawyer, Robert Harris of Durham, N.C. Harrison, who won gold medals as part of the 1996 and 2000 U.S. 1,600-metre relay teams, could not be reached. He and his twin, Calvin Harrison, denied in July that they took illegal drugs. The brothers railed against the anti-doping agency for trying to ban Alvin without a positive test. Calvin Harrison is serving a two-year suspension after testing positive for modafinil, his second flunked drug screen. Alvin Harrison admitted to using THG, testosterone cream, insulin, erythropoietin (EPO), the human growth hormone and modafinil -- the catalogue of drugs connected to BALCO. Harrison's admission came because he wants to move on, his lawyer said. Harris said the 400-metre runner took the drugs only after the 2000 Olympics and that his accomplishments should not be diminished because of it. "He wants to show how this is being done and even forced on athletes," Harris said, adding that the runner might write a book as well as try to play professional football. The anti-doping agency used evidence based in large part on material subpoenaed by the Senate Commerce Committee and then handed to drug testers. Travis Tygart, USADA's legal director, said Harrison's admission validated the anti-doping agency's pursuit of athletes based on BALCO evidence, which included calendars of drug schedules. Three cases based on similar evidence -- involving Tim Montgomery, Chryste Gaines and Michelle Collins -- are scheduled before the Court of Arbitration for Sport next month in San Francisco. Alvin Harrison and his Sydney relay teammates face the possibility of losing their gold medals because runner Jerome Young tested positive for steroids a year before the 2000 Games. LOAD-DATE: October 20, 2004 LANGUAGE: ENGLISH DOCUMENT-TYPE: Sports PUBLICATION-TYPE: Newspaper Copyright 2004 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 531 of 998 DOCUMENTS Reuters Health Medical News October 15, 2004 Friday 9:00 PM EST Modafinil added to SSRIs alleviates sedation SECTION: CLINICAL LENGTH: 280 words DATELINE: NEW YORK Excessive sleepiness and fatigue related to therapy with serotonergic antidepressants can be alleviated with adjunctive use of modafinil, according to a report in the September issue of the Journal of Clinical Psychiatry. Dr. Thomas L. Schwartz and colleagues at the New York Upstate Medical University in Syracuse, New York enrolled 20 adults in a 3-week, open label study to determine the effect of modafinil, given once daily, on sedation related to serotonergic drugs. All patients had major depressive disorder, but all reported that sedation, fatigue, and low energy had developed only after they began to take selective serotonin reuptake inhibitors. In the 16 patients who completed the study, the addition of modafinil "significantly improved overall depressive symptoms, as shown by reductions in mean Hamilton Rating Scale for Depression total scores," the researchers report. Also, the investigators found, modafinil therapy was associated with improved subjective impressions of wakefulness and reduced fatigue. By their final study visit, the study participants had improvements in their overall health status and health-related quality of life, as shown by their significantly improved mean total scores on the Medical Outcomes Study Short-Form 12-Item Health Survey, and by improved physical health and mental health subscores. "Generalization of these findings is limited by the open-label nature of [the study], exclusion of a control group, and selective entry criteria for study participants," the investigators admit. Still, they conclude, "These positive findings, as well as the effects of adjunctive modafinil on responder rates, warrant further systematic study." LOAD-DATE: March 4, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2004 Reuters Health All Rights Reserved 532 of 998 DOCUMENTS Business Wire September 14, 2004 Tuesday Orphan Medical Announces Positive Xyrem Clinical Results in Second Excessive Daytime Sleepiness Trial -- Trial Supports Use of Xyrem as Monotherapy for Narcolepsy LENGTH: 1159 words DATELINE: MINNEAPOLIS, Sept. 14, 2004 BODY: Orphan Medical, Inc. (Nasdaq:ORPH) announced positive results from a Phase III (b) trial designed to evaluate the improvement of excessive daytime sleepiness (EDS) associated with narcolepsy when Xyrem(R) (sodium oxybate) oral solution is used alone or with modafinil (Provigil(R)), a wakefulness promoting agent approved for the treatment of EDS. The primary endpoint of the trial was EDS as measured by the objective Maintenance of Wakefulness Test (MWT). The secondary endpoint also measured EDS using the Epworth Sleepiness Score. The trial demonstrated that Xyrem monotherapy is effective in the treatment of EDS associated with narcolepsy as measured by objective response in the MWT. The combined use of Xyrem and modafinil showed a greater response than either agent alone. EXCEEDS (Evaluation of Xyrem to Check Efficacy in Excessive Daytime Sleepiness) was a double-blind, placebo-controlled, parallel group multi-center randomized study. This data follows the June announcement of positive clinical results from the Company's SXB-15 trial which evaluated the benefits of Xyrem in EDS associated with narcolepsy where the use of Xyrem was incremental to the use of stimulants or wakefulness-promoting drugs. In that trial, adding Xyrem resulted in statistically significant improvement in EDS as measured by The Epworth Sleepiness Score (ESS), the Clinical Global Impression of Change (CGIc) and the MWT. Bill Houghton, M.D., Orphan Medical Chief Medical & Scientific Officer, said, "Together, these two trials now demonstrate that Xyrem can be proposed as first-line therapy in narcolepsy, since Xyrem data has been produced to show efficacy in treating the symptoms of EDS, cataplexy and fragmented nighttime sleep." John H. Bullion, Orphan Medical Chief Executive Officer, stated, "The results of EXCEEDS further support our belief that Xyrem represents the foundation for the treatment of narcolepsy. We intend to file a Supplemental New Drug Application (sNDA) incorporating the results of both EDS trials with the U.S. Food and Drug Administration (FDA) by the end of the year. The sNDA timing will position the Company for an FDA decision in 2005 that could allow us to expand the use of Xyrem to all of narcolepsy." Narcolepsy is a chronic, debilitating neurological disease characterized by symptoms of excessive daytime sleepiness, cataplexy (sudden loss of muscle tone) and fragmented nighttime sleep. Excessive daytime sleepiness is experienced by all narcolepsy patients and is usually treated with stimulants during the day to help keep patients awake. Xyrem is currently the only approved medication for the treatment of cataplexy. Trial Results The trial was conducted in narcoleptic patients with established EDS for which they were treated with modafinil at doses of 200-600 mg daily. After meeting entry criteria, and following two weeks of blinded randomized treatment with modafinil and Xyrem placebo, they were randomized to four evenly distributed groups in the trial with one group receiving active Xyrem only, another with active modafinil alone, a third group with both active medications, and a final group receiving both Xyrem and modafinil placebo. As expected, the group receiving both active medications saw the greatest mean change of 2.7 minutes from baseline while maintained in blinded fashion on unchanged dose of modafinil . It is not yet known if the two products are additive or synergistic in their benefit. The Xyrem, modafinil and combined drug treatment groups were highly statistically significant compared to the placebo group. Changes in the Epworth Sleepiness Score (ESS) were also measured and those results further support the MWT data. The safety profile seen in this study was consistent with other controlled clinical trials, with a relatively uniform distribution across all groups. The side effect of nausea occurred more often for groups receiving Xyrem and both Xyrem and modafinil together, as did vomiting which had a markedly lower rate of incidence. Headache was a common symptom in all groups, including placebo, but dizziness and tremor were more common in the group on both drugs, as was anxiety. The incidence of sleep walking and enuresis, previously reported in our studies as associated with Xyrem showed a very low incidence in this study that was not significantly different between groups. Background Information Narcolepsy is a chronic, debilitating neurological disease. Cataplexy, a sudden loss of muscle tone, is usually triggered by strong emotions such as laughter, anger, or surprise. As such, patients often selectively isolate themselves from interaction with others resulting in a dramatic effect on a patient's quality of life. Narcolepsy afflicts approximately 100,000 to 140,000 Americans with about 50,000 to 75,000 patients receiving some form of treatment for their symptoms. An estimated sixty to ninety percent of those with narcolepsy suffer from cataplexy. All patients with narcolepsy suffer from excessive daytime sleepiness. Orphan Medical acquires, develops, and markets pharmaceuticals of high medical value for inadequately treated and uncommon CNS diseases treated by specialist physicians. The lead product for the company is Xyrem, which is the first and only approved treatment for cataplexy associated with narcolepsy. Xyrem has now been assessed as a treatment for the full range of narcolepsy symptoms including excessive daytime sleepiness. Orphan Medical's pipeline includes development stage products for fibromyalgia and pain. Orphan Medical's Internet Web site address is www.orphan.com. The information in this press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. In some cases, you can identify forward looking statements by terminology such as "expects," "anticipates," "intends," "may," "should," "plans," "believes," "seeks," "estimates," "could," "would" or the negative of such terms or other comparable terminology. Such forward-looking statements are based upon current expectations and beliefs and involve numerous risks and uncertainties, both known and unknown, that could cause actual events or results to differ materially from these forward-looking statements. A number of factors could cause actual results to differ materially from the Company's assumptions and expectations. These are set forth in the cautionary statements included in Orphan Medical's most recent Form 10-Q or Form 10-K filed with the Securities and Exchange Commission. (These documents can be accessed through the Orphan Medical Web site at http://www.orphan.com). All forward-looking statements are qualified by, and should be considered in conjunction with, such cautionary statements. CONTACT: Orphan Medical, Inc. Tim McGrath, 952-513-6900 or David Folkens, 952-513-6994 URL: http://www.businesswire.com LOAD-DATE: September 15, 2004 LANGUAGE: ENGLISH DISTRIBUTION: Health/Medical Writers; Business Editors Copyright 2004 Business Wire, Inc. 533 of 998 DOCUMENTS The New Atlantis Summer 2004 Doping for Seconds SUBTITLE: The Shadow of Drugs on American Athletics BYLINE: The Editors of The New Atlantis SECTION: Pg. 124-125 No. 6 LENGTH: 739 words With the return of the Summer Olympics, the world of athletics is once again focusing its attention on allegations, investigations, and confessions of drug use -- especially in light of doping scandals throughout the sports world over the last year. In August 2003, track and field fans watched Kelli White become the first American and third woman in history to clinch both the 100- and 200-meter sprints at the world championships in Paris. But not long after she was awarded two gold medals, it was announced that she had tested positive for the stimulant modafinil, used to treat narcolepsy. White admitted to taking modafinil for a sleep disorder, and claimed she hadn't reported it to proper authorities because it was not on the official list of banned substances. But soon after, three other American track and field athletes tested positive for modafinil, and international drug-testing officials suggested they were not the only guilty Americans. In the fall of 2003, the U.S. Anti-Doping Agency conducted a raid of the Bay Area Laboratory Co-Operative (BALCO), a company suspected of serving an underground market for steroids and designer drugs. Investigators discovered correspondence between Kelli White and Victor Conte, Jr., founder of BALCO, which linked White to a number of designer drugs -- which work by producing the same result as a banned substance, but sneak past drug screeners due to slightly different molecular structures. White was linked to such drugs dating back to 2000. In exchange for her cooperation and confession, White escaped lifetime banishment from her sport -- but she will sit out the next two years of track and field competition (including this year's Olympics), and all her placements and medals between 2000 and 2004 were annulled. The Kelli White drug investigations also implicated several other runners, as well as numerous athletes from other sports. Craig Masback, chief executive of the U.S. Track and Field Team, declared that "the situation in which we find ourselves is not a track and field problem, or even a baseball problem; it is an American problem." He pointed out that "more than four percent of American high school seniors" say they have used steroids in the last year. This figure is backed up by recent studies showing that steroid use decreased slightly among the overall population of U.S. high school students, but usage increased among student athletes. While steroids and supplements are used by young athletes to build muscle, other performance-enhancing drugs -- like asthma medications -- are increasingly used by young athletes to improve their lung capacity. The studies show that most teenage boys are aware that steroids can lead to impotence, and that the side effects of other performance-enhancing drugs include nausea, diarrhea, and vomiting. Perhaps most alarming is that the number of students who have a moral or ethical problem with the use of steroids is declining -- even though drug education and prevention programs are at an all-time high. At a recent Senate hearing on steroid use by adolescent athletes, one of the witnesses was Don Hooten of Plano, Texas, whose high school son suffered from severe depression due to withdrawal from steroids and eventually killed himself. Thanks to the Internet, Mr. Hooten said, "all our kids need is a credit card number or a money order and they can have hard-core prescription anabolic steroids delivered right to their doorstep." An anonymous college football player testified about the "competitive edge" that steroids give athletes trying to keep up with their peers. Sports doping was deemed important enough by President Bush to earn a mention in his 2004 State of the Union address: "The use of performance-enhancing drugs like steroids in baseball, football, and other sports is dangerous, and it sends the wrong message -- that there are shortcuts to accomplishment, and that performance is more important than character." Surely Tori Edwards, a sprinter who competed against Kelli White, would agree with this sentiment. Upon hearing that White's medals were being annulled, she said: "I am disappointed, because she took something from me.... The honor of winning that race, crossing the finish line first, throwing my hands up in the air and having my family seeing me on the podium.... Even if they send me a gold medal in the mail, it's not going to be the same. It's a moment I'll never get back." LOAD-DATE: November 4, 2004 LANGUAGE: ENGLISH PUBLICATION-TYPE: Magazine Copyright 2004 Ethics and Public Policy Center All Rights Reserved 534 of 998 DOCUMENTS CNS Drug News Pharmaceuticals August 20, 2004 Cephalon obtains positive results with new modafinil formulation for younger ADHD patients LENGTH: 335 words Cephalon has released results from three multi-centre trials showing that new proprietary once-daily dosage forms of Provigil C-IV tablets ( modafinil ) significantly improved symptoms of attention deficit hyperactivity disorder (ADHD) in children and adolescents. Based upon the study results, the company plans to accelerate the filing of its application with the FDA from the first quarter of 2005 to the fourth quarter of 2004. In three nine-week, double-blind, placebo-controlled studies, 600 children and adolescents between the ages of six and 17 years with ADHD were randomised to either placebo or an optimised new dosage form of modafinil. The primary endpoint in all studies was the teacher-completed school version of the ADHD Rating Scale IV. All of the modafinil-treated groups showed a highly statistically significant improvement on the primary endpoint compared to placebo (p<0.0001). Modafinil was generally well tolerated and the most common side effects observed in these studies were consistent with those observed in other studies of this compound and included insomnia, headache and loss of appetite. The complete Phase III study data are expected to be presented at major medical meetings over the next 12 months. Cephalon focused its clinical efforts on identifying optimal doses of modafinil for these studies because children metabolise the drug in a different way to adults. The resulting dosage strengths of 340 and 425mg produced robust symptom improvement in children and adolescents with ADHD in these studies. The company was encouraged by the robust effects of modafinil on both the inattentive and hyperactive symptoms of the disorder. Modafinil is currently available in 100 and 200mg strengths and is indicated for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnoea and shift work sleep disorder. Modafinil for the treatment of children and adolescents with ADHD will be manufactured as smaller, film-coated tablets in unique dosage strengths. LOAD-DATE: August 25, 2004 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2004 ESPICOM Business Intelligence Ltd. All Rights Reserved 535 of 998 DOCUMENTS Knobias.com This content is provided to LexisNexis by Comtex News Network, Inc. August 19, 2004 Thursday CEPH: Positive Trial Results of Modafinil in ADHD LENGTH: 109 words DATELINE: Ridgeland, MS Cephalon, Inc. (CEPH) announced results from three multi-center clinical trials, which show that new proprietary once-daily dosage forms of modafinil significantly improve symptoms of Attention Deficit Hyperactivity Disorder (ADHD) in children and adolescents. The primary endpoint in all studies was the teacher-completed school version of the ADHD Rating Scale IV. All of the modafinil treated groups showed a highly statistically significant improvement on the primary endpoint compared to placebo. The company plans to accelerate the filing of its application with the FDA from the first quarter of 2005 to the fourth quarter of 2004. LOAD-DATE: August 20, 2004 LANGUAGE: ENGLISH Copyright 2004 Comtex News Network, Inc. All Rights Reserved Copyright 2004 Knobias.com, LLC, All rights reserved 536 of 998 DOCUMENTS PR Newswire August 19, 2004 Thursday Cephalon Announces Positive Results with a New Modafinil Formulation for the Treatment of Children with Attention Deficit Hyperactivity Disorder; Results with New Pediatric Doses Were Highly Significant in All Three Studies; Regulatory Filing Accelerated to Late 2004 SECTION: FINANCIAL NEWS LENGTH: 1096 words DATELINE: WEST CHESTER, Pa. Aug. 19 Cephalon, Inc. (Nasdaq: CEPH) today announced results from three multi-center clinical trials, which show that new proprietary once-daily dosage forms of modafinil significantly improve symptoms of Attention Deficit Hyperactivity Disorder (ADHD) in children and adolescents. In three nine-week, double-blind, placebo-controlled studies, 600 children and adolescents between the ages of six and 17 with ADHD were randomized to either placebo or an optimized new proprietary dosage form of modafinil. The primary endpoint in all studies was the teacher-completed school version of the ADHD Rating Scale IV. All of the modafinil treated groups showed a highly statistically significant improvement on the primary endpoint compared to placebo (p<0.0001). Modafinil was generally well tolerated, and the most common side effects observed in these studies were consistent with those observed in other studies of this compound and included insomnia, headache and loss of appetite. The complete Phase III study data are expected to be presented at major medical meetings over the next 12 months. "Because children metabolize modafinil differently from adults, our clinical efforts focused on identification of optimal doses of modafinil for these studies," said Dr. Paul Blake, MB, FRCP, Senior Vice President of Clinical Research and Regulatory Affairs at Cephalon. "The result was the development of proprietary dosage strengths of 340 and 425 milligrams, which in these Phase III studies demonstrated robust symptom improvement in children and adolescents with ADHD. The most encouraging aspects of these results were the strength and consistency of the effects of modafinil across the three studies and the robust effects of modafinil on both the inattentive and hyperactive symptoms of ADHD." Based upon the demonstrated strength of the study results, the company plans to accelerate the filing of its application with the Food and Drug Administration from the first quarter of 2005 to the fourth quarter of 2004. Frank Baldino Jr., Ph.D., Chairman and CEO of Cephalon, said, "We are excited about these data and the promise they hold for the ADHD community. We expect this product, once approved, to command a substantial presence in this large and growing market that today exceeds several billion dollars. With its excellent clinical profile and strong intellectual property protection for use in ADHD, we anticipate this product will be an important contributor to Cephalon's revenue growth for many years to come." Modafinil Modafinil (PROVIGIL(R) C-IV Tablets) is currently available in 100 and 200 milligrams and is indicated for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea and shift work sleep disorder. Modafinil for the treatment of children and adolescents with ADHD will be manufactured as smaller, film-coated tablets in unique dosage strengths. Attention Deficit Hyperactivity Disorder According to the National Institutes of Mental Health, ADHD is one of the most common psychiatric disorders among children, affecting three to five percent of American children. ADHD is associated with dysfunction in the prefrontal cortex area of the brain. The most common ADHD behaviors fall into three categories: inattention, hyperactivity, and impulsivity. A diagnosis of ADHD is generally made when these behaviors become excessive, long-term, and pervasive. Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products to treat sleep and neurological disorders, cancer and pain. Cephalon currently employs more than 2,000 people in the United States and Europe. U.S. sites include the company's headquarters in West Chester, Pennsylvania, and offices and manufacturing facilities in Salt Lake City, Utah and Eden Prairie, Minnesota. Cephalon's major European offices are located in Guildford, England, Martinsried, Germany, and Maisons-Alfort, France. The company currently markets three proprietary products in the United States: PROVIGIL, GABITRIL(R) (tiagabine hydrochloride) and ACTIQ(R) (oral transmucosal fentanyl citrate) $(C-II$) and more than 20 products internationally. Further information about Cephalon and full prescribing information on its U.S. products is available at http://www.cephalon.com or by calling 1-800-896-5855. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs, development of potential pharmaceutical products, interpretation of clinical results, including the results of the three multi- center clinical trials of modafinil in ADHD, prospects for regulatory approval of modafinil for ADHD and the anticipated timetable for filing a marketing application for the use of modafinil in ADHD, manufacturing development and capabilities, market prospects for its products, particularly with respect to the Company's ability to effectively compete in the ADHD marketplace with modafinil, sales and earnings guidance, and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. SOURCE Cephalon, Inc. CONTACT: Media: Sheryl Williams, +1-610-738-6493, swilliam@cephalon.com, or Investors: Robert (Chip) Merritt, +1-610-738-6376, cmerritt@cephalon.com, both of Cephalon URL: http://www.prnewswire.com LOAD-DATE: August 20, 2004 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS AND MEDICAL EDITORS PUBLICATION-TYPE: Newswire Copyright 2004 PR Newswire Association, Inc. 537 of 998 DOCUMENTS Agence France Presse -- English -- English August 11, 2004 Wednesday US athletes who have tested positive for drugs SECTION: Sports LENGTH: 255 words DATELINE: ATHENS, Aug 11 Following the two-year suspension handed down to sprinter Torri Edwards on Wednesday, here is a list of athletes from the United States who have tested positive for banned substances since last August's world championships in Paris: BANNED Kelli White (100 metres/200m): two years (steroids and erythropoietin/EPO) Regina Jacobs (middle distance): four years (tetrahydrogestrinone/THG) Calvin Harrison (400m): two years (Modafinil) Torri Edwards (100m/200m): two years (nikethamide, pending Court of Arbitration for Sport appeal) Kevin Toth (shot putt): two years (tetrahydrogestrinone/THG and Modafinil) Melissa Price (hammer): two years (tetrahydrogestrinone/THG) John McEwen (hammer): two years (tetrahydrogestrinone/THG) CASES UNDER INVESTIGATION Jerome Young (400m): life suspension (erythropoietin/EPO) Larry Wade (110m hurdles): (norandrosterone) Mickey Grimes (100m/200m): (norandrosterone) WARNINGS (WITHOUT BAN) Chryste Gaines (100m/200m): Modafinil) Sandra Glover (400m hurdles): (Modafinil) Eric Thomas (400m hurdles): (Modafinil) Tim Rusan (triple jump): (marijuana) Bernard Williams (100m/200m): (marijuana) Note: Erythropoietin (EPO) is used to boost endurance. Tetrahydrogestrinone (THG) is a previously undetectable anabolic steroid which came to light last year when a sample was sent anonymously to the US Anti-Doping Agency. Norandrosterone is a steroid. Modafinil is a stimulant. Nikethamide is a stimulant. sg/gj04 Oly-2004-Athletics-USA-doping-list LOAD-DATE: August 12, 2004 LANGUAGE: ENGLISH Copyright 2004 Agence France Presse 538 of 998 DOCUMENTS PNG Post-Courier August 4, 2004 Wednesday US sprinter gets 2-year suspension for doping SECTION: SPORT; Pg. 40 LENGTH: 462 words RALEIGH, North Carolina: American sprinter Calvin Harrison has been suspended for two years for a second doping violation and will be ineligible for the Athens Olympics, the US Anti-Doping Agency (USADA) said yesterday. The ruling could also cost the United States its 2003 world 4x400 metres relay gold medal since Harrison, according to the decision, was ineligible to compete at the time. In a similar case last month, the International Association of Athletics Federations (IAAF) recommended that the International Olympic Committee (IOC) strip the US 4x400 metres relay team of its Sydney Olympics gold medal because another sprinter, Jerome Young, was ineligible following a 1999 positive doping test. Harrison ran on US 4x400 metres relay teams at both the 2000 Games and 2003 world championships. He tested positive for the banned stimulant modafinil at the 2003 US national championships, the USADA said in a statement. Harrison s first doping offence occurred at the 1993 US junior national championships, which also involved a prohibited stimulant. He had been named to the preliminary 4x400 metres relay pool for Athens after finishing fifth in the individual event at last month s Olympic trials. Harrison s lawyer, Edward Williams said he did not know whether his client would appeal the decision, made by a three-member panel of the American Arbitration Association (AAA)/North American Court of Arbitration for Sport (CAS). He s disappointed, particularly about the fact that the arbitrators didn t essentially nullify the repercussions of the first offence, which dealt with pseudoephedrine, which is no longer on the (banned) list... It was then but is not now,  Williams said in a telephone interview from New York. Williams also said Harrison s due process was denied in the 1993 hearing process. The lawyer also expressed disappointment that the hearing panel did not accept the testimony of his expert witness, a pharmacologist once employed by the manufacturer of modafinil, that the drug was not a stimulant. USADA officials said modafinil was prohibited at the time of the test because it is related to the classes of substances banned under IAAF rules. Harrison admitted in an October 2003 telephone interview with Reuters that he tested positive for modafinil at the nationals.  He said a coach in California had given him this pill and he had taken it. He (the coach) emphasised that it was not on the banned substance list and assured me that it was not an illegal substance,  Harrison said. The doping agency said Harrison would lose all competitive results and winnings from June 21, 2003, the date of his positive test for modafinil, including his second place finish in the 400m at the 2003 US championships. LOAD-DATE: August 4, 2004 LANGUAGE: ENGLISH JOURNAL-CODE: PTC Copyright 2004 Nationwide News Pty Limited 539 of 998 DOCUMENTS The Associated Press August 3, 2004, Tuesday, BC cycle Harrison ineligible for Athens Games, U.S. could forfeit more medals BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Sports News LENGTH: 541 words DATELINE: ATHENS, Greece Calvin Harrison has been suspended for two years for a second doping violation, knocking the sprinter off the U.S. Olympic team and likely forcing the United States to forfeit a relay gold medal in the world championships. The U.S. Anti-Doping Agency said Monday that Harrison was found guilty of using the stimulant modafinil at the U.S. track and field championships in June 2003. The case was heard last week by a three-member arbitration panel, which rejected Harrison's appeal of the test results. Harrison also tested positive for the stimulant pseudoephedrine during the 1993 U.S. junior indoor championships and served a three-month suspension. As a repeat offender, he got the two-year ban. Harrison's lawyer, Ed Williams, said Monday he was not sure whether he will appeal the ruling to the Swiss-based Court of Arbitration for Sport. Williams said he was disappointed the arbitrators did not accept his argument that the 1993 suspension should have been nullified because athletes were not accorded adequate due process at that time. He also argued unsuccessfully before the panel that because modafinil was not specifically named on the banned substance list in 2003, that Harrison would have had no way of knowing it was prohibited. USADA's director of legal affairs, Travis Tygart, said modafinil - now on the banned list - was prohibited in 2003 because it was chemically related to stimulants named on the list of banned substances. "Modafinil is a banned substance and is a stimulant. You can only get it in the U.S. by prescription. It is classified by the federal government as a central nervous system stimulant," Tygart said in a telephone interview. "Athletes are generally warned not to take drugs when they compete, and they should be held accountable when they do so." Harrison, part of the 1,600-meter gold medal relay team in the Sydney Olympics that already faces loss of its medals because of a positive drug test by Jerome Young, had been selected to the U.S. squad for Athens as part of the relay pool. He also was on the 1,600 relay team that won a gold medal in the 2003 world championships in Paris, and that squad now could face loss of its medals. All of Harrison's results from the time of the positive drug test - two months before the world championships - will be nullified. The International Association of Athletics Federations will decide whether to strip the U.S. squad of its gold and award it to silver medalist France. Harrison ran the opening leg in the relay final in Paris. The other runners were Tyree Washington, Derrick Brew and Young. Harrison's twin brother, Alvin, faces a lifetime ban after being charged by USADA with steroid use. His case is awaiting arbitration. The 2000 Sydney relay gold medals could be forfeited because Young failed a steroid test in 1999. The Court of Arbitration for Sport ruled in late June that Young should be stripped of his relay medal, and the IAAF has recommended that the entire team - including Michael Johnson - be stripped of its medals. A final decision rests with the International Olympic Committee, which is expected to rule days before the Athens Games and is expected to endorse the IAAF recommendation. LOAD-DATE: August 4, 2004 LANGUAGE: ENGLISH GRAPHIC: AP Photos Copyright 2004 Associated Press All Rights Reserved 540 of 998 DOCUMENTS The Associated Press State & Local Wire August 3, 2004, Tuesday, BC cycle Harrison ruled ineligible for Athens Games BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Sports News LENGTH: 547 words DATELINE: ATHENS, Greece Calvin Harrison has been suspended for two years for a second doping violation, knocking the sprinter off the U.S. Olympic team and likely forcing the United States to forfeit a relay gold medal in the world championships. The U.S. Anti-Doping Agency, which is based in Colorado Springs, said Monday that Harrison was found guilty of using the stimulant modafinil at the U.S. track and field championships in June 2003. The case was heard last week by a three-member arbitration panel, which rejected Harrison's appeal of the test results. Harrison also tested positive for the stimulant pseudoephedrine during the 1993 U.S. junior indoor championships and served a three-month suspension. As a repeat offender, he got the two-year ban. Harrison's lawyer, Ed Williams, said Monday he was not sure whether he will appeal the ruling to the Swiss-based Court of Arbitration for Sport. Williams said he was disappointed the arbitrators did not accept his argument that the 1993 suspension should have been nullified because athletes were not accorded adequate due process at that time. He also argued unsuccessfully before the panel that because modafinil was not specifically named on the banned substance list in 2003, that Harrison would have had no way of knowing it was prohibited. USADA's director of legal affairs, Travis Tygart, said modafinil - now on the banned list - was prohibited in 2003 because it was chemically related to stimulants named on the list of banned substances. "Modafinil is a banned substance and is a stimulant. You can only get it in the U.S. by prescription. It is classified by the federal government as a central nervous system stimulant," Tygart said in a telephone interview. "Athletes are generally warned not to take drugs when they compete, and they should be held accountable when they do so." Harrison, part of the 1,600-meter gold medal relay team in the Sydney Olympics that already faces loss of its medals because of a positive drug test by Jerome Young, had been selected to the U.S. squad for Athens as part of the relay pool. He also was on the 1,600 relay team that won a gold medal in the 2003 world championships in Paris, and that squad now could face loss of its medals. All of Harrison's results from the time of the positive drug test - two months before the world championships - will be nullified. The International Association of Athletics Federations will decide whether to strip the U.S. squad of its gold and award it to silver medalist France. Harrison ran the opening leg in the relay final in Paris. The other runners were Tyree Washington, Derrick Brew and Young. Harrison's twin brother, Alvin, faces a lifetime ban after being charged by USADA with steroid use. His case is awaiting arbitration. The 2000 Sydney relay gold medals could be forfeited because Young failed a steroid test in 1999. The Court of Arbitration for Sport ruled in late June that Young should be stripped of his relay medal, and the IAAF has recommended that the entire team - including Michael Johnson - be stripped of its medals. A final decision rests with the International Olympic Committee, which is expected to rule days before the Athens Games and is expected to endorse the IAAF recommendation. LOAD-DATE: August 4, 2004 LANGUAGE: ENGLISH GRAPHIC: AP Photos Copyright 2004 Associated Press All Rights Reserved 541 of 998 DOCUMENTS Associated Press Online August 3, 2004 Tuesday Harrison Ineligible for Athens Olympics BYLINE: ROB GLOSTER; AP Sports Writer SECTION: SPORTS LENGTH: 552 words DATELINE: ATHENS, Greece Calvin Harrison has been suspended for two years for a second doping violation, knocking the sprinter off the U.S. team for the Athens Olympics and likely forcing the United States to forfeit a relay gold medal from last year's world championships. The U.S. Anti-Doping Agency said Monday that Harrison was found guilty of using the stimulant modafinil at the U.S. track and field championships in June 2003. His case was heard last week by a three-member arbitration panel, which rejected Harrison's appeal of the test results. Harrison did not attend the 8-hour arbitration hearing. Harrison also tested positive for the stimulant pseudoephedrine at the 1993 U.S. junior indoor championships and served a three-month suspension. As a repeat offender, he got the 2-year ban. Harrison's lawyer, Ed Williams, said Monday he was not sure whether he will appeal the ruling to the Swiss-based Court of Arbitration for Sport. Williams said he was disappointed the arbitrators did not accept his argument that the 1993 suspension should have been nullified because athletes were not accorded adequate due process at that time. He also argued unsuccessfully before the panel that since modafinil was not specifically named on the banned substance list in 2003, that Harrison would have had no way of knowing it was prohibited. USADA's director of legal affairs, Travis Tygart, said modafinil - which is now on the banned list - was prohibited in 2003 because it was chemically related to stimulants named on the list of banned substances. "Modafinil is a banned substance and is a stimulant. You can only get it in the U.S. by prescription. It is classified by the federal government as a central nervous system stimulant," Tygart said in a telephone interview. "Athletes are generally warned not to take drugs when they compete, and they should be held accountable when they do so." Harrison, part of the 1,600-meter gold medal relay team at the Sydney Olympics that already faces loss of its medals because of a positive drug test by Jerome Young, had been named to the U.S. squad for Athens as part of the relay pool. He also was on the 1,600 relay team that won a gold medal at the 2003 world championships in Paris, and that squad now could face loss of its medals. All of Harrison's results from the time of the positive drug test - two months before the world championships - will be nullified. The International Association of Athletics Federations will decide whether to strip the U.S. squad of its gold and award it to silver medalist France. Harrison ran the opening leg in the relay final in Paris. The other runners were Tyree Washington, Derrick Brew and Young. Harrison's twin brother, Alvin, faces a lifetime ban after being charged by USADA with steroid use. His case is awaiting arbitration. The 2000 Sydney relay gold medals could be forfeited because Young had failed a steroid test in 1999. The Court of Arbitration for Sport ruled in late June that Young should be stripped of his relay medal, and the IAAF has recommended that the entire team - including Michael Johnson - be stripped of its medals. A final decision rests with the International Olympic Committee, which is expected to rule days before the Athens Games and is expected to endorse the IAAF recommendation. LOAD-DATE: August 4, 2004 LANGUAGE: ENGLISH Copyright 2004 Associated Press All Rights Reserved 542 of 998 DOCUMENTS Ottawa Citizen August 3, 2004 Tuesday Final Edition American sprinter ineligible for Athens: Harrison doping violation could cost U.S. world relay gold SOURCE: The Associated Press BYLINE: Rob Gloster SECTION: Sports; Pg. C12 LENGTH: 475 words DATELINE: ATHENS ATHENS - Calvin Harrison has been suspended for two years for a second doping violation, knocking the sprinter off the U.S. team for the Athens Olympics and likely forcing the United States to forfeit a relay gold medal from last year's world championships. The U.S. Anti-Doping Agency said Monday that Harrison was found guilty of using the stimulant modafinil at the U.S. track and field championships in June 2003. His case was heard last week by a three-member arbitration panel, which rejected Harrison's appeal of the test results. Harrison did not attend the eight-hour arbitration hearing. Harrison also tested positive for the stimulant pseudoephedrine at the 1993 U.S. junior indoor championships and served a three-month suspension. As a repeat offender, he received a two-year ban. Harrison's lawyer, Ed Williams, said yesterday he was not sure whether he will appeal the ruling to the Swiss-based Court of Arbitration for Sport. Williams said he was disappointed the arbitrators did not accept his argument that the 1993 suspension should have been nullified because athletes were not accorded adequate due process at that time. He also argued unsuccessfully before the panel that since modafinil was not specifically named on the banned substance list in 2003, that Harrison would have had no way of knowing it was prohibited. USADA's director of legal affairs, Travis Tygart, said modafinil -- which is now on the banned list -- was prohibited in 2003 because it was chemically related to stimulants named on the list of banned substances. "Modafinil is a banned substance and is a stimulant. You can only get it in the U.S. by prescription. It is classified by the federal government as a central nervous system stimulant," Tygart said in a telephone interview. "Athletes are generally warned not to take drugs when they compete, and they should be held accountable when they do so." Harrison, part of the 1,600-metre gold medal relay team at the Sydney Olympics that already faces loss of its medals because of a positive drug test by Jerome Young, had been named to the U.S. squad for Athens as part of the relay pool. He also was on the 1,600 relay team that won a gold medal at the 2003 world championships in Paris, and that squad now could face loss of its medals. All of Harrison's results from the time of the positive drug test -- two months before the world championships -- will be nullified. The International Association of Athletics Federations will decide whether to strip the U.S. squad of its gold and award it to silver medallist France. Harrison ran the opening leg in the relay final in Paris. The other runners were Tyree Washington, Derrick Brew and Young. Harrison's twin brother, Alvin, faces a lifetime ban after being charged by USADA with steroid use. His case is awaiting arbitration. LOAD-DATE: August 3, 2004 LANGUAGE: ENGLISH GRAPHIC: Colour Photo: The Associated Press; Calvin Harrison tested positive for the prohibited stimulant modafinil at the USA Outdoor Track & Field Championships at Stanford, California on June 21, 2003. TYPE: Sports Copyright 2004 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 543 of 998 DOCUMENTS The San Francisco Chronicle AUGUST 3, 2004, TUESDAY, FINAL EDITION His run has ended; Calvin Harrison given 2-year ban by USADA SOURCE: Chronicle Staff Writer BYLINE: John Crumpacker SECTION: SPORTS; Pg. D1 LENGTH: 807 words Olympic gold-medal relay runner Calvin Harrison lost his spot on the 2004 U.S. team Monday and was suspended for two years because he tested positive for the stimulant modafinil, 11 years after testing positive for a substance no longer on the banned list. In the vast quagmire that is sports doping, two positive tests for stimulants equals one positive test for steroids. That is, a two-year ban from competition. Harrison had been named to the pool of runners for the 4x400m relay; he and his twin brother Alvin ran on the gold-medal-winning relay team at the Sydney Olympic Games in 2000. Following a hearing before a three-person panel of the American Arbitration Association, the U.S. Anti-Doping Agency announced a two-year ban for Harrison, 30, of Salinas, effective July 26. Harrison tested positive for modafinil, a prescription medicine used to treat sleep disorders such as narcolepsy and also attention deficit disorder, on June 21, 2003, at the U.S. outdoor track and field championships at Stanford. He was one of seven athletes to test positive for the substance at the U.S. nationals. That modafinil test, combined with a 1993 positive test for pseudoephedrine, resulted in the two-year ban. USADA noted, pointedly, that Harrison "loses all competitive results and winnings" from the date of the positive test. Harrison won a gold medal on the 4x400 relay at last year's World Championships; relay teams split $80,000 for gold medals. "He's just disappointed that the panel did not recognize he did not receive due process in 1993," said Harrison's attorney, Edward Williams. "What it means is they rejected my argument that the first offense from 1993 should be a nullity." Edwards said Harrison did not receive a hearing after his positive '93 test for pseudoephedrine at the U.S. Junior Championships. The 1978 Amateur Sports Act guarantees athletes the right to a hearing in doping cases. "(U.S.) track and field's rules back then provided that as soon as you tested positive on the 'B' sample, you were automatically suspended before any hearing ... which is contrary to the Sports Act," Williams said. Pseudoephedrine since has been taken off the banned list because of its common usage in cold medications. It is listed by USADA under "examples of permitted medications -- 2004." Calvin Harrison was named to the relay pool for Athens based on his fifth-place finish in the 400 meters at last month's Olympics track and field trials. The runners who finished behind him, Andrew Rock, Kelly Willie and Jerry Harris, probably will move into consideration for the relay. Harrison attended North Salinas High School and lives now in Raleigh, N.C. He is coached by Trevor Graham, who has had seven of his athletes test positive for banned substances. The Chronicle reported that sprinter Tim Montgomery testified before a federal grand jury investigating the BALCO case that Graham gave steroids to some of his athletes. Alvin and Calvin Harrison testified before the grand jury in San Francisco last fall. The Harrison brothers did not have an easy upbringing and their athletic careers have been checkered. They moved from Orlando to Salinas when their father found work on the Monterey Bay Aquarium project. They were homeless for a time and lived in their car around the time they enrolled in, and later dropped out of, Hartnell College. Their careers peaked in 2000 when they both made the Olympics team and ran on the relay. Alvin also won a silver medal in the 400 meters when he finished behind Michael Johnson. The brothers are credited with writing an inspirational book titled "Go to Your Destiny" and they appeared on the "Oprah Winfrey Show" after the Olympics. Now Calvin is suspended and Alvin is under investigation by USADA for a suspected doping violation, although his case has not been resolved and he remains eligible for competition. Alvin Harrison did not advance to the final of the 400 at the Olympics trials and is not a member of the Olympics team. Meanwhile, the makers of modafinil, under the trade name Provigil, say it is not a stimulant in the common sense of the word in that it does not have amphetamine-like qualities "like hyper-arousal and irritability," said Dr. Jeffry Vaught, president of research and development for Cephalon, Inc., the West Chester, Pa., company that makes Provigil. "There's no reason why anyone who is healthy should be prescribed any prescription-based product. That would include modafinil," Vaught said. "Am I surprised they're taking modafinil? I suppose so." In addition to Calvin Harrison, other track and field athletes who tested positive for modafinil in 2003 were Kelli White, Chryste Gaines, John McEwen, Eric Thomas, Chris Phillips and Sandra Glover.E-mail John Crumpacker at jcrumpacker@sfchronicle.com. LOAD-DATE: August 3, 2004 LANGUAGE: ENGLISH GRAPHIC: PHOTO, Calvin Harrison / Vincent Laforet / New York Times Copyright 2004 The Chronicle Publishing Co. 544 of 998 DOCUMENTS The Associated Press August 2, 2004, Monday, BC cycle Harrison ineligible for Athens Games, U.S. could forfeit more medals BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Sports News LENGTH: 555 words DATELINE: ATHENS, Greece Calvin Harrison has been suspended for two years for a second doping violation, knocking the sprinter off the U.S. team for the Athens Olympics and likely forcing the United States to forfeit a relay gold medal from last year's world championships. The U.S. Anti-Doping Agency said Monday that Harrison was found guilty of using the stimulant modafinil at the U.S. track and field championships in June 2003. His case was heard last week by a three-member arbitration panel, which rejected Harrison's appeal of the test results. Harrison did not attend the 8-hour arbitration hearing. Harrison also tested positive for the stimulant pseudoephedrine at the 1993 U.S. junior indoor championships and served a three-month suspension. As a repeat offender, he got the 2-year ban. Harrison's lawyer, Ed Williams, said Monday he was not sure whether he will appeal the ruling to the Swiss-based Court of Arbitration for Sport. Williams said he was disappointed the arbitrators did not accept his argument that the 1993 suspension should have been nullified because athletes were not accorded adequate due process at that time. He also argued unsuccessfully before the panel that since modafinil was not specifically named on the banned substance list in 2003, that Harrison would have had no way of knowing it was prohibited. USADA's director of legal affairs, Travis Tygart, said modafinil - which is now on the banned list - was prohibited in 2003 because it was chemically related to stimulants named on the list of banned substances. "Modafinil is a banned substance and is a stimulant. You can only get it in the U.S. by prescription. It is classified by the federal government as a central nervous system stimulant," Tygart said in a telephone interview. "Athletes are generally warned not to take drugs when they compete, and they should be held accountable when they do so." Harrison, part of the 1,600-meter gold medal relay team at the Sydney Olympics that already faces loss of its medals because of a positive drug test by Jerome Young, had been named to the U.S. squad for Athens as part of the relay pool. He also was on the 1,600 relay team that won a gold medal at the 2003 world championships in Paris, and that squad now could face loss of its medals. All of Harrison's results from the time of the positive drug test - two months before the world championships - will be nullified. The International Association of Athletics Federations will decide whether to strip the U.S. squad of its gold and award it to silver medalist France. Harrison ran the opening leg in the relay final in Paris. The other runners were Tyree Washington, Derrick Brew and Young. Harrison's twin brother, Alvin, faces a lifetime ban after being charged by USADA with steroid use. His case is awaiting arbitration. The 2000 Sydney relay gold medals could be forfeited because Young had failed a steroid test in 1999. The Court of Arbitration for Sport ruled in late June that Young should be stripped of his relay medal, and the IAAF has recommended that the entire team - including Michael Johnson - be stripped of its medals. A final decision rests with the International Olympic Committee, which is expected to rule days before the Athens Games and is expected to endorse the IAAF recommendation. LOAD-DATE: August 3, 2004 LANGUAGE: ENGLISH GRAPHIC: AP Photo NY154 Copyright 2004 Associated Press All Rights Reserved 545 of 998 DOCUMENTS The Associated Press State & Local Wire August 2, 2004, Monday, BC cycle Harrison ineligible for Athens Games, U.S. could forfeit more medals BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Sports News LENGTH: 561 words DATELINE: ATHENS, Greece Calvin Harrison has been suspended for two years for a second doping violation, knocking the sprinter off the U.S. team for the Athens Olympics and likely forcing the United States to forfeit a relay gold medal from last year's world championships. The U.S. Anti-Doping Agency, based in Colorado Springs, Colo., said Monday that Harrison was found guilty of using the stimulant modafinil at the U.S. track and field championships in June 2003. His case was heard last week by a three-member arbitration panel, which rejected Harrison's appeal of the test results. Harrison did not attend the 8-hour arbitration hearing. Harrison also tested positive for the stimulant pseudoephedrine at the 1993 U.S. junior indoor championships and served a three-month suspension. As a repeat offender, he got the 2-year ban. Harrison's lawyer, Ed Williams, said Monday he was not sure whether he will appeal the ruling to the Swiss-based Court of Arbitration for Sport. Williams said he was disappointed the arbitrators did not accept his argument that the 1993 suspension should have been nullified because athletes were not accorded adequate due process at that time. He also argued unsuccessfully before the panel that since modafinil was not specifically named on the banned substance list in 2003, that Harrison would have had no way of knowing it was prohibited. USADA's director of legal affairs, Travis Tygart, said modafinil - which is now on the banned list - was prohibited in 2003 because it was chemically related to stimulants named on the list of banned substances. "Modafinil is a banned substance and is a stimulant. You can only get it in the U.S. by prescription. It is classified by the federal government as a central nervous system stimulant," Tygart said in a telephone interview. "Athletes are generally warned not to take drugs when they compete, and they should be held accountable when they do so." Harrison, part of the 1,600-meter gold medal relay team at the Sydney Olympics that already faces loss of its medals because of a positive drug test by Jerome Young, had been named to the U.S. squad for Athens as part of the relay pool. He also was on the 1,600 relay team that won a gold medal at the 2003 world championships in Paris, and that squad now could face loss of its medals. All of Harrison's results from the time of the positive drug test - two months before the world championships - will be nullified. The International Association of Athletics Federations will decide whether to strip the U.S. squad of its gold and award it to silver medalist France. Harrison ran the opening leg in the relay final in Paris. The other runners were Tyree Washington, Derrick Brew and Young. Harrison's twin brother, Alvin, faces a lifetime ban after being charged by USADA with steroid use. His case is awaiting arbitration. The 2000 Sydney relay gold medals could be forfeited because Young had failed a steroid test in 1999. The Court of Arbitration for Sport ruled in late June that Young should be stripped of his relay medal, and the IAAF has recommended that the entire team - including Michael Johnson - be stripped of its medals. A final decision rests with the International Olympic Committee, which is expected to rule days before the Athens Games and is expected to endorse the IAAF recommendation. LOAD-DATE: August 3, 2004 LANGUAGE: ENGLISH GRAPHIC: AP Photo NY154 Copyright 2004 Associated Press All Rights Reserved 546 of 998 DOCUMENTS Associated Press Online August 2, 2004 Monday Harrison Ineligible for Athens Olympics BYLINE: ROB GLOSTER; AP Sports Writer SECTION: SPORTS LENGTH: 552 words DATELINE: ATHENS, Greece Calvin Harrison has been suspended for two years for a second doping violation, knocking the sprinter off the U.S. team for the Athens Olympics and likely forcing the United States to forfeit a relay gold medal from last year's world championships. The U.S. Anti-Doping Agency said Monday that Harrison was found guilty of using the stimulant modafinil at the U.S. track and field championships in June 2003. His case was heard last week by a three-member arbitration panel, which rejected Harrison's appeal of the test results. Harrison did not attend the 8-hour arbitration hearing. Harrison also tested positive for the stimulant pseudoephedrine at the 1993 U.S. junior indoor championships and served a three-month suspension. As a repeat offender, he got the 2-year ban. Harrison's lawyer, Ed Williams, said Monday he was not sure whether he will appeal the ruling to the Swiss-based Court of Arbitration for Sport. Williams said he was disappointed the arbitrators did not accept his argument that the 1993 suspension should have been nullified because athletes were not accorded adequate due process at that time. He also argued unsuccessfully before the panel that since modafinil was not specifically named on the banned substance list in 2003, that Harrison would have had no way of knowing it was prohibited. USADA's director of legal affairs, Travis Tygart, said modafinil - which is now on the banned list - was prohibited in 2003 because it was chemically related to stimulants named on the list of banned substances. "Modafinil is a banned substance and is a stimulant. You can only get it in the U.S. by prescription. It is classified by the federal government as a central nervous system stimulant," Tygart said in a telephone interview. "Athletes are generally warned not to take drugs when they compete, and they should be held accountable when they do so." Harrison, part of the 1,600-meter gold medal relay team at the Sydney Olympics that already faces loss of its medals because of a positive drug test by Jerome Young, had been named to the U.S. squad for Athens as part of the relay pool. He also was on the 1,600 relay team that won a gold medal at the 2003 world championships in Paris, and that squad now could face loss of its medals. All of Harrison's results from the time of the positive drug test - two months before the world championships - will be nullified. The International Association of Athletics Federations will decide whether to strip the U.S. squad of its gold and award it to silver medalist France. Harrison ran the opening leg in the relay final in Paris. The other runners were Tyree Washington, Derrick Brew and Young. Harrison's twin brother, Alvin, faces a lifetime ban after being charged by USADA with steroid use. His case is awaiting arbitration. The 2000 Sydney relay gold medals could be forfeited because Young had failed a steroid test in 1999. The Court of Arbitration for Sport ruled in late June that Young should be stripped of his relay medal, and the IAAF has recommended that the entire team - including Michael Johnson - be stripped of its medals. A final decision rests with the International Olympic Committee, which is expected to rule days before the Athens Games and is expected to endorse the IAAF recommendation. LOAD-DATE: August 3, 2004 LANGUAGE: ENGLISH Copyright 2004 Associated Press All Rights Reserved 547 of 998 DOCUMENTS Associated Press Worldstream August 2, 2004 Monday Harrison ineligible for Athens Games, U.S. could forfeit more medals BYLINE: ROB GLOSTER; AP Sports Writer SECTION: SPORTS LENGTH: 544 words DATELINE: ATHENS, Greece Calvin Harrison has been suspended for two years for a second doping violation, knocking the sprinter off the U.S. team for the Athens Olympics and likely forcing the United States to forfeit a relay gold medal from last year's world championships. The U.S. Anti-Doping Agency said on Monday that Harrison was found guilty of using the stimulant modafinil at the U.S. track and field championships in June 2003. His case was heard last week by a three-member arbitration panel, which rejected Harrison's appeal of the test results. Harrison did not attend the 8-hour arbitration hearing. Harrison also tested positive for the stimulant pseudoephedrine at the 1993 U.S. junior indoor championships and served a three-month suspension. As a repeat offender, he got the 2-year ban. Harrison's lawyer, Ed Williams, said Monday he was not sure whether he will appeal the ruling to the Swiss-based Court of Arbitration for Sport. Williams said he was disappointed the arbitrators did not accept his argument that the 1993 suspension should have been nullified because athletes were not accorded adequate due process at that time. He also argued unsuccessfully before the panel that since modafinil was not specifically named on the banned substance list in 2003, that Harrison would have had no way of knowing it was prohibited. USADA's director of legal affairs, Travis Tygart, said modafinil - which is now on the banned list - was prohibited in 2003 because it was chemically related to stimulants named on the list of banned substances. "Modafinil is a banned substance and is a stimulant. You can only get it in the U.S. by prescription. It is classified by the federal government as a central nervous system stimulant," Tygart said in a telephone interview. "Athletes are generally warned not to take drugs when they compete, and they should be held accountable when they do so." Harrison, part of the 1,600-meter gold medal relay team at the Sydney Olympics that already faces losing its medals because of a positive drug test by Jerome Young, had been named to the U.S. squad for Athens as part of the relay pool. He also was on the 1,600 relay team that won a gold medal at the 2003 world championships in Paris, and that squad now could lose its medals. All of Harrison's results from the time of the positive drug test - two months before the world championships - will be nullified. The IAAF will decide whether to strip the U.S. squad of its gold and award it to silver medalist France. Harrison ran the opening leg in the relay final in Paris. The other runners were Tyree Washington, Derrick Brew and Young. Harrison's twin brother, Alvin, faces a lifetime ban after being charged by USADA with steroid use. His case is awaiting arbitration. The 2000 Sydney relay gold medals could be forfeited because Young had failed a steroid test in 1999. The Court of Arbitration for Sport ruled in late June that Young should be stripped of his relay medal, and the IAAF has recommended that the entire team - including Michael Johnson - be stripped of its medals. A final decision rests with the International Olympic Committee, which is expected to rule days before the Athens Games and is expected to endorse the IAAF recommendation. LOAD-DATE: August 3, 2004 LANGUAGE: ENGLISH Copyright 2004 Associated Press All Rights Reserved 548 of 998 DOCUMENTS The Times (London) July 27, 2004, Tuesday Seize the daytime BYLINE: Jerome Burne SECTION: Features; Times2; 8 LENGTH: 588 words A CONTROVERSIAL NEW DRUG HAS SOUNDED A WAKE-UP CALL FOR NARCOLEPTICS, SAYS JEROME BURNE AS A TEENAGER, Brendan Maguire had to be careful not to laugh. If he did, he could fall to the floor in a deep sleep. He spent most of his days in bed because he always felt sleepy. Maguire has narcolepsy and his life was transformed two years ago by a new drug, Provigil, that allows him to live an almost normal life. "Now I can do a 12 hour shift at a call centre," he says. The only remedies for overwhelming sleepiness used to be coffee, cigarettes or amphetamines -all linked with unpleasant side-effects such as jitteriness. What seems to distinguish Provigil is that it is precisely targeted. It keeps the user awake for about six hours then allows them to sleep normally, with no comedown. In the US, it is largely used for non-medical reasons -to sustain a party or business lifestyle without apparent penalties. In the UK, however, it was tightly regulated until a few months ago. Last year only 17,000 prescriptions were written for the treatment of narcolepsy and an insomnia disorder known as sleep apnoea. Now it can be prescribed for any chronic condition that involves "excessive daytime sleepiness", such as Parkinson's disease or multiple sclerosis. "Studies show it's safe, effective and well tolerated," says Dr Paul Reading, a neurologist who runs the sleep clinic in Newcastle where Maguire is treated. The drug is also used for "chronic shiftworker sleep disorder", a condition that isn't recognised medically in the UK but is regularly diagnosed in the US and usually involves older people who keep falling asleep on the job. "Until now GPs would normally either suggest you get a different job or prescribe barbiturates to take in the day," says Reading. "Giving Provigil, which is associated with far fewer problems, seems to make more sense. But it shouldn't be given to people who are just overworked or overdoing it." Provigil is controversial because, like Viagra, it blurs the line between treating a medical condition and a lifestyle choice. "We don't know the long-term effects of using drugs to stay awake longer," says Professor Jim Horne, of the Sleep Research Centre at Loughborough University. "What we do know is that there are powerful mechanisms for sleep and no natural ways to override them, so it's potentially a dangerous thing to do." If the promise of research is fulfilled, Provigil may event-ually have a wider range of targets, including attention deficit hyperactivity disorder and weight loss; it may also be used to boost antidepressants. Scientists still don't know exactly how the drug, known generically as modafinil , works. The consensus seems to be that it targets the hypo-thalamus -an area of the brain also involved in regulating other body systems such as sex and appetite -in a precise way. Unlike the general state of arousal produced by other stimulants, modafinil seems only to target neurones involved in wakefulness. That still allows a number of other applications. A study at the University of Pennsylvania found that both modafinil and amphetamine reduced appetite but that, unlike amphetamine, modafinil didn't raise heart rate and blood pressure. American psychiatrists are increasingly prescribing modafinil to boost the effectiveness of antidepressants. Fans of the drug claim that it not only keeps them painlessly awake but also makes them more focused and effective at work, and there is research to support this. LOAD-DATE: July 27, 2004 LANGUAGE: ENGLISH Copyright 2004 Times Newspapers Limited 549 of 998 DOCUMENTS Chemist & Druggist July 10, 2004 DTB: little proof for new modafinil uses SECTION: Pg. 22 LENGTH: 294 words Use of modafinil, the non-amphetamine wake promoter, may prevent the underlying cause of excessive sleepiness from being treated. There is also little proof for its newly approved uses, claims the Drug and Therapeutics Bulletin. Extending the drug's use to include shift work sleep disorder and obstructive sleep apnoea could mean the underlying cause of excessive sleepiness is overlooked or not addressed, says the DTB. Evidence for modafinil's benefit for these patients is "limited or unconvincing". The drug may also reduce the use of continuous positive airway (CPAP) therapy in patients with obstructive sleep apnoea, says DTB. Although modafinil is effective in patients with narcolepsy, no head to head studies of modafinil and dexamphetamine have been carried out, DTB says. DTB acting editor Ike Iheanacho said: "The broader licensing of modafinil is of concern; there is little compelling evidence to justify this potentially indiscriminate use and the drug may increasingly be used as an unsatisfactory alternative to addressing whatever's causing the sleepiness." Dr John Shneerson, Papworth Hospital's Respiratory Support and Sleep Centre director, said: "In addition to its first-line use in narcolepsy, modafinil has been shown to relieve persisting excessive sleepiness in obstructive sleep apnoea patients despite CPAP treatment. Long-term data appears to show no clinically relevant reduction in CPAP compliance amongst patients taking modafinil for this reason. "Unfortunately, excessive sleepiness is frequently under-diagnosed in the UK and its impact is underestimated. It is always important to identify and treat any underlying cause." For more information: Drug and Therapeutics Bulletin 2004; 42: 52-6 LOAD-DATE: July 13, 2004 LANGUAGE: English PUB-TYPE: Magazine Copyright 2004 CMP Information Ltd 550 of 998 DOCUMENTS American Health Line June 30, 2004 Wednesday SLEEP: NEW YORK TIMES EXAMINES USE OF MODAFINIL SECTION: TRENDS & TIMELINES LENGTH: 345 words The New York Times on Tuesday looked at how modafinil, a drug that "revs up the central nervous system without the jitteriness of caffeine or the addiction and euphoria of amphetamines" and keeps people "awake for hours or even days," is being prescribed. The Cephalon drug, which is marketed as Provigil, was approved in 1998 as a narcolepsy treatment, and FDA this year broadened its approved uses to include obstructive sleep apnea and sleeping problems caused by shift work. Sales have been "skyrocketing," but "[n]o one knows exactly how" the drug works, according to the Times. Global sales in 2003 exceeded $290 million. About 90% of modafinil prescriptions are for off-label uses, including as a treatment for attention deficit hyperactivity disorder, depression, fatigue and drowsiness caused by other medications, according to Cephalon officials. The drug is also being tested as an appetite suppressant and a cocaine addiction treatment. However, some scientists worry that modafinil might be dangerous because taking it could mask underlying causes of fatigue, such as diabetes and sleep apnea. The drug "might also pose a more subtle danger: to the countless Americans in search of an extra edge, modafinil could be a cure for sleep," and losing sleep over an extended period of time can have long-term cardiovascular and neurological effects, according to the Times. Dr. Neil Kavey, director of the Sleep Disorders Center at Columbia Presbyterian Medical Center, said, "[I]ncreasing mounds of data sho[w] that sleep is a restorative, protective health process [that] ... affects performance, blood pressure, heart rate, insulin, various hormone secretions." He added, "No matter what medications come out that make sleep seem like a waste of time, we know that the sleep-deprived state is a bad one to be in." Studies have shown that sleep deprivation weakens the immune system, increases the likelihood of illness and is associated with a shorter life span (O'Connor, New York Times, 6/29). LOAD-DATE: June 30, 2004 LANGUAGE: ENGLISH Copyright 2004 National Journal Group, Inc. 551 of 998 DOCUMENTS The New York Times June 29, 2004 Tuesday Late Edition - Final Wakefulness Finds a Powerful Ally BYLINE: By ANAHAD O'CONNOR SECTION: Section F; Column 2; Health & Fitness; Pg. 1 LENGTH: 2250 words Laurie Coots, a marketing executive who flies to meetings in other countries twice a week, spent years trying to conquer sleepless nights and chronic jet lag. But nothing worked, she says, and every day was a struggle to stay awake. ''It was debilitating,'' said Ms. Coots, 46, who is from Los Angeles. ''I couldn't give an effective presentation because I was always shaky and nervous from being amped up on caffeine and stimulants.'' Then she found modafinil, a small white pill that revs up the central nervous system without the jitteriness of caffeine or the addiction and euphoria of amphetamines. ''Without it my life would not be possible,'' she said. Since 1998, modafinil, made by Cephalon and sold under the brand name Provigil, has quietly altered the lives of millions of people. No one knows exactly how it works, but sales of the drug are skyrocketing. People who take it say it keeps them awake for hours or even days. It has been described as a nap in the form of a pill, making most users feel refreshed and alert but still able to go to bed when they are ready. And because its side effects are rarely worse than a mild headache or slight nausea, experts fear that it has rapidly become a tempting pick-me-up to a nation that battles sleep with more than 100 million cups of coffee a day. Few numbers are available, but experts say that as modafinil grows more widely available, it is becoming a fixture among college students, long-haul truckers, computer programmers and others determined to burn the midnight oil. Some worry that an array of common disorders, like diabetes and sleep apnea, will go undiagnosed if doctors dole out Provigil instead of seeking the underlying diseases that cause fatigue. In a culture of 24-hour stores, graveyard shifts and coffee shops on every corner, modafinil might also pose a more subtle danger: to the countless Americans in search of an extra edge, modafinil could be a cure for sleep. ''This drug enables us to be that much more workaholic and that much more obsessed with accomplishments and productivity, and I think our society is already extreme along those lines,'' said Dr. Martha J. Farah, director of the Center for Cognitive Neuroscience at the University of Pennsylvania. ''The natural checks on that tendency, like needing to go to bed, are being rolled back by modafinil.'' To the extent that modafinil becomes the latest lifestyle drug, as ubiquitous as Viagra, scientists warn that cutting back on sleep, even by one hour a night, can have long-term neurological and cardiovascular effects that are only now being recognized. ''It's almost fortuitous that at the same time that this drug has come out, we have increasing mounds of data showing that sleep is a restorative, protective health process,'' said Dr. Neil B. Kavey, director of the Sleep Disorders Center at Columbia Presbyterian Medical Center. ''It affects performance, blood pressure, heart rate, insulin, various hormone secretions. No matter what medications come out that make sleep seem like a waste of time, we know that the sleep-deprived state is a bad one to be in.'' Discovered by French researchers in the late 1970's, modafinil went on the market in the United States in 1998 as a treatment for narcolepsy, a severe sleep disorder. Earlier this year, the Food and Drug Administration broadened its approved uses to include obstructive sleep apnea, a narrowing or blockage of the airways, and sleeping problems caused by shift work. An effort by Cephalon to have the drug approved for a third indication, excessive sleepiness from any cause, was rejected. But the three conditions modafinil is approved to treat make up only a fraction of its total uses. According to Cephalon, based in West Chester, Pa., 90 percent of all prescriptions for the drug are for ''off-label'' uses, including fatigue, depression, attention deficit hyperactivity disorder, and sleepiness caused by other prescription medications. In the last year, six American track and field athletes have tested positive for the substance, which is on the United States Olympic Committee's list of banned stimulants. One group of scientists is testing its effectiveness as an appetite suppressant in people who are overweight. And a government-financed study found that it blunts the high produced by cocaine, making it a promising treatment for addiction. ''The off-label use of this drug is staggering,'' said Dr. Eric Heiligenstein, a psychiatrist at the University of Wisconsin who studies substance abuse by teenagers. ''This is a very clean drug that affects all the things that help people with their cognitive functioning,'' he said. ''The main barrier to more widespread use is that it's expensive, which will change as more insurance companies start to cover it.'' For doctors, modafinil's biggest lure is its safety profile. It was used in France for several years without reports of major problems before reaching the United States. In clinical trials, only about 1 percent of people complained of side effects, including nausea, mild headache and nervousness. But scientists point out that as with any drug, more serious side effects could appear as modafinil is used more widely. ''I'm not aware of any terrible outcomes, but I don't think there have been enough long-term studies of modafinil to rule out all dangers,'' said Dr. Jerome M. Siegel, chief of neurobiology research at the Veterans Affairs Greater Los Angeles Healthcare System. Total worldwide sales of Provigil soared above $290 million in 2003, up from $207 million in 2002. Marc Goodman, a pharmaceutical analyst at Morgan Stanley, expects that figure to reach $409 million this year. More than 90 percent of that revenue, he said, will come from sales in the United States alone. ''If you look back before the drug was launched, no one would ever have believed it would be this big,'' Mr. Goodman said. ''Everyone viewed narcolepsy as the market and didn't appreciate the benign side-effect profile and how that would play into off-label uses.'' Between 2002 and 2003, Provigil's share of the stimulants market grew by 39 percent, according to IMS Health, a company that tracks the pharmaceutical industry. In the near future, modafinil could find its way into even more medicine cabinets. Mr. Goodman said it was likely that Cephalon's patent for the compound would be challenged by several drug companies seeking to market generic versions. If they succeed, it would increase the availability of modafinil and almost certainly drive down the price of a monthly supply, which is now $120 or more. Cephalon is working on Provigil's successor, a longer lasting version the company calls Nuvigil. It also hopes to win approval for modafinil as a treatment for children with attention deficit disorder, the most commonly diagnosed behavioral disorder of childhood. Some experts think this would open the door to the drug becoming even more of a household name. Of all the questions surrounding modafinil, perhaps the most intriguing is how it works. After more than two decades of research, scientists are still trying to figure out just how it manipulates the brain. ''It is amazing that this drug has become so widely used without any real understanding of the basic science behind it,'' Dr. Siegel said. Researchers know that modafinil is distinctly different from conventional stimulants, which ramp up arousal and set off a flurry of activity throughout the brain. Such stimulants, like cocaine and amphetamines, for example, produce wakefulness but also produce a high and can lead to dependence. Modafinil appears to steer clear of those side effects by aiming at specific structures and chemicals. One neurotransmitter that is thought to be involved is dopamine, which mediates the reward pathways in the brain, producing euphoria, pleasure and addiction. Cocaine and amphetamines cause a surge in dopamine levels, while modafinil's effects are much weaker. A study of animals lacking a protein that helps process dopamine found that they did not respond to modafinil. Dr. Thomas Scammell, an associate professor of neurology at Harvard's medical school who was involved in preclinical trials of the drug, believes that modafinil may home in on a single poorly understood dopamine circuit that is specific for wakefulness, while amphetamines and other stimulants activate all three of the brain's dopamine pathways, including those involved in addiction and locomotor activity. That selectivity, he said, might be crucial in modafinil's lack of unwanted side effects. ''I think it is a subtle enough drug that it doesn't just activate everything,'' he said. Modafinil's impact on the brain is so subtle that brain scans of people who have taken it hardly register any change in activity at all. Give them amphetamine or a drug for Parkinson's disease, Dr. Scammell said, and ''the changes in brain function are spectacular,'' but give them modafinil, and they show little more than ordinary wakefulness. Most scientists suspect that at least three other transmitters are involved. One of them, histamine, is responsible for the sleep-inducing effects of many cold and allergy medications. In a study last month, Dr. Siegel, who is also a professor of psychiatry and biobehavioral sciences at the University of California at Los Angeles, found that histamine in the brain helps control consciousness. In the rapid-eye-movement stage of sleep, lower levels of norepinephrine and serotonin keep the body still, producing the characteristically slack muscle tone of sleep. Lower levels of histamine, however, specifically reduce consciousness and awareness. In studies on animals last year, Japanese researchers found that modafinil releases histamine. French researchers this year found that it elevates levels of norepinephrine. And a smaller number of scientists suspect minor involvement by orexin, a substance that is severely depleted in narcoleptics. Several researchers, including Dr. Siegel, have proposed a unified theory suggesting that all these chemicals are necessary for modafinil to take effect. ''Many things have to work together to achieve alertness,'' he said. ''Modafinil might activate dopamine, which then activates norepinephrine, which then activates histamine, for example. But we still want to know where the initial action is.'' Scientists think that the chain of reactions set off by modafinil leads to the hypothalamus, a small structure embedded in the forebrain that controls the body's hormones and regulatory functions. One part of the hypothalamus, known as the ventrolateral preoptic nucleus, appears to act as the body's sleep generator. When it is active, it produces a chemical, GABA, that inhibits the firing of cells involved in wakefulness and arousal. Scientists suspect that by increasing norepinephrine levels, modafinil may block the region from promoting sleep. Just next door, in the posterior hypothalamus, are bundles of thousands of neurons that produce histamine. Damage to this region, scientists have found, causes excessive sleepiness. Dr. Rod Hughes, senior director of scientific communications for Cephalon, thinks the histamine center may generate wakefulness, counteracting the effects of its sleep-inducing neighbor. Modafinil might increase output in this region, coaxing a tired body into switching on its natural alertness system. Some scientists say that regularly manipulating this system to skimp on sleep could have dire consequences. Studies have shown that chronic sleep deprivation damages health, weakening the immune system and increasing the likelihood of illness. It is also associated with a shorter life span. But other experts counter that Americans will continue to cut back on sleep, whether they have modafinil or not. The toll of this deprivation has been visible for years on the nation's highways, where impaired judgment from sleepiness is blamed for about 100,000 accidents a year. Lack of sleep is also believed to have played a role in the space shuttle Challenger disaster, the nuclear meltdown at Chernobyl and the Exxon Valdez oil spill. ''In terms of error rate, 18 hours of no sleep, which many of us regularly do, is equivalent to a blood alcohol level of about .05,'' said Dr. Ronald Chervin, who was involved in clinical trials of modafinil and is the director of the University of Michigan sleep disorders center. ''Twenty-one hours of no sleep is equivalent to a blood alcohol level of .08, which is illegal in many states.'' If someone is falling asleep on the highway, and has no other option than driving to work, Dr. Chervin said, ''I think many sleep experts would give that patient modafinil, and I think many do.'' Dr. Farah, at the Center for Cognitive Neuroscience, is more concerned about the people who are taking modafinil simply so they can get ahead at work or finish a term paper. As it becomes more and more popular to use it for those reasons, she said, people might feel they have to take it just to seem as if they are performing normally. ''It would be a shame for a generation of young adults to come of age believing that the only way they can take on a challenging project is with some kind of pharmacological help,'' she said. ''It's quite possible that modafinil will be the next Ritalin on campus, something that kids go off to college with. If it is widely used for A.D.H.D., then it will probably end up being readily available to the undergraduate masses.'' URL: http://www.nytimes.com LOAD-DATE: June 29, 2004 LANGUAGE: ENGLISH GRAPHIC: Photo: ''I don't think there have been enough long-term studies of modafinil to rule out all dangers,'' Dr. Jerome M. Siegel said. (Photo by Stephanie Diani for The New York Times)(pg. F6) (Illustration by Frank Ippolito)(pg. F1)Chart/Diagram: ''The Brain, Awake and Asleep''Scientists do not know exactly how modafinil works. But they are finding out more about the brain chemistry of sleep and waking.CORTEXControls coordination of movement, organization and planning among other things.THALAMUSA relay between the cortex and the rest of the brain.HYPOTHALAMUSControls regulatory functions and hormones.FOR WAKEFULNESSClusters of brain cells, or neurons, send signals (neurotransmitters) to activate the cortex.FOR LIGHT AND DEEP SLEEPOther clusters of neurons send signals that turn off the neurons that are active during wakefulness.THE DETAILS: WAKEFULNESSFour neurotransmitters -- istamine, dopamine, serotonin and norepinephrine -- are thought to work together to activate the cortex. A fifth, acetylcholine, activates the thalamus and cortex.NON-DREAMING SLEEPPart of the hypothalamus produces a neurotransmitter called GABA (gamma amino-butyric acid), which silences the brain cells that are active during wakefulness.DREAMING SLEEP (RAPID EYE MOVEMENT)Cells in the medial medulla are activated, inhibiting the motor neurons up and down the spinal cord and paralyzing nearly all muscles in the body.(Sources by Dr. Thomas Scammell and Rodrigo Espaa, Harvard Medical School and Beth Israel Deaconess Medical Center)(pg. F1) PUBLICATION-TYPE: Newspaper Copyright 2004 The New York Times Company 552 of 998 DOCUMENTS The Guardian (London) - Final Edition June 9, 2004 Athletics: American sprinters fear ban BYLINE: James Hammond SECTION: Guardian Sport Pages, Pg. 34 LENGTH: 471 words Tim Montgomery and Chryste Gaines came under threat of suspension from the Olympics yesterday as the Balco scandal continued to spread its shadow over US sprinting. Montgomery, the world 100 metres record holder, has received a letter from the US Anti-Doping Agency alleging that he used banned substances. And Chryste Gaines, a member of the 1996 Olympic 4x100m gold medal-winning team, was last night charged with a doping violation. "Tim Montgomery has not done anything wrong and we intend to fight any attempt to prevent Tim from running in the Olympics," his lawyer Cristina Arguedas said last night. "The evidence that we have been shown by Usada and that we are still reviewing is inconclusive and internally inconsistent. It is fundamentally unfair to try and take away (an) athlete's reputation, his work and his dreams based on meagre information, flimsy documents and a flawed process." Gaines's lawyer Cameron A Myler said: "We have received a letter from Usada. (It) has charged Chryste with a doping violation based on documents obtained in the Balco investigation." Gaines was one of the athletes coached by Remi Korchemny, who also coached Britain's European and 100 metres record holder Dwain Chambers. Korchemny has been charged along with three other men with being involved in a conspiracy to supply banned drugs to elite athletes. He has pleaded not guilty. Also charged is Victor Conte, the founder of Balco, which allegedly supplied Chambers with the designer steroid tetrahydrogestrinone (THG). Chambers tested positive last August and was this year handed a two-year suspension. It was announced last October that Gaines had tested positive for modafinil, which is used to treat narcolepsy. Modafinil had not been on the International Association of Ath- letics Federations' banned list of drugs although it was proscribed after the world championships in August. Gaines had tested positive in June, at the US Championships. Modafinil can be used as a masking agent for steroids. Her fellow sprinter Kelli White and the hurdler Chris Phillips, who both trained with Korchemny, also tested positive for modafinil. Korchemny denied giving modafinil to Gaines. In May White, the world champion at 100m and 200m, became the first athlete in history to be banned for a doping offence without having tested positive. Montgomery is the partner of the triple Olympic champion Marion Jones, who has also been linked with Balco. A representative for Jones told the New York Times that she had not received any letter from Usada. Jones competed in the long jump at the Golden Spike meeting in Ostrava last night but failed to break seven metres. She is returning from a year off after giving birth to Montgomery's son last year. Bekele breaks world record, page 29 LOAD-DATE: June 9, 2004 LANGUAGE: ENGLISH Copyright 2004 Guardian Newspapers Limited 553 of 998 DOCUMENTS The Washington Post May 20, 2004 Thursday Final Edition USADA Bans White for 2 Years; Evidence Seized in Raid on BALCO Is Used to Prove Track Star's Steroid Use BYLINE: Amy Shipley, Washington Post Staff Writer SECTION: Sports; D01 LENGTH: 1044 words U.S. sprinter Kelli White, the winner of two gold medals at last year's world track and field championships, accepted a two-year ban for taking a host of performance-enhancing drugs including undetectable steroids, the U.S. Anti-Doping Agency announced yesterday. The case is significant not only because it will keep one of the sport's top stars out of the 2004 Olympic Games, but also because USADA for the first time used evidence seized in a federal raid of the Bay Area Laboratory Co-Operative (BALCO) last fall in building its case and exacting punishment. The penalty includes the nullification of all of White's results since late 2000, when she began taking drugs. "In doing this, I have not only cheated myself, but also my family, friends and sport," White said in a statement released by her attorney, Jerrold D. Colton of Voorhees, N.J. "I am sorry for the poor choices I have made." White, 27, said that she expected charges to be brought against others by USADA, but she did not elaborate. USADA agreed to the two-year ban in exchange for White's cooperation in its continuing investigation, which also entitles her to apply for early reinstatement to the world track and field governing body (IAAF) in accordance with the organization's bylaws. Colton said White would apply for early reinstatement. Colton also said he expected USADA to seek four-year bans against others caught up in the BALCO scandal. Yesterday's disclosure illuminated White's success in masking the use of sophisticated and powerful drugs for more than two years despite frequent unannounced drug-testing, raising questions about the pervasiveness of performance-enhancing drug use in track and field and other sports. White received the minimum ban for a host of violations that had not previously been publicly known, which included taking multiple designer steroids and the blood-boosting drug erythropoietin (EPO), along with the stimulant modafinil. Last year, White tested positive for modafinil, which is considered a relatively minor drug compared with steroids and EPO. She never failed a drug test for any other performance-enhancing drug. BALCO is at the center of a federal steroid investigation that has thus far resulted in the indictments of four men, including BALCO founder Victor Conte Jr. and White's coach, Remi Korchemny, on steroid distribution charges. Colton said USADA confronted White last Tuesday with incriminating information from the BALCO files, which had been turned over to USADA by the Senate Commerce Committee about 10 days ago. The files consist of thousands of pages of documents obtained in the raid of the lab, including drug schedules with White's name on them, according to a source. Before the Tuesday meeting, Colton said, White was aware only of the positive tests for modafinil and had been talking with USADA only about that matter. "When USADA received the documents [from the Senate], the conversation changed," Colton said. "USADA said they thought we might be interested in reviewing those materials and having discussions with them." White's two-year suspension, first reported by the San Jose Mercury News, began Monday. All of her results since Dec. 15, 2000, the date she began using performance-enhancing drugs, have been nullified -- including the double gold medals she won at last year's U.S. championships and world championships in the 100 and 200 meters. The disqualifications mean that U.S. sprinter Torri Edwards becomes the world champion in the 100 meters and the U.S. champion in the 100 and 200. Edwards finished second to White in all three races, and she won the bronze in the 200 final at the world championships. In New York on Monday, Edwards, who toiled in White's shadow all season, said she would be bitter if it turned out that White used performance-enhancing drugs. "I am disappointed, because she took something away from me," Edwards said. "The honor of winning that race, crossing the finish line first, throwing my hands up in the air and having my family seeing me on the podium. . . . Even if they send me a gold medal in the mail, it's not going to be the same. It's a moment I'll never get back." White's agent, Robert Wagner, said he had been unaware White had taken anything other than modafinil. "The modafinil is one thing," Wagner said by cell phone from Germany. Steroids "is another thing, and EPO on top of that -- this is crazy." With Marion Jones taking time off to have a child, White emerged last year as the biggest female star in the sport and was considered a threat to Jones's dominance this season. Like White, Jones also has connections to BALCO and two Bay Area newspapers reported she received steroids from Conte. But Jones's lawyer, Joe Burton, said in a statement yesterday that Jones had not been contacted by USADA and did not expect to be contacted. At a news conference in New York on Sunday, Jones said she had never taken performance-enhancing drugs and would sue if USADA tried to ban her from the Olympics without solid evidence. It is unclear to what extent White plans to cooperate with USADA. She said she wanted to help in "cleaning up the sport" but declined to discuss other athletes in the statement. Colton said he and White believed she would have been subject to a four-year ban -- and no hope of reinstatement -- if she did not cooperate because of the compelling nature of the evidence in USADA's possession. Colton also said White was motivated by a desire to tell the truth. At last year's world championships, she denied in front of dozens of reporters taking any performance-enhancing drugs and claimed she took modafinil to combat the sleep disorder narcolepsy. "I have had a very difficult time since winning the world championships last August," White said in the statement. "I have had to continue to train while knowing I had acted improperly. With my suspension, I now have some time to evaluate my life, the choices I have made and the direction in which I would like it to go." Said USADA CEO Terry Madden in a statement: "Ms. White has made mistakes, but I admire her courage in acknowledging these mistakes and accepting responsibility for them. It is not easy to admit you have done wrong and then stand up to do something about it." LOAD-DATE: May 20, 2004 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2004 The Washington Post 554 of 998 DOCUMENTS The San Francisco Chronicle APRIL 30, 2004, FRIDAY, FINAL EDITION DRUGS AND SPORTS; Agency issues first bans; USADA suspends Price, McEwen 2 years for steroids SOURCE: Chronicle Staff Writer BYLINE: John Crumpacker SECTION: SPORTS; Pg. D1 LENGTH: 756 words Hammer throwers Melissa Price and John McEwen were the first U.S. athletes to be suspended for positive tests of the designer steroid THG when the U.S. Anti-Doping Agency announced two-year bans from competition for the pair Thursday. Price, 24, and McEwen, 30, both tested positive for THG last June at the U.S. national track and field championships at Stanford and are not eligible to compete until April 2006. McEwen also tested positive for the stimulant modafinil. "This decision confirms the tremendous work of all those who believe in drug-free sport," said Terry Madden, executive director of USADA. "Today is a great day for those athletes who want to compete on a level playing field." Howard Jacobs, the attorney for Price and McEwen, said, "I talked to both of them briefly today. They're both disappointed but they realized this was a distinct possibility." Two other American athletes who tested positive for THG last year await rulings from USADA after their appeals are heard by arbitrators from the North American Court of Arbitration for Sport. They are shot-putter Kevin Toth and middle distance runner Regina Jacobs of Oakland, no relation to Howard Jacobs. At 40, Jacobs' career likely would be over if she's suspended for two years. A year ago she became the oldest woman to establish a world record when she ran the indoor 1,500 meters in 3:59.98. Toth, 36, previously announced his retirement from the sport; he unleashed a world-leading mark of 74 feet, 4 1/2 inches two months before his positive THG test in 2003. U.S. anti-doping officials allege the THG came from BALCO, the Burlingame laboratory of Victor Conte, who, along with three other men, was indicted on federal charges of money laundering and distributing steroids and other banned substances to elite athletes. Sprinter Dwain Chambers of Great Britain, a client of Conte's, tested positive for THG last summer and has been suspended for two years by his federation. Chambers' competitive results from last August were thrown out Thursday by track's world governing body, the IAAF. In rejecting the appeals of Price and McEwen, the arbitration panel concluded that, "The use of such a powerful anabolic steroid could be for no other purpose than to enhance an athlete's performance in violation of the spirit and absolute proscription of the IAAF doping rules." Attorney Jacobs said he did not know if either athlete plans to return to competition once the suspensions are up in 2006. "Certainly they're young enough to do it," he said. "I know a lot of athletes' initial response is they're not going to compete, but they are competitive athletes. I've had athletes return from two-year suspensions and do phenomenally well." The suspensions of Price and McEwen come less than a week after The Chronicle reported that investigators were told that a number of elite track athletes, including sprinters Marion Jones and Tim Montgomery, received steroids from Conte's Bay Area Laboratory Co-Operative. In addition to the adjudication for Jacobs and Toth, still to be resolved are the appeals of sprinters Kelli White of Union City and Calvin Harrison of Salinas, both of whom tested positive last year for modafinil. It is believed that Jacobs, Toth and White will have their appeals heard sometime in May. All told, 10 American track and field athletes tested positive for banned drugs in the watershed summer of 2003, according to USADA. Seven came up positive for modafinil and four for THG, with McEwen testing positive for both substances. Modafinil use does not carry a ban from competition, which is why four athletes recently accepted relatively mild sanctions for what is considered a stimulant of the central nervous system. Stanford graduate Chryste Gaines, a sprinter, and hurdlers Sandra Glover, Eric Thomas and Chris Phillips received public warnings and were disqualified from the competitions where their positive tests occurred in 2003 (the World Championships for Phillips, U.S. nationals for Gaines, Glover and Thomas). White and Harrison chose to file appeals with the North American arbitration court because their consequences are greater. White won the 100- and 200-meter dashes at last summer's World Championships in Paris and would have earned $120,000 in prize money had she not tested positive for modafinil. Harrison tested positive for a stimulant in 1993. A second positive test for a stimulant, in this case modafinil, could result in a two-year ban from competition. LOAD-DATE: April 30, 2004 LANGUAGE: ENGLISH Copyright 2004 The Chronicle Publishing Co. 555 of 998 DOCUMENTS Hamilton Spectator (Ontario, Canada) April 21, 2004 Wednesday Final Edition Sports Notebook SOURCE: Spectator wire services SECTION: SPORTS; Pg. SP10 LENGTH: 1085 words Hasek, Jagr and '98 Czech team subject of opera tribute PRAGUE The Olympic champion Czech Republic hockey team is getting a curtain call. Dominik Hasek, Jaromir Jagr and the rest of the 1998 gold-medal winning hockey team are the subjects of a new opera that re-enacts their victory at the Nagano Olympics. "Nagano," billed as "an opera in three periods and one overtime," is the first Czech opera about a sports event. Characters include Hasek, Jagr, Robert Reichel and Martin Rucinsky as well as Vaclav Havel, the former anti-communist dissident turned Czech president. The opera, based on a script written by Jaroslav Dusek, follows the final stages of the Czech team's Olympic run and the celebrations afterward, during which a chorus of fans yell Hasek is God and Hasek for president. The Czechs defeated the United States and Canada before beating arch-rival Russia to win their first Olympic title. U.S. track and field athletes receive 'public warnings' COLORADO SPRINGS, COLO. Four U.S. track and field athletes received public warnings for using the stimulant modafinil, but they can compete at the Athens Olympics and other events this year. Sprinter Chryste Gaines and hurdlers Sandra Glover and Eric Thomas tested positive for modafinil at the U.S. championships in June. Hurdler Chris Phillips tested positive at the world championships in August. Thomas was stripped of his national championship in the 400-metre hurdles. Last year modafinil was considered a minor stimulant that warranted only a disqualification. This year modafinil is classified as a serious stimulant by the World Anti-Doping Agency and carries a two-year ban. Sprint champion Kelli White is contesting her positive tests for modafinil at the U.S. and world championships. Spaniard Corretja sends defending champion home MONTE CARLO Two-time defending champion Juan Carlos Ferrero was upset by fellow Spaniard Alex Corretja in the first round of the Monte Carlo Masters yesterday. Ferrero, the reigning French Open champion, lost 6-2, 6-3 in a match that lasted just a little more than an hour. Corretja broke Ferrero in his first service game and took leads of 3-0 in the first set and 5-2 in the second. In other first-round matches, former U.S. Open champions Lleyton Hewitt of Australia and Marat Safin of Russia both rallied from a set down to win. Hewitt beat Frenchman Julien Benneteau 3-6, 6-3, 6-4, while Safin got past Olivier Rochus of France 4-6, 6-3, 6-3. Organization and purse of Opens will improve for tennis fans The U.S. Open Series will include 10 North American tennis tournaments -- six men's and four women's -- leading up to the U.S. Open. Players finishing in the top three in the new series will receive bonus money at the U.S. Open in 2004 and 2005. The top male and female player in the series will have 50 per cent added to their Open winnings in 2004, while their Open take will be doubled in 2005. Stacey Allaster, tournament director for this year's Tennis Masters Series in Toronto, said the objective is to "try to create a more consistent platform for fans to follow our sport." She said the Canadian events will benefit from greater television coverage in the U.S., making them more attractive to sponsors. This year's series begins with the men's event in Los Angeles and the women's tournament at Stanford, Calif., both the week of July 12-18. Pipe-swinging attack leads to lifetime ban for boxer MEXICO CITY A 17-year-old amateur Mexican boxer has been banned from the sport for life after he was accused of attacking a fellow athlete with a metal pipe at the national Olympic training centre, according to the national amateur boxing federation. Jorge Alfonso Montoya, 17, allegedly attacked Jose Andres Romero, 20, early Monday in a dormitory. Romero's cheek bone was broken. Both had been preparing for youth tournaments. Amateur boxing officials said Montoya was apparently angry over a scuffle the two had a week earlier. Clarett tries another legal hip swivel to get into NFL draft COLUMBUS, OHIO Maurice Clarett filed an emergency appeal with the U.S. Supreme Court yesterday to try to force his way into this weekend's NFL draft. Clarett's lawyer, Alan Milstein, asked for a stay of a decision by the 2nd U.S. Circuit Court of Appeals preventing the former Ohio State tailback from entering the draft. Monday's decision put on hold a lower-court ruling that said the NFL can't force players to wait three years after high school before turning pro. Report says Old Trafford a target for terrorist bombing MANCHESTER, ENGLAND Manchester United dismissed speculation yesterday that the club's 67,000-seat Old Trafford stadium was a target for al-Qaeda terrorists. British media reported that seven people arrested in anti-terrorist raids in the Manchester area Monday were planning suicide bomb attacks at the soccer team's high-profile Premier League game against Liverpool on Saturday. Quoting unidentified police sources, the Sun tabloid said the suspected terrorists had bought tickets for the game and planned to sit at various points around the sold-out stadium before detonating bombs. Police declined to comment on the reports. "We're not getting involved in speculation," a Greater Manchester Police spokeswoman said on condition of anonymity. United spokesman Phil Townsend said the club had received no specific warnings from police. He said no special security arrangements were made for last night's game against Charlton or Saturday's match against Liverpool. Keane back in Irish lineup for friendly with Poland DUBLIN Almost two years after walking out on the team at the World Cup, Roy Keane was back on the Ireland squad Tuesday for a friendly against Poland. The Manchester United star missed the 2002 World Cup in Korea and Japan after he had a blazing argument with coach Mick McCarthy over the team's preparations and training facilities. He flew home while the team played on without him and reached the second round. With McCarthy in charge, Keane refused to return to the Ireland fold. But he announced last week that he was willing to play for the team under McCarthy's successor, Brian Kerr. Kerr named the vastly experienced but volatile midfielder in his squad to go to Poznan for a friendly April 28. That likely will upset Manchester United manager Sir Alex Ferguson, who believed his injury-prone star would only play in World Cup qualifying games. LOAD-DATE: April 21, 2004 LANGUAGE: ENGLISH GRAPHIC: Photo: Ian Hodgson, Reuters; A police officer on horseback stands guard outside Manchester United's Old Trafford stadium after reports 10 terrorist suspects had tickets to yesterday's game. TYPE: Brief Copyright 2004 Metroland Media Group Ltd 556 of 998 DOCUMENTS National Post (Canada) April 21, 2004 Wednesday National Edition Track and Field: Modafinil warning issued SOURCE: National Post news services SECTION: Sports; Pg. S7 LENGTH: 65 words Four U.S. track and field athletes received public warnings for using the stimulant modafinil, but they can compete at the Athens Olympics and other events this year. Sprinter Chryste Gaines and hurdlers Sandra Glover and Eric Thomas tested positive for modafinil at the U.S. championships in June. Another hurdler, Chris Phillips, tested positive at the world championships in August. LOAD-DATE: April 21, 2004 LANGUAGE: ENGLISH TYPE: Sports; Brief Copyright 2004 National Post, All Rights Reserved 557 of 998 DOCUMENTS The New York Post April 21, 2004 Wednesday THE SPORTS BLOTTER SECTION: Sports+Late City Final; Pg. 83 LENGTH: 180 words DROPPED: Prosecutors dropped assault charges against former heavyweight boxing champion Joe Frazier yesterday after the alleged victim refused to testify. Frazier was arrested after a domestic dispute in February and charged with assaulting the mother of his 12-year-old son. The case was scheduled to go to trial in Philadelphia yesterday, but prosecutors said there was no way to move forward without testimony from the woman. The alleged victim maintained all along that she would not cooperate. STRIPPED: The U.S. Anti-Doping Agency stripped Eric Thomas of his national 400-meter hurdles title and reprimanded sprinter Chryste Gaines and hurdlers Sandra Glover and Christopher Phillips for using the banned stimulant modafinil, which was found in their systems following major competitions last year. They remain eligible for the Summer Olympics in Athens. Starting this year, athletes who test positive for modafinil will automatically be banned from competition for two years. ACQUITTED: Former Olympic boxer Tim Austin was acquitted of charges he raped a 16-year-old girl. LOAD-DATE: April 21, 2004 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2004 N.Y.P. Holdings, Inc. All Rights Reserved 558 of 998 DOCUMENTS San Jose Mercury News (California) April 21, 2004 Wednesday MORNING FINAL EDITION DRUG REPRIMANDS HANDED OUT; GAINES, THREE HURDLERS ACCEPT PENALTIES FOR POSITIVE TESTS BYLINE: PETE CAREY, Mercury News SECTION: SPORTS; Pg. 4D LENGTH: 459 words Four U.S. track athletes who tested positive for the mild stimulant modafinil last year have accepted public warnings that leave them eligible to compete at the Athens Olympics and any other event. Sprinter Chryste Gaines and hurdlers Sandra Glover, Eric Thomas and Christopher Phillips tested positive in 2003 for the drug, which is prescribed for sleep disorders. The sanction was announced by the U.S. Anti-Doping Agency. The athletes will lose their results for the competitions at which they tested positive. Gaines, Glover and Thomas failed their drug tests at the U.S. outdoor track and field championships last summer at Stanford. Thomas loses a first-place finish in the 400-meter hurdles, Glover a third in the 400 hurdles and Gaines a fifth in the 100 dash. Phillips loses a fifth-place finish in the 110 hurdles at the IAAF world championships. Sprinter Kelli White is still in the anti-doping agency's adjudication process and probably will contest the finding before a panel of arbitrators. The Union City athlete has continued to compete. "I don't know how her case will be handled," said White's agent, Robert Wagner. "I am sure they will make a right and fair decision. Let's leave it up to them." White -- who says she took modafinil as treatment for narcolepsy -- could lose gold medals in the 100 and 200 meters and $120,000 in prize money. She and Gaines are coached by Remi Korchemny, one of four men indicted on charges of distributing prescription drugs and illegal steroids to athletes through Burlingame-based Balco Laboratories. Calvin Harrison tested positive for modafinil at the U.S. track championships. Because he tested positive once before for a stimulant found in cold medicines, he faces a possible two-year ban from competition. His lawyers are in federal court trying to expand the pool of arbitrators that could hear his case. By accepting sanctions, the four athletes have put the issue behind them. Had they contested the sanction, there was a small risk of a two-year sanction depending on how USADA argued the case in arbitration, said Cameron Myler, the lawyer for Gaines, Glover and Thomas. The athletes decided they couldn't take that risk, Myler said. Modafinil was not named on the IAAF's list of banned substances and is being treated as a substance related to others on its list. Myler said her clients didn't know it was banned. Under the new World Anti-Doping Agency Code, which was adopted by the IAAF on March 1, the penalty for a positive test for modafinil is a two-year ban from competition. The athletes received only a public warning because the violations took place last year, when the old IAAF rules called for only a public warning for a first offense. LOAD-DATE: August 24, 2005 LANGUAGE: ENGLISH Copyright 2004 San Jose Mercury News All Rights Reserved 559 of 998 DOCUMENTS The Washington Post April 21, 2004 Wednesday Final Edition Athletes Are Warned About Modafinil, but Can Compete SECTION: Sports; D02 LENGTH: 232 words Four U.S. track and field athletes received public warnings for using the stimulant modafinil, but they can compete at the Athens Olympics and other events this year. Sprinter Chryste Gaines and hurdlers Sandra Glover and Eric Thomas tested positive for modafinil at the U.S. championships in June. Another hurdler, Chris Phillips, tested positive at the world championships in August. Thomas was stripped of his national championship in the 400-meter hurdles. The U.S. Anti-Doping Agency announced yesterday that all four accepted their sanctions, including a public warning and forfeiting results from the event where they tested positive. In 2003, modafinil was considered a minor stimulant that warranted only a disqualification. Starting this year, modafinil is classified as a serious stimulant on the World Anti-Doping Agency banned list and carries a two-year ban. Sprint champion Kelli White is still contesting her positive tests for modafinil at the U.S. and world championships. White, who could lose world titles in the 100 and 200, said she was prescribed modafinil for a sleeping disorder. White and Gaines are coached by Remi Korchemny, who was charged in February with distributing performance- enhancing drugs in the Bay Area Laboratory Co-Operative case. Phillips said Korchemny gave him a modafinil pill for jet lag at the world championships. -- From News Services LOAD-DATE: April 21, 2004 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2004 The Washington Post 560 of 998 DOCUMENTS XINHUA GENERAL NEWS SERVICE April 21, 2004, Wednesday Athletes warned for using stimulant SECTION: WORLD NEWS; SPORTS LENGTH: 131 words DATELINE: WASHINGTON, April 20 Four U.S. track and field athletes had been warned by the U.S. Anti-Doping Agency Tuesday for using the stimulant modafinil, but still could compete in the Athens Olympic Games this summer. Eric Thomas, U.S. 400-meter hurdles champion, was tested positive for modafinil at the U.S. championships last June, along with sprinter Chryste Gaines and hurdler Sandra Glover. Another hurdler, Chris Phillips, tested positive at the world championships in August. The four were striped of all their results at the competitions at which they tested positive, but remain eligible for the Olympics. Modafinil, the stimulant that Kelli White used at the world championships, is classified as a serious stimulant on the World Anti-Doping Agency banned list and carries a two-year ban. LOAD-DATE: April 22, 2004 LANGUAGE: ENGLISH COPYRIGHT 2004 XINHUA NEWS AGENCY 561 of 998 DOCUMENTS The Associated Press April 20, 2004, Tuesday, BC cycle Four athletes get warning for stimulant use SECTION: Sports News LENGTH: 252 words DATELINE: COLORADO SPRINGS, Colo. Four U.S. track and field athletes received public warnings for using the stimulant modafinil, but they can compete at the Athens Olympics and other events this year. Sprinter Chryste Gaines and hurdlers Sandra Glover and Eric Thomas tested positive for modafinil at the U.S. championships in June. Another hurdler, Chris Phillips, tested positive at the world championships in August. Thomas was stripped of his national championship in the 400-meter hurdles. The U.S. Anti-Doping Agency announced Tuesday that all four accepted their sanctions, including a public warning and forfeiting results from the event where they tested positive. In 2003, modafinil was considered a minor stimulant that warranted only a disqualification. Starting this year, modafinil is classified as a serious stimulant on the World Anti-Doping Agency banned list and carries a two-year ban. Sprint champion Kelli White is still contesting her positive tests for modafinil at the U.S. and world championships. She expects an arbitration hearing next month. White, who could lose world titles in the 100 and 200, said she was prescribed modafinil for a sleeping disorder. White and Gaines are coached by Remi Korchemny, one of four men charged in February with distributing performance-enhancing drugs. Phillips said Korchemny gave him a modafinil pill at the world championships to help him overcome jet lag. Korchemny and his three co-defendants, including Barry Bonds' personal trainer, pleaded innocent. LOAD-DATE: April 21, 2004 LANGUAGE: ENGLISH Copyright 2004 Associated Press All Rights Reserved 562 of 998 DOCUMENTS Associated Press Online April 20, 2004 Tuesday 4 Athletes Get Warning for Stimulant Use SECTION: SPORTS LENGTH: 251 words DATELINE: COLORADO SPRINGS, Colo. Four U.S. track and field athletes received public warnings for using the stimulant modafinil, but they can compete at the Athens Olympics and other events this year. Sprinter Chryste Gaines and hurdlers Sandra Glover and Eric Thomas tested positive for modafinil at the U.S. championships in June. Another hurdler, Chris Phillips, tested positive at the world championships in August. Thomas was stripped of his national championship in the 400-meter hurdles. The U.S. Anti-Doping Agency announced Tuesday that all four accepted their sanctions, including a public warning and forfeiting results from the event where they tested positive. In 2003, modafinil was considered a minor stimulant that warranted only a disqualification. Starting this year, modafinil is classified as a serious stimulant on the World Anti-Doping Agency banned list and carries a two-year ban. Sprint champion Kelli White is still contesting her positive tests for modafinil at the U.S. and world championships. She expects an arbitration hearing next month. White, who could lose world titles in the 100 and 200, said she was prescribed modafinil for a sleeping disorder. White and Gaines are coached by Remi Korchemny, one of four men charged in February with distributing performance-enhancing drugs. Phillips said Korchemny gave him a modafinil pill at the world championships to help him overcome jet lag. Korchemny and his three co-defendants, including Barry Bonds' personal trainer, pleaded innocent. LOAD-DATE: April 21, 2004 LANGUAGE: ENGLISH Copyright 2004 Associated Press All Rights Reserved 563 of 998 DOCUMENTS Associated Press Worldstream April 20, 2004 Tuesday Four athletes get warning for stimulant use SECTION: SPORTS LENGTH: 254 words DATELINE: COLORADO SPRINGS, Colorado Four U.S. track and field athletes received public warnings for using the stimulant modafinil, but they can compete at the Athens Olympics and other events this year. Sprinter Chryste Gaines and hurdlers Sandra Glover and Eric Thomas tested positive for modafinil at the U.S. championships in June. Another hurdler, Chris Phillips, tested positive at the world championships in August. Thomas was stripped of his national championship in the 400-meter hurdles. The U.S. Anti-Doping Agency announced on Tuesday that all four accepted their sanctions, including a public warning and forfeiting results from the event where they tested positive. In 2003, modafinil was considered a minor stimulant that warranted only a disqualification. Starting this year, modafinil is classified as a serious stimulant on the World Anti-Doping Agency banned list and carries a two-year ban. Sprint champion Kelli White is still contesting her positive tests for modafinil at the U.S. and world championships. She expects an arbitration hearing next month. White, who could lose world titles in the 100 and 200, said she was prescribed modafinil for a sleeping disorder. White and Gaines are coached by Remi Korchemny, one of four men charged in February with distributing performance-enhancing drugs. Phillips said Korchemny gave him a modafinil pill at the world championships to help him overcome jet lag. Korchemny and his three co-defendants, including baseball slugger Barry Bonds' personal trainer, pleaded innocent. LOAD-DATE: April 21, 2004 LANGUAGE: ENGLISH Copyright 2004 Associated Press All Rights Reserved 564 of 998 DOCUMENTS The Associated Press State & Local Wire These materials may not be republished without the express written consent of The Associated Press April 20, 2004, Tuesday, BC cycle Four track athletes get public warning for stimulant use BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Sports News LENGTH: 326 words Four U.S. track and field athletes have received public warnings for using the stimulant modafinil during 2003 competitions, but all remain eligible for this summer's Athens Olympics and other events. Sprinter Chryste Gaines and hurdlers Sandra Glover and Eric Thomas all tested positive for modafinil at the U.S. championships last June. Another hurdler, Chris Phillips, tested positive at the world championships in August. The U.S. Anti-Doping Agency said Tuesday all four had accepted their sanctions, which includes a public warning and the forfeiture of all results from the competition at which they tested positive. As a result, Thomas loses his U.S. championship in the 400-meter hurdles. At the time of their positive tests, modafinil was considered a minor stimulant warranting only a disqualification. Starting this year, modafinil is classified as a serious stimulant on the World Anti-Doping Agency banned list and carries a two-year ban. Sprint champion Kelli White is still contesting her positive tests for modafinil at both the U.S. and world championships, and expects to have an arbitration hearing next month. White, who faces the loss of world championship gold medals in the 100 and 200 meters, said she was prescribed modafinil for a sleeping disorder - a claim ridiculed by international track officials after word emerged of other athletes using the banned stimulant. White and Gaines are coached by Remi Korchemny, one of four men charged in February with distributing performance-enhancing drugs to professional athletes. Phillips said Korchemny gave him a modafinil pill at the world championships to help him overcome jet lag. Korchemny and his three co-defendants - Bay Area Laboratory Co-Operative founder Victor Conte, BALCO vice president James Valente and Greg Anderson, the personal trainer for baseball slugger Barry Bonds - have pleaded innocent to all charges in the drug distribution case. LOAD-DATE: April 21, 2004 LANGUAGE: ENGLISH Copyright 2004 Associated Press All Rights Reserved 565 of 998 DOCUMENTS Espicom Business Intelligence April 14, 2004 Cephalon receives broad label for Provigil in UK LENGTH: 161 words Cephalon has received marketing approval in the UK to expand the label of Provigil (modafinil) tablets [C-IV] to include the treatment of excessive sleepiness in patients with chronic pathological conditions, including narcolepsy, obstructive sleep apnoea/hypopnoea syndrome and moderate-to-severe chronic shift work sleep disorder. Cephalon is planning to launch the new indication later in April and the company anticipates additional approvals for expanded indications for modafinil in Europe during 2004. Modafinil is the first in a new class of wake-promoting agents believed to work through the sleep-wake centres to activate the cortex of the brain. The medication currently is approved in more than 20 countries under several brandnames. Provigil was originally approved in the UK in 1998 for the treatment of narcolepsy, and in 2002, for the treatment of excessive daytime sleepiness associated with obstructive sleep apnoea/hypopnoea syndrome. LOAD-DATE: April 15, 2004 LANGUAGE: ENGLISH Copyright 2004 ESPICOM Business Intelligence Ltd. 566 of 998 DOCUMENTS PR Newswire April 13, 2004 Tuesday Cephalon Receives Broad Label for PROVIGIL in the United Kingdom SECTION: FINANCIAL NEWS LENGTH: 797 words DATELINE: WEST CHESTER, Pa. April 13 Cephalon, Inc. (Nasdaq: CEPH) announced that it has received marketing approval in the United Kingdom to expand the label of PROVIGIL(R) (modafinil) Tablets $(C-IV$) to include the treatment of excessive sleepiness in patients with chronic pathological conditions, including narcolepsy, obstructive sleep apnea/hypopnea syndrome and moderate to severe chronic shift work sleep disorder. Cephalon UK Limited is planning to launch the new indication later this month. "This UK approval and the recent U.S. approval are significant milestones in our global regulatory strategy," said Dr. Paul Blake, MB, FRCP, Senior Vice President of Clinical Research and Regulatory Affairs at Cephalon. "We anticipate additional approvals for expanded indications for modafinil in Europe this year." John Dawson, Vice President, Pharmaceutical Operations Europe, added: "This broader indication offers us a tremendous opportunity to address the unmet needs of many patients with excessive sleepiness and to accelerate our already strong sales growth in the European market." PROVIGIL PROVIGIL is the first in a new class of wake-promoting agents believed to work through the sleep-wake centers to activate the cortex of the brain. The medication currently is approved in more than 20 countries under several brand names. PROVIGIL initially was approved in the United Kingdom in 1998 for the treatment of narcolepsy, and in 2002, for the treatment of excessive daytime sleepiness associated with obstructive sleep apnea/hypopnea syndrome. Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products to treat sleep and neurological disorders, cancer and pain. Cephalon currently employs more than 1,600 people in the United States and Europe. U.S. sites include the company's headquarters in West Chester, Pennsylvania, and offices and manufacturing facilities in Salt Lake City, Utah. Cephalon's major European offices are located in Guildford, England, Martinsried, Germany, and Maisons-Alfort, France. The company currently markets three proprietary products in the United States: PROVIGIL, GABITRIL(R) (tiagabine hydrochloride) and ACTIQ(R) (oral transmucosal fentanyl citrate) $(C-II$) and more than 20 products internationally. Further information about Cephalon and full prescribing information on its U.S. products is available at www.cephalon.com or by calling 1-800-896-5855. Cephalon UK Limited has headquarters in Guildford and markets drugs to treat a number of central nervous system disorders. In collaboration with Novartis Pharma AG, Cephalon UK markets Tegretol(R) (carbamazepine), Ritalin(R) (methylphenidate), Anafranil(R) (clomipramine) and Lioresal(R) (baclofen). Also included in this collaboration is PROVIGIL for the UK and Ireland. In addition, Cephalon UK markets GABITRIL(R) and ACTIQ(R) in the UK and Ireland. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs, development of potential pharmaceutical products, interpretation of clinical results, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, sales and earnings guidance, and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. SOURCE Cephalon, Inc. CONTACT: Media: Sheryl Williams, +1-610-738-6493, swilliam@cephalon.com, or Investors: Robert (Chip) Merritt, +1-610-738-6376, cmerritt@cephalon.com, both of Cephalon URL: http://www.prnewswire.com LOAD-DATE: April 14, 2004 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS EDITOR PUBLICATION-TYPE: Newswire Copyright 2004 PR Newswire Association, Inc. 567 of 998 DOCUMENTS Agence France Presse -- English -- English April 8, 2004 Thursday White to appear at doping hearing in May: IAAF SECTION: Sports LENGTH: 146 words DATELINE: PARIS, April 8 American sprinter Kelli White could be called to appear "around May 18th" at a hearing for her positive dope test for modafinil in June of last year, the athletics world ruling body IAAF said Thursday. According to an IAAF spokesperson, the United States Anti-Doping Agency (USADA) plans to convene all American athletes who are concerned with positive dope tests for the banned substances modafinil or THG (tetrahydrogestrinone) between "mid-April and May 25". White, along with six other athletes, tested positive for modafinil during the American national championships in June 2003. White's agent, Robert Wagner, said he has no news about the date of her hearing but said White - who won the 100 and 200 metre titles in Paris at last year's world championships - could return to competition at Mexico on May 22. ep/cyb/jd/dj04 Athletics-USA-White-doping LOAD-DATE: April 9, 2004 LANGUAGE: ENGLISH Copyright 2004 Agence France Presse 568 of 998 DOCUMENTS Pharma Marketletter March 18, 2004 Cephalon's Provigil shows promise in schizophrenia LENGTH: 131 words Researchers from the department of Psychiatry at the University of Cambridge, UK, have shown that Cephalon's narcolepsy drug Provigil (modafinil) may produce cognitive enhancement in schizophrenia patients. The study found that, after taking a tablet of modafinil, subjects performed significantly better at memory tests involving short-term memory and, importantly, showed improved mental flexibility, a core deficit normally oberved in patients with schizophrenia, noted the scientists. However, they also point out that these results need to be confirmed in long-term studies with modafinil. The agent is currently approved in more than 20 countries, including the USA, for the treatment of excessive daytime sleepiness associated with narcolepsy (Marketletters passim). LOAD-DATE: March 18, 2004 LANGUAGE: ENGLISH Copyright 2004 Marketletter Publications Ltd. 569 of 998 DOCUMENTS World Markets Analysis February 26, 2004 Ranbaxy Receives Tentative FDA Approval for Modafinil Tablets BYLINE: Sacha Baggili SECTION: IN BRIEF LENGTH: 204 words India's Ranbaxy Laboratories has announced tentative approval from the US Food and Drug Administration (FDA) for a generic version of US company Cephalon's Provigil (modafinil), a treatment for the improvement of wakefulness in people with excessive daytime sleepiness associated with narcolepsy. Asia Pulse reports that the Indian firm's modafinil tablets will be made available to pharmacies throughout the US once final approval has been granted. Sales and marketing of the product will be backed by the generic company's wholly-owned US subsidiary Ranbaxy Pharmaceutical Inc. Significance: This tentative approval comes just a few weeks after Barr Laboratories (US) received a similar FDA nod for generic modafinil in 100mg and 200mg strengths. According to Asia Pulse, the total market value for modafinil tablets is estimated at around US$297m. As with Barr's provisional approval, a transition to full approval is contingent on the outcome of litigation currently pending over the branded drug's patent status; however, the case is not due to be heard before January 2005. Despite this, Ranbaxy's early move on this drug illustrates the company's increasingly raised profile on the US generics market. LOAD-DATE: February 26, 2004 LANGUAGE: ENGLISH Copyright 2004 World Markets Research Limited; All Rights Reserved 570 of 998 DOCUMENTS Asia Pulse February 23, 2004 Monday INDIA'S RANBAXY LABS GETS USFDA APPROVAL FOR MODAFINIL SECTION: Northern Territory Regional LENGTH: 116 words DATELINE: NEW DELHI, Feb 23 Ranbaxy Laboratories (BSE:RANB) on Monday said it has received tentative approval from US Food and Drug Administration to manufacture and market Modafinil tablets, a generic of Cepahalon's Provigil. Sales and marketing of the product will be supported by Ranbaxy Pharmaceutical Inc, a wholly-owned subsidiary of Ranbaxy Laboratories, and will be made available to all pharmacy outlets located throughout the US after final approval is granted by USFDA, a company statement said here. Modafinil is indicated to improve wakefulness in patients with excessive daytime sleepiness associated with narcolepsy. Total market for Modafinil tablets is estimated at US$297 million. (PTI) LOAD-DATE: February 24, 2004 LANGUAGE: ENGLISH Copyright 2004 Asia Pulse Pte Limited 571 of 998 DOCUMENTS Espicom Business Intelligence February 23, 2004 Ranbaxy granted tentative FDA approval for modafinil LENGTH: 88 words On 8th February, Ranbaxy Laboratories received tentative FDA approval to manufacture and market modafinil tablets in 100 and 200mg strengths. Currently marketed by Cephalon as Provigil, modafinil is indicated to improve wakefulness in patients with excessive daytime sleepiness associated with narcolepsy. Ranbaxy's product will be made available to all pharmacy outlets located throughout the US, including chain and independent pharmacies, wholesalers and generic distributors, at the time final FDA approval is granted. LOAD-DATE: February 24, 2004 LANGUAGE: ENGLISH Copyright 2004 ESPICOM Business Intelligence Ltd. 572 of 998 DOCUMENTS The Press Trust of India February 23, 2004 Monday Ranbaxy Labs gets tentative USFDA approval for Modafinil SECTION: Nationwide International News LENGTH: 122 words DATELINE: New Delhi, Feb 23 Ranbaxy Laboratories, one of the major pharmaceutical companies in India, on Monday said it has received tentative approval from US Food and Drug Administration to manufacture and market Modafinil tablets, a generic of Cepahalon's Provigil. Sales and marketing of the product will be supported by Ranbaxy Pharmaceutical Inc, a wholly-owned subsidiary of Ranbaxy Laboratories, and will be made available to all pharmacy outlets located throughout the US after final approval is granted by USFDA, a company release said here. Modafinil is indicated to improve wakefulness in patients with excessive daytime sleepiness associated with narcolepsy. Total market for Modafinil tablets is estimated at 297 million dollar. LOAD-DATE: February 23, 2004 LANGUAGE: ENGLISH Copyright 2004 The Press Trust of India 573 of 998 DOCUMENTS PR Newswire February 20, 2004 Friday Ranbaxy is Granted Tentative Approval for the Manufacturing and Marketing of Modafinil SECTION: FINANCIAL NEWS LENGTH: 396 words DATELINE: JACKSONVILLE, Fla. Feb. 20 Ranbaxy Pharmaceuticals Inc. (RPI), a wholly owned subsidiary of Ranbaxy Laboratories Limited (RLL), announced today that RLL has received tentative approval from the U.S. Food and Drug Administration, Office of Generic Drugs, to manufacture and market Modafinil Tablets in 100 mg and 200 mg strengths. Total market sales for Provigil(R) (Modafinil) tablets were $297 million (IMS - MAT: December 2003). Modafinil is indicated to improve wakefulness in patients with excessive daytime sleepiness associated with narcolepsy. Sales and marketing for this product will be supported by the Ranbaxy Pharmaceuticals Inc. Sales and Marketing Team. Product will be made available to all pharmacy outlets located throughout the U.S. including chain and independent pharmacies, wholesalers, and generic distributors at the time final approval is granted by the U.S. FDA. "When approved, this product will provide a CNS product to RPI's expanding product portfolio, along with our commitment to bring affordable generic alternatives to the U.S. healthcare system," according to Jim Meehan, Vice President of Sales and Marketing for RPI. Ranbaxy Pharmaceuticals Inc. ("RPI") based in Jacksonville, Florida, is the wholly owned subsidiary of Ranbaxy Laboratories Limited ("RLL"), India's largest pharmaceutical company. RPI is engaged in the sale and distribution of generic and branded prescription products in the U.S. healthcare system. Ranbaxy Laboratories Limited, India's largest pharmaceutical company, manufactures and markets branded generic pharmaceuticals and Active Pharmaceutical Ingredients. Ranbaxy's continued focus on R&D has resulted in several approvals in developed markets and significant progress in New Drug Discovery Research.Ranbaxy's foray into Novel Drug Delivery Systems has led to proprietary "platform technologies" resulting in a number of products under development. The Company is selling its products in over 70 countries and has an expanding international portfolio of affiliates, joint ventures and alliances, ground operations in 34 countries and manufacturing operations in 7 countries. * Provigil(R) is a registered trademark of Cephalon SOURCE Ranbaxy Pharmaceuticals Inc. CONTACT: Charles M. Caprariello, Vice President, Business Development, Ranbaxy Pharmaceuticals Inc., +1-609-720-5615; Janine Lang of RF Binder Partners, +1-212-994-7525, for Ranbaxy URL: http://www.prnewswire.com LOAD-DATE: February 21, 2004 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS AND MEDICAL EDITORS PUBLICATION-TYPE: Newswire Copyright 2004 PR Newswire Association, Inc. 574 of 998 DOCUMENTS The Age (Melbourne, Australia) February 18, 2004 Wednesday National Edition Email link to White drugs scandal; DRUGS IN SPORT BYLINE: Jacquelin Magnay SECTION: SPORT; Pg. 19 LENGTH: 435 words Sydney Balco laboratory president Victor Conte knew several months before world sprint champion Kelli White tested positive to the stimulant modafinil that the drug was on the banned list for sports. White is facing the loss of her two Paris world championship medals and being stripped of the 100 metres and 200 metres titles because of a positive test to modafinil, a drug she claims was used to treat the medical condition narcolepsy. But on June 8, 2003, two months before White tested positive, an unnamed international track and field coach sent Conte an email warning him of the new anti-doping list, which specified modafinil, and suggesting that unknown numbers of athletes had been using an old, but specially made, designer steroid. White's coach is Remi Korchemny, who along with Conte and two others has been charged in the United States with distribution of illegal drugs. The unnamed coach wrote in the email: "As you can see at the stimulant list, modafinil is on it!!! Of course after (US drug tester Don) Catlin's norbolethone detection this AAS is also included. I guess the party is over." US federal agent Jeff Novitzky said the steroid norbolethone was first synthesised in 1966 and is not marketed by a pharmaceutical company, leading him to conclude that the steroid had been manufactured by an unauthorised source. Only one competitor has been caught using norbolethone. Balco is at the centre of the steroid tetrahydragestrinone (THG) and it is believed it manufactured several other undetectable steroids. The email raises questions as to why White, who is linked to Conte through Korchemny, was not told about the developments. Another of Korchemny's sprinters, Chryste Gaines, has also tested positive to modafinil. At the time of the world championships, modafinil was classified a minor stimulant, but it now attracts a two-year ban. The email also indicates that Conte had an inside informant, tipping him off about drug-testing developments. In August 2002, he wrote to an international track and field coach: "I need for you to advise xxx to discontinue using the clear (a code word for steroids). I recently found out that . . . xxx, xxx and xxx sent a sample of the clear to the IOC testers on an anonymous basis. "I will be getting more information shortly regarding exactly when they will be testing for it . . . We might also want to somehow get this information to the coach for the Greek athletes xxx and xxx so that nobody tests positive." Meanwhile, officials have confirmed that US shot putter Kevin Toth tested positive for THG and modafinil at the 2003 US championships in June. LOAD-DATE: June 18, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2004 The Age Company Limited All Rights Reserved 575 of 998 DOCUMENTS The Age (Melbourne, Australia) February 18, 2004 Wednesday Late Edition Email link to White drugs scandal; DRUGS IN SPORT BYLINE: Jacquelin Magnay SECTION: SPORT; Pg. 19 LENGTH: 438 words Sydney Balco laboratory president Victor Conte knew several months before world sprint champion Kelli White tested positive to the stimulant modafinil that the drug was on the banned list for sports. White is facing the loss of her two Paris world championship medals and being stripped of the 100 metres and 200 metres titles because of a positive test to modafinil, a drug she claims was used to treat the medical condition narcolepsy. But on June 8, 2003, two months before White tested positive, an unnamed international track-and-field coach sent Conte an email warning him of the new anti-doping list, which specified modafinil, and suggesting that unknown numbers of athletes had been using an old, but specially made, designer steroid. White's coach is Remi Korchemny, who along with Conte and two others has been charged in the United States with distribution of illegal drugs. The coach wrote in the email: "As you can see at the stimulant list, modafinil is on it!!! Of course after (US drug tester Don) Catlin's norbolethone detection this AAS is also included. I guess the party is over." US federal agent Jeff Novitzky said the steroid norbolethone was first synthesised in 1966 and is not marketed by a pharmaceutical company, leading him to conclude that the steroid had been manufactured by an unauthorised source. Only one competitor has been caught using norbolethone. Balco is at the centre of the steroid tetrahydragestrinone (THG) and it is believed it manufactured several other undetectable steroids. Another of Korchemny's sprinters, Chryste Gaines, has also tested positive to modafinil. At the time of the world championships, modafinil was classified a minor stimulant, but it now attracts a two-year ban. The email also indicates that Conte had an inside informant, tipping him off about drug-testing developments. In August 2002, he wrote to an international track-and-field coach: "I need for you to advise xxx to discontinue using the clear (a code word for steroids). I recently found out that . . . xxx, xxx and xxx sent a sample of the clear to the IOC testers on an anonymous basis. "I will be getting more information shortly regarding exactly when they will be testing for it . . . We might also want to somehow get this information to the coach for the Greek athletes xxx and xxx so that nobody tests positive." · Cricket could lose its Federal Government funding and elite development programs if it failed to comply with a world standard anti-doping code by January, a senate committee was told yesterday. Cricket is currently receiving $900,000 over three years from the Australian Sports Commission. LOAD-DATE: June 18, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2004 The Age Company Limited All Rights Reserved 576 of 998 DOCUMENTS Sydney Morning Herald (Australia) February 18, 2004 Wednesday Late Edition Why White should have known; DRUGS IN SPORT BYLINE: Jacquelin Magnay SECTION: SPORT; Pg. 34 LENGTH: 446 words BALCO laboratory president Victor Conte knew several months before world sprint champion Kelli White tested positive to the stimulant Modafinil that the drug was on the banned list. White is facing the loss of her Paris world championship gold medals for the 100 metres and 200m because of a positive test to Modafinil, which she claims she used to treat narcolepsy . But on June 8, 2003, two months before White tested positive, an unnamed international track and field coach sent Conte an email warning him of the new anti-doping list, which specified Modafinil, and suggesting that unknown numbers of athletes had been using an old but specially made designer steroid. White's coach is Remi Korchemny, who with Conte and two others has been charged in the US with distribution of illegal drugs including steroids, growth hormone and erythropoietin . The unnamed coach wrote in the email: "As you can see at the stimulant list Modafinil is on it!!! Of course after [US drug tester Don] Catlin's Norbolethone detection this AAS is also included. I guess the party is over." Federal agent Jeff Novitzky said the steroid norbolethone was first synthesised in 1966 but not marketed by a pharmaceutical company, leading him to the conclusion that it had been manufactured by a clandestine, unauthorised source. Only one athlete, a female cyclist, has been caught using norbolethone. BALCO is accused of manufacturing another steroid, tetrahydrogestrinone (THG) and it is believed it made several other undetectable designer steroids. The email raises questions as to why White, linked to Conte through Korchemny, was not told about the list. Another of Korchemny's sprinters, Chryste Gaines , also tested positive to Modafinil. At the time of the world championships Modafinil was classified a minor stimulant, but it now attracts a two-year ban. The email correspondence also indicates that Conte had an inside informant, tipping him off about drug testing developments. In August 2002 he wrote to an international coach: "I need for you to advise [name deleted] to discontinue using the clear [a code word for steroids]. I recently found out that [three names deleted] sent a sample of the clear to the IOC testers on an anonymous basis. This is very unfortunate. "We might also want to somehow get this information to the coach for the Greek athletes [two names deleted] so that nobody tests positive." Officials have confirmed that US shot putter Kevin Toth tested positive for THG and Modafinil at the 2003 US championships in late June. Toth says he will now retire, but continues to dispute the results. Europe's fastest man, Dwain Chambers, will have his THG drugs hearing on Friday. LOAD-DATE: July 17, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2004 John Fairfax Publications Pty Ltd All Rights Reserved 577 of 998 DOCUMENTS The Associated Press February 16, 2004, Monday, BC cycle USOC: Shot putter Kevin Toth tested positive for THG, modafinil BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Sports News LENGTH: 494 words American shot put champion Kevin Toth tested positive for the newly discovered steroid THG and the stimulant modafinil at the U.S. championships and faces a two-year suspension, the U.S. Olympic Committee announced Monday. Toth is one of four athletes who flunked THG tests during the meet last June at Stanford. The others were middle-distance runner Regina Jacobs, hammer thrower John McEwen and hammer thrower Melissa Price. Jacobs and Price also won titles at that national meet. The 36-year-old Toth, of Hudson, Ohio, shocked the track and field world with a throw of 74 feet, 4 1/2 inches at the Kansas Relays in April - the best performance in the world in 13 years. His winning throw at the national championships was 69-7 1/2. The USOC said Toth also tested positive for THG during an out-of-competition test on July 27, 2003, a month after winning his first U.S. title. Toth is disputing the THG test results through the U.S. Anti-Doping Agency's arbitration process, as are McEwen and Price. Jacobs has gone outside the USADA process, filing an arbitration claim with the American Arbitration Association. All four face two-year bans if the positive tests are upheld. Final decisions on their cases are expected this spring. European 100-meter champion sprinter Dwain Chambers also tested positive last year for THG and faces a two-year ban. THG was unveiled when a track coach sent a syringe with the substance to the USADA last summer. That coach said the substance came from Victor Conte, founder of the Bay Area Laboratory Co-Operative, a nutritional supplements lab in Burlingame, Calif. Conte was one of four men named in a 42-count indictment last week that charges they participated in a steroid-distribution ring that provided drugs to dozens of top athletes. All four men pleaded innocent on Friday. Conte has said he was not the source of the syringe provided to the USADA. Toth was one of dozens of athletes who appeared before a grand jury probing BALCO last fall. In addition to the four U.S. athletes who tested positive for THG at the national championships, the USOC has announced in recent months that several athletes tested positive for modafinil at that meet. Those athletes include Kelli White, whose positive test for modafinil at the world championships means she likely will be forced to forfeit her 100- and 200-meter gold medals. Another is Calvin Harrison, whose flunked test could affect several U.S. teammates. It is a second drug violation for Harrison, who also tested positive for the stimulant pseudoephedrine at the 1993 U.S. junior indoor championships and served a three-month suspension. As a repeat offender, he would face a two-year ban. That means Harrison should not have been eligible for last summer's world championships, at which he ran the opening leg on the winning U.S. 1,600-meter relay team. And that means the U.S. squad could lose its gold medal from that relay. LOAD-DATE: February 17, 2004 LANGUAGE: ENGLISH Copyright 2004 Associated Press All Rights Reserved 578 of 998 DOCUMENTS The Associated Press February 16, 2004, Monday, BC cycle USOC: Toth tested positive for THG, modafinil BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Sports News LENGTH: 437 words American shot put champion Kevin Toth tested positive for the steroid THG and the stimulant modafinil at the 2003 national championships and could be suspended for two years, the U.S. Olympic Committee announced Monday. Toth is one of four athletes who flunked THG tests during the U.S. championships in June. The others, announced earlier, were Regina Jacobs, John McEwen and Melissa Price. Jacobs and Price also were national champions. All four face two-year bans if the positive tests are upheld. Final decisions on their cases are expected this spring. Later Monday, agent John Nubani announced Toth was retiring, though he still plans to go through with the appeals process. Toth stunned the track and field world with a throw of 74 feet, 4 1/2 inches at the Kansas Relays in April - the best performance in the world in 13 years. His winning throw at the national championships was 69-7 1/2. The USOC said Toth also tested positive for THG during an out-of-competition test in July. Toth, McEwen and Price are disputing the THG test results through the U.S. Anti-Doping Agency's arbitration process. Jacobs instead filed a claim with the American Arbitration Association. "We're contesting the charges, and the case will proceed through the USADA process," said Toth's attorney, Howard Jacobs, no relation to Regina. European 100-meter champion Dwain Chambers also tested positive last year for THG and faces a two-year ban. He will appear before a UK Athletics disciplinary panel Thursday. Toth was one of dozens of athletes who appeared before a grand jury probing a nutritional supplements lab. The lab's founder and Barry Bonds' personal trainer were among four people indicted last week on charges they participated in a steroid-distribution ring that provided drugs to top athletes. All four pleaded innocent Friday. The USOC has announced in recent months that several athletes tested positive for modafinil at the U.S. championships, including Kelli White and Calvin Harrison. White's positive test for modafinil at the world championships means she probably will lose 100- and 200-meter gold medals. Harrison's flunked test could affect several U.S. teammates. He also tested positive for the stimulant pseudoephedrine at the 1993 U.S. junior indoor championships and served a three-month suspension. As a repeat offender, he would face a two-year ban. That means Harrison should not have been eligible for last summer's world championships, at which he ran the opening leg on the U.S. 1,600 relay team. That means the relay team members could lose their gold medals. LOAD-DATE: February 17, 2004 LANGUAGE: ENGLISH GRAPHIC: AP Photos CAPS104-105 Copyright 2004 Associated Press All Rights Reserved 579 of 998 DOCUMENTS The Associated Press State & Local Wire February 16, 2004, Monday, BC cycle USOC: Toth tested positive for THG, modafinil BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Sports News LENGTH: 437 words American shot put champion Kevin Toth tested positive for the steroid THG and the stimulant modafinil at the 2003 national championships and could be suspended for two years, the U.S. Olympic Committee announced Monday. Toth is one of four athletes who flunked THG tests during the U.S. championships in June. The others, announced earlier, were Regina Jacobs, John McEwen and Melissa Price. Jacobs and Price also were national champions. All four face two-year bans if the positive tests are upheld. Final decisions on their cases are expected this spring. Later Monday, agent John Nubani announced Toth was retiring, though he still plans to go through with the appeals process. Toth stunned the track and field world with a throw of 74 feet, 4 1/2 inches at the Kansas Relays in April - the best performance in the world in 13 years. His winning throw at the national championships was 69-7 1/2. The USOC said Toth also tested positive for THG during an out-of-competition test in July. Toth, McEwen and Price are disputing the THG test results through the U.S. Anti-Doping Agency's arbitration process. Jacobs instead filed a claim with the American Arbitration Association. "We're contesting the charges, and the case will proceed through the USADA process," said Toth's attorney, Howard Jacobs, no relation to Regina. European 100-meter champion Dwain Chambers also tested positive last year for THG and faces a two-year ban. He will appear before a UK Athletics disciplinary panel Thursday. Toth was one of dozens of athletes who appeared before a grand jury probing a nutritional supplements lab. The lab's founder and Barry Bonds' personal trainer were among four people indicted last week on charges they participated in a steroid-distribution ring that provided drugs to top athletes. All four pleaded innocent Friday. The USOC has announced in recent months that several athletes tested positive for modafinil at the U.S. championships, including Kelli White and Calvin Harrison. White's positive test for modafinil at the world championships means she probably will lose 100- and 200-meter gold medals. Harrison's flunked test could affect several U.S. teammates. He also tested positive for the stimulant pseudoephedrine at the 1993 U.S. junior indoor championships and served a three-month suspension. As a repeat offender, he would face a two-year ban. That means Harrison should not have been eligible for last summer's world championships, at which he ran the opening leg on the U.S. 1,600 relay team. That means the relay team members could lose their gold medals. LOAD-DATE: February 17, 2004 LANGUAGE: ENGLISH GRAPHIC: AP Photos CAPS104-105 Copyright 2004 Associated Press All Rights Reserved 580 of 998 DOCUMENTS Associated Press Worldstream February 16, 2004 Monday USOC: Toth tested positive for THG, modafinil BYLINE: ROB GLOSTER; AP Sports Writer SECTION: SPORTS LENGTH: 438 words DATELINE: SAN FRANCISCO American shot put champion Kevin Toth tested positive for the steroid THG and the stimulant modafinil at the 2003 national championships and could be suspended for two years, the U.S. Olympic Committee said. Toth is one of four athletes who flunked THG tests during the U.S. championships in June. The others, announced earlier, were Regina Jacobs, John McEwen and Melissa Price. Jacobs and Price also were national champions. All four face two-year bans if the positive tests are upheld. Final decisions on their cases are expected this spring. Later Monday, agent John Nubani announced Toth was retiring, though he still plans to go through with the appeals process. Toth stunned the athletics world with a throw of 22.67 meters (74 feet, 4 1/2 inches) at the Kansas Relays in April - the best performance in the world in 13 years. His winning throw at the national championships was 21.22 meters (69-7 1/2). The USOC said Toth also tested positive for THG during an out-of-competition test in July. Toth, McEwen and Price are disputing the THG test results through the U.S. Anti-Doping Agency's arbitration process. Jacobs instead filed a claim with the American Arbitration Association. "We're contesting the charges, and the case will proceed through the USADA process," said Toth's attorney, Howard Jacobs, no relation to Regina. European 100-meter champion Dwain Chambers also tested positive last year for THG and faces a two-year ban. He will appear before a UK Athletics disciplinary panel Thursday. Toth was one of dozens of athletes who appeared before a grand jury probing a nutritional supplements lab. The lab's founder and Barry Bonds' personal trainer were among four people indicted last week on charges they participated in a steroid-distribution ring that provided drugs to top athletes. All four pleaded innocent Friday. The USOC has announced in recent months that several athletes tested positive for modafinil at the U.S. championships, including Kelli White and Calvin Harrison. White's positive test for modafinil at the world championships means she probably will lose 100- and 200-meter gold medals. Harrison's flunked test could affect several U.S. teammates. He also tested positive for the stimulant pseudoephedrine at the 1993 U.S. junior indoor championships and served a three-month suspension. As a repeat offender, he would face a two-year ban. That means Harrison should not have been eligible for last summer's world championships, at which he ran the opening leg on the United States 4x400 relay team. That means the relay team members could lose their gold medals. LOAD-DATE: February 17, 2004 LANGUAGE: ENGLISH Copyright 2004 Associated Press All Rights Reserved 581 of 998 DOCUMENTS The San Francisco Chronicle FEBRUARY 13, 2004, FRIDAY, FINAL EDITION Drugs involved in BALCO case BYLINE: Keay Davidson SECTION: NEWS; Pg. A23 LENGTH: 938 words Here is a look at some of the performance-enhancing drugs named in Thursday's indictment of BALCO founder Victor Conte and others for alleged involvement in a widespread drug distribution ring: -- Erythropoietin, or EPO Commercially sold as Epogen, erythropoietin (EPO) improves the ability of red blood cells to transport oxygen. It is a favorite of some athletes in endurance sports. Erythropoietin is a hormone naturally produced by the kidneys and liver. When oxygen levels are abnormally low, the kidneys respond by manufacturing erythropoietin, which stimulates the bone marrow into producing more red blood cells. Erythropoietin also spurs the production of hemoglobin, the oxygen-carrying molecule within red blood cells. Doctors can spot kidney disease, bone marrow disease and illegal use of Epogen by testing a patient's blood levels of erythropoietin. The drug's legitimate uses include treating anemia, a deficiency in the body's ability to transport oxygen. -- Human growth hormone, or HGH Human growth hormone's legitimate medical uses include treatment of children diagnosed as pituitary dwarfs, although even these legal uses can have dangerous side effects, according to the U.S. Food and Drug Administration. In theory, HGH builds muscle mass. However, some scientists have questioned whether human growth hormone builds muscle mass enough to benefit athletes. Some studies suggest that the muscles of athletes who take the hormone don't grow bigger than those in a control group given a placebo. Researchers have long struggled to develop techniques for identifying human growth hormone in athletes' blood or urine. A new diagnostic technique will most likely be available in time for this year's Athens Olympics. -- Modafinil A mild stimulant, modafinil is typically prescribed as a treatment for narcolepsy and other sleep disorders. It is marketed under the name Provigil. Some organizers of athletic competitions seem to view modafinil more benignly than they do other drugs. Several U.S. track and field athletes have recently tested positive for modafinil, such as double World Champion Kelli White. But in November, in an interview with The Chronicle, Dick Pound, chair of the World Anti-Doping Agency, spoke caustically of the drug's users. "It is a stimulant," he stressed. "You look at the excuse given -- narcolepsy? Please. So (the athlete) wouldn't fall asleep in the starting blocks in the 100 meters? Oh, please. "You live by the sword, you die by the sword. How would you feel if your daughter got beat by Kelli White by a hundredth of a second?" -- Testosterone cream In males, the natural production of the hormone testosterone surges at puberty. It tends to decline with age, especially after age 50. The hormone is responsible for development of primary and secondary male physical characteristics, including genitalia, fat distribution, and muscle and bone mass. Testosterone can give athletes an edge by helping them trim body fat and build up muscles. It can be injected, applied as a patch to the skin, or rubbed as a cream onto the arms and torso. Cream applications are considerably less effective than injections. -- Tetrahydrogestrinone, or THG THG is a designer steroid whose effects are probably similar to related classes of anabolic steroids. THG users become bigger and stronger, but it has side effects: Men become more feminine, and women become more masculine. It will make women grow hair on their face and make men more bald. A man's testicles will shrink and his breasts grow, while a woman's breasts will get smaller. For now, routine tests for detecting anabolic steroids are blind to THG. However, Dr. Don Catlin, director of the UCLA Olympic Analytical Laboratory in Los Angeles, and other researchers are developing ways to detect THG in athletes' urine. -------------------------------------- STEROID PRIMER The sports doping scandal playing out before a federal grand jury in San Francisco focuses on elite athletes' use of performance-enhancing drugs, particularly a previously undetectable anabolic steroid called THG. Athletes use such steroids to get bigger, stronger and faster, but health experts say there is a risk to users. HOW STEROIDS WORK Blood carries steroid to muscle Steroid is drawn toward muscle cell's wall and attaches to a receptor Steroid enters cell nucleus, interacts with chromosomes Nucleus sends out information to increase protein production, which strengthens muscle. WAYS OF TAKING STEROIDS Oral steroids Pill or liquid taken daily Steroid is absorbed by stomach Steroids travel to liver and enter the blood stream Injectable steroids last longer than oral and are injected into thigh or buttocks Dose enters blood for several days Blood carries steroid into body Other methods: Inhaler and skin patch SIDE EFFECTS -- Men: Shrinking of testicles Reduced sperm count Impotence Hair loss Enlarged breasts -- Women: Facial hair appears Voice deepens Breasts shrink Menstruation disrupted Male-pattern baldness -- Both sexes: Acne High blood pressure Increased cholesterol level Jaundice Aggressiveness Weight gain Blood clots Increased body hair HEALTH RISKS Heart disease Caused by the increase in cholesterol Liver damage Principal site for oral input of steroids. Makes liver vulnerable to damage and tumors Tendon ruptures Muscle tissue strengthens faster than tendons, elevating the risk for damage Sources: Associated Press; Bantam Medical Dictionary; Chronicle research LOAD-DATE: February 13, 2004 LANGUAGE: ENGLISH GRAPHIC: GRAPHIC, John Blanchard / The Chronicle Copyright 2004 The Chronicle Publishing Co. 582 of 998 DOCUMENTS FD (Fair Disclosure) Wire February 12, 2004 Thursday Event Brief of Q4 2003 Cephalon, Inc. Earnings Conference Call - Final LENGTH: 6224 words CORPORATE PARTICIPANTS . Robert Grupp, Cephalon, Inc., VP, Corporation Communications . Frank Baldino, Cephalon, Inc., Chairman & CEO . Kevin Buchi, Cephalon, Inc., SVP & CFO . Robert Roche, Cephalon, Inc., SVP, Pharmaceutical Operations . Paul Blake, Cephalon, Inc., SVP, Clinical Research and Regulatory Affairs . John Osborn, Cephalon, Inc., SVP, General Counsel and Secretary OVERVIEW CEPH reported 2003 sales of $685.3m and an adjusted EPS of $1.54. The co. secured an expanded US label for Provigil to treat apnea, shift work sleep disorder and narcolepsy. EPS guidance for 2004 is expected to be $2.00 per share, up 30% over 2003. Q&A Focus: new indication for Provigil, GM, international sales, CEP-1347, tax rate, Actiq, Gabatril and product sales. FINANCIAL DATA A. Key Data From Call 1. Total Revenues 2003: $714.8m, up 41% over 2002. 2. Product sales 2003: $685.3m, up 47% over 2002. 3. SG&A 2003: $252m. 4. R&D 2003: $170.3m, or 24% of revenues. 5. Cash balance as of Dec. 31: $1.2b. PRESENTATION SUMMARY S1. Business Overview (F.B.) 1. 4Q03 and 2003 Results: 1. 2003 was the most profitable year ever. 2. Total prescriptions and sales for Provigil, Actiq and Gabitril reached record levels. 3. 2003 Sales: $685.3m. 4. EPS: adjusted diluted net income per share was $1.54, surpassing co. guidance. 5. Provigil sales: grew at compound annual rate of over 40% over the last three years. 1. Gabitril was 60%, Actiq was 110% in same period. 2. European operations: 1. Expanded Provigil with a sleep apnea indication in UK, Germany and Ireland. 2. These expanded labels drove ex-US Provigil sales, up by 60% over 2002. 3. Clinical Research in 2003: 1. Secured an expanded US label for Provigil to treat apnea, shift work sleep disorder and narcolepsy. 1. Provigil is the first drug for these disorders. 2. ADHD: 1. Results from a 248-patient study of ADH in children were reported at American Psychiatric Association's annual meeting in May. 1. Reported statistically significant results with one daily dose of Provigil. 2. Investigated Gabitril for the treatment of anxiety, insomnia, and neuropathic pain. 1. Goal was to demonstrate effectiveness in one of these disorders; it may be effective in treating all three. 3. Doubled total number of publications for marketed products. 4. Received FDA approval for a new Actiq formulation. 1. World-wide production is being carried out at Salt Lake City facility. 4. 2004 Outlook: 1. Expect strong year. 2. Expanded sales force will call on approx. double the number of doctors in 2003. 3. Will move beyond specialty physician universe. 4. Clinical Research: 1. Will conduct numerous registrations studies in several areas. 5. Pipeline: 1. Neurogenerative disease: Cep-1347 inhibits cell-signaling pathways. 1. Will complete enrollment for an 800-patient clinical trial evaluating Cep 1347 for treatment of Parkinson's disease. 1. This has the potential to be the first drug to mitigate the death of neurons in Parkinson's disease. 2. Publications concerning this drug are authored by co. and by other academic labs, such as NIH. 6. Other programs: 1. Label expansions for existing products: 1. Modafinil study for ADHD application is underway. 2. Should be completed by mid-year, with data available by year end. 2. R-modafinil: 1. Enrolling patients in three clinical trials for R-modafinil for the treatment narcolepsy and obstructive sleep apnea. 1. This formulation has longer duration of action than Provigil . 2. With approval, it will be a once-a-day wakeness medicine. 3. Will also study potential drug interaction. 2. Studying the role of R-modafinil in improving cognitive function. 1. Several publications have addressed the positive affects of R-modafinil on cognition. 2. Collaborating with a UK co. to study R-modafinil 's affects on attention, information processing, working and long-term memory. 3. Goal is to support submission of an NDA at end of 2004. 3. Gabitril Development: 1. Could potentially treat anxiety, insomnia and neuropathic pain. 2. Two large 200+ patient studies in generalized anxiety disorder and post-traumatic stress disorder should be completed in 2Q04. 3. Pending positive results, will begin a larger clinical program in 2H04 to evaluate Gabitril for one of these anxiety states. 4. It may be effective for insomnia and neuropathic pain. 1. Co. will evaluate these applications as well, starting with insomnia patients in 2004. 2. An earlier study showed it decreases wake after sleep onset and increased slow-wave sleep. 4. Co. expects the combined impact of its R&D program will transform the co. 1. ADHD, R-modafinil, sugarfree Actiq, Gabitril anxiety and Gabitril insomnia represent a significant increase over the previous level of R&D. 1. 2003: 1200 patients were enrolled in clinical programs. 2. 2004: approx. 3000 patients are expected to be enrolled. 3. In 2004 the topline data will become available to the investment community. 5. Believe that beginning 2006, the co. will achieve even more significant growth. 7. Cima Labs Transaction: 1. Complying with Federal Trade Commission's request for more information. 2. Co. believes it will get FTC clearance to close the transaction. 3. The HSR process makes it difficult to predict the timing of the closing. S2. Financial Overview (K.B.) 1. 4Q03 and 2003: 1. Total Revenues 2003: $714.8m, up 41% over 2002. 2. Product sales 2003: $685.3m, up 47% over 2002. 3. Sales by product: 1. Provigil: $290.5m. 2. Actiq: $237.5m. 3. Gabitril: $63.7m. 4. Other European product sales: $93.6m. 4. Prescription metrics: 1. Provigil 2003: 1.4m prescriptions filled in US, up 31% over 2002. 2. Provigil 4Q03: 398,000, more than 30,000 a week. 3. Actiq 2003: 326,000 in 2003, up 76% over 2002. 4. Actiq 4Q03: 97,000, more than 7400 per week. 5. Gabitril 2003: 680,000, up 53% over 2002. 6. Gabitril 4Q03: 196,000, more than 15,000 per week. 7. Physicians are exploring new uses for Gabitril, including anxiety, insomnia and neuropathic pain. 8. US channel inventory levels: flat. 5. SG&A 2003: $252m, reflecting investment and enhanced marketing. 6. R&D 2003: $170.3m or 24% of revenues. 1. Drivers: Research on Cep-1347 for Parkinson's disease, Modafinil for ADHD, R- modafinil for excessive sleepiness, and Gabitril for anxiety, insomnia and neuropathic pain. 7. Fully diluted GAAP EPS in 2003: $1.44. 8. Retired the balance of 5.25% convertible debt and a portion of 3.875% debt. 1. Total cash outlays: $192m. 2. These early retirements resulted in pre-tax charges of $9.8m. 3. Excluding these 3Q03 charges, the adjusted fully diluted 2003 EPS is $1.54 vs. guidance of $1.52. 9. Cash balance as of Dec. 31: $1.2b. 2. 2004 Guidance: 1. Reiterating 2004 guidance. 2. Total product sales: expected $900-950m in sales. 1. Provigil sales: expected $375-425m. 2. Actiq sales: expected $325-375m. 3. Gabitril sales: expected $80-90m. 4. Other product sales: expected $80-90m. 3. SG&A: expected $320-330m. 4. R&D: expected $250-270m. 5. EPS: expected $2.00 per share, up 30% over the $1.54 in 2003. 3. 1Q04 guidance: 1. Product sales: expected $210-215m. 2. Diluted EPS: $0.28 per share, up 33% over $0.21 YoverY. 3. This does not include impact of the pending CIMA transaction. 4. Expect increased sales throughout 2004 and flat expenses, resulting in greater EPS as the year progresses. 5. Will no longer provide sales guidance for individual products. 1. With comparable margins for the three products, the product sales mix in any qtr. is not relevant to profitability. QUESTION AND ANSWER SUMMARY Q1. (Cory Davis, JP Morgan) My question is on the new indication for Provigil and if we're trying to gauge when you might see an uptake in the growth rate for Provigil as a function of the new roll-out. The question would be, how many times does the sales rep have to hit a new doctor before they write one prescription and how long is that period of time, a month, couple of months or weeks? A. (Kevin Buchi) Well Cory, I'm going to pass that question over to Bob Roche who built and reconstructed the sales force to address that very issue. So Bob, won't you answer Cory's question. A. (Robert Roche) We are really excited about the prospects that the new label has for Provigil and we expect to see a positive evolution for the product throughout 2004 and very importantly, beyond that as well. We've already seen good growth in the first month of the year, we're about 30 percent over where we were last year and that's right in line with our expectations for 2004. And now we've got this big new sales organization in the field actually operating today. We're about three or four months ahead of where we were last year at this point in time and I'm very confident that we're going to be seeing the positive affects of that as well as of our marketing operations right throughout the rest of 2004 and beyond. Q2. (Cory Davis, JP Morgan) And I'll ask Kevin a question on the gross margin, I know you gave pretty detailed guidance for '04 but always want a little bit more. Directionally is it going to be - should it be up or down over this quarter? A. (Kevin Buchi) I think the expectation here, Cory, is it's going to be relatively flat. Q3. (Cory Davis, JP Moran) And last question, can you just break out the international sales on all three products for the quarter? A. (Kevin Buchi) Sure, I'd be happy to. For the fourth quarter, Provigil sales U.S. 78 million dollars. Provigil sales international 7.4. Actiq sales U.S. 71.9 million dollars, international 1.3. Gabitril U.S. 18 million dollars, international 1.2. And of course the other is all international, 24.7. That should give you total U.S. 167.9, total international 34.6. Q4. (Cory Davis, JP Morgan) If there's any thoughts that you guys have on the Lundbeck/Gaboxadol deal with Merck and any parallels that that product may have to Gabitril in insomnia? A. (Kevin Buchi) Well, first of all, I think it's a good deal between Lundbeck and Mercks, I'm happy for them. Gaboxadol is a different kind of compound, just to remind you that that's a directing acting agonist on the GABA-A receptor. It's nice to know that other people believe that the GABA [indiscernible] is a great target for pharmaceutical development so I think that deal underscores that concept. There's other GABA agonists that have been developed over the years, as you might remember way back when when the GABA-B agonist, Baclophin [phonetic] was developed. We like the more of a modulatory approach to the GABA ergics system. If you look back in the history at the benzodiazaphines and older drugs that have been very successful in that category and today looking at the Ambiens and Neurontins and that category, of course, Gabatril are real modulators of the GABA ergic system and not direct acting agonists and we're very comfortable with that approach, given the history and given what we've seen in our clinical data. Q5. (Matt Geller, CIBC WorldMarkets) Frank, could you talk a little bit about what you've seen thus far with Armadaphin patients. A little bit about - go into a little more detail about what kind of safety and efficacy benefits maybe you've seen already. And also can you talk a little bit about your strategy for switching people over from Provigil to Armadaphenol [phonetic] and why you think it will be successful A. (Frank Baldino) I'm going to hand this over to Paul Blake to answer the specific data questions now. But just to remind you that I did show data at the JP Morgan conference that I think was picked up by the analysts, Cory did a great job of reporting on the data that he saw, this Pharmacokinetic data, there's Efficacy's data and I'll pass it over to Paul Blake to give you some more details. A. (Paul Blake) The big difference that we're looking to see in the Phase III program that's underway now, that we've seen in the earlier work, is in duration of effect. As you may recall, Provigil is arrasinate and the bulk of the dose interval is due to the RIsomer, giving the RIsomer alone with SES we will see a longer duration of wakefulness. We've seen that in general and we've seen it specifically in sleep deprived people. A very similar side effect profile to Provigil, as you would expect, and the other different that we're going to look to explore is the potential for different drug interaction patent, hopefully with a lesser effect and a lower number of specific instances in the warning section of the new label that we're going to write. A. (Frank Baldino) The other question you asked, Matt, was about the switching program for patients from Provigil to Armadaphenol when that does get approved, and I'll ask Bob to talk about what his thoughts in that program at this very early stage. A. (Robert Roche) And it is indeed an early stage but the plan, Matt, as I know you're aware, is that we will be able to bring the RIsomer, Armadaphenol to the marketplace probably by the end of next year or early 2006 at the latest. And with the benefits that Paul has just described, I'm quite confident and our market research indicates that there will be a real tendency on the physician's part and on payer's parts as well to move towards the new product. Now this all has to be borne out in the clinical development program and through the regulatory process but we're very confident that we can get patients onto Armadaphenol from Provigil when we choose to do so. A. (Frank Baldino) Just to remind you Matt, that the - there is no competition out there for Provigil. One thing to remember is all the switches we have data on that have been successful are in the context of a lot of competitve products. The most recent example that's been very, very well done by Forest with their [indiscernible] selexa. Remember, they've done a really great job with that. They also did it in the context of seven competitive agents and a generic Prozac that's on the market today. We have a little bit of an advantage in our switching program, is that we are the only manufacture of Provigil out there, we have the only wakefulness promotor in the world and we certainly don't intend to compete against ourself in this process. So I hope that helps your thinking along those lines. Q6. (David Buck, Buckingham Research) The first question is for Paul Blake on CEP1347 since Frank made a point of highlighting it. Can you give us a refresher on the protocol in this study that you're expecting to complete enrollment this year and again what the milestones are in that study and what's the duration of that study will be? And just a couple of housekeeping questions for Kevin, could you give us the interest to add back for the convert and can you give us a sense of sales force size right now and are we - do we have all the additions that we were planning? A. (Frank Baldino) Let's start with Paul answering your first question because you can always come back with some others. A. (Paul Blake) David, 1347 is being developed as a neuro protective agent in the treatment of patients who have early symptoms of Parkinson's Disease. And the primary end point is a delay in the need for the physician to institute dopamenergic therapy for that patient. We're looking to get 800 patients through to two years of therapy and we're using 64 sights in the U.S. and Canada with the help of the Parkinson's study group who are the leading experts in this area in consortia type studies in Parkinson's Disease. We've agreed to this protocol with the FDA and we've agreed it with their Canadian equivalents and this a North American, not just a U.S. study. Each patient has a chance to be randomized to one of three active doses that they take twice a day or placebo. Between screening and randomization, they're all flown to an imaging center in New Haven, Connecticut associated with Yale University and they're all imaged in the same unit on the same machinery by the same team for spect - measurement of their dopamenergic transporter activity. As I said at randomization and at two years or if possible at any point if that occurs earlier. We're coming close to recruiting the 800th patient in the first half of this year. We have a planned interim analysis when 200 patients get to one year of treatment which will be around the turn of the first and second quarter next year. And if all remains well then, as we expect and the science still in this blinded study are good, we should finish that up two years after the 800th patient goes in which will be in the first half of 2006. Does that answer the - this 1347 question for you? Q7. (David Buck, Buckingham Research) Yes, it does. And just a couple of housekeeping for Kevin, just the interest add back and on sales force are we at the 500 level and can you give us some sense of timing of sales and promotional spending for the year? A. (Frank Baldino) Yeah, let's get the interest add back from Kevin and then I'll pass you over to Bob for the sales force answer. A. (Kevin Buchi) The interest add back for the fourth quarter was 2.3 million dollars, which can easily add back to the full year was 8.4 million. Q8. (David Buck, Buckingham Research) And would that be constant into the first quarter? A. (Frank Baldino) It should be, yeah. And Bob? A. (Bob Roche) Yeah, and - we are at full capacity in the sales force. Right now we have all the territories filled, managerial slots filled and are going into our national sales meeting in the next couple of weeks, after which the actual launch of the new expanded label will take place. Q9. (David Buck, Buckingham Research) And timing of expenses throughout the year? A. (Bob Roche) I would expect that expenses are going to be relatively flat throughout the year, David. Q10. (Mike King, Bank of America Security) I was wondering, Bob Roche, could you talk about what kind of prelaunch activities you're doing now with sales force training, CME programs and the like of that to get aggressive about marketing the new label? A. (Robert Roche) We have really jacked up the Provigil promotional expense number for 2004 to reflect the terrific opportunity the new label provides us. And we actually began the process of market sensitization and working with primary care physicians the middle of last year and then began a process which had primary care docs meeting with psychiatrists, learning about the product and so forth through medical education kind of peer-to-peer influencing strategy sessions that have now been going on for over six months. The premarketing of the product from a marketing perspective has also been going on for quite some time. But as we've just received approval for the new label and just now finalizing all the promotional materials which of course have to be prereviewed and so forth and advertising campaign and that sort of thing, that will all be coming together and being pushed out along with the sales force launch of the product in early March. Q11. (Mike King, Bank of America Security) Early March, okay. And so the first meeting where we should see some new material - marketing materials and such would be what, APA? A. (Robert Roche) Yes, whichever is first, the APA or the APSS or ANA and I'm not quite sure which is which, I can check that for you. A. (Frank Baldino) Mike, I think it's usually the ANA meeting end of April and then rolling into the psychiatric meetings in May and then the fleet meetings later in June. Q12. (Mike King, Bank of America Security) And then just a quick finance question, the shelf that you announced recently, what's the purpose of that? A. (Kevin Buchi) We have no current intentions to issue any additional securities, Mike, as you know a shelf just gives you the flexibility in the event that you need to raise monies, that it gives you the ability to go and do it quickly. And that would principly from our perspective be around, as you can imagine transactions where we're still aggressively looking for additional products to add to our portfolio, additional companies that have products, those types of things. Q13. (Mike King, Bank of America) But more for product acquisition as opposed to taking out higher coupon debt? A. (Kevin Buchi) Well, as you know, the two and a half percent debt is callable at par at the end of this year, that is a potential use of it for sure. A. (Frank Baldino) But for the record, Mike, to repeat what Kevin initially said, we have no plans to issue any securities at the moment. Q14. (Eric Schmidt, SG Cowan) Kevin, looking for a little bit of help on the tax rate for '04, directionally? A. (Kevin Buchi) I think we're expecting at this point in time the tax rate for '04 to be about 36 percent, which would be consistent with the '03 tax rate. Q15. (Eric Schmidt, SG Cowan) And then Bob, I know you've taken great pains not to cause any sales force disruption as you've gone through this expansion period. Any feedback from the sales force in that regard? Scripts have been a little bit sluggish on Actiq over the last couple of months. A. (Bob Roche) Yeah, well we aboslutely have done everything in our power to minimize any sales force disruption but when you implement a change of this magnitude, you're always going to get something. I think the important message is that whatever we would have anticipated is already behind us or we expect that it's behind us. We really began this sales force build out in September of last year and trained and put into the field about 150 new sales reps at the end of December. We've just fielded another 50 new people in the last couple of weeks so if there is any disruption to the process, I'm really confident that it's behind us and we're moving forward very, very positively. Q16. (Mark Goodman, Morgan Stanley) Bob, could you talk a little bit about Actiq and just the different patient populations that we're treating now? Like how many patients were treated with Actiq this year? How many new patients are you seeing and the new patient populations that it's moving into? And then Frank, can you just maybe talk about the Cima deal just a little bit. I mean is there anything incremental that you can help us with to better understand what's happening there? A. (Kevin Baldino) I'm going to answer the question first so Bob can get his - he can dig out some of the numbers that you were asking for. I think you're - is your question why we didn't do, Mark, or.... Q17. (Mark Goodman, Morgan Stanley) No, no, no, of course not. No, I know exactly why you did it. I'm just saying like from the FTC's perspective, like what - have you learned anything new that you can help us with just to better understand what they're thinking right now? A. (Kevin Baldino) Yeah, I wish I could tell you that the - we are hot and heavy in discussions with the FTC on these major issues. But I think fundamentally FTC takes time. The timing of our filing wasn't necessarily prudent because it was during the Christmas holidays and they couldn't even get any meetings together there. So there's been some of that kind of delay and they really haven't brought any substantive issues to the floor. We hope to get an audience with them in the near term that would help this out. Now on the phone with us, he couldn't be with us today, is John Osborn. Maybe John could provide some color for you Mark, he's much more closely aligned with this process than I am. But John, are you there? A. (John Osborn) I mean I don't think there's anything that's particularly unusual about this, it's - we made our filing, it was as Frank said, in the midst of a holiday period. We have had some preliminary discussions with the FTC and we've been providing documents as you do when you go through this process. I think it - it's not parciularly surprising to see that they've wanted to take a bit of time in looking at this, they're always interested in pharmaceutical industry acquisition. And there's a relationship between OS and Actiq that's been commented upon. But having said that, I think it's going reasonably well. We've had frequent contact with them and we're pretty confident that, although as Frank said earlier, you can never predict the precise timing of it, we're pretty confident that we're moving in the right direction that we are answering the concerns that they have and that we're going to get clearance and be able to move forward with the deal. A. (Kevin Baldino) Mark, your question about Actiq, do you want to repeat that just so the audience will remember what it was? Q18. (Mark Goodman, Morgan Stanley) Yeah, I mean basically Bob, I'm just trying to understand how many patients have been taking Actiq now? How many new patients came in during this past year? What types of patients are they? Just so I can understand, are we broadening it to new populations and just try to understand what's going on in Actiq. A. (Bob Roche) Yeah, I mean Actiq is really a remarkable asset and it surprises even us I think by how well it continues to do quarter after quarter, year after year. We grew prescriptions, Mark, in 2003 by over 75 percent to well over 325,000. Now this would probably translate to somewhere around 30 to 40,000, maybe a little more patients than that treated during the course of the year. So you can figure that that's probably 75 percent greater than what we treated in the year 2002. So we're really making terrific progress there. On average, at the beginning of 2003 around 2,500 physicians per month were writing prescriptions for Actiq. By the end of the year that was over 4,000. So really significant growth in the prescriber base and what they're using it for is a mix of cancer pain and non-malignant pain. We're getting additional useage because of Fentonal is really a well understood pain fighting utility and in a wide variety of areas and we're now beginning to explore these a little more systematically from a clinical perspective as well. Does that - did that answer the question more or less? Q19. (Mark Goodman, Morgan Stanley) Yes. Q20. (Louis Webb, WR Hambreck) Yes, a question for Frank. Assuming a late 2005 approval of Armadaphenal, you would agree that the original formulation would be phased out over a period of a few months. And the second part would be is there any reason that you'd continue to market the original? A. (Frank Baldino) Well, the second part of your question is about marketing the original, don't forget we did sell the Racmid [phonetic] in Europe which is a different environment, as you well know, so we'll continue to do that. Also the Racmid will be used in the new proprietary formulation that we're selling to patients with - the doctors for the indication with ADHD provided that approval is there at that time. So yes, we'll be selling it in that context. But regarding the switch to the R, we're going to switch this as fast as practicably possible. And again, we're not going to compete against ourselves and it's a pretty straight-forward approach we're going to use to do this, nothing out of the ordinary. You slow down the manufacture of one and put the other one in place and go forward with it and make sure all of the elements of the supply chain know what's going on and they're properly informed of the process and educated as to the process as we continue. I don't know if that answers your question? Q21. (Louis Webb, WR Hambreck) Yes, that's clear, thanks. Q22. (Jim Birchnell, Lehman Brothers) Just a maintenance question to start with, I just want to see if we should expect the same EPS distribution relative quarter by quarter that we had in '03 and '04? A. (Paul Blake) Yes, I would. That's certainly the path that we set with the first quarter guidance, yes. Q23. (Jim Birchnell, Lehman Brothers) And then I think you mentioned that we should expect expenses to be flat throughout the year but I know in the past we've had front end weighted expenses for SG&A around conferences, front end weighted. Is there a change there or shall we expect the same distribution there as well? A. (Paul Blake) No, I think overall I'd expect expenses to be fairly flat throughout the year, you may see some front end weighting of the SG&A and some back end weighting of the R&D. But I think generally it's going to be - overall I would expect it to be relatively flat. Q24. (Jim Birchnell, Lehman Brothers) And then just looking at product sales going into the first quarter, it seems like sequentially, I mean it's relatively flat, four to five percent sequential growth. Is that just territory realingment or is there a seasonal aspect that we tend to see in the first quarter? A. (Frank Baldino) Bob, do you want to answer that question? A. (Bob Roche) You're talking about growth from December into January, Jim? Q25. (Jim Birchnell, Lehman Brothers) Just from fourth quarter '03 to first quarter '04, it seems like we're growing sequentially four percent or so and that seems a little flatish versus what we've seen previously. A. (Bob Roche) Well don't forget, I mean the only data that exists thus far for first quarter '04 are a couple of - well, four weekly prescription numbers from IMS. And as I mentioned earlier, it means those numbers are well up on where we were last year and right within our expectations. Q4 '03 grew for Provigil, about six percent on Q3 '03, for Gabatril it grew about 11 percent on Q3 '03, and for Actiq it grew - the prescription numbers grew by about seven percent. So I mean I - if we can generate that kind of sequential quarter on quarter growth and we certainly believe that we will do that and probably more, then we're certainly making the numbers that we've put forward for you guys today. A. (Frank Baldino) But clearly there's certainly a - you have to consider some impact of the sales force realignment and all of that and I think the good news, after our experience last year, that in our calculus for the guidance we provided and our calculus for the expectations that we have for the quarter, we figured - we factored that in. Q26. (Jim Birchnell, Lehman Brothers) And then just one final question with perhaps some evolving focus on Gabatril. Do you have a sense of what the distribution of scripts are in terms of whether you're getting business right now from GAD and how much versus use in epilepsy and other indications? And could we expect data like that as the year progresss? A. (Frank Baldino) We are happy to share that kind of data with you, Jim. The most recent data set that I have in front of me today is from September of 2003 for Gabatril where we're expecting the fourth quarter data to come in any day. But where we are at the end of 200 - and September '03, and it probably isn't going to change a whole lot was neuropathic pain was about 17 percent of the total Gabitril prescribing activity, up from about 11 percent in the same period of 2002, so September of 2002. Anxiety, depression and other psychiatric disorders made up well over 60 percent of the total Gabatril prescribing by September '03 and that was up from about 50 percent in 2002. Epilepsy was around 15 percent of total Gabitril prescribing, up from - pardon me, down from around 30 percent in the previous year. A. (Bob Roche) I mean clearly we're following the positions of Utility [phonetic] here. I mean they are the ones who pointed us in the direction of anxiety and that's why the trials are going on. So it's not surpising distribution is as it is. Q27. (Steve Slaughter, UBS) Frank, I'd just be interested in what you thought of the label now that the final approved text is out for the expanded label on Provigil. Anything in there that was a surprise and I guess one specific question, the comment on the label that prescribers should be aware that patients may not acknowledge sleepiness or drowsiness unless directly questioned about drowsiness or sleepiness, which kind of begs the question not short term but maybe intermediate term or perhaps with the R, is there a DTC opportunity with an expanded label for this product or the follow on? A. (Frank Baldino) Well Steve, first of all regarding the label and I'll have Paul comment specifically on your question and I'll answer the other part of your question so it gives him time to think about the answer for you. But we're pretty excited about this label. I mean being first in this category in the United States is a big deal, it allows us to continue to develop the franchise as we expected to and we've got just about everything we need to in the label to have a big impact on this product in this patient population. Regarding - Paul, do you have a specific answer to his question on that one - in the label about sleepiness? A. (Paul Blake) Yes, I think that's a very pragmatic and realistic statement that you could apply to many drugs and many diseases, that most people sadly are not cured completely in every instance by every drug. And while people may feel better, it's a reasonable public health caution just to make sure they check and say am I completely normalized or do I still need to be careful. So I think it's something that's reasonable and logical that we're very comfortable with. In terms of are we surprised by anything in the label, I think given the negotiation period and review period and comments that we've had, in the end we weren't surprised at all. If we look back through the whole process, we might say we're a little surprised that the broadest label wasn't granted given that was something we were encouraged to seek by the agency rather than the specific one but we're very happy with the way its come out and I think it's supported by the data wonderfully. Q28. (Steve Slaughter, UBS) And Paul, thank you for that. I'm just wondering maybe a question for Bob, is there an opportunity for direct to consumer advertising? If patients aren't necessarily highlighting for a physician then sleepiness or drowsiness if they experience for example in shift work situations, is there a targeted way to heighten the awareness in the patient's eyes with some type of DTC down the road? A. (Bob Roche) I think somewhere down the road, Steve, there may absolutely be. We do not - we don't have that in our immediate plans, what we're doing for the first six to nine months of this at least is going out there and making sure that physicians understand the importance of sleepiness in their patient populations because not a great deal of time and effort is being put on sleep issues per se, in med school or thereafter and so there's a lot of education that has to happen with the docs before we would consider going to the patients. But there's enough opportunity here I think for us to certainly consider doing both at some point in time. A. (Frank Baldino) Yeah, I think Steve, the message we get from the major players, a lesson learned from the majors out there, is that you don't want to go too early with DTC and you, being a guy who was in the field selling your products know this more than anybody, you don't want to DTC ad out there before the doctors really understand the drug, what they're prescribing, what its limitations are because they don't like to be surprised, like any other profession doesn't like to be surprised. And especially when you have first in class drug, the first label ever for these indications. So we're - it will be something we pursue going forward once we increase the base of understanding amongst the largest group of prescribers, the general practitioner going forward. [CCBN reserves the right to make changes to documents, content, or other information on this web site without obligation to notify any person of such changes. In the conference calls upon which Event Briefs are based, companies may make projections or other forward-looking statements regarding a variety of items. Such forward-looking statements are based upon current expectations and involve risks and uncertainties. Actual results may differ materially from those stated in any forward-looking statement based on a number of important factors and risks, which are more specifically identified in the companies' most recent SEC filings. Although the companies may indicate and believe that the assumptions underlying the forward-looking statements are reasonable, any of the assumptions could prove inaccurate or incorrect and, therefore, there can be no assurance that the results contemplated in the forward-looking statements will be realized. THE INFORMATION CONTAINED IN EVENT BRIEFS REFLECTS CCBN'S SUBJECTIVE CONDENSED PARAPHRASE OF THE APPLICABLE COMPANY'S CONFERENCE CALL AND THERE MAY BE MATERIAL ERRORS, OMISSIONS, OR INACCURACIES IN THE REPORTING OF THE SUBSTANCE OF THE CONFERENCE CALLS. IN NO WAY DOES CCBN ASSUME ANY RESPONSIBILITY FOR ANY INVESTMENT OR OTHER DECISIONS MADE BASED UPON THE INFORMATION PROVIDED ON THIS WEB SITE OR IN ANY EVENT BRIEF. USERS ARE ADVISED TO REVIEW THE APPLICABLE COMPANY'S CONFERENCE CALL ITSELF AND THE APPLICABLE COMPANY'S SEC FILINGS BEFORE MAKING ANY INVESTMENT OR OTHER DECISIONS. Copyright 2004, CCBN, Inc. All Rights Reserved.] LOAD-DATE: February 27, 2004 LANGUAGE: ENGLISH Transcript 021204so.765 Copyright 2004 FDCHeMedia, Inc. All Rights Reserved Copyright 2004 CCBN, Inc. All Rights Reserved 583 of 998 DOCUMENTS The San Francisco Chronicle FEBRUARY 8, 2004, SUNDAY, FINAL EDITION LETTERS TO THE GREEN SECTION: SPORTS; Pg. B2; LETTERS TO THE GREEN LENGTH: 538 words Korchemny responds to USATF story Editor -- On Saturday, Jan. 31, The Chronicle published an article entitled "USATF removes local coach" that contained some misinformation. The article stated that Remi Korchemny "gave the stimulant modafinil to some of the athletes he coaches, including Kelli White and Chryste Gaines." That is incorrect information and I would like to set the record straight. First of all, modafinil has not been scientifically determined to be a stimulant. In fact, many credible scientists at major universities, including Stanford, have published that modafinil is a non-stimulant. Furthermore, there is absolutely zero scientific evidence suggesting that modafinil enhances athletic performance. Modafinil is approved for narcolepsy and recently for shift workers, plus it is commonly recommended by physicians for off-label purposes including jet-lag and excess daytime sleepiness. Secondly, I have not ever, at any time, given modafinil to either Kelli White or Chryste Gaines. I have nothing to do with either of their pending modafinil cases involving USADA. Modafinil was not even listed as a "prohibited substance" by USADA, USATF, IAAF or WADA at the times the samples were collected from the athletes involved in the modafinil controversy. In the meantime, no one should forget that guilt or innocence can only be determined after due process, and there has been no due process, as of yet. REMI KORCHEMNY Via e-mail -------------------------------- No hiring freeze Editor -- I applaud the Washington Redskins after reading that coach Joe Gibbs and owner Daniel Snyder have made 21 coaching hires. The Redskins and the NFL have made a significant impact reducing the nation's unemployed ranks. This is certain fuel for George Bush's re-election. I hope these jobs will not be outsourced to India or China. DONALD G. PETER San Mateo -------------------------------- The next one Editor -- I suspect the next halftime entertainment package will include the Del Courtney Orchestra with vocal performances from Steve Lawrence and Eydie Gorme. RON FELL San Francisco -------------------------------- Azinger fan Editor -- Paul Azinger was right to spurn the AT&T out of loyalty to his amateur partner, ("Azinger decries Pebble," Feb. 3) but he was wrong when he said, "My being there isn't going to sell one ticket." I won't be buying one, nor will a sizable cadre I joined to follow him in the Arizona desert last weekend. The man has serious fans. Ollie Nutt must indeed be daft to alienate not only a popular player but a past champion who has done more than his share for the tournament. Will I buy a ticket? No way. Watch the broadcast? Probably not. And AT&T? I'm taking my cell-phone number and hitting the highway. It won't make one bit of difference to their big bottom line, but I'll sleep better at night, as I'm sure Azinger does. NANCY SCHLESINGER Carlsbad (San Diego County) Address correspondence to Letters to the Green, Chronicle Sports Department, 901 Mission Street, S.F., CA 94103. E-mail: letterstogreen@sfchronicle.com. Fax: 415-543-3754. Letters may be edited for brevity/clarity; include hometown and daytime phone number. LOAD-DATE: February 8, 2004 LANGUAGE: ENGLISH Copyright 2004 The Chronicle Publishing Co. 584 of 998 DOCUMENTS San Jose Mercury News (California) February 1, 2004 Sunday MORNING FINAL EDITION SPRINT COACH KORCHEMNY DISMISSED FROM WORLD TEAM; COACH DENIES PROVIDING ATHLETES BANNED DRUGS, HAS NOT BEEN SANCTIONED BYLINE: ELLIOTT ALMOND, Mercury News SECTION: SPORTS; Pg. 2C LENGTH: 577 words USA Track & Field officials dismissed Remi Korchemny of Castro Valley from coaching the world indoor championship team because he admitted giving a drug to an athlete. The action signals a new era in drug testing as coaches, trainers and physicians could face more scrutiny if athletes they help test positive for banned substances. Stephanie Hightower, chair of the women's track and field committee, said Saturday that the group didn't want negative publicity regarding drugs to overshadow the athletes at the March championships in Budapest, Hungary. She said they were acting in the best interests of the sport, although Korchemny, 72, has not been sanctioned or called before a hearing panel. "A lot of people were uncomfortable sending someone on a national team with this kind of cloud over their head," Hightower said, referencing the ongoing federal grand jury investigation in San Francisco of Balco and its owner, Victor Conte Jr. Korchemny said he has sent athletes to Conte's Burlingame laboratory to test for nutritional purposes. The renowned sprint coach denied Saturday giving athletes banned drugs. Korchemny gave hurdler Chris Phillips the sleep disorder medication modafinil during last summer's world championships because it wasn't on the banned list of the international track and field federation. Korchemny, who did not coach Phillips, has maintained that the medication is not performance enhancing and was used to combat jet lag. Officials announced that six athletes last summer tested positive for modafinil, which was banned under the "related substances" clause in the rules. The athletes would receive only a disqualification from the meet in which they took the drug test if they lose pending arbitration hearings. But the World Anti-Doping Agency last week classified modafinil as a stimulant that warrants a two-year ban in the future. Hightower acknowledged that Korchemny is caught in a bigger battle involving USA Track & Field. The group is particularly sensitive to questions about drugs because international officials have harshly criticized it over the handling of the Jerome Young case. Young, a 400-meter sprinter, tested positive for the steroid nandrolone in1999 but was cleared by USA Track & Field and went on to win a gold medal at the Sydney Games. The International Association of Athletics Federations is going to the Court of Arbitration for Sport this year to try the case again. Furthermore, the revised IAAF drug code, which goes into effect this spring, says anyone helping athletes cheat could be sanctioned by losing credentials to meets. Hightower said the IAAF was refusing to give Korchemny a credential for the indoor championships. Korchemny could be the test case for the new rule. He is being singled out because two of his athletes -- sprint stars Kelli White of Union City and Chryste Gaines of Lithonia, Ga. -- were among those testing positive for modafinil last summer. Now the question is whether the new rules will affect other coaches whose athletes have tested positive in the past. For example, John Smith of Los Angeles has had three sprinters penalized for taking stimulants -- Ato Boldon, Mickey Grimes and Inger Miller. Smith is the head coach of the men's 2005 outdoor world championship team. Marion Jones' former coach, Trevor Graham, has had at least six athletes with positive drug tests, including Young and Olympic sprinter Dennis Mitchell. LOAD-DATE: August 22, 2005 LANGUAGE: ENGLISH Copyright 2004 San Jose Mercury News All Rights Reserved 585 of 998 DOCUMENTS The San Francisco Chronicle JANUARY 31, 2004, SATURDAY, FINAL EDITION Correction Appended USATF removes local coach; Korchemny not going to Indoors SOURCE: Chronicle Staff Writer BYLINE: John Crumpacker SECTION: SPORTS; Pg. C2 LENGTH: 434 words Track coach Remi Korchemny of Castro Valley was removed Friday from his position as a coach of the U.S. team for the World Indoor Championships in March because he gave the stimulant modafinil to some of the athletes he coaches, including sprinters Kelli White and Chryste Gaines. "I don't care," the 71-year-old Korchemny said. "I did not elect myself (to the U.S. team) and I did not reject myself. ... It's a very symbolic job. It's not important in the life of a person. You volunteer your time. They don't need you? It's their problem." Korchemny was informed of the decision in a letter from Bill Roe, president of USA Track & Field. USATF will send a team to the World Indoor Championships March 5-7 in Budapest, Hungary. In removing Korchemny from the coaching staff, Roe said the IAAF, track and field's world governing body, would not issue him a credential and in any event, his presence in Budapest would send a wrong message. Having Korchemny on the U.S. staff would be a "futile endeavor," Roe said. "The IAAF said publicly and confirmed to us privately they would not credential Remi as a U.S. coach. And we wouldn't want someone on the staff who would be more of a focus than the athletes." Although not on the list of banned substances by name, modafinil is considered a mild stimulant by the U.S. Anti-Doping Agency. The World Anti-Doping Agency on Thursday announced that from now on a positive test for modafinil would result in a two-year ban from competition. White, Gaines and four others tested positive for modafinil last summer, when sanctions included a public warning and disqualification from the event where the test occurred. It is yet another spin-off from the ongoing federal investigation into Victor Conte, whose Burlingame laboratory was raided by the Internal Revenue Service and the Food and Drug Administration in September. U.S. anti-doping officials claim the designer steroid THG came from the Conte-owned Bay Area Laboratory Co-Operative. Korchemny was introduced to Conte by NFL linebacker Bill Romanowski, then of the Denver Broncos. "It did not hurt when they decided not to take me," Korchemny said. "I can travel where I want and I can buy my own ticket." Korchemny said he is the victim of a "double standard" in U.S. track and field in that other prominent coaches were not singled out when some of their athletes tested positive for banned substances. "Other coaches have athletes who have had violations," he said. "There's issues more important than Remi Korchemny."E-mail John Crumpacker at jcrumpacker@sfchronicle.com. LOAD-DATE: February 4, 2004 LANGUAGE: ENGLISH CORRECTION-DATE: February 3, 2004 CORRECTION: A story in Saturday's Sporting Green misstated the reason USA Track and Field gave for removing Remi Korchemny as a coach of the U.S. track team in the World Indoor Championships. The organization said it had removed Korchemny because of his association with athletes who tested positive for the drug modafinil. Korchemny denies he provided banned stimulants to athletes. (02/03/04, P. A2) Copyright 2004 The Chronicle Publishing Co. 586 of 998 DOCUMENTS The San Francisco Chronicle JANUARY 30, 2004, FRIDAY, FINAL EDITION 2-year ban for using modafinil SOURCE: Chronicle Staff Writer BYLINE: John Crumpacker SECTION: SPORTS; Pg. C2 LENGTH: 424 words The federal grand jury investigating possible sports doping and money laundering by Burlingame laboratory owner Victor Conte and personal trainer Greg Anderson met Thursday but apparently did not hear witness testimony in the case. Nevertheless, fallout from the ongoing probe continued to be felt around the sporting world. In Lausanne, Switzerland, headquarters of the International Olympic Committee, the World Anti-Doping Agency announced that henceforth, positive tests for the stimulant modafinil will result in two-year bans from competition. Current sanctions call for a public warning and disqualification from the competition where the test occurred. Several clients of Conte's tested positive for modafinil, including world-class sprinters Kelli White and Chryste Gaines. Six track and field athletes came up positive for the putative narcolepsy medication last year but they will not be subjected to retroactive sanctions. White received modafinil in a prescription from Bay Area psychiatrist Dr. Brian Goldman, who said the Union City sprinter was referred to him by Conte. In another development Thursday in Lausanne, WADA said a test for human growth hormone will likely be available in time for the Athens Olympics in August. If not, blood samples from athletes will be stored and examined later when a reliable test is available and retroactive sanctions will be imposed on cheaters. Human growth hormone, or hGH, works like an anabolic steroid in building strength and aiding in recovery time. Until now, it has gone undetected in urine screening. In 1999, the wife of Raiders linebacker Bill Romanowski told investigators in a Colorado prescription drug-fraud case that her husband obtained hGH from Conte's Bay Area Laboratory Co-Operative and injected it in his knee. "We've never been so close to having a test in our hands," said Olivier Rabin, science director for WADA. "There will be new substances detected in Athens, there's no question about that. We hope hGH is one of them. But we don't want to tell the athletes when it's coming." In New York, the attorney for Gaines said the former Stanford sprinter and two-time Olympian is now the first alternate to get a lane for the 60-meter dash in next week's Millrose Games indoor track meet. Skip Stolley, the Millrose meet director, initially said Gaines had not been invited because her modafinil -inspired role in the Conte saga would be a focal point of the competition. The Associated Press and Reuters contributed to this report. LOAD-DATE: January 30, 2004 LANGUAGE: ENGLISH Copyright 2004 The Chronicle Publishing Co. 587 of 998 DOCUMENTS XINHUA GENERAL NEWS SERVICE January 30, 2004, Friday Athletes faces two-year ban for testing positive for modafinil SECTION: WORLD NEWS; SPORTS LENGTH: 138 words GENEVA, Jan. 29 (Xinhua) -- Athletes testing positive for modafinil, the subtance double American sprint champion Kelli White took at last year's world championships in Paris, will be banned for two years from competition. World Anti-Doping Agency (WADA) officials told a one-day media symposium in Lausanne, Switzerland on Thursday that modafinil was considered a serious drug on the banned list which came into application at the beginning of this month. White tested positive for modafinil after winning the 100 meters title in Paris last August.  She later said she was being treated for a sleeping disorder. At the time the International Association of Athletics Federation (IAAF) said it regarded modafinil as a related substance to minor stimulants, which meant the only sanction was the loss of her medal. LOAD-DATE: January 31, 2004 LANGUAGE: ENGLISH COPYRIGHT 2004 XINHUA NEWS AGENCY 588 of 998 DOCUMENTS Associated Press Worldstream January 29, 2004 Thursday Doping agency set to test for human growth hormone in Athens BYLINE: STEPHEN WILSON; AP Sports Writer SECTION: SPORTS LENGTH: 768 words DATELINE: LAUSANNE, Switzerland Athletes using human growth hormone be warned: The drug police will be waiting to catch you at the Olympics next summer. A test for the previously undetectable drug - considered one of the most widely used banned substances in sports - is all but finalized and likely to be introduced at the Athens Games, World Anti-Doping Agency officials said Thursday. And, even if the test isn't quite ready for Athens, officials will be able to retest samples later to punish cheaters retroactively. "We've never been so close to having a test in our hands," said Olivier Rabin, WADA's science director. Human growth hormone, or hGH, works like an anabolic steroid, building muscle mass and helping athletes recover faster from hard training. Although hGH has been around for decades, standard doping controls haven't been able to distinguish between the naturally produced hormone and the synthetic version used by cheaters. Attempts to devise a test for hGH have dragged on for years, with a number of projects stalled by a lack of funding. Rabin said WADA was now in the final phase of validating two hGH tests developed by scientists in Britain and Germany. Both involve blood, not urine, tests. "We are doing everything we can to bring it in as quickly as possible," Rabin said in an interview during a WADA symposium. WADA, however, will not announce when or if the test is ready, preferring to keep the drug cheats guessing. Rabin said WADA could also have new tests for blood-based oxygen carriers, illegal blood transfusions, insulin and new steroids. "There will be new substances detected in Athens, there's no question about that," Rabin said. "We hope hGH is one of them. But we don't want to tell the athletes when it's coming. They know it's prohibited. The day we catch one or several athletes, then it will be revealed to the world that the test has been validated." Rabin stressed that if a test is not used in Athens, it will be put into practice shortly after the Olympics. The Athens samples will be stored and reanalyzed for hGH once the test is finalized, he said. Retesting of drug samples took place in several sports last year following the unmasking of the designer steroid THG, the drug at the center of a major U.S.-based scandal. Rabin said WADA had evidence that at least one other designer steroid - devised specifically to avoid detection - was in circulation in the sports world. "We are tracking some of these substances," he said. "We are asking labs if they see any unusual readings to keep the samples and retest them to identify any unique pattern." Meanwhile, WADA officials said Kelli White and five other U.S. athletes who tested positive last year for the stimulant modafinil were fortunate to have escaped without two-year bans. White tested positive at the World Championships in Paris, claiming she used modafinil for treatment of the sleep disorder narcolepsy. She faces being stripped of her gold medals in the 100 and 200 meters. The International Association of Athletics Federations ruled at the time that modafinil was a "minor" stimulant and warranted a public warning and disqualification from the event but not a ban. WADA's list of banned substances, which went into effect on Jan. 1, classifies modafinil in the group of stimulants carrying a two-year ban. WADA medical director Alain Garnier said medical research has shown that modafinil can enhance performance by stimulating the reflex action of the muscles, particularly useful in sprint events. Others who tested positive for modafinil were sprinters Calvin Harrison and Chryste Gaines and hurdlers Chris Phillips, Sandra Glover and Eric Thomas. The cases are being handled by the U.S. Anti-Doping Agency. Despite WADA's ruling on modafinil, agency and IAAF officials said the athletes would likely be judged by the rules in place at the time. "If Kelli White was to test positive today, she would get two years," IAAF spokesman Nick Davies said. "But I can't see how she could be banned for last year's test." Also Thursday, basketball's world governing body became the 24th summer Olympic federation to adopt WADA's anti-doping code, which sets out uniform rules and sanctions cutting across all sports and countries. Under the accord, NBA players eligible for Olympic teams will be subjected to out-of-competition drug tests before Athens just like athletes in other sports. Soccer, cycling, volleyball and badminton are the four sports yet to formally enact the code, but WADA director general David Howman said he expects all to sign up as required before Athens. LOAD-DATE: January 30, 2004 LANGUAGE: ENGLISH Copyright 2004 Associated Press All Rights Reserved 589 of 998 DOCUMENTS PR Newswire January 28, 2004 Wednesday Cephalon, Inc. Selects Cognitive Drug Research's Computerized Cognitive Function Assessment System for Pivotal Phase III Clinical Trials for The R-isomer of Modafinil SECTION: FINANCIAL NEWS LENGTH: 614 words DATELINE: READING, England Jan. 28 Cognitive Drug Research, Ltd. (CDR) announced today that Cephalon, Inc., of West Chester Pennsylvania, has selected Cognitive Drug Research's, Computerized Cognitive Function Assessment System (CDRSystem) for inclusion in four Phase III clinical trials of the R- isomer of modafinil. The CDRSystem is being used to assess the degree to which the R-isomer of modafinil effects cognitive function in the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome (OSAHS) and chronic shift work sleep disorder (SWSD). The CDRSystem is a sensitive computer based cognitive assessment tool that has been specifically developed to definitively assess both enhancement and impairment in the four major aspects of cognitive functioning: attention, working memory, episodic secondary memory and motor control. "The decision to use Cognitive Drug Research was based on the sensitivity and validity of their computerized tests as well as their proven ability to provide cognitive function testing in a large multi-national clinical program," said Dr. Paul Blake, Senior Vice President, Clinical Research and Regulatory Affairs, at Cephalon. The CDRSystem is being used in this Phase III program to assess R-modafinil's affect on attention, working memory, and episodic secondary memory. The program with R-modafinil consists of 2 twelve-week clinical trials in patients with OSA/HS, one in patients with narcolepsy and one planned in patients with chronic shift work sleep disorder. These randomized, double-blind, placebo-controlled clinical trials are expected to include over 800 patients with trials being conducted concurrently at sites in the United States, Europe, Canada, Russia and Australia. "We are delighted to be working with Cephalon on these important trials and I congratulate Cephalon for their forward thinking in taking the time to study how the R-isomer of modafinil may lessen cognitive impairment" said Professor Keith Wesnes, CDR's founder. "Cephalon's decision reconfirms our strategy of creating computerized clinical research tools that meet the emerging needs of pharmaceutical researchers and the belief that our system delivers real business value in Phase III programs." About Cognitive Drug Research, Ltd. Founded in 1986, Cognitive Drug Research Ltd. (CDR) is the world's leading provider of innovative cognitive function assessment technology and services to the pharmaceutical industry. CDR combines innovative technology and validated psychometric tests to definitively measure the effects of pharmaceuticals on the mental efficiency of volunteers and patients in clinical trials. CDR has experience assessing cognitive function in areas including cancer, depression, pain, epilepsy, age related cognitive decline, schizophrenia, sleep disorders, diabetes, stroke and hypertension. CDR also has extensive experience in dementia with international studies involving Alzheimer's Disease, Parkinson's Disease with Dementia, Vascular Dementia and Dementia with Lewy Bodies. CDR is a privately held company with headquarters in the Goring-on-Thames, U.K and sales offices in New Jersey, U.S. CDR has established a significant record of achievement with methods that have been used in over 500 studies and has been proven through wide spread independent scientific validation. It is also documented in accordance with FDA 21 Code of Federal Regulations part 11. Additional information about CDR can be found by visiting the company's website on www.cdr.org.uk. SOURCE Cognitive Drug Research, Ltd. CONTACT: U.S. - Roman Kruchowy, roman@cdr.us.com, U.K - Paula Stubbs, paulas@cdr.org.uk, both of Cognitive Drug Research, Ltd. URL: http://www.prnewswire.com LOAD-DATE: January 29, 2004 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS, TECHNOLOGY AND MEDICAL EDITORS PUBLICATION-TYPE: Newswire Copyright 2004 PR Newswire Association, Inc. 590 of 998 DOCUMENTS PR Newswire Europe January 28, 2004 Wednesday Cephalon, Inc. Selects Cognitive Drug Research's Computerised Cognitive Function Assessment System for Pivotal Phase III Clinical Trials for The R-isomer of Modafinil LENGTH: 620 words READING, England, January 28 /PRNewswire/ -- Cognitive Drug Research, Ltd. [CDR] announced today that Cephalon, Inc ., of West Chester Pennsylvania, has selected Cognitive Drug Research's, Computerized Cognitive Function Assessment System [CDRSystem] for inclusion in four Phase III clinical trials of the R- isomer of modafinil. The CDRSystem is being used to assess the degree to which the R-isomer of modafinil effects cognitive function in the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome [OSAHS] and chronic shift work sleep disorder [SWSD]. The CDRSystem is a sensitive computer based cognitive assessment tool that has been specifically developed to definitively assess both enhancement and impairment in the four major aspects of cognitive functioning: attention, working memory, episodic secondary memory and motor control. "The decision to use Cognitive Drug Research was based on the sensitivity and validity of their computerised tests as well as their proven ability to provide cognitive function testing in a large multi- national clinical program," said Dr. Paul Blake, Senior Vice President, Clinical Research and Regulatory Affairs, at Cephalon. The CDRSystem is being used in this Phase III program to assess R- modafinil's affect on attention, working memory, and episodic secondary memory. The program with R-modafinil consists of 2 twelve-week clinical trials in patients with OSA/HS, one in patients with narcolepsy and one planned in patients with chronic shift work sleep disorder. These randomised, double-blind, placebo-controlled clinical trials are expected to include over 800 patients with trials being conducted concurrently at sites in the United States, Europe, Canada, Russia and Australia. "We are delighted to be working with Cephalon on these important trials and I congratulate Cephalon for their forward thinking in taking the time to study how the R-isomer of modafinil may lessen cognitive impairment" said Professor Keith Wesnes, CDR's founder. "Cephalon's decision reconfirms our strategy of creating computerised clinical research tools that meet the emerging needs of pharmaceutical researchers and the belief that our system delivers real business value in Phase III programs." About Cognitive Drug Research, Ltd. Founded in 1986, Cognitive Drug Research Ltd. [CDR] is the world's leading provider of innovative cognitive function assessment technology and services to the pharmaceutical industry. CDR combines innovative technology and validated psychometric tests to definitively measure the effects of pharmaceuticals on the mental efficiency of volunteers and patients in clinical trials. CDR has experience assessing cognitive function in areas including cancer, depression, pain, epilepsy, age related cognitive decline, schizophrenia, sleep disorders, diabetes, stroke and hypertension. CDR also has extensive experience in dementia with international studies involving Alzheimer's Disease, Parkinson's Disease with Dementia, Vascular Dementia and Dementia with Lewy Bodies. CDR is a privately held company with headquarters in the Goring-on- Thames, U.K and sales offices in New Jersey, U.S. CDR has established a significant record of achievement with methods that have been used in over 500 studies and has been proven through wide spread independent scientific validation. It is also documented in accordance with FDA 21 Code of Federal Regulations part 11. Additional information about CDR can be found by visiting the company's website on www.cdr.org.uk. Web site: http://www.cdr.org.ukCognitive Drug Research, Ltd. CONTACT: CONTACT: U.S. - Roman Kruchowy, roman@cdr.us.com, U.K - Paula Stubbs, paulas@cdr.org.uk, both of Cognitive Drug Research, Ltd. FCMN Contact: roman@CDR.us.com LOAD-DATE: January 29, 2004 LANGUAGE: ENGLISH Copyright 2004 PR Newswire Europe Limited 591 of 998 DOCUMENTS San Jose Mercury News (California) January 24, 2004 Saturday MORNING FINAL EDITION GAINES' LAWYERS SET A DEADLINE; DECISION ON ENTRY MUST BE BY MONDAY BYLINE: ELLIOTT ALMOND, Mercury News SECTION: SPORTS; Pg. 2D LENGTH: 402 words Chryste Gaines' lawyers have given U.S. track officials until Monday to pave the way for the Olympic sprinter to compete at the Verizon Millrose Games in New York. Gaines' attorney, Cameron Myler, would not say Friday what action is planned if Millrose officials refuse to allow the athlete to enter the 60-meter race at the Feb. 6 meet in Madison Square Garden. Myler said a meeting with officials from USA Track & Field and the U.S. Olympic Committee failed to resolve the dispute. "We're trying to come up with ways to get the result that we want," Myler said. Gaines, a former Stanford sprinter who ranked second in the world last year, is being banished by meet organizers because of a pending drug case involving the sleep-disorder-medication modafinil. Her lawyers say this is unfair because Gaines, 33, of Lithonia, Ga., is eligible under International Association of Athletics Federations rules. Even if she were to lose her case in an upcoming arbitration hearing, Gaines would remain eligible because the punishment for modafinil is solely disqualification from the meet at which the athlete tested positive. That occurred in June, at the U.S. championships at Stanford, when the drug was not named on the IAAF banned list. Gaines and five others who tested positive for modafinil are being prosecuted under the "related substance" clause of the drug code. Lawyers for many of the athletes say they will argue that modafinil is not a stimulant and has no performance-enhancing qualities. Although Gaines' drug case is minor, she and others have been banned from some indoor meets this season. Myler is focusing on the Millrose Games, where sprint star Marion Jones is planning to mark her return after taking last year off to have a son. Myler said USA Track & Field's chief executive, Craig Masback, agreed totry to help Gaines' cause. But track officials say they cannot tell organizers who to invite, or which events they should hold, at individual meets -- even those that the group sanctions. The Millrose Games is one of four meets that will make up USA Track & Field's Indoor Golden Spike Tour this winter. Gaines has entered a non-paying 60 meters at one of those meets, the Tyson Foods Invitational on Feb. 14. Myler filed a complaint with the USOC this week, alleging that USA Track & Field has failed to protect athletes' rights as stated in the USOC constitution. LOAD-DATE: August 21, 2005 LANGUAGE: ENGLISH GRAPHIC: Photo; PHOTO: Gaines Eligible, but drug test has brought some meet bans Copyright 2004 San Jose Mercury News All Rights Reserved 592 of 998 DOCUMENTS San Jose Mercury News (California) January 23, 2004 Friday MORNING FINAL EDITION GAINES FILES A COMPLAINT IN EFFORT TO RACE; EVENTS BARRING HER BECAUSE OF DRUG TEST BYLINE: ELLIOTT ALMOND, Mercury News SECTION: SPORTS; Pg. 6D LENGTH: 643 words A lawyer for Chryste Gaines has filed a complaint with the U.S. Olympic Committee this week in an effort to force track and field officials to open their events to the former Stanford sprinter. In what Olympic experts say is the first case of its kind, the complaint alleges that USA Track & Field, the sport's national governing body, has an obligation to ensure that eligible athletes are not excluded from events it sanctions. Gaines, 33, of Lithonia, Ga., tested positive for modafinil, a sleep-disorder medication, last June. According to track officials, athletes who test positive for modafinil face disqualification from the event where the test occurred but no further sanctions. However, Gaines was not invited to the prestigious Verizon Millrose Games in New York next month because of the test. She also is being barred from a meet in Stuttgart, Germany, and on Thursday, organizers of the Athens indoor meet told her she is not welcome even though she is eligible for this summer's Olympics there. Gaines' attorney, Cameron Myler, alleges that meet organizers' actions are preventing the sprinter from qualifying for next month's indoor national championships in Boston. A spokeswoman for USA Track & Field, Jill Geer, said Thursday that if Gaines files a waiver she would be allowed to run the 60 meters at the championships. She added that USA Track & Field has no control over the meets, which are invitationals and are part of its Indoor Golden Spike Tour. The parties are scheduled to discuss the situation today. Myler said she would decide afterward whether to file for arbitration. "We're still hoping to gain entrance into the Millrose Games," Myler said. "It is about Chryste being denied the opportunity to compete." Gaines, a two-time Olympian who is training in Miami, asked that her lawyer discuss the case. Myler said that Gaines hopes to qualify for the world indoor championships in March in Budapest, Hungary. The complaint alleges that USA Track & Field has responsibilities under federal and USOC regulations to make sure the rights of its athletes are protected. It claims Gaines is being blocked because of publicity over a minor drug case. Modafinil is not on the banned list provided by the International Association of Athletics Federations, track and field's worldwide governing body, but Gaines and five other track athletes, including training partner Kelli White of Union City, are being prosecuted under a related-substanceclause in the guidelines. Officials must prove the medication is a stimulant beyond a reasonable doubt, and sleep-disorder experts have questioned that claim. Myler wrote in the complaint that modafinil is not related to any substances included on the prohibited list. Gaines' case has received extra attention because the modafinil positives have been linked to nine others involving THG, a previously undetected steroid. U.S. Anti-Doping Agency officials have alleged that a Burlingame nutrition company, Balco Laboratories, is the likely source of the steroid. An ongoing federal grand jury investigation in San Francisco, involving testimony from scores of athletes from baseball, football and Olympic sports, has kept the case in the news. That led Skip Stolley of the Millrose Games to deny Gaines a chance to run. He said he did not want attention from the drug case to distract from his meet, but he happily signed on sprint star Marion Jones, who was one of the biggest names to testify before the grand jury. Art Huff of the Tyson Foods Invitational in Fayetteville, Ark., does not want to decide who is eligible: "Who am I to say no?" he asked. Huff recently added the women's 60 meters, but it is a race without prize money. Gaines, Torri Edwards and Inger Miller have asked for lanes, turning it into one of the winter's premier sprint races. LOAD-DATE: August 21, 2005 LANGUAGE: ENGLISH GRAPHIC: Photo; PHOTO: LIONEL CIRONNEAU -- ASSOCIATED PRESS Chryste Gaines says USA Track & Field must ensure that eligible athletes can race in its events. Copyright 2004 San Jose Mercury News All Rights Reserved 593 of 998 DOCUMENTS San Jose Mercury News (California) January 22, 2004 Thursday MORNING FINAL EDITION GAINES IS BANNED FROM GERMAN MEET BYLINE: ELLIOTT ALMOND, Mercury News SECTION: SPORTS; Pg. 4D LENGTH: 439 words The director of a track and field meet to be held in Germany this month decided Wednesday to ban Chryste Gaines from his event, the latest move against the Olympic sprinter who tested positive for a stimulant last summer but is eligible to compete. Fredy Schafer said he did not invite Gaines, the world's second-ranked female sprinter, or hurdler Chris Phillips to the Jan. 31 meet in Stuttgart because of their positive tests for modafinil, the controversial sleep-disorder medication. Athletes who test positive for modafinil face disqualification from the event in which they tested positive but no further sanctions. Schafer's action underscores how track and field is struggling to be fair at a time when its image is suffering over drugs. "This is a difficult thing in Germany with the main sponsors, because they don't want track being involved in doping," Schafer said. "We want to be onthe safe side." While Gaines and Phillips await hearings with the U.S. Anti-Doping Agency, some officials are worried that athletes are being unfairly ostracized because of the federal grand jury investigation of Balco Laboratories, the Burlingame nutritional-supplement company that has been linked with the designer steroid THG. "It's very disturbing to us people are being judged before the process," said Bill Roe, president of USA Track & Field, the sport's national governing body. Roe said of Gaines' situation: "They want to make sure we are tough on doping, but here is a specific instance that it has not worked." Gaines, a former Stanford sprinter who is among six athletes who tested positive for modafinil, also has been banned from next month's Verizon Millrose Games in New York. USA Track & Field recently addressed the fairness issue with American promoters, who have control of their events. "The only thing in our power is to guarantee to Chryste that she will not have to worry about gaining entry into our national championships," Roe said. Gaines declined to talk, but her agent, Renaldo Nehemiah, said, "We are the most dysfunctional, functioning body in professional sports." Nehemiah said he sent a memo to European meet promoters and leaders of the International Athletics Federations Association, track and field's worldwide governing body, asking them to clarify their positions. "Chryste is being a scapegoat for maybe some other kind of issue," said Nehemiah, a former world-class hurdler and San Francisco 49er. Nehemiah said Gaines might run the 60 meters at the Tyson Indoor meet in Arkansas next month, but added she could also be banished from a meet in Birmingham, England. LOAD-DATE: August 21, 2005 LANGUAGE: ENGLISH GRAPHIC: Photo; PHOTO: Gaines U.S. sprinter tested positive for modafinil but is eligible Copyright 2004 San Jose Mercury News All Rights Reserved 594 of 998 DOCUMENTS The San Francisco Chronicle JANUARY 21, 2004, WEDNESDAY, FINAL EDITION Jacobs won't be at youth clinic SOURCE: Chronicle Staff Writer BYLINE: John Crumpacker SECTION: SPORTS; Pg. C8 LENGTH: 546 words The organizer of a prestigious track and field clinic in Union City has decided against inviting Olympic runner Regina Jacobs to next month's event at James Logan High School because of her recent positive test for the designer steroid THG. Logan track coach Lee Webb, who annually lines up a who's-who of current and retired track stars for his youth clinic, said he did not want the attention Jacobs would bring to the Feb. 14 event. "I don't want that to be the focus of the whole thing," Webb said. "We've already had plenty of attention." That was in reference to Remi Korchemny, a Castro Valley coach who volunteers his time working with high school athletes at Logan. Korchemny, who coaches several athletes who have tested positive for the stimulant modafinil and one for THG, said he will not be at the clinic. For next month's clinic, Webb has invited such track stars of the past as Tommie Smith, John Carlos, Dick Fosbury, Mac Wilkins, Andre Phillips, Tom Petranoff, Charlie Greene and Jim Hines. Jacobs, world-record holder for the women's indoor 1,500 meters, would have worked with middle- and long-distance runners. Jacobs, 40, of Oakland, is in the process of appealing her positive test for THG from last June's U.S. Championships at Stanford, where she won the 1,500. Her appeal will be heard by the American Arbitration Association. If unsuccessful, she could be banned from competition for two years. Through her attorney, Edward G. Williams of New York, Jacobs is seeking to broaden the pool of potential arbitrators for what will be a three-person panel. Jacobs could not be reached for comment. Korchemny, who said he provided modafinil to some of his athletes to combat the effects of jet leg, said he has not been called to testify before the federal grand jury in San Francisco investigating Victor Conte, owner of a nutritional supplement laboratory in Burlingame. The grand jury is expected to reconvene Thursday at the federal building. Korchemny said he is currently in Florida working with sprinter Chryste Gaines, a two-time Olympian who tested positive for modafinil at the U.S. Championships. The sanctions for modafinil use include a public warning and disqualification from the event where the test occurred. Gaines remains eligible for all competition, including the Olympic Games, but because of the furor over the investigation into Conte and his lab, she was not invited to run in next month's Millrose Games in New York. "It's just a warning," Korchemny said. "Why should professional athletes suffer loss of income? Unfortunately, the Millrose director, he has double standards for athletes. People dealing with BALCO (Conte's lab) are not going to run in his meet." Gaines testified before the grand jury in San Francisco, as did fellow sprinters Marion Jones and Tim Montgomery. Jones was invited to run in the Millrose Games. "Both of them were subpoenaed," Korchemny said. "They are also clients of BALCO. Why can they run? People are afraid to ask the meet director why he has double standards." Millrose director Skip Stolley said he did not invite Gaines because he did not want the focus of the meet to be on a continuing drug story.E-mail John Crumpacker at jcrumpacker@sfchronicle.com. LOAD-DATE: January 21, 2004 LANGUAGE: ENGLISH GRAPHIC: PHOTO, Regina Jacobs is the world-record holder for the women's indoor 1,500 meters. / Carlos Avila Gonzalez / The Chronicle Copyright 2004 The Chronicle Publishing Co. 595 of 998 DOCUMENTS Edmonton Journal (Alberta) January 18, 2004 Sunday Final Edition A life without ZZZZZs: Doze of reality: Eager to try a new prescription drug that lets you stave off sleep for up to 40 hours? Here's a wake-up call: get used to disrupted routines and lonely nights SOURCE: Sunday Telegraph BYLINE: Julia Llewellyn Smith SECTION: Sunday Reader; Pg. D9 LENGTH: 1477 words DATELINE: LONDON LONDON - It's 4 a.m., I've been up for 20 hours, but I don't feel tired. I'm not at a wild party, nor rocking a wailing infant, nor am I lying miserably in bed cursing my insomnia. I am sitting at my desk paying my bills on the Internet as if it were mid-afternoon. I put some washing in the machine, then paint my toenails. I look at the clock: 4:45 a.m. I haven't yawned once. The reason for my alertness is 200 milligrams of modafinil, a new prescription drug that staves off sleep for hours on end. (In Canada, it has been available since 1999 under the name Alertec.) Unlike the drugs we've traditionally used to keep us going, modafinil appears to have few side-effects. While coffee drinkers shake and amphetamine-users jabber aggressively, on modafinil I feel calm, focused -- and able to work all night. According to Leon Kreitzman, author of The 24-Hour Society, drugs like modafinil will transform society. "Modafinil belongs to a new class of awakening drugs known as eugeroics, which are unravelling the mechanisms of sleepiness. Once you've done that you will end up in a world where the need to sleep is optional. I would say that will happen within the next quarter of a century." When I tell my friends about Kreitzman's vision, they react in unison. "But I love sleep," they protest. "A world without it would be horrible." A moment later, they ask: "Where did you say you got those pills? Could I have one?" But at what price? Round-the-clock supermarkets, 24-hour television, electric lighting, demanding bosses all make it harder and harder to get the eight hours' rest most of us need to function properly. Last month, the research group Demos pointed out that too many crucial decisions, such as the one that launched the Challenger space shuttle, are made by people handling complex data after days of sleep deprivation. Already, the armed forces are committed to modafinil, having used it to help British and American troops "power on" to Baghdad: marching for 40 hours, sleeping for eight, and repeating the pattern without noticeable ill-effect. If it works for the military, who else could it help? New mothers, long-distance truck drivers, hospital interns? The truth is we'd love to burn the candle at both ends: we just need to find the wax. Modafinil was developed in France a decade ago as an aid for narcoleptics -- people who fall asleep uncontrollably. Henry Nicholls, 30, a London-based science writer with narcolepsy, has been using the drug for two years to control his condition, thought to affect 2,500 people in Britain. "For me, it works amazingly well," he says. "No one knows what the long-term effects of taking it daily will be, but I'm happy to be a guinea pig. "Before, I used to worry that I'd never be able to hold down a normal job, because when the sleepiness took over there really was nothing I could do. Now I am able to function like anyone else. " Nicholls needs a prescription for his supply. It is, however, easy to bypass the system, because the drug is available to anyone with a credit card and a computer. It takes me two clicks on the Internet to find a site that offers to send me 30 tablets for about $175. The pills arrive six days later. DRUG'S DEVELOPERS NOT SURE EXACTLY HOW IT WORKS I call Ian Davison, of Cephalon, which makes modafinil in Britain and in the U.S. under the name ProVigil, and is developing even more powerful versions. "We are not 100-per-cent sure how ProVigil works," he says. "We know it has an effect on the hypothalamus region of the brain, which controls our sleep-wake generating sites, whereas amphetamines control the completely separate dopaminergic side. "Both sides stimulate the cerebral cortex, which keeps people awake, but the dopaminergic also stimulates the heart rate and blood pressure. When the amphetamines wear off there is a crash, while with modafinil people just go back to their normal rhythm of sleep-wake." Davison stresses modafinil is intended solely for narcoleptics: "You really should only take a medicine for what it's prescribed for. In any case, you're wrong to think you will get to a situation where you won't sleep at all. In the end, the overwhelming drive to sleep will come whether you use modafinil or not." He is backed up by Dr. Irshaad Ebrahim of the London Sleep Centre. Sleep, he points out, helps the brain store memories and recuperate from work, and helps the body build its immune system. "If you use a drug to overcome that, you will deprive yourself of those things." There are no feelings of euphoria associated with modafinil, so it is unlikely to become fashionable; sleep experts certainly hope it won't. Nonetheless, when I swallow my first one I am surprised to feel absolutely nothing. I've started slowly with a 100 milligram dose -- half the recommended amount -- to avoid potential nausea and headaches, the most common side-effects. As usual, I've crawled out of bed reluctantly at 8 a.m., after too-late a night and with a mountain of tasks ahead of me. My day passes well: I feel sharp, moderately energetic but certainly not like superwoman. But as the hours wear on, I notice what doesn't happen: no yawning, no intense yearning for a 2 p.m. nap. Instead I steadily work through my to-do list. It's in the evening that things get interesting: I go out to dinner with friends. We stay until after midnight. Normally I'd be flagging, but now I sit and talk cheerfully as if it were mid-morning (it may help I'm not drinking, since Cephalon has not yet tested the effects of mixing alcohol with modafinil). I get home and rather than dive into bed as I usually do, I watch some TV and read for half an hour. I turn the light out at about 2 a.m., worried that I won't sleep at all, but in fact I crash out at once. Astonishingly, I'm awake before 7 a.m., at least two hours earlier than I usually would after such a late night, and instantly want to jump out of bed and get going. I pop another pill and look forward to enjoying another busy day and a late night. I'm thrilled. It's time to push my boundaries. I am going to a party in a pub. Just before I go out I take a 200-milligram dose. At the party I am surrounded by thirtysomethings who, shattered after a long week, can't conceal their yawns. Yet I don't glance once at my watch. My friends are disappointed that I'm not grinding my teeth or acting "wired." I explain that I'm not taking amphetamines. One by one, as they start calling taxis, I am still there talking animatedly (but not maniacally) and having fun. I'm surprised to feel my legs shake slightly -- a symptom of exhaustion. I realize modafinil may stop you from feeling sleepy but you still feel tired. My limbs grow heavier, but that doesn't stop the wakefulness. If wake-up drugs catch on, "tiredness" and "sleepiness" will have to be separated: a hard concept to grasp. I go home around 1:30 a.m., where again I feel no desire to sleep. At the same time, when it's cold and dark the prospect of a cosy bed is very appealing. Why would I want to work all night when I could be snuggled under a duvet? I can't resist climbing under the covers, but instead of turning off the light, I read. After an hour, I remember I need to check my tax bill. I might as well do it now. Having done so, there seems no particular reason -- tradition apart -- to go back to bed. It's 3 a.m. There's an article I have to finish, a letter I need to write. I really should do some washing. Why not do it now? I MAY NOT BE SLEEPY, BUT I AM BONE-WEARY Yet although it's satisfying to power through my work, it's unpleasant. It's tiredness versus sleepiness again: I am awake enough to function efficiently but plowing through the backlog is still physically wearying. The loneliness is miserable. I feel as if I'm the only person in the world. Yes, I could go out and find an all-night supermarket, but it's freezing outside and I might get mugged. I end up behaving like insomniacs everywhere and I go online, surfing wildly and sending silly e-mails to feel connected to humanity. I'm starting to understand how sleep gives a fundamental pattern to your life. Without that break, time stretches ahead of you dauntingly like a desert. I worry what would happen if wake-up drugs were widely available. If your biggest rival at work was taking them, would you really be able to resist? Would people who slept be seen as losers? By 6 a.m. I have had a bath and breakfast. I can't wait for the rest of the world to wake up. As soon as the newspaper shop opens at 7 a.m., I'm out of the house, desperate for human contact. I realize now how much more bushy-tailed I was on modafinil days. I hated my sleepless night because it felt so unnatural, but I still think modafinil could be the perfect response to a broken night, an urgent deadline or jet lag. LOAD-DATE: January 18, 2004 LANGUAGE: ENGLISH GRAPHIC: Graphic;Diagram: Journal Stock; (See hard copy for illustration). TYPE: News Copyright 2004 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 596 of 998 DOCUMENTS The San Francisco Chronicle JANUARY 17, 2004, SATURDAY, FINAL EDITION Track organizers are wary; Wait-and-see attitude on positive-testing athletes BYLINE: John Crumpacker SECTION: SPORTS; Pg. C2; OLYMPIC BEAT LENGTH: 825 words Organizers of several outdoor track and field meets scheduled for the spring said they will take a wait-and-see approach toward inviting athletes caught up in the ongoing doping scandal emanating from Victor Conte's nutritional supplement lab in Burlingame. The meet director for the Feb. 6 Millrose Games in New York said he did not invite sprinter Chryste Gaines, who tested positive for the mild stimulant modafinil, because he wanted the meet to focus on performance -- not performance-enhancing drugs. Gaines also will not compete in an indoor meet Jan. 31 in Boston. A positive test for modafinil does not call for a ban from competition, unlike steroids, and Gaines and others who used the stimulant are subject only to a public warning and a disqualification from competition where the test occurred. Gaines and fellow sprinter and modafinil positive Kelli White, recovering from a knee injury, remain eligible for all domestic and international competition, including the Olympic Games. "We're going to be real careful with regards to modafinil," said Gregg Miller, meet director for the May 8 Tom Moore Modesto Relays. "It's something I want to look at and consider the individual athletes. I want to protect the integrity of the events because I don't want to invite someone who may be suspended. That would have ramifications for everybody." In recent years the Modesto meet has featured sprinter Dwain Chambers of Great Britain and American shot putter Kevin Toth -- both of whom tested positive for THG and face two-year bans from competition. "It's really a shame," Miller said of Chambers. "Maybe I'm nave. I'd like to think he's one person who didn't realize what was going on. I really consider him a good guy." U.S. anti-doping officials alleged the THG came from Conte's lab in Burlingame, prompting Miller to say, "Overall, he's really hurt our sport. Not just our sport, but a lot of others. We're going to be careful." Asked whether he would invite Gaines, White or any of the other four athletes who tested positive for modafinil to the prestigious Prefontaine Classic June 19 in Eugene, Ore., meet director Tom Jordan said, "I guess you could say it would be a case-by-case decision. Certainly I can understand the motivation of the indoor meet directors. You don't want the focus to be on that." Nancy Ditz, executive director of the Grand Prix II meet at Stanford on June 6, said, "We'll wait and see how the adjudication process goes. There's a lot more to learn until we make a blanket judgment." Ditz is sensitive to the many facets of the BALCO story because Stanford's Cobb Track & Angell Field is Ground Zero, the place in June where an anonymous coach sent to U.S. anti-doping officials a syringe loaded with what was determined to be the designer steroid THG. "You don't want to diminish the caliber of the meet by including people who are deemed to have had an unfair advantage," said Ditz, a Stanford graduate and 1988 Olympian in the marathon. "I wouldn't make a step until I talked to USA Track & Field. We in no way condone people trying to get an unfair advantage." Meanwhile, the man who coaches Gaines and White, Remi Korchemny of Castro Valley, could be banned by U.S. track officials from coaching the U.S. team at the World Indoor Championships in March in Budapest, Hungary. USATF is considering sanctioning coaches, doctors and trainers of athletes who test positive for banned substances. Korchemny maintains modafinil is not a performance-enhancing drug. Paddlers coming to Oakland: The Olympic trials in flatwater canoe and kayak will be held April 15-18 at Lake Merritt in Oakland, site of the U.S. national championships last August. Because of the job done by the host Lake Merritt Rowing Club, the canoe and kayak federation chose to return for its trials. "That event came off so well, the governing body decided they would award us the Olympic trials," said Scott Whitney of the local organizing committee. Twelve finals will be held over the three days at the lake, starting with two that will send the winners directly to the Athens Olympics without having to go through further competition at a Pan Am qualifying event in Brazil in June. Winners of the men's and women's K1 500-meter races (kayak singles) on April 15 will be able to call themselves Olympians after paddling across the finish line. Other events to be contested include men's and women's kayak pairs at 500 and 1,000 meters, men's and women's kayak fours and canoe singles and pairs at 500 and 1,000. The world at large: Superstar Marion Jones, returning to competition after giving birth to a son in June, will contest the long jump indoors for the first time in her career Feb. 20 in Birmingham, England. She'll also run the 60-meter dash. Jones and her boyfriend, Tim Montgomery, currently are training in the Cayman Islands.E-mail John Crumpacker at jcrumpacker@sfchronicle.com. LOAD-DATE: January 17, 2004 LANGUAGE: ENGLISH GRAPHIC: PHOTO, Chryste Gaines was not invited to the Millrose Games due to a positive test for modafinil. / Michael Probst / Associated Press Copyright 2004 The Chronicle Publishing Co. 597 of 998 DOCUMENTS Espicom Business Intelligence January 14, 2004 Cephalon begins Phase III trials for the R-isomer of modafinil LENGTH: 215 words Cephalon has released data from its earlier clinical trials with R-modafinil and information about the Phase III programme for the compound that the company initiated in December 2003. R-modafinil, a single-isomer of the active pharmaceutical ingredient contained in Provigil (modafinil) Tablets, is initially being developed for the treatment of excessive sleepiness associated with narcolepsy and obstructive sleep apnoea/hypopnoea syndrome (OSA/HS). The efficacy portion of the Phase III programme with R-modafinil consists of two 12-week clinical trials in patients with OSA/HS and one in patients with narcolepsy. These randomised, double-blind, placebo-controlled trials are expected to include approximately 800 patients. The primary outcome measures of the trials are the Maintenance of Wakefulness Test and the CGI of Change-Clinician. The trials are being conducted concurrently at sites in the US, Europe, Canada and Australia. The company remains on schedule to complete the OSA/HS programme, and expects to file an NDA for R-modafinil with the FDA in the fourth quarter of 2004. In addition, the company will commence a study of R-modafinil in patients with shift work sleep disorder in early 2004 and intends to file an sNDA for that additional indication as well. LOAD-DATE: January 14, 2004 LANGUAGE: ENGLISH Copyright 2004 ESPICOM Business Intelligence Ltd. 598 of 998 DOCUMENTS Knobias.com This content is provided to LexisNexis by Comtex News Network, Inc. January 13, 2004 Tuesday CEPH Launches Phase III Study of R-modafinil LENGTH: 100 words DATELINE: Ridgeland, MS Cephalon, Inc. (CEPH) announced data from its clinical trials with R-modafinil and information about the Phase III clinical program for the compound. R- modafinil, a single-isomer of the active pharmaceutical ingredient contained in PROVIGIL(R) (modafinil) Tablets [C-IV], is initially being developed for the treatment of excessive sleepiness associated with narcolepsy and obstructive sleep apnea/hypopnea syndrome. The efficacy portion of the Phase III program with R-modafinil consists of 2 twelve-week clinical trials in patients with OSA/HS syndrome and one in patients with narcolepsy. LOAD-DATE: January 14, 2004 LANGUAGE: ENGLISH Copyright 2004 Comtex News Network, Inc. All Rights Reserved Copyright 2004 Knobias.com, LLC, All rights reserved. 599 of 998 DOCUMENTS PR Newswire January 13, 2004 Tuesday Cephalon, Inc. Initiates Phase III Clinical Trials for the R-isomer of Modafinil ; Clinical Program Remains on Schedule SECTION: FINANCIAL NEWS LENGTH: 857 words DATELINE: WEST CHESTER, Pa. Jan. 13 Cephalon, Inc. (Nasdaq: CEPH) announced today, at the JP Morgan Healthcare Conference, data from its earlier clinical trials with R-modafinil and information about the Phase III clinical program for the compound that the company initiated in December 2003. R-modafinil, a single-isomer of the active pharmaceutical ingredient contained in PROVIGIL(R) (modafinil) Tablets $(C-IV$), is initially being developed for the treatment of excessive sleepiness associated with narcolepsy and obstructive sleep apnea/hypopnea syndrome (OSA/HS). The efficacy portion of the Phase III program with R-modafinil consists of 2 twelve-week clinical trials in patients with OSA/HS and one in patients with narcolepsy. These randomized, double-blind, placebo-controlled clinical trials are expected to include approximately 800 patients. The primary outcome measures of the trials are the Maintenance of Wakefulness Test (MWT) and the Clinical Global Impression of Change-Clinician (CGI-C). The trials are being conducted concurrently at sites in the United States, Europe, Canada and Australia. The company remains on schedule to complete the OSA/HS program, and expects to file a New Drug Application (NDA) for R-modafinil with the U.S. Food and Drug Administration in the fourth quarter of 2004. In addition, the company will commence a study of R-modafinil in patients with Shift Work Sleep Disorder in early 2004 and intends to file a supplemental New Drug Application (sNDA) for that additional indication as well. "The decision to move forward with this Phase III program was based on earlier placebo-controlled clinical trials that demonstrated that R-modafinil maintained wakefulness and had a longer duration of effect than does PROVIGIL," said Dr. Paul Blake, Senior Vice President, Clinical Research and Regulatory Affairs, at Cephalon. Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products to treat sleep and neurological disorders, cancer and pain. Cephalon currently employs approximately 1,600 people in the United States and Europe. U.S. sites include the company's headquarters in West Chester, Pennsylvania, and offices and manufacturing facilities in Salt Lake City, Utah. Cephalon's major European offices are located in Guildford, England, Martinsried, Germany, and Maisons-Alfort, France. The company currently markets three proprietary products in the United States: PROVIGIL, GABITRIL(R) (tiagabine hydrochloride) and ACTIQ(R) (oral transmucosal fentanyl citrate) $(C-II$) and more than 20 products internationally. Full prescribing information on its U.S. products is available at www.cephalon.com or by calling 1-800-896-5855. Cephalon is a leader in optimizing a data-driven approach to developing new drugs and in expanding the therapeutic potential of existing products. Cephalon's research pipeline is focused on the identification of novel molecules that affect cell survival and death. Additional information about Cephalon and its subsidiaries can be obtained by visiting the company's website at http://www.cephalon.com. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs including clinical trials of R-modafinil, the duration of effect for R- modafinil, timing of the completion of trials and the filing of the NDA, development of potential pharmaceutical products, interpretation of clinical results, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, sales and earnings projections, and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties such as those set forth below and in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-lookingstatement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. SOURCE Cephalon, Inc. CONTACT: Investor - Chip Merritt, +1-610-738-6376, cmerritt@cephalon.com, or Media - Robert Grupp, +1-610-738-6402, rgrupp@cephalon.com, both for Cephalon, Inc. URL: http://www.prnewswire.com LOAD-DATE: January 14, 2004 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS AND MEDICAL EDITORS PUBLICATION-TYPE: Newswire Copyright 2004 PR Newswire Association, Inc. 600 of 998 DOCUMENTS San Jose Mercury News January 12, 2004, Monday Track might ban coach from world indoor meet BYLINE: By Elliott Almond SECTION: SPORTS LENGTH: 795 words SAN JOSE, Calif. _ U.S. track officials might banish Remi Korchemny from coaching the American team at the world indoor championships in March because of his connection to a Burlingame nutrition company under grand jury investigation. A ranking USA Track & Field official, Stephanie Hightower, said the group is exploring the legality of excluding the Castro Valley coach because he worked with Victor Conte Jr., president of Balco Laboratories. Conte is the target of a money-and-drug investigation involving athletes from baseball, football, boxing and Olympic sports. "We don't have any regulations for this," said Hightower, chair of the women's track committee. "We haven't had to deal with this kind of stuff before." Three of Korchemny's sprinters _ Kelli White of Union City, Chryste Gaines of Georgia and Dwain Chambers of England _ had positive drug tests last summer. White and Gaines had taken modafinil, a sleep-disorder medication that Olympic drug officials classify as a mild stimulant. "It bothers me that people continue to attack us," Korchemny said. "I know that I don't feel I have committed any crime because I strongly believe modafinil is not something that makes athletes perform better." Chambers tested positive for THG, the newly discovered steroid at the center of a growing international scandal. Korchemny said he never gave THG to Chambers, who faces a suspension from UK Athletics. The scandal has continued to fuel criticism that USA Track defies worldwide drug standards, and some in the organization worry about Korchemny's presence during the championships in Budapest, Hungary. "The feeling is that his going would be a manifestation that the United States is not serious about drugs," said Brooks Johnson, director of high performance at the U.S. Olympic Training Center in Chula Vista. Johnson said he doesn't endorse sanctions without giving the coach a hearing. Korchemny, one of the indoor team's three assistants, has not been subpoenaed by the grand jury nor charged with any wrongdoing. A handful of track athletes tested positive for modafinil or tetrahydrogestrinone, which at the time were not on the International Association of Athletics Federation's banned list. Officials from the U.S. Anti-Doping Agency said Conte was the source of THG, a previously undetectable steroid for which four Raiders players, four American track athletes and Chambers have tested positive. Athletes who test positive for modafinil face disqualification from the event in which they tested positive but no further sanctions. White, Gaines and four other track athletes tested positive for the medication, which they say doesn't help them run faster. A physician said he gave White the medication to combat narcolepsy. Many of the athletes who tested positive are connected to the ZMA Track Club, which Korchemny started with Conte in 2001. But Korchemny coaches only three of those implicated. Another who was caught with modafinil, Chris Phillips of Arkansas, received the drug from Korchemny at the world championships in Paris. But Korchemny does not coach Phillips, who placed fifth in the 110-meter hurdles in Paris. Korchemny accused USA Track of a double standard against him. For instance, no one has suggested that John Smith of the HSI team in Los Angeles face similar treatment, although three of his athletes _ Inger Miller, Ato Bolden and Mickey Grimes _ have tested positive for mild stimulants since 1999. Smith, a 1972 Olympian, is men's coach of the 2005 world championship team. Another coach to escape scrutiny is Trevor Graham, who is based in Raleigh, N.C. A handful of his athletes have tested positive, including 400 runner Jerome Young, who Olympic officials say was allowed to compete in Sydney although the Americans knew he had tested positive for a steroid in 1999. Agent Emanuel Hudson, Smith's business partner, said it is unfair to compare the positives of the HSI athletes with those in the Balco case. For example, he said Grimes took a cold medication at the Pan American Games last summer, whereas the rash of modafinil cases seems concentrated in one group. "It sounds very suspicious when you have a new substance that hadn't been on the circuit and all of a sudden shows up and shows up with those associated with one another," said Hudson, a bitter rival of the ZMA team. But Korchemny, a former Soviet coach, said he learned about modafinil from European coaches a year before the scandal _ in 2002. He said the drug was to help fight his fatigue from traveling to meets around the world, not to give to athletes. ___ (c) 2004, San Jose Mercury News (San Jose, Calif.). Visit MercuryNews.com, the World Wide Web site of the Mercury News, at http://www.mercurynews.com. LOAD-DATE: January 12, 2004 LANGUAGE: ENGLISH KR-ACC-NO: K3371 JOURNAL-CODE: SJ Copyright 2004 Knight Ridder/Tribune News Service Knight Ridder/Tribune News Service 601 of 998 DOCUMENTS San Jose Mercury News (California) January 12, 2004 Monday MORNING FINAL EDITION USA TRACK MIGHT BAN COACH FROM WORLD INDOOR MEET; OFFICIALS LEERY OF TIES WITH BALCO BYLINE: ELLIOTT ALMOND, Mercury News SECTION: SPORTS; Pg. 4D LENGTH: 768 words U.S. track officials might banish Remi Korchemny from coaching the American team at the world indoor championships in March because of his connection to a Burlingame nutrition company under grand jury investigation. A ranking USA Track & Field official, Stephanie Hightower, said the group is exploring the legality of excluding the Castro Valley coach because heworked with Victor Conte Jr., president of Balco Laboratories. Conte is the target of a money-and-drug investigation involving athletes from baseball, football, boxing and Olympic sports. "We don't have any regulations for this," said Hightower, chair of the women's track committee. "We haven't had to deal with this kind of stuff before." Three of Korchemny's sprinters -- Kelli White of Union City, Chryste Gaines of Georgia and Dwain Chambers of England -- had positive drug tests last summer. White and Gaines had taken modafinil, a sleep-disorder medication that Olympic drug officials classify as a mild stimulant. "It bothers me that people continue to attack us," Korchemny said. "I know that I don't feel I have committed any crime because I strongly believe modafinil is not something that makes athletes perform better." Chambers tested positive for THG, the newly discovered steroid at the center of a growing international scandal. Korchemny said he never gave THG to Chambers, who faces a suspension from UK Athletics. The scandal has continued to fuel criticism that USA Track defies worldwide drug standards, and some in the organization worry about Korchemny's presence during the championships in Budapest, Hungary. "The feeling is that his going would be a manifestation that the United States is not serious about drugs," said Brooks Johnson, director of high performance at the U.S. Olympic Training Center in Chula Vista. Johnson said he doesn't endorse sanctions without giving the coach a hearing. Korchemny, one of the indoor team's three assistants, has not been subpoenaed by the grand jury nor charged with any wrongdoing. A handful of track athletes tested positive for modafinil or tetrahydrogestrinone, which at the time were not on the International Association of Athletics Federation's banned list. Officials from the U.S. Anti-Doping Agency said Conte was the source of THG, a previously undetectable steroid for which four Raiders players, four American track athletes and Chambers have tested positive. Athletes who test positive for modafinil face disqualification from the event in which they tested positive but no further sanctions. White, Gaines and four other track athletes tested positive for the medication, which they say doesn't help them run faster. A physician said he gave White the medication to combat narcolepsy. Many of the athletes who tested positive are connected to the ZMA Track Club, which Korchemny started with Conte in 2001. But Korchemny coaches only three of those implicated. Another who was caught with modafinil, Chris Phillips of Arkansas, received the drug from Korchemny at the world championships in Paris. But Korchemny does not coach Phillips, who placed fifth in the 110-meter hurdles in Paris. Korchemny accused USA Track of a double standard against him. For instance, no one has suggested that John Smith of the HSI team in Los Angeles face similar treatment, although three of his athletes -- Inger Miller, Ato Bolden and Mickey Grimes -- have tested positive for mild stimulants since 1999. Smith, a 1972 Olympian, is men's coach of the 2005 world championship team. Another coach to escape scrutiny is Trevor Graham, who is based in Raleigh, N.C. A handful of his athletes have tested positive, including 400 runner Jerome Young, who Olympic officials say was allowed to compete in Sydney although the Americans knew he had tested positive for a steroid in 1999. Agent Emanuel Hudson, Smith's business partner, said it is unfair to compare the positives of the HSI athletes with those in the Balco case. For example, he said Grimes took a cold medication at the Pan American Games last summer, whereas the rash of modafinil cases seems concentrated in one group. "It sounds very suspicious when you have a new substance that hadn't been on the circuit and all of a sudden shows up and shows up with those associated with one another," said Hudson, a bitter rival of the ZMA team. But Korchemny, a former Soviet coach, said he learned about modafinil from European coaches a year before the scandal -- in 2002. He said the drug was to help fight his fatigue from traveling to meets around the world, not to give to athletes. LOAD-DATE: August 21, 2005 LANGUAGE: ENGLISH GRAPHIC: Photo; PHOTO: JIM GENSHEIMER -- MERCURY NEWS Remi Korchemny has not been charged with wrongdoing and says: "It bothers me that people continue to attack us." Copyright 2004 San Jose Mercury News All Rights Reserved 602 of 998 DOCUMENTS SUNDAY TELEGRAPH(LONDON) January 11, 2004, Sunday This 'stay-awake' drug is far from safe SECTION: Pg. 22 LENGTH: 223 words Your article "The 44 hour day" (Review, January 4) gives the impression that Modafinil is a drug without significant side effects that can be used, as required, to stay awake. Nothing could be further from the truth. Modafinil is a prescription-only medicine for the debilitating condition of narcolepsy. Your reporter attempts to reassure us that Modafinil is "non-addictive and non-carcinogenic" and mentions none of the dangers associated with taking it. She even gives the website address for readers to order the drug. The British National Formulary states that the side effects of Modafinil are anorexia, abdominal pain, headache, personality disorder, CNS stimulation, excitation, euphoria, nervousness, dry mouth, palpitations, tachycardia, hypertension, tremor, gastro-intestinal disturbances, rashes, pruritis and liver disorders. It also states that dependence cannot be ruled out and that it should be used with caution. The availability of prescription-only medication over the internet is a matter of great concern and about which the medical profession in this country is trying to educate the public. This prominent article, giving such an unbalanced view, will contribute to this growing and dangerous problem. (Dr) Angus Ross MRCP Barnard Castle, County Durham [PS]Features: [ES] Letter to the Editor: LOAD-DATE: January 11, 2004 LANGUAGE: ENGLISH Copyright 2004 The Telegraph Group Limited 603 of 998 DOCUMENTS World Markets Analysis January 09, 2004 FDA Gives Barr Tentative Backing for Excessive Sleeping Generic BYLINE: Henry Dummett SECTION: IN BRIEF LENGTH: 159 words Barr Laboratories - a subsidiary of Barr Pharmaceuticals - has obtained tentative FDA approval for a generic version of Cephalon's Provigil (modafinil) in 100mg and 200mg strengths. When formally cleared for sale, the drug will be indicated for use in improving wakefulness in patients suffering from excessive daytime sleepiness associated with narcolepsy. Significance: According to IMS Health data, modafinil tablets achieved sales valued at US$289m in the 12 months ending November 2003. It will be some time, however, before Barr is able to seize some of the market through its generic version. Full approval is contingent on the outcome of litigation pending over the drug's patent status. The case is not due to be heard before January 2005. Barr initiated a legal challenge against two patents held by Cephalon over modafinil in February 2003, which provoked Cephalon into filing a patent infringement suit against Barr in response. LOAD-DATE: January 09, 2004 LANGUAGE: ENGLISH Copyright 2004 World Markets Research Limited; All Rights Reserved 604 of 998 DOCUMENTS PR Newswire January 8, 2004 Thursday Barr Receives Tentative Approval for Modafinil Tablets, 100 mg and 200 mg SECTION: FINANCIAL NEWS LENGTH: 738 words DATELINE: WOODCLIFF LAKE, N.J. Jan. 8 Barr Pharmaceuticals, Inc. (NYSE: BRL) today announced that its wholly-owned subsidiary, Barr Laboratories, Inc., has received tentative approval from the U.S. Food and Drug Administration (FDA) for its generic version of Cephalon's Provigil(R) Tablets (Modafinil Tablets), 100 mg and 200 mg. The Company is currently litigating whether its products infringe a patent held by Cephalon. A trial in the U.S. District Court of New Jersey is currently scheduled for January 2005. Barr's tentatively approved Modafinil Tablets is indicated to improve wakefulness in patients with excessive daytime sleepiness associated with narcolepsy. Modafinil Tablets had annual sales of approximately $289 million, based on IMS data for the twelve months ended November 2003. Barr filed an Abbreviated New Drug Application (ANDA) for Modafinil Tablets, 100 mg and 200 mg, with the FDA on December 24, 2002, and received notification of the application's acceptance for filing in early February 2003. Following receipt of notice from FDA, Barr notified Cephalon on February 20, 2003 of Barr's challenge to the two patents that Cephalon had listed in the Orange Book in connection with Provigil(R). On March 28, 2003, Cephalon filed suit against four generic pharmaceutical companies, including Barr, for alleged infringement of one of two listed Cephalon patents in U.S. District Court for the District of New Jersey. A tentative approval reflects FDA's preliminary determination that a generic product satisfies the substantive requirements for approval, subject to the expiration of all statutorily imposed non-approval periods. A tentative approval does not allow the applicant to market the generic drug product. Barr Pharmaceuticals, Inc. and its subsidiaries are engaged in the development, manufacture and marketing of generic and proprietary pharmaceuticals. Forward-Looking Statements The following press release contains a number of forward-looking statements. To the extent that any statements made in this press release contain information that is not historical, these statements are essentially forward-looking. Forward-looking statements can be identified by their use of words such as "expects," "plans," "will," "may," "anticipates," "believes," "should," "intends," "estimates" and other words of similar meaning. These statements are subject to risks and uncertainties that cannot be predicted or quantified and, consequently, actual results may differ materially from those expressed or implied by such forward-looking statements. Such risks and uncertainties include: the difficulty in predicting the timing and outcome of legal proceedings, including patent-related matters such as patent challenge settlements and patent infringement cases; the difficulty of predicting the timing of U.S. Food and Drug Administration, or FDA, approvals; court and FDA decisions on exclusivity periods; the ability of competitors to extend exclusivity periods for their products; the success of our product development activities; market and customer acceptance and demand for our pharmaceutical products; our dependence on revenues from significant customers; reimbursement policies of third party payors; our dependence on revenues from significant products; the use of estimates in the preparation of our financial statements; the impact of competitive products and pricing; the ability to develop and launch new products on a timely basis; the availability of raw materials; the availability of any product we purchase and sell as a distributor; our mix of product sales between manufactured products, which typically have higher margins, and distributed products; the regulatory environment; our exposure to product liability and other lawsuits and contingencies; the increasing cost of insurance and the availability of product liability insurance coverage; our timely and successful completion of strategic initiatives, including integrating companies and products we acquire and implementing new enterprise resource planning systems; fluctuations in operating results, including the effects on such results from spending for research and development, sales and marketing activities and patent challenge activities; and other risks detailed from time to time in our filings with the Securities and Exchange Commission. SOURCE Barr Pharmaceuticals, Inc. CONTACT: Carol A. Cox of Barr Pharmaceuticals, Inc., +1-201-930-3720, ccox@barrlabs.com URL: http://www.prnewswire.com LOAD-DATE: January 9, 2004 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS AND MEDICAL EDITORS PUBLICATION-TYPE: Newswire Copyright 2004 PR Newswire Association, Inc. 605 of 998 DOCUMENTS San Jose Mercury News January 8, 2004, Thursday Sprinter White out for indoor season BYLINE: By Elliott Almond SECTION: SPORTS LENGTH: 636 words SAN JOSE, Calif. _ World champion sprinter Kelli White has not trained for four months because of a knee injury that could hinder preparations for the 2004 Summer Olympics. Coach Remi Korchemny told the San Jose Mercury News that White, of Union City, Calif., had knee surgery last month to correct a bone-tissue problem and will not compete during the upcoming indoor season. White left Thursday to stay with fiance Boris Henry, a javelin thrower in Germany, where she plans to continue treatment. She did not respond to an e-mail request for an interview. "Nobody knows what is wrong with her knee," Korchemny said. "It is very hard to say what the diagnosis is." If the problem persists, it could affect White's ability to prepare for the U.S. Olympic trials in Sacramento in July and the Summer Games in Athens in August. White, 26, became the first American woman to sweep the sprint races at a world championships when she won the 100 meters and 200 titles in Paris last year. But since the August meet, she has been ensnarled in a drug scandal involving a Burlingame nutrition company and its owner, Victor Conte Jr. White tested positive for the controversial medication modafinil, which drug-testing officials classify as a mild stimulant. A physician formerly connected to Conte's Balco laboratories said he gave White samples of the medication to combat narcolepsy, which she suffers along with her mother. White faces the loss of her gold medals in Paris, as well as $120,000 in prize money. She also tested positive for the drug at the U.S. nationals in Stanford in June and faces the loss of her American titles as well. Modafinil was not on a banned list last summer, but officials are using a clause in the drug code _ "related substances" _ to prosecute athletes caught with the medication. The World Anti-Doping Agency, which sets the standards for Olympic drug testing, added the medication to its banned list last week. Korchemny maintains White did nothing wrong because the medication was not on the list when she took it, and points out many sleeping disorder researchers say modafinil is not a stimulant. It is an argument expected to be decided in hearings with the U.S. Anti-Doping Agency, the group adjudicating the American cases. Others who tested positive for modafinil were sprinter Chryste Gaines; hurdlers Sandra Glover, Chris Phillips and Eric Thomas; and hammer thrower John McEwen, who also was found with the designer steroid THG. The modafinil cases could lead to disqualification from the event in which the athletes participated. While White's case continues to shadow her, Korchemny has other concerns. "I mostly worry about Kelli's knee," he said. Korchemny, who also coaches Gaines, estimated that White would be ready to walk on a track in a few weeks. She is able to complete drills in a swimming pool but cannot lift weights, he said. "It is the kind of injury you cannot overload," Korchemny added. The coach said physicians suggested White's tissue problems are related to an allergy to milk products. Korchemny said skipping the indoor season would not jeopardize White's chances for spring and summer if she recovers in time to begin training. The knee problem is the latest injury to beset White, a former James Logan High star. She returned from a tendon tear in 2002, an injury so severe that Korchemny wondered whether she would walk again. Last spring a painful foot injury almost forced White to quit. Instead, she blossomed to become the world's top-ranked sprinter and had hopes of challenging defending Olympic champion Marion Jones, who took last year off to have a son. ___ (c) 2004, San Jose Mercury News (San Jose, Calif.). Visit MercuryNews.com, the World Wide Web site of the Mercury News, at http://www.mercurynews.com. LOAD-DATE: January 8, 2004 LANGUAGE: ENGLISH KR-ACC-NO: K1289 JOURNAL-CODE: SJ Copyright 2004 Knight Ridder/Tribune News Service Knight Ridder/Tribune News Service 606 of 998 DOCUMENTS San Jose Mercury News (California) January 8, 2004 Thursday MORNING FINAL EDITION KNEE INJURY COULD THREATEN KELLI WHITE'S OLYMPIC DREAM BYLINE: ELLIOTT ALMOND, Mercury News SECTION: SPORTS; Pg. 1D LENGTH: 606 words World champion sprinter Kelli White has not trained for four months because of a knee injury that could hinder preparations for the 2004 Summer Olympics. Coach Remi Korchemny told the Mercury News that White, of Union City, had knee surgery last month to correct a bone-tissue problem and will not compete during the upcoming indoor season. White left today to stay with fiance Boris Henry, a javelin thrower in Germany, where she plans to continue treatment. She did not respond to an e-mail request for an interview. "Nobody knows what is wrong with her knee," Korchemny said. "It is very hard to say what the diagnosis is." If the problem persists, it could affect White's ability to prepare for the U.S. Olympic trials in Sacramento in July and the Summer Games in Athens in August. White, 26, became the first American woman to sweep the sprint races at a world championships when she won the 100 meters and 200 titles in Paris last year. But since the August meet, she has been ensnarled in a drug scandal involving a Burlingame nutrition company and its owner, Victor Conte Jr. White tested positive for the controversial medication modafinil, which drug-testing officials classify as a mild stimulant. A physician formerly connected to Conte's Balco laboratories said he gave White samples of the medication to combat narcolepsy, which she suffers along with her mother. White faces the loss of her gold medals in Paris, as well as $120,000 in prize money. She also tested positive for the drug at the U.S. nationals in Stanford in June and faces the loss of her American titles as well. Modafinil was not on a banned list last summer, but officials are using a clause in the drug code -- "related substances" -- to prosecute athletes caught with the medication. The World Anti-Doping Agency, which sets the standards for Olympic drug testing, added the medication to its banned list last week. Korchemny maintains White did nothing wrong because the medication was not on the list when she took it, and points out many sleeping disorder researchers say modafinil is not a stimulant. It is an argument expected to be decided in hearings with the U.S. Anti-Doping Agency, the group adjudicating the American cases. Others who tested positive for modafinil were sprinter Chryste Gaines; hurdlers Sandra Glover, Chris Phillips and Eric Thomas; and hammer thrower John McEwen, who also was found with the designer steroid THG. The modafinil cases could lead to disqualification from the event in which the athletes participated. While White's case continues to shadow her, Korchemny has other concerns. "I mostly worry about Kelli's knee," he said. Korchemny, who also coaches Gaines, estimated that White would be ready to walk on a track in a few weeks. She is able to complete drills in a swimming pool but cannot lift weights, he said. "It is the kind of injury you cannot overload," Korchemny added. The coach said physicians suggested White's tissue problems are related to an allergy to milk products. Korchemny said skipping the indoor season wouldnot jeopardize White's chances for spring and summer if she recovers in time to begin training. The knee problem is the latest injury to beset White, a former James Logan High star. She returned from a tendon tear in 2002, an injury so severe that Korchemny wondered whether she would walk again. Last spring a painful foot injury almost forced White to quit. Instead, she blossomed to become the world's top-ranked sprinter and had hopes of challenging defending Olympic champion Marion Jones, who took last year off to have a son. LOAD-DATE: August 21, 2005 LANGUAGE: ENGLISH GRAPHIC: Photo; PHOTO: White Sprinter from Union City had surgery last month Copyright 2004 San Jose Mercury News All Rights Reserved 607 of 998 DOCUMENTS The Vancouver Sun (British Columbia) January 5, 2004 Monday Final Edition Prescription drug keeps you going without feeling tired: Modafinil appears to offer alertness without side-effects, but doctors remain cautious SOURCE: The Sunday Telegraph BYLINE: Julia Llewellyn Smith SECTION: News; Pg. D8 LENGTH: 811 words DATELINE: LONDON LONDON -- It's 4 a.m., I've been up for 20 hours, but I don't feel tired. The reason for my alertness is 200 milligrams of modafinil, a new prescription drug that staves off sleep for hours on end. Unlike the drugs we've traditionally used to keep us going, modafinil appears to have few, if any, side effects. While coffee-drinkers shake and amphetamine-users jabber aggressively, on modafinil I feel calm, focused -- and able to work all night. According to Leon Kreitzman, author of The 24-Hour Society, drugs like modafinil will transform society. "Modafinil belongs to a new class of awakening drugs known as eugeroics, which are unravelling the mechanisms of sleepiness. Once you've done that you will end up in a world where the need to sleep is optional. I would say that will happen within the next quarter of a century." As Kreitzman points out to me, "The idea of a world without sleep may sound too bizarre to contemplate, but that doesn't mean it won't be acceptable to future generations." He adds, "We spend one-third of our lives asleep. If we eliminated that, we'd have another 25 years to do things." But at what price? Round-the-clock supermarkets, 24-hour television, electric lighting, and demanding bosses all make it harder to get the eight hours rest most of us need to function properly. Last month, the research group Demos even declared Britain's creativity and productivity was at risk because the average British person has accumulated a "sleep deficit" of 25 to 30 hours. It pointed out that too many crucial decisions, such as the one that launched the Challenger space shuttle, are made by people handling complex data after days of sleep deprivation. Already, the armed forces are committed to the drug, having used it to help British and U.S. troops "power on" to Baghdad: marching for 40 hours, sleeping for eight, and repeating the pattern without noticeable ill-effect. In previous conflicts, armies stoked up on amphetamines, but these made soldiers jumpy and caused terrible "crashes" of fatigue and depression when they were withdrawn. Worse, such drugs were thought to be responsible for some fatal lapses in judgment, such as the recent "friendly fire" killing of four Canadian soldiers in Afghanistan. By contrast, helicopter pilots given modafinil were shown to be more alert, energetic and confident than those who were not. If it works for the military, who else could it help? New mothers, long-distance truck drivers? Modafinil, which was developed in France a decade ago, was approved in 1998 as an aid for narcoleptics -- people who fall asleep uncontrollably. Anyone who wants to get the drug from a pharmacist in Britain needs a prescription. It is, however, easy to bypass the system, for the drug is readily available to anyone with a credit card and a computer. Studies in the U.S. show that while only 150,000 Americans are narcoleptics, 250,000 are using modafinil. It takes me two clicks on the Internet to find the aurapharm.com site, which will send me 30 tablets for about $175 Cdn. The pills arrive six days later. I call Ian Davison, of Cephalon, which manufactures modafinil in the U.S. under the name ProVigil, and is developing even more powerful versions. "We are not 100 per cent sure how ProVigil works," he says. "We know it has an effect on the hypothalamus region of the brain, which controls our sleep-wake generating sites, whereas amphetamines control the completely separate dopaminergic side. "Both sides stimulate the cerebral cortex, which keeps people awake, but the dopaminergic also stimulates the heart rate and blood pressure. When the amphetamines wear off there is a crash, while with modafinil people just go back to their normal rhythm of sleep-wake." A couple of years ago the U.S. Food and Drug Administration admonished Cephalon for "over-reaching" its marketing of ProVigil. Davison stresses that modafinil is intended solely for narcoleptics: "We think we are responsible in how we market and portray the drug. We certainly don't condone its use 'off-label.' You really should only take a medicine for what it's prescribed for. In any case, you're wrong to think you will get to a situation where you won't sleep at all. In the end, the overwhelming drive to sleep will come whether you use modafinil or not." He is backed up by Dr. Irshaad Ebrahim of the London Sleep Centre. "Modafinil is very effective, and occasionally I prescribe it to insomniacs who can't function during the day. But to see it as a panacea for all is ridiculous. I would always try to promote a good night's sleep through natural methods like diet and exercise." Sleep, he points out, helps the brain store memories and recuperate from work, and helps the body build its immune system. "If you use a drug to overcome that, you will deprive yourself of those things." LOAD-DATE: January 5, 2004 LANGUAGE: ENGLISH TYPE: Business Copyright 2004 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 608 of 998 DOCUMENTS SUNDAY TELEGRAPH(LONDON) January 04, 2004, Sunday The 44-Hour Day BYLINE: BY JULIA LLEWELLYN SMITH SECTION: Pg. 01 LENGTH: 2328 words It's 4am, I've been up for 20 hours, but I don't feel tired. I'm not at a wild party, nor rocking a wailing infant, nor am I lying miserably in bed cursing my insomnia. I am sitting at my desk paying my bills on the internet as if it were mid-afternoon. There is none of the usual roar of traffic from outside, just my keyboard tapping into eerie silence. I call friends in Australia - where it's mid-afternoon and they're very surprised to hear from me. I put some washing in the machine, then paint my toenails. I look at the clock: 4.45am. I haven't yawned once. The reason for my alertness is 200mg of modafinil, a new prescription drug that staves off sleep for hours on end. Unlike the drugs we've traditionally used to keep us going, modafinil appears to have few, if any, side effects. While coffee-drinkers shake and amphetamine-users jabber aggressively, on modafinil I feel calm, focused - and able to work all night. According to Leon Kreitzman, author of The 24-Hour Society, drugs like modafinil (pronounced modafinil) will transform society. "Modafinil belongs to a new class of awakening drugs known as eugeroics, which are unravelling the mechanisms of sleepiness. Once you've done that you will end up in a world where the need to sleep is optional. I would say that will happen within the next quarter of a century." When I tell my friends about Kreitzman's vision, they react in unison. "But I love sleep," they protest. "A world without it would be horrible." A moment later, they ask: "Where did you say you got those pills? Could I have one?" As Kreitzman points out to me, "The idea of a world without sleep may sound too bizarre to contemplate, but that doesn't mean it won't be acceptable to future generations. After all, I am talking to you from a mobile phone in a car and 20 years ago we couldn't contemplate that. We spend one-third of our lives asleep. If we eliminated that we'd have another 25 years to do things." But at what price? Round-the-clock supermarkets, 24-hour television, electric lighting, demanding bosses all make it harder and harder to get the eight hours rest most of us need to function properly. Last month, the research group Demos even declared the nation's creativity and productivity was at risk because the average British person has accumulated a "sleep deficit" of 25 to 30 hours. It pointed out that too many crucial decisions, such as the one that launched the Challenger space shuttle, are made by people handling complex data after days of sleep deprivation, and it urged the Government to promote "sleep days" for bleary-eyed employees to catch up on their rest. There has been no official response to this report, but it's worth noting that when Tony Blair was admitted to hospital in October with an irregular heartbeat, his condition was blamed on too little sleep (he rarely gets more than six hours) and too much caffeine. Recently, an aide to Lady Thatcher revealed that the former Prime Minister's famed ability to get by on a mere four hours was achieved with the help of vitamin B12 injections. These days, modafinil enables ordinary mortals to imitate her. Already, the armed forces are committed to the drug, having used it to help British and American troops "power on" to Baghdad: marching for 40 hours, sleeping for eight, and repeating the pattern without noticeable ill-effect. In previous conflicts, armies stoked up on amphetamines, but these made soldiers jumpy and caused terrible "crashes" of fatigue and depression when they were withdrawn. Worse, such drugs were thought to be responsible for some fatal lapses in judgment, such as the recent "friendly fire" killing of four Canadian soldiers in Afghanistan. By contrast, helicopter pilots given modafinil were shown to be more alert, energetic and confident than those who were not. If it works for the military, who else could it help? New mothers, long-distance lorry drivers, junior doctors, the holiday motorist hell-bent on reaching the Cote d'Azur in one unbroken drive? Or City traders working 14-hour days, who resent spending most of the remaining 10 asleep? Or perhaps the contestants in Shattered, Channel 4's barbaric new game show which starts tonight, who have to stay awake for a week to win? Recently six American athletes were banned from competition after it was discovered that they were dosing themselves with the drug. The truth is that we would love to burn the candle at both ends: we just need to find the wax. Modafinil, which was developed in France a decade ago, was approved here and in America in 1998 as an aid for narcoleptics - people who fall asleep uncontrollably. Henry Nicholls, 30, a London-based science writer with narcolepsy, has been using the drug for two years to control his condition, thought to affect 2,500 people in Britain. "For me, it works amazingly well," he says. "No one knows what the long-term effects of taking it daily will be, but I'm happy to be a guinea-pig. "Before, I used to worry that I'd never be able to hold down a normal job, because when the sleepiness took over there really was nothing I could do. Now I am able to function like anyone else. I take a 100mg dose in the morning and in the evening I go to sleep like anyone else. Conversely, if I forget to take it, the symptoms come back almost immediately." Nicholls, like anyone who wants to get the drug from a pharmacist in this country, needs a prescription for his supply. It is, however, easy to by-pass the system, for the drug is readily available to anyone with a credit card and a computer. Studies in the US show that while only 150,000 Americans are narcoleptics, 250,000 are using modafinil. It takes me two clicks on the internet to find the aurapharm.com site, which will send me 30 tablets for 125 ( pounds 87). The pills arrive six days later in a tiny blister packet, like aspirin. The instructions are in Turkish - although words like kardiosvaskuuler and depresyon jump out at me. Alarmed, I go on-line again to find the English instructions and read that the drugs are non-addictive and non-carcinogenic. More clicking reveals that the drug seems to slow the release of an amino-acid called GABA, a sleep-promoter in the brain, and may also help release histamines that promote wakefulness. I call Ian Davison, of Cephalon, which manufactures modafinil here and in the US under the name ProVigil, and is developing even more powerful versions. "We are not 100 per cent sure how ProVigil works," he says. "We know it has an effect on the hypothalamus region of the brain, which controls our sleep-wake generating sites, whereas amphetamines control the completely separate dopaminergic side. "Both sides stimulate the cerebral cortex, which keeps people awake, but the dopaminergic also stimulates the heart rate and blood pressure. When the amphetamines wear off there is a crash, while with modafinil people just go back to their normal rhythm of sleep-wake." A couple of years ago the US Food and Drug Administration admonished Cephalon for "over-reaching" its marketing of ProVigil. Davison stresses that modafinil is intended solely for narcoleptics: "We think we are responsible in how we market and portray the drug. We certainly don't condone its use 'off-label'. You really should only take a medicine for what it's prescribed for. In any case, you're wrong to think you will get to a situation where you won't sleep at all. In the end, the overwhelming drive to sleep will come whether you use modafinil or not." He is backed up by Dr Irshaad Ebrahim of the London Sleep Centre. "Modafinil is very effective, and occasionally I prescribe it to insomniacs who can't function during the day. But to see it as a panacea for all is ridiculous. I would always try to promote a good night's sleep through natural methods like diet and exercise." Sleep, he points out, helps the brain store memories and recuperate from work, and helps the body build its immune system. "If you use a drug to overcome that, you will deprive yourself of those things." There are no feelings of euphoria associated with modafinil, so it is unlikely to become fashionable; sleep experts certainly hope it won't. None the less, when I swallow my first one I am surprised to feel absolutely nothing. I've started slowly with a 100mg dose - half the recommended amount - to avoid potential nausea and headaches, the most common side effects. As usual, I've crawled out of bed reluctantly at 8am, after too-late a night and with a mountain of tasks ahead of me. My day passes well: I feel sharp, moderately energetic but certainly not like superwoman. But as the hours wear on, I notice what doesn't happen: no yawning, no intense yearning for a 2pm nap. Instead I steadily work through my to-do list. It's in the evening that things get interesting: I go out to dinner with friends. We stay until after midnight. Normally I would be flagging, but now I sit and talk cheerfully as if it were mid-morning (it may help that I'm not drinking, since Cephalon has not yet tested the effects of mixing alcohol with modafinil). I get home and rather than dive into bed as I usually do, I watch some television and read for half an hour. I turn the light out at about 2am, worried that I won't sleep at all, but in fact I crash out at once. Astonishingly, I'm awake before 7am, at least two hours earlier than I usually would after such a late night, and instantly want to jump out of bed and get going. I pop another pill and look forward to enjoying another busy day and a late night. I'm thrilled. It's time to push my boundaries. I am going to a party in a pub. Just before I go out I take a 200mg dose. At the party I am surrounded by thirty-somethings who, shattered after a long week, can't conceal their yawns. Yet I don't glance once at my watch. My friends are disappointed that I am not grinding my teeth or acting "wired". I explain again and again that I am not taking amphetamines. They study my face for signs of drug-abuse but find nothing. A few accuse me of taking a placebo. But as, one-by-one, they start calling taxis, I am still there talking animatedly (but not manically) and having fun. I'm surprised to feel my legs shake slightly - a symptom of exhaustion. I realise modafinil may stop you from feeling sleepy but you still feel tired. My limbs grow heavier, but that doesn't stop the wakefulness. If wake-up drugs catch on, "tiredness" and "sleepiness" will have to be separated: a hard concept to grasp. I go home around 1.30am, where again I feel no desire to sleep. At the same time, when it's cold and dark the prospect of a cosy bed is very appealing. Why would I want to work all night when I could be snuggled under a duvet? I can't resist climbing under the covers, but instead of turning off the light, I read. After an hour, I remember I need to check my tax bill. I might as well do it now. Having done so, there seems no particular reason - tradition apart - to go back to bed. It's 3am. There's an article I have to finish, a letter I need to write. I really should do some washing. Why not do it now? Yet although it's satisfying to power through my work, it's unpleasant. It's tiredness versus sleepiness again: I am awake enough to function efficiently but ploughing through the backlog is still physically wearying. I need a break, and turn on the television: only BBC News 24. I curse myself for not having cable and return to the keyboard. The loneliness is miserable. I feel as if I'm the only person in the world. Yes, I could go out and find an all-night supermarket, but it's freezing outside and I might get mugged. I end up behaving like insomniacs everywhere and I go on-line, surfing wildly and sending silly e-mails in order to feel connected to humanity. I am beginning to understand how sleep gives a fundamental pattern to your life. Without that break, time stretches ahead of you dauntingly like a desert. I worry about what would happen if wake-up drugs were widely available. If your biggest rival at work was taking them, would you really be able to resist? Would people who slept be seen as losers? Will this be the 21st-century version of Eve's apple? By 6am I have had a bath and breakfast. I can't wait for the rest of the world to wake up. As soon as the paper shop opens at 7am, I'm out of the house, desperate for human contact. I bump into a neighbour. "I can tell you've been up all night, you look terrible," he says. Modafinil works, yes, but you need to invest heavily in under-eye concealer. I've now been 24 hours without sleep. The rest of the day isn't much fun, although I get through it. There's a family brunch, followed by more long hours on-line organising a complicated trip to Australia. By now, the gulf between fatigue and sleepiness is even more apparent. I still feel no urge to put my head down, but I am just as irritable and subdued as I always am without a decent night's sleep. If I were a pilot, I wouldn't want to fly a mission right now. After a meal, I cheer up considerably. (The most important thing is to remember to eat - if you are going to stay awake for double the normal amount of time, you'll need double the amount of fuel.) I try to nap during the day, but can't. I go to bed at 11pm and don't fall asleep until gone 2am. Modafinil has given me well over 40 hours on the trot - as promised. As I write this, the following morning, I have a nasty cold - I suspect the effect of no sleep on my immune system. I don't feel as if I've missed a night's sleep, but by mid-afternoon I'm yawning as I normally would. I realise now how much more bushy-tailed I was on modafinil days. I hated my sleepless night because it felt so unnatural, but I still think modafinil could be the perfect response to a broken night, an urgent deadline or jet-lag. And no, I will not share the rest of my tablets with my friends. If they want to get ahead, they can get their own. LOAD-DATE: January 4, 2004 LANGUAGE: ENGLISH Copyright 2004 The Telegraph Group Limited 609 of 998 DOCUMENTS Aberdeen Evening Express January 2, 2004 US track stars test positive SECTION: Sport; Soccer; Scots1/2/3; Pg. 38 LENGTH: 301 words Athletics: Sprint champion Kelli White is one of six American athletes to have tested positive for the stimulant modafinil, the US Olympic Committee confirmed. She tested positive at the USA Track and Field Championships in June, which was the qualifying event for American athletes for the World Championships in Paris. The 26-year-old White went on to win the 100 and 200 metre gold medals at the Paris competition two months later, and also tested positive there. Fellow sprinter Chryste Gaines and hurdlers Sandra Glover, Chris Phillips and Eric Thomas had modafinil in their system, while hammer thrower John McEwen produced a positive sample for both modafinil and tetrahydrogestrinone (THG). football: Chelsea are 4/1 favourites for the FA Cup with bookmaker William Hill, who also offer 6/1 Arsenal, Manchester United; 7 Liverpool; 14 Middlesbrough, Newcastle; 16 Everton, Tottenham; 20 Blackburn, Fulham, Portsmouth; 25 Manchester City. Champs out to impress HOCKEY: Dundee Wanderers men's team is the only Scottish side to be competing in this weekend's Coaching Solutions Indoor Invitational Tournament at centres in Kidderminster and Birmingham. As reigning Scottish Indoor champions, Wanderers are expected to get to the quarter-finals, but will need to qualify from Pool B by finishing ahead of Stourport, Kingston upon Hull and Swansea. The tournament is being played over January 3 and 4. Cove Lottery FOOTBALL: Numbers drawn at Cove Rangers Lottery were: 3, 8, 9, 16, 22, 25. There were no winners. Consolation £10 winners were: D Boyd, c/o McIntosh Donalds; Ernie Hay, c/o Cove Rangers; Jim Gillespie, c/o Three Lums. Next week's prize is £1,400 using 1-25. Alickie quiz ANSWERS: 1 Sir Clive Woodward; 2 Hibernian; 3 Sydney; 4 Romania; 5 Gregor Townsend. LOAD-DATE: January 3, 2004 LANGUAGE: English Copyright 2004 Aberdeen Evening Express 610 of 998 DOCUMENTS Akron Beacon Journal (Ohio) January 1, 2004 Thursday 1 STAR EDITION U.S. ATHLETES FLUNK DRUG TEST; WHITE, NORTH CANTON'S MCEWEN AND FIVE OTHERS ARE APPEALING THE RESULTS BYLINE: From staff and wire reports SECTION: SPORTS; Pg. C3 LENGTH: 302 words Sprint champion Kelli White and six other American athletes flunked drug tests this summer, according to a report issued by the U.S. Olympic Committee. White and five other track and field athletes tested positive for the banned stimulant modafinil. Hammer thrower John McEwen of North Canton tested positive for modafinil and the newly discovered steroid THG. Cyclist Adham Sbeih tested positive for the endurance-boosting hormone EPO. The USOC announced the test results after the substances were found in two urine samples from each of the athletes, and following a 30-day review of the tests by the U.S. Anti-Doping Agency. All seven athletes are appealing the test results, the USOC said in a news release from its base in Colorado Springs, Colo. Any suspensions or other penalties would come only after appeals. U.S. shot put champion Kevin Toth of Hudson, who reportedly tested positive for THG, said Wednesday he is still awaiting word from his lawyer about his status. "We're still in a wait-and-see mode," Toth said. McEwen and Toth both have a goal of competing in the U.S. Track and Field Trials to make the 2004 Olympics Games next August in Athens, Greece. Also testing positive for modafinil at the national track championships were sprinter Chryste Gaines, 400-meter runner Sandra Glover, McEwen, and hurdler Eric Thomas of Houston. Hurdler Chris Phillips of Little Rock, Ark., tested positive for modafinil at the world championships. McEwen's attorney, Howard Jacobs, said McEwen would consider working with the International Association of Athletics Federations, which floated an offer of leniency for drug cheaters who provide valuable information about doping. No such offer has yet been made by the IAAF, Jacobs said in an interview with the Associated Press. LOAD-DATE: August 24, 2005 LANGUAGE: ENGLISH NOTES: 2004 Olympics Copyright 2004 Akron Beacon Journal All Rights Reserved 611 of 998 DOCUMENTS The Australian January 1, 2004 Thursday All-round Country Edition White among seven US athletes to fail tests SOURCE: AFP SECTION: SPORT; Pg. 22 LENGTH: 422 words * Drugs DUAL sprint world champion Kelli White tested positive for the banned substance modafinil in June, two months before returning another positive sample at the world titles, the US Olympic Committee announced yesterday. White was the biggest name among the seven leading US athletes to fail drug tests during the northern summer. Also testing positive for modafinil at the national titles were former US champion sprinter Chryste Gaines, four-time national champion 400metre hurdler Sandra Glover, reigning US 400m hurdles champion Eric Thomas and hammer thrower John McEwen. Hurdler Chris Phillips tested positive for modafinil at the 2003 world championships in Paris in August. Cyclist Adham Sbeih became the first American to test positive for the hormone EPO at the US championships in August, the USOC said. McEwen also tested positive for the new designer steroid tetrahydrogestrinone, or THG. All seven plan to appeal. Modafinil use results in disqualification at the event at which a positive test has occurred but no suspension. THG use can lead to a two-year ban. US Anti-Doping Agency spokesman Rich Wanninger said yesterday's announcement was made after samples taken from the athletes went through a series of confirmation tests and a 30-day review. White won the 100m-200m double at the world championships, where she also tested positive to modafinil. She could lose her two gold medals and $US120,000 ($160,650) prizemoney from the world titles after testing positive for modafinil, a stimulant which is used to treat narcolepsy. White is one of 40 athletes who have been subpoenaed to testify into a federal government investigation of a San Francisco lab, BALCO, which has been linked to THG. White's doctor, Brian Goldman, is BALCO's former medical director. Gaines, 33, won the US 100m championship in 2001 but is running faster now than ever before. She set her best time of 10.86sec in the 100m at the season-ending World Athletics Finals in Monaco in 2003. Glover, 34, is a four-time US 400m hurdle champion and won the silver medal at the world titles behind Sydney's Jana Pittman last year. The 31-year-old Phillips finished fourth at the national titles last year and fifth at the world titles in the 110m hurdles. Thomas is the reigning US champion in the 400m hurdles and won silver medals at the Pan American Games in 2003 and 1999. McEwen, 29, placed second at the 2003 US championships at Stanford in the hammer throw with a toss of 72.96m. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH JOURNAL-CODE: AUS Copyright 2004 Nationwide News Pty Limited 612 of 998 DOCUMENTS The Australian January 1, 2004 Thursday All-round Metro Edition White among seven in US to fail tests SOURCE: AFP SECTION: SPORT; Pg. 22 LENGTH: 373 words * Drugs DUAL sprint world champion Kelli White tested positive for the banned substance modafinil in June, two months before returning another positive sample at the world titles, the US Olympic Committee announced yesterday. Also testing positive for modafinil at the national titles were former US champion sprinter Chryste Gaines, four-time national champion 400metre hurdler Sandra Glover, reigning US 400m hurdles champion Eric Thomas and hammer thrower John McEwen. Hurdler Chris Phillips tested positive for modafinil at the 2003 world championships in Paris in August. Cyclist Adham Sbeih became the first American to test positive for the hormone EPO at the US championships in August, the USOC said. McEwen also tested positive for the new designer steroid tetrahydrogestrinone, or THG. All seven plan to appeal. US Anti-Doping Agency spokesman Rich Wanninger said yesterday's announcement was made after samples taken from the athletes went through a series of confirmation tests and a 30-day review. White won the 100m-200m double at the world championships, where she also tested positive to modafinil. She could lose her two gold medals and $US120,000 ($160,650) prizemoney from the world titles after testing positive for modafinil, a stimulant. White is one of 40 athletes who have been subpoenaed to testify into a federal government investigation of a San Francisco lab, BALCO, which has been linked to THG. White's doctor, Brian Goldman, is BALCO's former medical director. Gaines, 33, won the US 100m championship in 2001 but is running faster now than ever before. She set her best time of 10.86sec in the 100m at the season-ending World Athletics Finals in Monaco in 2003. Glover, 34, is a four-time US 400m hurdle champion and won the silver medal at the world titles behind Sydney's Jana Pittman last year. The 31-year-old Phillips finished fourth at the national titles last year and fifth at the world titles in the 110m hurdles. Thomas is the reigning US champion in the 400m hurdles and won silver medals at the Pan American Games in 2003 and 1999. McEwen, 29, placed second at the 2003 US championships at Stanford in the hammer throw with a toss of 72.96m. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH JOURNAL-CODE: AUS Copyright 2004 Nationwide News Pty Limited 613 of 998 DOCUMENTS Courier Mail (Queensland, Australia) January 1, 2004 Thursday Top US athletes fail tests for drugs SECTION: SPORT; Pg. 32 LENGTH: 391 words DUAL sprint world champion Kelli White tested positive for the banned substance modafinil in June, two months before returning another positive sample at the world titles, the United States Olympic Committee announced in Colorado yesterday. White was the biggest name among seven leading US athletes to fail drug tests during the northern hemisphere summer. Also testing positive for modafinil at the nationals were former US champion sprinter Chryste Gaines, four-time national champion 400m hurdler Sandra Glover, reigning US 400m hurdles champion Eric Thomas and hammer thrower John McEwen. Hurdler Chris Phillips tested positive for modafinil at the Paris world championships in August. Cyclist Adham Sbeih became the first American to test positive for the hormone EPO at the US cycling championships in August, the USOC said. McEwen also tested positive for the new designer steroid tetrahydrogestrinone, or THG. The seven Americans all plan to appeal. Modafinil use results in disqualification at the event at which a positive test has occurred, but no suspension, while THG use can lead to a two-year ban. White, who won the 100m-200m double at the world championships where she also tested positive to modafinil, is the most prominent name to fail the drug tests. She is one of 40 athletes who have been subpoenaed to testify into a federal government probe of a San Francisco-area lab, BALCO, that has been linked to THG. She could lose her two gold medals and $US120,000 ($A160,650) in prizemoney from the world titles after testing positive for modafinil, a stimulant used to treat narcolepsy. White's doctor Brian Goldman is BALCO's former medical director. Gaines won the US 100m championship in 2001 but is running faster now than she ever has. She set a personal best of 10.86sec in the 100m at the World Athletics Finals in Monaco in 2003. Glover, 34, is a four-time US 400m hurdle champion and won the silver medal at the worlds in Paris this year. The 31-year-old Phillips finished fourth at the nationals this year and fifth at the worlds in the 110m hurdles. Thomas is the reigning US champion in the 400m hurdles and won silver medals at the Pan American Games in 2003 and 1999. McEwen, 29, placed second at the 2003 US championships in Stanford in the hammer throw with a toss of 72.96m. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH JOURNAL-CODE: CML Copyright 2004 Nationwide News Pty Limited 614 of 998 DOCUMENTS Geelong Advertiser (Regional Daily) January 1, 2004 Thursday Stars fail drug tests SOURCE: AFP SECTION: SPORT; Pg. 46 LENGTH: 390 words DUAL sprint world champion Kelli White tested positive for the banned substance Modafinil in June, two months before returning another positive sample at the world titles, the United States Olympic Committee has announced. White was the biggest name among the seven leading US athletes to fail drug tests during the northern hemisphere summer. Also testing positive for Modafinil at the nationals were former US champion sprinter Chryste Gaines; four-time national champion 400m hurdler Sandra Glover; reigning US 400m hurdles champion Eric Thomas and hammer thrower John McEwen. Hurdler Chris Phillips tested positive for Modafinil at the 2003 Paris world championships in August. Cyclist Adham Sbeih became the first American to test positive for the hormone EPO at the US cycling championships in August, the USOC said. McEwen also tested positive for the new designer steroid tetrahydrogestrinone, or THG. The seven Americans all plan to appeal. Modafinil use results in disqualification at the event at which a positive test has occurred, but no suspension. THG use can lead to a two-year ban. The announcement was made after samples went through a series of confirmation tests and a 30-day review. White, who won the 100m-200m double at the world championships where she also tested positive to Modafinil, is the most prominent name to fail the drug tests. Her first positive sample was returned at the national track and field championships in June. White is one of 40 athletes who have been subpoenaed to testify into a US government probe of a San Francisco-area lab, BALCO, that has been linked to THG. She could lose her two gold medals and $160,650 in prizemoney from the world titles after testing positive for Modafinil, a stimulant used to treat narcolepsy. Gaines won the US 100m championship in 2001. She set a personal best of 10.86 seconds in the 100m at the World Athletics Finals in 2003. Glover, 34, is a four-time US 400m hurdle champion and won silver at the worlds in Paris this year. The 31-year-old Phillips finished fourth at the nationals this year and fifth at the worlds in the 110m hurdles. Thomas is the reigning US champion in the 400m hurdles and won silver at the Pan American Games in 2003 and 1999. McEwen, 29, was second at the 2003 US championships in the hammer throw. LOAD-DATE: January 2, 2004 LANGUAGE: ENGLISH JOURNAL-CODE: GAT Copyright 2004 Nationwide News Pty Limited All Rights Reserved 615 of 998 DOCUMENTS The Sun January 1, 2004 TRACK ACE KELLI FAILS TEST NO2 BYLINE: Harry Talbot SECTION: ATHLETICS LENGTH: 243 words THE world's fastest woman Kelli White has tested positive for drugs again. White, 26, won the 100 and 200 metre titles at the athletics World Championships in August -but subsequently tested positive for the banned stimulant modafinil. She currently faces the loss of both her world championship gold medals. Now the US Olympic committee have revealed White is one of seven athletes who failed drugs tests last summer -in her case for the same substance, modafinil. The other six athletes implicated are hammer thrower John McEwen, cyclist Adham Sbeih, sprinter Chryste Gaines and hurdlers Sandra Glover, Eric Thomas and Chris Phillips. White won both 100m and 200m events at the US championships -where she tested positive -and qualified for the World Championships in Paris in the process. Steroid She is coached by Remy Korchemny, who also guides British sprinter Dwain Chambers. Chambers currently faces a two-year ban for using the newly-discovered steroid THG. At the time of her positive test for modafinil in August, White said she was taking it to combat a sleep disorder. This claim was ridiculed by international track officials after word emerged of other athletes using the banned stimulant. All seven athletes who failed tests last summer are challenging the results. If modafinil use is proved, it results in disqualification at the event at which a positive test occurred -but no suspension. LOAD-DATE: January 2, 2004 LANGUAGE: English PUB-TYPE: Newspaper Copyright 2004 NEWS GROUP NEWSPAPERS LTD 616 of 998 DOCUMENTS Agence France Presse -- English December 31, 2003 Wednesday Seven leading US athletes failed drug tests: USOC SECTION: Sports LENGTH: 482 words DATELINE: COLORADO SPRINGS, Colorado, Dec 30 Seven leading US athletes, including American sprint champion Kelli White, failed drug tests this summer, the United States Olympic Committee announced on Tuesday. White tested positive for the banned substance Modafinil at the June United States Track and Field Championships in Stanford, California, the USOC revealed. Also testing positive for Modafinil at the nationals were former US champion sprinter Chryste Gaines; four-time national champion hurdler Sandra Glover; reigning US hurdles champion Eric Thomas and hammer thrower John McEwen. Hurdler Chris Phillips tested positive for Modafinil at the 2003 Paris World Championships in August, the USOC said in a news release. Cyclist Adham Sbeih tested positive for the hormone EPO at the US cycling championships in August. McEwen also tested positive for the new designer steroid tetrahydrogestrinone, or THG. The seven Americans all plan to appeal, the USOC said. Rich Wanninger, spokesman for the US Anti-Doping Agency, said Tuesday's announcement was made after samples taken from the athletes went through a series of confirmation tests and a 30-day review. Wanninger downplayed the significance of Tuesday's announcement but others have said the number of positive tests this summer is unprecedented for American athletes. "It is not our announcement," said Wanninger. White, the reigning world and US champion in both the 100 and 200 metres, is the most prominent name to fail the drug tests. The USOC said she also tested positive for Modafinil at the worlds. The 26-year-old White ran a personal best time of 10.85secs to capture the world 100m title. She also won 100m races in Brussells, Los Angeles and Portland, Oregon in 2003. White is one of 40 athletes who has been subpoenaed to testify into a federal government probe of a San Francisco-area lab, BALCO, that has been linked to THG. White could lose her two gold medals and 120,000 dollars in prize money from the world titles after testing positive for Modafinil, a stimulant used to treat narcolepsy, White's doctor Brian Goldman is BALCO's former medical director. Gaines won the US 100m championship in 2001 but is running faster now than she ever has. She set a personal best of 10.86secs in the 100m at the World Athletics Finals in Monaco in 2003. The 33-year-old Gaines also ran a 10.88 this year in Brussells. Glover, 34, is a four-time US 400m hurdle champion and won the silver medal at the worlds in Paris this year. The 31-year-old Phillips finished fourth at the nationals this year and fifth at the worlds in the 110-metre hurdles. Thomas is the reigning US champion in the 400m hurdles and won silver medals at the Pan American Games in 2003 and 1999. McEwen, 29, placed second at the 2003 US championships in Stanford in the hammer throw with a toss of 72.96 metres. gph03 Athletics-USA-doping LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH Copyright 2003 Agence France Presse 617 of 998 DOCUMENTS The Associated Press December 31, 2003, Wednesday, BC cycle White's agent wants case settled quickly SECTION: Sports News LENGTH: 251 words DATELINE: LONDON Kelli White's agent wants the sprint champion's drug case settled quickly, saying it is hurting her financially and damaging her reputation. White and six other American athletes tested positive for banned substances, the U.S. Olympic Committee said Tuesday following a review by the U.S. Anti-Doping Agency. White faces the loss of two world championship gold medals because of use of the stimulant modafinil. The USOC said White also tested positive for modafinil at the national championships in June, when she swept the 100 and 200 meters. Modafinil, considered a minor stimulant, carries a public warning and disqualification from the event where the test took place, but no ban. All seven athletes are challenging the results, the USOC said from its Colorado headquarters. Any penalties would come only after arbitration. White's agent, Robert Wagner, said the sprinter is awaiting a final decision from the USADA. "If they don't make a decision, we have to find a court because it's hurting us, financially, reputationwise, everything," he said Wednesday by telephone from Austria. White said she was prescribed modafinil for a sleeping disorder - a claim dismissed by international track officials after word emerged of other athletes using the substance. Wagner wants the matter decided before this summer's Athens Olympics. "This USOC announcement won't do them any good," he said. "We tried to follow the rules. Can we get a position from someone so we can move forward?" LOAD-DATE: January 1, 2004 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 618 of 998 DOCUMENTS Associated Press Online December 31, 2003 Wednesday White's Agent Wants Case Settled Quickly SECTION: SPORTS LENGTH: 250 words DATELINE: LONDON Kelli White's agent wants the sprint champion's drug case settled quickly, saying it is hurting her financially and damaging her reputation. White and six other American athletes tested positive for banned substances, the U.S. Olympic Committee said Tuesday following a review by the U.S. Anti-Doping Agency. White faces the loss of two world championship gold medals because of use of the stimulant modafinil. The USOC said White also tested positive for modafinil at the national championships in June, when she swept the 100 and 200 meters. Modafinil, considered a minor stimulant, carries a public warning and disqualification from the event where the test took place, but no ban. All seven athletes are challenging the results, the USOC said from its Colorado headquarters. Any penalties would come only after arbitration. White's agent, Robert Wagner, said the sprinter is awaiting a final decision from the USADA. "If they don't make a decision, we have to find a court because it's hurting us, financially, reputationwise, everything," he said Wednesday by telephone from Austria. White said she was prescribed modafinil for a sleeping disorder - a claim dismissed by international track officials after word emerged of other athletes using the substance. Wagner wants the matter decided before this summer's Athens Olympics. "This USOC announcement won't do them any good," he said. "We tried to follow the rules. Can we get a position from someone so we can move forward?" LOAD-DATE: January 1, 2004 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 619 of 998 DOCUMENTS The Associated Press State & Local Wire December 31, 2003, Wednesday, BC cycle White's agent wants case settled quickly SECTION: Sports News LENGTH: 256 words DATELINE: LONDON Kelli White's agent wants the sprint champion's drug case settled quickly, saying it is hurting her financially and damaging her reputation. White and six other American athletes tested positive for banned substances, the U.S. Olympic Committee said Tuesday following a review by the U.S. Anti-Doping Agency. White, of Union City, Calif., faces the loss of two world championship gold medals because of use of the stimulant modafinil. The USOC said White also tested positive for modafinil at the national championships in June, when she swept the 100 and 200 meters. Modafinil, considered a minor stimulant, carries a public warning and disqualification from the event where the test took place, but no ban. All seven athletes are challenging the results, the USOC said from its Colorado headquarters. Any penalties would come only after arbitration. White's agent, Robert Wagner, said the sprinter is awaiting a final decision from the USADA. "If they don't make a decision, we have to find a court because it's hurting us, financially, reputation-wise, everything," he said Wednesday by telephone from Austria. White said she was prescribed modafinil for a sleeping disorder - a claim dismissed by international track officials after word emerged of other athletes using the substance. Wagner wants the matter decided before this summer's Athens Olympics. "This USOC announcement won't do them any good," he said. "We tried to follow the rules. Can we get a position from someone so we can move forward?" LOAD-DATE: January 1, 2004 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 620 of 998 DOCUMENTS Birmingham Evening Mail December 31, 2003, Wednesday ATHLETICS: WHITE FAILS DRUGS TEST SECTION: SPORT; Pg. 40 LENGTH: 119 words Sprint champion Kelli White is one of six American athletes to have tested positive for the stimulant modafinil. White was one of two athletes to provide two positive urine samples. Her first was taken at the USA Track and Field Championships in June, the qualifying event for American athletes for the World Championships in Paris. The 26-year-old White went on to win the 100 and 200 metre gold medals at the Paris competition two months later, and also tested positive there. Fellow sprinter Chryste Gaines and hurdlers Sandra Glover, Chris Phillips and Eric Thomas had modafinil in their system, while hammer thrower John McEwen produced a positive sample for both modafinil and THG. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH PUB-TYPE: PAPER Copyright 2003 Midland Independent Newspapers plc 621 of 998 DOCUMENTS Bristol Evening Post December 31, 2003 Seven Us Stars Test Positive SECTION: Sport; Athletics; Athletes; Pg. 46 LENGTH: 159 words Sprint champion Kelli White is just one of seven American athletes to have tested positive for the stimulant modafinil, the US Olympic Committee confirmed. White's first positive urine sample was taken at the USA Track and Field Championships in June, which was the qualifying event for American athletes for the World Championships in Paris. The 26-year-old went on to win the 100 and 200 metre gold medals at the Paris competition two months later, and also tested positive there. Fellow sprinter Chryste Gaines and hurdlers Sandra Glover, Chris Phillips and Eric Thomas had modafinil in their system, while hammer thrower John McEwen produced a positive sample for both modafinil and tetrahydrogestrinone (THG). Meanwhile, a sample provided by cyclist Adham Sbeih at the US National Championships has shown up the endurance-boosting EPO. All seven dispute the findings and will now argue their case to the US AntiDoping Agency. LOAD-DATE: January 1, 2004 3112BRISEP211seven LANGUAGE: English PUB-TYPE: News Copyright 2003 Bristol United Press 622 of 998 DOCUMENTS Calgary Herald (Alberta, Canada) December 31, 2003 Wednesday Final Edition Women's sprint champ fails test SOURCE: The Associated Press BYLINE: Rob Gloster SECTION: Sports; Pg. E2 LENGTH: 449 words Capping a year of sports drug scandals, the U.S. Olympic Committee announced Tuesday that sprint champion Kelli White and six other American athletes tested positive for banned substances. White and five other track and field athletes tested positive for the banned stimulant modafinil. Hammer thrower John McEwen tested positive for modafinil and the newly discovered steroid THG, and cyclist Adham Sbeih became the first U.S. athlete to test positive for the endurance-boosting hormone EPO. The USOC announced the test results after the substances were found in two urine tests from each athlete, and following a review by the U.S. Anti-Doping Agency. All seven are challenging their test results, the USOC said in a news release from its base in Colorado Springs, Colo. Any suspensions or other penalties would come only after an arbitration process. White already faces the loss of two world championship gold medals because of modafinil use. The USOC said Tuesday that White also tested positive for modafinil at the national championships in June, when she swept the 100 and 200 metres. White said she was prescribed modafinil for a sleeping disorder -- a claim ridiculed by international track officials after word emerged of other athletes using the banned stimulant. Also testing positive for modafinil at the national track championships were sprinter Chryste Gaines and hurdlers Sandra Glover and Eric Thomas. Another hurdler, Chris Phillips, tested positive for modafinil at the world championships. Modafinil use results in disqualification at the event at which a positive test has occurred, but no suspension. THG use can lead to a two-year ban. Sbeih, who tested positive for EPO at the national cycling championships in August, faces up to a two-year ban. White and Gaines are coached by Remy Korchemny, who also coaches British sprinter Dwain Chambers, now facing a two-year suspension for THG. Phillips said Korchemny gave him a modafinil pill at the world championships to help him overcome jet lag. At least five track and field athletes -- including McEwen and Chambers -- have tested positive for THG, and a source who requested anonymity has told The Associated Press that four Oakland Raiders also flunked THG tests. The discovery of THG led to a grand jury probe in San Francisco. Athletes from at least five sports -- including baseball sluggers Barry Bonds and Jason Giambi -- appeared before the panel. McEwen's lawyer, Howard Jacobs, said the hammer thrower would consider working with the International Association of Athletics Federations, which floated an offer of leniency for drug cheaters who provide valuable information about doping. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH GRAPHIC: Photo: Herald Archive, Associated Press; Kelli White has tested positive for banned stimulant modafinil. TYPE: Sports Copyright 2003 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 623 of 998 DOCUMENTS THE DAILY TELEGRAPH(LONDON) December 31, 2003, Wednesday US reveal failed tests BYLINE: By Tom Knight SECTION: Pg. 08 LENGTH: 460 words THE extent of the doping problem facing officials in the United States was outlined yesterday when the sprinter Kelli White was named among seven American athletes who failed drug tests during the year. In addition to those seven, three other so-far unnamed US athletes are facing disciplinary hearings after testing positive for the new designer steroid, THG. White tested positive for the banned stimulant modafinil as did her fellow sprinter, Chryste Gaines, the 400 metres hurdlers Sandra Glover and Eric Thomas, the 110m hurdler Chris Phillips and hammer thrower John McEwen, who was also among the four Americans reported to have failed tests for THG. Urine samples provided by the cyclist, Adham Sbeih, were found to contain the blood-boosting hormone, EPO. All seven athletes, who were listed by the US Olympic Committee, are appealing against their test results and, to the continued frustration of the World Anti-Doping Agency, none of the cases have been resolved. White tested positive for modafinil on two occasions during the summer. The first time was at the World Championships in Paris, where she became the first woman to win the 100m and 200m sprint double. She claimed that she had been prescribed the drug to combat narcolepsy and did not know that it was a banned substance. She said she was careful about doping issues but, while she listed other medication on the form she handed to drug testing officials in Paris, she did not include the drug that contained modafinil. Speaking during the World Championships, she said: "Because I took it so early in the day, I never thought to mention it. After a competition, it is quite hard to remember everything you have taken in the day." The French dope testers have long thought that the drug in the White case was being used by athletes seeking a way round the system. For their part, the International Association of Athletics Federations insisted that modafinil was classified as a stimulant and carried the punishment of instant disqualification and a public warning. White's positive test in Paris means she faces being stripped of her two gold medals. Her case was not helped by the fact that she was also found to have tested positive for modafinil at the US Championships in June, a result which means she should not have even been included in the American team for Paris. Gaines, Glover, McEwen and Thomas were also found to have modafinil in their system when the urine samples collected at the national championships were revisited in the wake of the THG scandal. Phillips, meanwhile, tested positive for modafinil at the World Championships, where he claimed he was given the drug by his coach to combat jet-lag and fatigue. [PS]Sport: [ES] Rugby Union: LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH Copyright 2003 Telegraph Group Limited 624 of 998 DOCUMENTS Edmonton Journal (Alberta) December 31, 2003 Wednesday Final Edition Seven American athletes flunked tests: USOC SOURCE: The Associated Press SECTION: Sports; Pg. D1 LENGTH: 401 words Capping a year of sports drug scandals, the U.S. Olympic Committee announced Tuesday that sprint champion Kelli White and six other American athletes tested positive for banned substances. White and five other track and field athletes tested positive for the banned stimulant modafinil. Hammer thrower John McEwen tested positive for modafinil and the newly discovered steroid THG, and cyclist Adham Sbeih became the first U.S. athlete to test positive for the endurance-boosting hormone EPO. The USOC announced the test results after the substances were found in two urine tests from each athlete, and following a review by the U.S. Anti-Doping Agency. All seven are challenging their test results, the USOC said in a news release. Any suspensions or other penalties would come only after an arbitration process. White already faces the loss of two world championship gold medals because of modafinil use. The USOC said Tuesday White also tested positive for modafinil at the national championships in June, when she swept the 100 and 200 metres. White said she was prescribed modafinil for a sleeping disorder -- a claim ridiculed by international track officials after word emerged of other athletes using the banned stimulant. Also testing positive for modafinil at the national track championships were sprinter Chryste Gaines and hurdlers Sandra Glover and Eric Thomas. Another hurdler, Chris Phillips, tested positive for modafinil at the world championships. Modafinil use results in disqualification at the event at which a positive test has occurred, but no suspension. THG use can lead to a two-year ban. - - - EPHEDRA UPDATE Steve Bechler's parents welcomed the U.S. government's ban on ephedra, saying it should save lives and ensure their son did not die in vain. The Baltimore Orioles pitcher's heat stroke in February was linked to the herbal weight-loss supplement, which has also been blamed for more than 150 other deaths. "In one aspect, I feel that it's not enough, because it won't bring Steve back," Bechler's mother, Pat, said from Medford, Ore. "But it will help and protect other people." While the NFL, NCAA and International Olympic Committee have banned ephedra, Major League Baseball has not. Steve Bechler, 23, died during spring training in Fort Lauderdale, Fla. The medical examiner said ephedra contributed to heat stroke. The Associated Press LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH GRAPHIC: Colour Photo: The Associated Press, File; Kelli White: Not a banner year. TYPE: Sports Copyright 2003 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 625 of 998 DOCUMENTS Facts on File World News Digest December 31, 2003 Sports; Bonds Testifies in Drug Probe; Other Developments SECTION: Pg. 1098A1 LENGTH: 851 words Left fielder Barry Bonds, who played for the San Francisco Giants of Major League Baseball (MLB), December 4 testified before a federal grand jury in San Francisco, California that was investigating Bay Area Laboratory Cooperative (BALCO), a nutritional supplement company in Burlingame, California. The grand jury was investigating alleged tax evasion by the company, which listed several high-profile athletes, including Bonds, among its clients. It was also looking into accusations that BALCO had provided banned performance-enhancing drugs to its clients. The probe had been prompted in part by the recent discovery of tetrahydrogestrinone (THG), an anabolic steroid previously unknown to drug testers. [See 2003 Sports: Bonds, Rodriguez Win Baseball MVPs; Other Developments; 2003 U.S. Anti-Doping Agency Finds New 'Designer' Steroid; Several Athletes Test Positive; Other Developments] The grand jury was reportedly focusing on Victor Conte Jr., the president of BALCO who was said to have been Bonds's nutritionist since 2000, and Greg Anderson, Bonds's personal trainer since the late 1990s. Bonds's appearance before the grand jury did not necessarily mean that he had been implicated in any wrongdoing. Bonds, the reigning National League most valuable player, had repeatedly denied using performance-enhancing drugs. Proceedings of the grand jury were closed to the public. Several other athletes December 11 testified before the grand jury. Those athletes included New York Yankees first baseman Jason Giambi; MLB outfielder Gary Sheffield, a free agent; center Barret Robbins and linebacker Bill Romanowski, who played for the Oakland Raiders of the National Football League; and boxer Shane Mosley. [See 2003 U.S. Anti-Doping Agency Finds New 'Designer' Steroid; Several Athletes Test Positive; Other Developments; 2003 Buccaneers Rout Raiders to Win Super Bowl XXXVII; Tampa Bay Defense Dominates] U.S. Announces Positive Tests The U.S. Olympic Committee (USOC) December 30 announced that seven U.S. athletes had tested positive for banned substances earlier in 2003. (Some of the athletes had already been publicly identified.) The USOC said that sprinters Kelli White and Chryste Gaines, hurdlers Sandra Glover and Eric Thomas, and hammer thrower John McEwen had tested positive for modafinil, a stimulant used to treat narcolepsy, a sleep disorder, at the U.S. Track and Field Championships in June. The USOC said that McEwen had also tested positive for THG. The USOC said that hurdler Chris Phillips had tested positive for modafinil at the World Track and Field Championships in August. The USOC also revealed that cyclist Adham Sbeih had tested positive for the banned drug erythropoietin, or EPO, which improved endurance. [See 2003 U.S. Anti-Doping Agency Finds New 'Designer' Steroid; Several Athletes Test Positive; Other Developments; 2001 Armstrong Wins Third Straight Tour de France; American Rider Joins Cycling's Elite] The USOC officially revealed the athletes' identities after two of their urine tests had been found to contain the banned substances, and after a 30-day review period. Since modafinil was not officially banned by the International Association of Athletics Federations (IAAF), track and field's world governing body, but was considered a related substance, the athletes who tested positive faced disqualification only from the event at which the tests were taken. Athletes who tested positive for THG faced a two-year ban. [See below] The IAAF November 22 had said that two athletes tested positive for THG at the sport's world championships in August, but did not identify the athletes. U.S. Ruling on Sprinter Questioned International Olympic Committee (IOC) President Jacques Rogge December 1 said that U.S. officials had failed to satisfactorily explain why U.S. sprinter Jerome Young had been cleared to participate in the 2000 Summer Olympics. Young in 1999 had tested positive for anabolic steroids, but had been cleared on appeal by USA Track and Field, the sport's U.S. governing body. Young had won a gold medal at the 2000 Olympics for the U.S. team's gold medal-winning performance in the 4x400-meter relay. (Young did not participate in the final race, but was awarded one of a total of six gold medals for having competed in an earlier round.) The U.S.'s handling of Young's case had been widely criticized by international Olympic, athletics and antidoping officials. [See 2000 2000 Summer Olympics: Medalists; 2000 Summer Olympics Conclude in Sydney, Australia; U.S. First in Medals] The USOC September 25 for the first time had confirmed that Young failed the 1999 test, and that he had not been disciplined under the rules applicable at the time. The IOC September 30 initiated disciplinary proceedings that could result in the relay team being stripped of its gold medals. USA Track and Field December 7 voted to impose a lifetime ban on athletes who tested positive for steroids. However, the ban, which was stricter than penalties imposed by the IAAF, would not take effect until the two governing bodies resolved several legal issues. LOAD-DATE: June 24, 2004 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2003 Facts on File, Inc. 626 of 998 DOCUMENTS Guelph Mercury (Ontario, Canada) December 31, 2003 Wednesday Final Edition U.S. star, six others failed tests SOURCE: Associated Press SECTION: SPORTS; Pg. B4 LENGTH: 289 words DATELINE: COLORADO SPRINGS, COLO. Champion sprinter Kelli White and six other American athletes flunked drug tests this summer, the U.S. Olympic Committee announced Tuesday. White and five other track and field athletes tested positive for the banned stimulant modafinil. Hammer thrower John McEwen tested positive for modafinil and the newly discovered steroid THG, and cyclist Adham Sbeih tested positive for the endurance-boosting hormone EPO. The USOC announced the test results after the substances were found in two urine tests from each of the athletes, and following a 30-day review of the tests by the U.S. Anti-Doping Agency. All seven athletes are appealing their test results, the USOC said in a news release. White already faces the loss of two world championship gold medals because of modafinil use. The USOC said Tuesday that White also tested positive for modafinil at the national championships in June, when she also swept the 100 and 200 metres. White said she was prescribed modafinil for a sleeping disorder - a claim ridiculed by international track officials after word emerged of other athletes using the banned stimulant. Also testing positive for modafinil at the national track championships were sprinter Chryste Gaines, hurdler Sandra Glover, McEwen, and hurdler Eric Thomas. Hurdler Chris Phillips tested positive for modafinil at the world championships. White and Gaines are coached by Remy Korchemny, who also coaches British sprinter Dwain Chambers, now facing a two-year suspension for THG. Phillips said Korchemny gave him a modafinil pill at the world championships to help him overcome jet lag. Sbeih tested positive for EPO at the U.S. Cycling Federation's Elite Track National Championships in August. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH TYPE: NEWS Copyright 2003 Metroland Media Group Ltd 627 of 998 DOCUMENTS Hamilton Spectator (Ontario, Canada) December 31, 2003 Wednesday Final Edition Seven failed drug tests; U.S. Olympic Committee releases names of athletes SOURCE: The Associated Press BYLINE: Rob Gloster SECTION: SPORTS; Pg. SP16 LENGTH: 235 words Champion sprinter Kelli White and six other American athletes flunked drug tests this summer, the U.S. Olympic Committee announced yesterday. White and five other track and field athletes tested positive for the banned stimulant modafinil. Hammer thrower John McEwen tested positive for modafinil and the newly discovered steroid THG, and cyclist Adham Sbeih tested positive for the endurance-boosting hormone EPO. The USOC announced the test results after the substances were found in two urine tests from each of the athletes, and following a 30-day review of the tests by the U.S. Anti-Doping Agency. All seven athletes are appealing their test results, the USOC said in a news release from its base in Colorado Springs, Colo. Any suspensions or other penalties would come only after appeals. White already faces the loss of two world championship gold medals because of modafinil use. The USOC said yesterday that White also tested positive for modafinil at the national championships in June, when she also swept the 100 and 200 metres. White said she was prescribed modafinil for a sleeping disorder -- a claim ridiculed by international track officials after word emerged of other athletes using the banned stimulant. Also testing positive for modafinil at the national track championships were sprinter Chryste Gaines, 400-metre runner Sandra Glover, McEwen, and hurdler Eric Thomas. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH GRAPHIC: Photo: White TYPE: News Copyright 2003 Metroland Media Group Ltd 628 of 998 DOCUMENTS The Houston Chronicle December 31, 2003, Wednesday 3 STAR EDITION Seven test positive for banned drugs; Appeals coming from White, others SOURCE: Houston Chronicle News Services SECTION: SPORTS; Pg. 3 LENGTH: 515 words DATELINE: COLORADO SPRINGS, Colo. COLORADO SPRINGS, Colo. - Capping a year of sports drug scandals, the U.S. Olympic Committee announced Tuesday that sprint champion Kelli White and six other American athletes tested positive for banned substances. White and five other track and field athletes tested positive for the banned stimulant modafinil. Hammer thrower John McEwen tested positive for modafinil and the newly discovered steroid THG, and cyclist Adham Sbeih became the first U.S. athlete to test positive for the endurance-boosting hormone EPO. The USOC announced the test results after the substances were found in two urine tests from each athlete, and following a review by the U.S. Anti-Doping Agency. All seven are challenging their test results, the USOC said in a news release from its base in Colorado Springs, Colo. Any suspensions or other penalties would come only after an arbitration process. White already faces the loss of two world championship gold medals because of modafinil use. The USOC said Tuesday that White also tested positive for modafinil at the national championships in June, when she swept the 100 and 200 meters. White said she was prescribed modafinil for a sleeping disorder - a claim ridiculed by international track officials after word emerged of other athletes using the banned stimulant. Also testing positive for modafinil at the national track championships were sprinter Chryste Gaines and hurdlers Sandra Glover of Sugar Land and Eric Thomas of Houston. Glover, 35, once ran for Stephen F. Austin and UH; Thomas, 30, was on the track teams at Abliene Christian and Blinn. Another hurdler, Chris Phillips, tested positive for modafinil at the world championships. Modafinil use results in disqualification at the event at which a positive test has occurred, but no suspension. THG use can lead to a two-year ban. Sbeih, who tested positive for EPO at the national cycling championships in August, faces up to a two-year ban. White and Gaines are coached by Remy Korchemny, who also coaches British sprinter Dwain Chambers, now facing a two-year suspension for THG. Phillips said Korchemny gave him a modafinil pill to help him overcome jet lag. At least five track and field athletes - including McEwen and Chambers - have tested positive for THG. The discovery of THG led to a grand jury probe in San Francisco. Athletes from at least five sports - including baseball sluggers Barry Bonds and Jason Giambi - appeared before the panel. Donovan leads soccer picks - Landon Donovan, star of the U.S. team at the 2002 World Cup, was among 25 players selected for the national Under-23 training camp leading to Olympic qualifying. Coach Glenn Myernick also chose DaMarcus Beasley, another member of the American team that went to the World Cup quarterfinals. Myernick will choose 20 players after the U-23 squad trains in Carson, Calif., for two weeks, and that team will play in the Olympic qualifying tournament in Guadalajara, Mexico from Feb. 2-12. The U.S. training camp roster includes Jose Burciaga Jr. of Duncanville and Ricky Lewis of Spring. LOAD-DATE: January 8, 2004 LANGUAGE: ENGLISH GRAPHIC: Mugs: 1. John McEwen; 2. Kelli White Copyright 2003 The Houston Chronicle Publishing Company 629 of 998 DOCUMENTS The Mirror December 31, 2003, Wednesday ATHLETICS: WHITE FAILS DRUGS TEST SECTION: SPORT; Pg. 52 LENGTH: 119 words SPRINT champion Kelli White is one of six US athletes to have tested positive for the stimulant modafinil, the US Olympic Committee confirmed. White was one of two athletes to provide two positive urine samples. Her first was taken at the qualifying event for the world championships and the second at the Paris championships themselves where White won 100 and 200m gold. Fellow sprinter Chryste Gaines and hurdlers Sandra Glover, Chris Phillips and Eric Thomas had modafinil in their system, while hammer thrower John McEwen produced a positive sample for modafinil and tetrahydrogestrinone (THG). The athletes dispute the findings and will argue their case with the US Anti-Doping Agency. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH Copyright 2003 MGN Ltd. 630 of 998 DOCUMENTS The New York Post December 31, 2003, Wednesday THE SPORTS BLOTTER SECTION: All Editions; Pg. 069 LENGTH: 234 words STEROID SCANDAL: Capping a year of sports drug scandals, the U.S. Olympic Committee announced yesterday that sprint champion Kelli White and six other American athletes tested positive for banned substances. White and five other track and field athletes tested positive for the banned stimulant modafinil. Hammer thrower John McEwen tested positive for modafinil and the newly discovered steroid THG, and cyclist Adham Sbeih became the first U.S. athlete to test positive for the endurance-boosting hormone EPO. All seven are challenging their test results, the USOC said. White already faces the loss of two world championship gold medals because of modafinil use. The USOC said that White also tested positive for modafinil at the national championships in June. Also testing positive for modafinil at the national track championships were sprinter Chryste Gaines and hurdlers Sandra Glover and Eric Thomas. Another hurdler, Chris Phillips, tested positive for modafinil at the world championships. PLAYER SHOT: South Florida safety Johnnie Jones was shot twice during a nightclub dispute in his hometown of Sarasota but was released from the hospital one day later. Jones, 21, was shot in the neck and shoulder and pistol-whipped around 1:15 Christmas morning at the Town Hall Bar. Police arrested Antonio T. Puente, 19, and charged him with aggravated battery with a firearm. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH Copyright 2003 N.Y.P. Holdings, Inc. All rights reserved. 631 of 998 DOCUMENTS The Record (Kitchener-Waterloo, Ontario) December 31, 2003 Wednesday Final Edition Seven American athletes revealed as drug cheats; Sprinter Kelli White faces loss of two gold medals from world championships SOURCE: Associated Press SECTION: SPORTS; Pg. C6 LENGTH: 461 words Capping a year of sports drug scandals, the U.S. Olympic Committee announced yesterday that sprint champion Kelli White and six other American athletes tested positive for banned substances. White and five other track and field athletes tested positive for the banned stimulant modafinil. Hammer thrower John McEwen tested positive for modafinil and the newly discovered steroid THG, and cyclist Adham Sbeih became the first U.S. athlete to test positive for the endurance-boosting hormone EPO. The USOC announced the test results after the substances were found in two urine tests from each athlete, and following a review by the U.S. Anti-Doping Agency. All seven are challenging their test results, the USOC said in a news release from Colorado Springs, Colo. Any suspensions or other penalties would come only after an arbitration process. White already faces the loss of two world championship gold medals because of modafinil use. The USOC said yesterday that White also tested positive for modafinil at the national championships in June, when she swept the 100 and 200 meters. White said she was prescribed modafinil for a sleeping disorder -- a claim ridiculed by international track officials after word emerged of other athletes using the banned stimulant. Also testing positive for modafinil at the national track championships were sprinter Chryste Gaines and hurdlers Sandra Glover and Eric Thomas. Another hurdler, Chris Phillips, tested positive for modafinil at the world championships. Modafinil use results in disqualification at the event at which a positive test has occurred, but no suspension. THG use can lead to a two-year ban. Sbeih, who tested positive for EPO at the national cycling championships in August, faces up to a two-year ban. White and Gaines are coached by Remy Korchemny, who also coaches British sprinter Dwain Chambers, now facing a two-year suspension for THG. Phillips said Korchemny gave him a modafinil pill at the world championships to help him overcome jet lag. At least five track and field athletes -- including McEwen and Chambers -- have tested positive for THG, and a source who requested anonymity has told Associated Press that four Oakland Raiders also flunked THG tests. The discovery of THG led to a grand jury probe in San Francisco. Athletes from at least five sports -- including baseball sluggers Barry Bonds and Jason Giambi -- appeared before the panel. McEwen's lawyer, Howard Jacobs, said the hammer thrower would consider working with the International Association of Athletics Federations, which floated an offer of leniency for drug cheaters who provide valuable information about doping. Jacobs said yesterday that no such offer has yet been made by the IAAF. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH TYPE: NEWS Copyright 2003 Metroland Media Group Ltd 632 of 998 DOCUMENTS Saint Paul Pioneer Press (Minnesota) December 31, 2003 Wednesday CITY EDITION WHITE AMONG SEVEN FROM U.S. TO FAIL DRUG TESTS SECTION: SPORTS; QUICK HITS; Pg. D2 LENGTH: 973 words Capping a year of sports drug scandals, the U.S. Olympic Committee announced Tuesday that sprint champion Kelli White and six other American athletes tested positive for banned substances. White and five other track and field athletes tested positive for the banned stimulant modafinil. Hammer thrower John McEwen tested positive for modafinil and the newly discovered steroid THG, and cyclist Adham Sbeih became the first U.S. athlete to test positive for the endurance-boosting hormone EPO. The USOC announced the test results after the substances were found in two urine tests from each athlete, and following a review by the U.S. Anti-Doping Agency. All seven are challenging their test results, the USOC said in a news release from its base in Colorado Springs, Colo. Any suspensions or other penalties would come only after an arbitration process. White already faces the loss of two world championship gold medals because of modafinil use. The USOC said Tuesday that White also tested positive for modafinil at the national championships in June, when she swept the 100 and 200 meters. White said she was prescribed modafinil for a sleeping disorder -- a claim ridiculed by international track officials after word emerged of other athletes using the banned stimulant. Also testing positive for modafinil at the national track championships were sprinter Chryste Gaines and hurdlers Sandra Glover and Eric Thomas. Another hurdler, Chris Phillips, tested positive for modafinil at the world championships. Modafinil use results in disqualification at the event at which a positive test has occurred, but no suspension. THG use can lead to a two-year ban. Sbeih, who tested positive for EPO at the national cycling championships in August, faces up to a two-year ban. BASEBALL Rose might say he bet on baseball in book A new autobiography of Pete Rose, "My Prison Without Bars'" is scheduled to hit bookstores Jan. 8 amid widespread expectations that Rose will use the book to admit publicly for the first time that he bet on baseball while managing the Cincinnati Reds. Rose was barred from baseball in August 1989 for illegally betting on sports events, although not specifically on baseball. Ever since then, he has denied that he bet on baseball, despite significant evidence to the contrary. But there have been increasing hints over the past year that Rose, who has the most base hits in major league history, now understood he would have to make such an admission to win reinstatement to baseball and entry to the Hall of Fame, and that he was prepared to do so. -- Right-handed pitcher Jason Johnson, who pitched the five previous seasons with Baltimore, agreed to a $7 million, two-year contract with the Detroit Tigers. Johnson, 30, was 10-10 with a 4.18 earned-run average in 189 2/3 innings last season. His victories matched a career high, set in 2001. -- Free-agent right-handed pitcher Mike DeJean agreed to a one-year contract with the Orioles. The contract is contingent on the right-hander passing a physical exam next week. DeJean went 5-8 with 19 saves and a 4.68 ERA in 76 games with the Milwaukee Brewers and St. Louis Cardinals last season. -- A major safety switch was missing from an escalator when it malfunctioned at Coors Field last summer, injuring dozens of baseball fans, Denver city inspectors said. Inspectors said the switch would have prevented the escalator from hurtling out of control July 2. MISCELLANEOUS CART sale nears court approval The Championship Auto Racing Teams racing series could win court approval of its proposed sale to a group of team owners by Jan. 28 under a plan approved by a bankruptcy judge in Indianapolis. U.S. District Judge Frank Otte's approval of CART's proposed sales procedures came two weeks after the series filed for Chapter 11 bankruptcy protection as part of an agreement with the series' buyers, Open Wheel Racing Series LLC. -- Former NASCAR rookie of the year Dick Brooks was in a plane crash, the Federal Aviation Administration said. The exact nature of Brooks' injuries were not immediately known. Brooks, 61, was taxiing a plane down the runway at his farm in Woodruff, S.C., on Sunday when a wheel caught in the grass and turned the plane over, a Spartanburg, S.C., newspaper reported. -- Brian Kelly was hired as football coach at Central Michigan. Kelly, who led Grand Valley State to the past two Division II championships, replaces Mike DeBord. Central Michigan finished 3-9 this season, and DeBord's four-year record at the school was 12-34. -- Nebraska receiver Grant Mulkey was arrested and charged with marijuana possession following the Cornhuskers' 17-3 victory over Michigan State in the Alamo Bowl in San Antonio on Monday. -- Landon Donovan, star of the U.S. team at the 2002 World Cup, was among 25 players selected for the national Under-23 training camp leading to Olympic qualifying. Coach Glenn Myernick will choose 20 players after the U-23 squad trains in Carson, Calif., for two weeks, and that team will play in the Olympic qualifying tournament in Guadalajara, Mexico from Feb. 2-12. WINTER SPORTS Werner's two goals lead U.S. victory Stephen Werner of the University of Massachusetts scored two goals, including the winner, as the United States beat Sweden 4-3 at the world junior hockey championships in Helsinki, Finland. The United States remained undefeated in the under-20 tournament and plays Russia today. The winner of that game will top Group A and get a bye into the tournament semifinals on Saturday. -- Ronny Ackermann of Germany swept to his fifth World Cup Nordic combined victory of the season in Oberhof, Germany. Ackermann finished 53.6 seconds ahead of Austria's Felix Gottwald, last year's winner, with American Todd Lodwick third, 1:06.6 behind. LOAD-DATE: August 19, 2005 LANGUAGE: ENGLISH GRAPHIC: PHOTO: ASSOCIATED PRESS FILE PHOTO Sprinter Kelli White was among seven American athletes identified Tuesday by the U.S. Olympic Committee as having failed drug tests last summer. Copyright 2003 Saint Paul Pioneer Press All Rights Reserved 633 of 998 DOCUMENTS The San Francisco Chronicle DECEMBER 31, 2003, WEDNESDAY, FINAL EDITION 7 U.S. athletes fail drug tests; Some tied to lab in Bay Area probed in doping scandal SOURCE: Chronicle Staff Writer BYLINE: John Crumpacker SECTION: NEWS; Pg. A1 LENGTH: 1268 words Union City sprinter Kelli White and Stanford graduate Chryste Gaines were among seven athletes who tested positive for banned substances last summer, according to an announcement Tuesday by the United States Olympic Committee after tests confirmed the presence of the drugs in backup samples. Whether or not seven positive tests is indicative of "intentional doping of the worst sort" as the U.S. Anti-Doping Agency claimed in October, the USOC released the names of six track and field athletes and a cyclist who tested positive in a new era of heightened awareness of doping in sport. Tuesday's announcement by the USOC furthers claims by international sports officials that U.S. athletes are as guilty of doping offenses as athletes from other countries that are easy targets of speculation, namely China, the former East Germany and other old Soviet-bloc nations. It is also the latest development in an ongoing story that began last summer with the discovery of THG, a previously unknown designer steroid said to have come from a Burlingame laboratory and been used by athletes in track and field and pro football to gain strength and speed. Victor Conte, owner of Bay Area Laboratory Co-operative, is the subject of a continuing federal grand jury investigation into his business practices. In keeping with its policy, the USOC announced the names of the athletes 30 days after a review by USADA confirmed their "B" samples showed the presence of banned substances detected earlier in "A" samples. The track athletes are White, Gaines of Lithonia, Ga., hammer thrower John McEwen of Ashland, Ohio, and hurdlers Sandra Glover of Sugarland, Texas, Chris Phillips of Little Rock, Ark., and Eric Thomas of Houston. The cyclist is Adham Sbeih of Sacramento. White, Gaines, Glover, Thomas and Phillips tested positive for the mild stimulant modafinil, a medication normally prescribed for treatment of sleep disorders like narcolepsy. McEwen tested positive for modafinil and the designer steroid THG, which USADA said came from Conte's lab in Burlingame. Sbeih tested positive for erythropoietin, or EPO, a banned substance that boosts the oxygen-carrying capacity of red blood cells and is used by athletes in endurance sports. BALCO was raided by the Internal Revenue Service, the Food and Drug Administration and the San Mateo County Narcotics Task Force on Sept. 3. Investigators found bottles indicating they contained steroids, human growth hormone and testosterone. Grand jury probe White and Gaines were two of at least 27 athletes known to have testified before a federal grand jury in San Francisco investigating Conte and personal trainer Greg Anderson, who serves as the weight trainer for Giants star Barry Bonds. In an announcement in October, U.S. anti-doping officials said the discovery of the designer steroid THG indicated "intentional doping of the worst sort" and said the case could lead to the biggest doping scandal in U.S. sports history. The man who made that announcement, USADA chief executive Terry Madden, was not available for comment on Tuesday. Earlier reports indicated four U.S. athletes had tested positive for THG, including shot putter Kevin Toth of Hudson, Ohio, and middle distance runner Regina Jacobs of Oakland. Toth and Jacobs are both clients of Conte and BALCO. But McEwen was the only athlete named Tuesday as testing positive for THG. Further announcements on THG positives are expected the last two weeks of January. According to USADA -- an independent agency in Colorado Springs, Colo., responsible for drug testing and adjudication for Olympic sports in the United States -- all seven athletes named Tuesday plan to challenge the results of their tests. They have two avenues of appeal: the North American Court of Arbitration for Sport in New York and the International Court of Arbitration for Sport. CAS is regarded as the Supreme Court for sports disputes, the last stop in the appeals process. If athletes take their cases to the North American CAS and lose, they can then appeal to the International CAS, based in Lausanne, Switzerland, whose ruling is binding. An appeal directly to the International CAS leaves an athlete without further recourse. To date, 14 athletes who tested positive for illegal performance-enhancing drugs appealed. Of those, three athletes with steroid positives took their appeals to the International CAS and received varying rulings: Swimmer Kicker Vencill's sanction was reduced from four years to two; bobsledder Pavle Jovanovic had his ban increased from nine months to two years; and boxer Joseph Pastorello's sanction was upheld at 18 months. 2 gold medals at stake White, who stands to lose two gold medals and $120,000 in prize money if her appeal is rejected, came up positive for the substance June 30 at the U.S. national track and field championships at Stanford and again in August at the World Championships in Paris. White, 26, a James Logan High School and University of Tennessee graduate, won world championship titles in the 100- and 200-meter sprints and ran 2003 world-best times in both races. Modafinil is considered a mild stimulant, and an athlete testing positive is not subject to a ban from competition, only a disqualification from the competition where the test occurred. The steroid THG, on the other hand, could result in a two-year suspension for a positive sample. At the time of her positive test for modafinil in August, White said she was taking the medication to combat narcolepsy, which she said runs in her family. "I still believe modafinil is not a stimulant," said Remi Korchemny of Castro Valley, who coaches White, Gaines and Phillips. Korchemny's athletes have received services from Conte, the lab owner under investigation. Korchemny and Conte were introduced by Oakland Raiders linebacker Bill Romanowski, and the coach remains a supporter of the embattled lab owner. "They did not do anything wrong," Korchemny said of his athletes. "They did not take anything to enhance their performance. Why should they be convicted of something that is not a crime?" Ridicule from other coaches Korchemny may be a lone voice crying in the wilderness. That modafinil is a benign substance is a charge ridiculed by other coaches and anti-doping officials in light of how many athletes have tested positive for it. "It is a stimulant," Dick Pound, head of the World Anti-Doping Agency in Montreal, said in an interview with The Chronicle. "You look at the excuse given -- narcolepsy? Please. So she wouldn't fall asleep in the starting blocks of the 100 meters? Oh, please." Like White, Phillips tested positive for modafinil at the World Championships. Korchemny questioned why White had tested positive for modafinil after her victory in the 100 meters at August's World Championship and not after the 200 meters several days later. "Kelli was negative for (modafinil) for the 200. Why did she take it for the 100 and not the 200?" her coach wondered. "I don't believe it is a stimulant; it is just a medication to relieve symptoms of some kind of problem." Gaines, Glover, McEwen and Thomas turned in positive samples for modafinil at the U.S. nationals at Stanford. It was at that competition that an anonymous "high profile" track coach sent a syringe containing an unknown substance to U.S. anti-doping officials in what was the starting point in the current fevered campaign against doping in sport. The syringe was later found to contain THG. E-mail John Crumpacker at jcrumpacker@sfchronicle.com. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH GRAPHIC: (1) Kelli White is a worldchampion sprinter from Union City., (2) Chryste Gaines is an Olympic gold medal sprinter., (3) John McEwenis a hammer thrower fromAshland, Ohio., (4) Sandra Glover is a hurdler from Sugarland, Texas., (5) Chris Phillips is a hurdler fromLittle Rock, Ark. (6) Eric Thomas, a Houston athlete, also runs the hurdles. Copyright 2003 The Chronicle Publishing Co. 634 of 998 DOCUMENTS San Jose Mercury News (California) December 31, 2003 Wednesday MORNING FINAL EDITION USOC TO PROCEED WITH CASE AGAINST ATHLETES; WHITE, GAINES AMONG SEVEN PEOPLE TARGETED JACOBS ARGUES SHE TOOK NO BANNED SUBSTANCE BYLINE: ELLIOTT ALMOND AND PETE CAREY, Mercury News SECTION: SPORTS; Pg. 1D LENGTH: 904 words U.S. Olympic officials announced Tuesday that there was sufficient evidence to proceed against seven athletes, including East Bay sprinters Kelli White and Chryste Gaines, for using performance-enhancing drugs. In response, athletes and their representatives criticized the country's Olympic drug-testing system, suggesting for the first time how they will defend themselves. All but one of these cases involves the mild stimulant modafinil, a sleeping disorder medication. The announcement signaled the next phase of a drug scandal that first surfaced in September with the federal investigation of a Burlingame nutrition company, Balco Laboratories, and that has brought dozens of athletes from baseball, football and Olympic sports before a grand jury in San Francisco. In November, the International Association of Athletics Federations announced that four athletes tested positive for a new designer steroid, THG, at the USA Outdoor Track and Field Championships at Stanford in June. One of those four, three-time Olympian Regina Jacobs of Oakland, spoke up for the first time Tuesday in a statement saying she had filed for arbitration although a review panel had not decided on her case yet. Suggesting the defense that athletes accused of taking THG may take, shesaid USA Track & Field and the U.S. Anti-Doping Agency "seek to deny me the opportunity to compete in the upcoming Olympics on the grounds that something I have never heard of, and which was not on any list of banned substances," should be considered "somehow 'related' to something" on track's list of banned substances. Jacobs, a former Stanford star, said the Anti-Doping Agency had refused to provide documents showing what THG is and had denied an expert she had retained a "meaningful opportunity" to observe the urine test that was positive for the substance. Howard Jacobs, a lawyer for the three others who tested positive for THG, or tetrahydrogestrinone -- John McEwen, Kevin Toth and a yet unnamed athlete -- also questioned the validity of the test developed this summer by Don Catlin, head of the UCLA Olympic drug laboratory, to detect THG. "They still have to prove, ultimately, that it is an anabolic steroid," Jacobs said, adding that USADA officials have not shown the test has had a scientific peer review. He said, "They have to prove it was legally just to retest all these samples" from the national meet, which took place before Catlin had identified THG, and from the world championships, which took place before the existence of THG was announced. "It is one thing to say it is obviously a steroid but it is another thing to prove it legally." USADA officials declined to comment because of the pending cases. In addition to White and Gaines, the others named Tuesday were 400-meter runner Sandra Glover of Texas, hammer thrower McEwen of Ohio, hurdlers Chris Phillips of Arkansas and Eric Thomas of Texas, and cyclist Adham Sbieh of Citrus Grove. Olympic officials said the track athletes had tested positive for modafinil, a sleep-disorder drug, and the cyclist for the blood-boosting EPO. Neither THG nor modafinil is on the list of banned substances maintained by the IAAF, track's governing body. The cases are proceeding because the mild stimulant falls under the "related substances" clause in the drug code. The owner of Balco Laboratories, Victor Conte Jr., has been identified by anti-doping officials as the source of THG. Jacobs said he did not know why officials failed to announce the THG case of Toth, a leading shot putter, Tuesday. Even before federal officials searched Balco in September, White tested positive for modafinil in August at the World Championships in Paris, where she had become the first American woman to win both the 100 meters and 200 meters. White, a James Logan High graduate, has repeatedly denied using the drug to aid performance. A doctor connected to Balco said he gave her the medication because White suffers from narcolepsy. White's mother, a one-time Olympic runner from Jamaica, also suffers from the illness, she said. Those who tested positive for modafinil have the same concern with the drug testers as those who tested positive for THG. They are questioning how they can be punished for a drug that was not on any banned list, and also lacks proof that it aids performance, something sleeping experts question. The questions surfacing could help frame the debate for the future of drug testing as sports officials worldwide try to develop a standard practice to include all sports. Thomas, from Houston, said Tuesday that he did not take modafinil to circumvent the system. "Not at all," he said. "I took it to be alert. It is just a pill that helps you be focused and alert." Cameron Myler, a New York lawyer who represents Thomas, Gaines and Glover, said her athletes, all of whom tested positive for modafinil, also are seeking arbitration. "As you probably know, USADA uses the rules of the international federation," said Myler, a four-time Olympian. "Modafinil has never been on a banned list of the IAAF. The only way USADA could prevail on this is if they could show that modafinil is 'chemically or pharmacologically related to' something on the banned list." Modafinil use results in disqualification at the event at which a positive test has occurred, but no suspension. THG use can lead to a two-year ban. LOAD-DATE: August 19, 2005 LANGUAGE: ENGLISH GRAPHIC: Photos (2); PHOTO: Gaines PHOTO: White Copyright 2003 San Jose Mercury News All Rights Reserved 635 of 998 DOCUMENTS THE SEATTLE POST-INTELLIGENCER December 31, 2003, Wednesday FINAL ROSE MAY ADMIT HE BET ON BASEBALL SECTION: SPORTS, Pg. D12 LENGTH: 901 words BASEBALL A new autobiography of Pete Rose is scheduled to hit bookstores next week amid widespread expectations Rose will use the book to admit publicly for the first time that he bet on baseball while managing the Cincinnati Reds, the New York Times reported. The book, "My Prison Without Bars," has a huge first printing, 500,000 copies, and is being handled in top-secret fashion by the publisher, Rodale Press, which has embargoed the book until Jan. 8, when Rose will conduct a series of interviews with reporters about the book's contents. Rose was barred from baseball in August 1989 for illegally betting on sports events, although not specifically on baseball. Ever since then, he has denied that he bet on baseball, despite significant evidence to the contrary. But there have been increasing hints over the past year that Rose, who has the most base hits in major league history, understood he would have to make such an admission to win reinstatement to baseball and entry to the Hall of Fame, and that he was prepared to do so. In fact, a major league official said yesterday, Rose made such an admission when he met with Commissioner Bud Selig in Milwaukee on Nov. 25, 2002. The official, who said he was aware of what was discussed at the meeting, said Rose was asked by Selig if he had bet on baseball and that he replied that he did. The official said Selig responded to Rose's admission by noting that every clubhouse in baseball had a sign stating that gambling on baseball was prohibited and proceeded to ask Rose why he had so blatantly ignored the warnings. Three days after he was gunned down at a bar, former Mariner Ivan Calderon was buried yesterday as dozens of relatives and friends recalled his intense love of baseball. Police said two men shot Calderon multiple times in the head and back Saturday evening in the Puerto Rican town of Loiza, where the 41-year-old lived. Detectives have ruled out robbery and are investigating revenge as a possible motive. Calderon sometimes loaned money to people and in retirement worked as a bondsman, police said. The former slugger played with the Mariners, White Sox, Expos and Red Sox during his 10-year Major League Baseball career, which ended in 1993. New York Yankees center fielder Bernie Williams visited Calderon's family at their home yesterday, and Yankees outfielder Ruben Sierra attended a wake Monday. Right-hander Jason Johnson signed a two-year, $7 million free-agent contract with the Detroit Tigers. Right-hander Mike DeJean agreed to a one-year contract with the Baltimore Orioles. Chris Speier was hired by the Oakland Athletics as bench coach to replace Terry Francona, who left to become the manager of the Boston Red Sox. TRACK AND FIELD White, others test positive Capping a year of sports drug scandals, the U.S. Olympic Committee announced sprint champion Kelli White and six other American athletes tested positive for banned substances. White and five other track and field athletes tested positive for the banned stimulant modafinil. Hammer thrower John McEwen tested positive for modafinil and the newly discovered steroid THG, and cyclist Adham Sbeih became the first U.S. athlete to test positive for the endurance-boosting hormone EPO. The USOC announced the test results after the substances were found in two urine tests from each athlete, and following a review by the U.S. Anti-Doping Agency. All seven are challenging their test results, the USOC said in a news release from its base in Colorado Springs, Colo. Any suspensions or other penalties would come only after an arbitration process. White already faces the loss of two world championship gold medals because of modafinil use. Also testing positive for modafinil at the national track championships were sprinter Chryste Gaines and hurdlers Sandra Glover and Eric Thomas. Another hurdler, Chris Phillips, tested positive for modafinil at the world championships. ETC. Donovan joins U.S. Olympic team Landon Donovan, star of the U.S. team at the 2002 World Cup, was among 25 players selected for the national Under-23 training camp leading to Olympic qualifying. Coach Glenn Myernick also chose DaMarcus Beasley, another member of the American team that went to the World Cup quarterfinals. Myernick will choose 20 players after the U-23 squad trains in Carson, Calif., for two weeks. That team will play in the Olympic qualifying tournament in Guadalajara, Mexico, from Feb. 2-12. The roster includes another veteran of the 2000 Under-23 squad, forward Conor Casey, who will be making his first appearance with the team since the Olympics. The CART racing series could win court approval of its proposed sale to a group of team owners by Jan. 28 under a plan a bankruptcy judge approved. U.S. District Judge Frank J. Otte's approval of CART's proposed sales procedures came two weeks after the series filed for Chapter 11 bankruptcy protection as part of an agreement with the series' buyers, Open Wheel Racing Series LLC. Stephen Werner of the University of Massachusetts scored two goals, including the winner, as the United States beat Sweden 4-3 at the world junior hockey championships in Helsinki, Finland. The United States remained undefeated in the under-20 tournament and plays Russia today. The winner of that game will top Group A and get a bye into the tournament semifinals Saturday. LOAD-DATE: January 1, 2004 LANGUAGE: ENGLISH NOTES: WORLD Copyright 2003 Seattle Post-Intelligencer 636 of 998 DOCUMENTS St. Petersburg Times (Florida) December 31, 2003 Wednesday 0 South Pinellas Edition USOC lists 7 who tested positive for banned substances SOURCE: Compiled from Wire Reports SECTION: SPORTS; Pg. 9C LENGTH: 560 words Capping a year of drug scandals, the U.S. Olympic Committee announced Tuesday that sprint champion Kelli White and six other Americans tested positive for banned substances. White and five other track and field athletes tested positive for the stimulant modafinil. Hammer thrower John McEwen also tested positive for the newly discovered steroid THG, and cyclist Adham Sbeih became the first U.S. athlete to test positive for the endurance-boosting hormone EPO. The USOC announced the results after the substances were found in two urine tests from each athlete, and following a review by the U.S. Anti-Doping Agency. All seven are challenging the results, the USOC said. Any suspensions or other penalties would come only after arbitration. White already faces the loss of two world championship gold medals because of modafinil use. The USOC said she also tested positive for the drug at the national championships in June, when she swept the 100 and 200 meters. White said she was prescribed modafinil for a sleeping disorder - a claim ridiculed by international track officials after word emerged of other athletes using the banned stimulant. Also testing positive for modafinil at the national championships were sprinter Chryste Gaines and hurdlers Sandra Glover and Eric Thomas. Another hurdler, Chris Phillips, tested positive for modafinil at the world championships. MOTORSPORTS CART sale moves ahead The CART racing series could win court approval of its proposed sale to a group of team owners by Jan. 28 under a bankruptcy plan approved by U.S. District Judge Frank J. Otte in Indianapolis. Otte overruled objections to the sales procedures and scheduled Jan. 23 as the deadline for alternative bids for CART's assets. If any such bids emerge, they could be considered during an auction Jan. 28. Without any qualifying bids, Otte could approve the sale to Open Wheel Racing Series LLC that day. OBITUARY: Rina Andretti, mother of retired auto racing great Mario Andretti, died in Bethlehem, Pa., at age 90. BASEBALL Missing switch mystery A major safety switch was missing from an escalator when it malfunctioned at Coors Field on July 2, hurtling out of control and injuring dozens of fans, Denver city inspectors said. The device was there when the escalator was originally certified, and contractors said they inspected it in March. CALDERON BURIAL: Former major-leaguer Ivan Calderon was buried in Loiza, Puerto Rico, three days after he was shot multiple times in the back at a Loiza bar. TIGERS: Right-hander Jason Johnson, who pitched the past five seasons for Baltimore, agreed to a $7-million, two-year contract. ET CETERA SOCCER: Florida State sophomore Leah Gallegos has been named a College Sports Television second-team All-American. FSU freshmen Julia Schnugg and India Trotter are training with the U.S. Under-19 National Team in Carson, Calif. HOCKEY: Stephen Werner scored two goals, including the winner, as the United States beat Sweden 4-3 at the world junior championships in Helsinki. The Americans play Russia today for a bye into the semifinals. BIATHLON: Jacob Beste of St. Cloud, Minn., won the men's 12.5-kilometer pursuit and Rachel Steer of Anchorage won the women's 10K pursuit at the national championships in Lake Placid, N.Y. - Compiled from Times wires. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH SERIES: IN BRIEF TYPE: DIGEST Copyright 2003 Times Publishing Company 637 of 998 DOCUMENTS Times Colonist (Victoria, British Columbia) December 31, 2003 Wednesday Final Edition Sprint star White on U.S. drug-cheat list SOURCE: The Associated Press SECTION: Sports; Pg. C12 LENGTH: 388 words Capping a year of sports drug scandals, the U.S. Olympic Committee announced Tuesday that sprint champion Kelli White and six other American athletes tested positive for banned substances. White and five other track and field athletes tested positive for the banned stimulant modafinil. Hammer thrower John McEwen tested positive for modafinil and the newly discovered steroid THG, and cyclist Adham Sbeih became the first U.S. athlete to test positive for the endurance-boosting hormone EPO. The USOC announced the test results after the substances were found in two urine tests from each athlete, and following a review by the U.S. Anti-Doping Agency. All seven are challenging their test results, the USOC said in a news release from its base in Colorado Springs, Colo. Any suspensions or other penalties would come only after an arbitration process. White already faces the loss of two world championship gold medals because of modafinil use. The USOC said Tuesday that White also tested positive for modafinil at the national championships in June, when she swept the 100 and 200 metres. White said she was prescribed modafinil for a sleeping disorder -- a claim ridiculed by international track officials after word emerged of other athletes using the banned stimulant. Also testing positive for modafinil at the national track championships were sprinter Chryste Gaines and hurdlers Sandra Glover and Eric Thomas. Another hurdler, Chris Phillips, tested positive for modafinil at the world championships. Modafinil use results in disqualification at the event at which a positive test has occurred, but no suspension. THG use can lead to a two-year ban. Sbeih, who tested positive for EPO at the national cycling championships in August, faces up to a two-year ban. White and Gaines are coached by Remy Korchemny, who also coaches British sprinter Dwain Chambers, now facing a two-year suspension for THG. Phillips said Korchemny gave him a modafinil pill at the world championships to help him overcome jet lag. At least five track and field athletes -- including McEwen and Chambers -- have tested positive for THG, and a source who requested anonymity has told The Associated Press that four Oakland Raiders also flunked THG tests. The discovery of THG led to a grand jury probe in San Francisco. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH TYPE: Sports Copyright 2003 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 638 of 998 DOCUMENTS Topeka Capital-Journal (Kansas) December 31, 2003, Wednesday Briefly in sports BYLINE: Capital-Journal Pg. D4 LENGTH: 1078 words General: Seven U.S. athletes test positive for banned steroids Capping a year of sports drug scandals, the U.S. Olympic Committee announced Tuesday that sprint champion Kelli White and six other American athletes tested positive for banned substances. White and five other track and field athletes tested positive for the banned stimulant modafinil. Hammer thrower John McEwen tested positive for modafinil and the newly discovered steroid THG, and cyclist Adham Sbeih became the first U.S. athlete to test positive for the endurance-boosting hormone EPO. The USOC announced the test results after the substances were found in two urine tests from each athlete, and following a review by the U.S. Anti-Doping Agency. All seven are challenging their test results, the USOC said in a news release from its base in Colorado Springs, Colo. Any suspensions or other penalties would come only after an arbitration process. White already faces the loss of two world championship gold medals because of modafinil use. The USOC said Tuesday that White also tested positive for modafinil at the national championships in June, when she swept the 100 and 200 meters. White said she was prescribed modafinil for a sleeping disorder --- a claim ridiculed by international track officials after word emerged of other athletes using the banned stimulant. Also testing positive for modafinil at the national track championships were sprinter Chryste Gaines and hurdlers Sandra Glover and Eric Thomas. Another hurdler, Chris Phillips, tested positive for modafinil at the world championships. THE KANSAS TICKET OFFICE has a limited number of tickets available for the Villanova game on Friday, KU officials announced Tuesday. Game time is 7 p.m. in Allen Fieldhouse. The tickets, which were returned by Villanova, cost $30 each. They can be purchased in person at the Fieldhouse ticket office, by calling 1-800-34-HAWKS, or (785) 864-3141, or online at www.kustore.com. HAYDEN will play a varsity basketball doubleheader starting at 1 p.m. Friday at Wamego. The starting times have been changed so they won't conflict with that night's Fiesta Bowl. Varsity girls will start at 1 p.m., followed by the varsity boys about 2:30 p.m. WICHITA STATE has announced its 2004 Pizza Hut Shocker Sports Hall of Fame inductees. They are two-time all-Missouri Valley Conference basketball player Greg Carney, two-time NCAA tennis qualifier and All-American Phil Cooper, two-time All-America second baseman Jim Thomas and All-America pitcher Shane Dennis. The induction will be at halftime of the WSU-Indiana State game at 7:05 p.m. on Jan. 17. A reception and dinner is set for 6:30 p.m. on Jan. 16 at the Charles Koch Arena Champions Club. KANSAS BASEBALL COACH Ritch Price will be a featured speaker at the 2004 American Baseball Coaches Association national clinic from Friday through Monday in San Antonio, Texas. The second-year Kansas coach will talk on "Zone Double Play Feeds and Pivots" on Sunday, speaking to an estimated 4,000 coaches from around the country. MLB: Malfunction discovered in Coors Field escalator incident A major safety switch was missing from an escalator when it malfunctioned at Coors Field this summer, injuring dozens of baseball fans, city inspectors said Tuesday. City inspectors said the switch would have prevented the escalator from hurtling out of control July 2. The device was there when the escalator was originally certified, and contractors said they inspected it in March, according to Julius Zsako, spokesman for the city Community Planning and Development Office. ''We don't know when it was removed,'' Zsako said. Escalators at Coors Field are maintained by Kone Inc., which disuputed the inspectors' finding. The company previously issued a report that blamed the accident on overcrowding and a misconnected wire, and said Tuesday that tests left ''no doubt'' that the misconnected wire was to blame. JASON JOHNSON likes the changes going on in Detroit, so he decided to join the Tigers. The right-hander who pitched the five previous seasons with Baltimore agreed to a $7 million, two-year contract with the Tigers on Tuesday. Football: Tice will return next season as Vikings coach Minnesota Vikings owner Red McCombs' silence led many people, including Mike Tice himself, to believe he was about to fire the head coach. But after waiting two days, McCombs said Tice would return next season and wondered what all the fuss was about. A relieved Tice began his offseason planning in earnest while continuing to commiserate with his assistants over what could've been. McCombs, on a conference call Tuesday, insisted he never had thoughts of replacing Tice --- or anyone else on staff. A 3-7 finish by the Vikings, including an unfathomable fourth-quarter failure in an 18-17 defeat at Arizona on Sunday that kept them out of the playoffs, prompted speculation Tice could be fired. Not so, said McCombs from his San Antonio office, a day after staying suspiciously mum on the subject. ''I don't know where all the smoke is coming from,'' said the owner, who more than once this season voiced his confidence in Tice's performance. ''It's not coming from me.'' TENNESSEE coach Phillip Fulmer was given a one-year contract extension and a $140,000 raise Tuesday, three days before the Volunteers play Clemson in the Peach Bowl. The agreement keeps Fulmer at Tennessee through the 2010 season and raises his salary to $1,789,500, up from $1.65 million this year. Fulmer ranks second in wins among active Division I-A coaches with at least five years experience. He has a 113-27 record for an .807 winning percentage. NEW YORK JETS coach Herman Edwards shook up his staff Tuesday by firing defensive coordinator Ted Cottrell and three assistants. Edwards said the Jets needed to go a different direction after finishing 28th against the run and 21st in yards allowed this season, when the team finished 6-10. TENNESSEE TITANS quarterback Steve McNair tossed a few balls and took some snaps in a 90-minute walk through Tuesday, and coach Jeff Fisher said McNair will practice Wednesday. That would be McNair's first practice in three weeks. A strained right calf and sprained left ankle that also has a cracked bone spur had kept him off the field and out of two of the past three games. Both injuries are significantly improved, according to Fisher. From staff and wire reports LOAD-DATE: January 6, 2004 LANGUAGE: ENGLISH Copyright 2003 The Topeka Capital-Journal 639 of 998 DOCUMENTS The Vancouver Sun (British Columbia) December 31, 2003 Wednesday Final Edition Kelli White, six others test positive for drugs SOURCE: Associated Press; Canadian Press SECTION: Sports; In Brief; Pg. E5 LENGTH: 136 words DATELINE: COLORADO SPRINGS COLORADO SPRINGS -- Capping a year of sports drug scandals, the U.S. Olympic Committee announced Tuesday that sprint champion Kelli White and six other American athletes tested positive for banned substances. White and five other track and field athletes tested positive for the banned stimulant modafinil. Hammer thrower John McEwen tested positive for modafinil and the newly discovered steroid THG, and cyclist Adham Sbeih became the first U.S. athlete to test positive for the endurance-boosting hormone EPO. Also testing positive for modafinil at the national track championships were sprinter Chryste Gaines and hurdlers Sandra Glover and Eric Thomas. Another hurdler, Chris Phillips, tested positive for modafinil at the world championships. All seven are challenging their test results, the USOC said. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH TYPE: Brief; Sports Copyright 2003 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 640 of 998 DOCUMENTS The Vancouver Province (British Columbia) December 31, 2003 Wednesday FINAL C Edition White among 7 to test positive SOURCE: The Associated Press SECTION: Sports; Pg. A37 LENGTH: 115 words The U.S. Olympic Committee announced Tuesday that sprint champion Kelli White and six other American athletes tested positive for banned substances. White and five other track and field athletes tested positive for the banned stimulant modafinil. Hammer thrower John McEwen tested positive for modafinil and the newly discovered steroid THG, and cyclist Adham Sbeih became the first U.S. athlete to test positive for the endurance-boosting hormone EPO. All seven are challenging their test results. White said she was prescribed modafinil for a sleeping disorder -- a claim ridiculed by international track officials after word emerged of other athletes using the banned stimulant. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH GRAPHIC: Colour Photo: The Associated Press; Kelli White plans to appeal her positive test result. TYPE: Sports Copyright 2003 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 641 of 998 DOCUMENTS The Vancouver Province (British Columbia) December 31, 2003 Wednesday Final Edition Top sprinter among seven U.S. athletes to fail drug test: Kelli White had taken banned stimulant modafinil SOURCE: News Services SECTION: Sports; Pg. A37 LENGTH: 291 words The U.S. Olympic Committee announced Tuesday that sprint champion Kelli White and six other American athletes tested positive for banned substances. White and five other track and field athletes tested positive for the banned stimulant modafinil. Hammer thrower John McEwen tested positive for modafinil and the newly discovered steroid THG, and cyclist Adham Sbeih became the first U.S. athlete to test positive for the endurance-boosting hormone EPO. All seven are challenging their test results. White said she was prescribed modafinil for a sleeping disorder -- a claim ridiculed by international track officials after word emerged of other athletes using the banned stimulant. Coulthard Nears Finish Long-serving McLaren Formula One driver David Coulthard looks set to be dropped from the team at the end of the upcoming season according to the BBC on Tuesday. The 32-year-old has had a disappointing two seasons being outshone by teammate Kimi Raikkonen last campaign when the Finn was second behind Michael Schumacher while the Scot was only seventh. EPHEDRA BAN WELCOMED Steve Bechler's parents welcomed the U.S. federal government's ban on ephedra, saying it should save lives and ensure their son did not die in vain. The Baltimore Orioles pitcher's heatstroke in February was linked to the herbal weight-loss supplement, which also has been blamed for more than 150 other deaths. "In one aspect, I feel that it's not enough, because it won't bring Steve back," Bechler's mother, Pat, said. "But it will help and protect other people." DEJEAN AN ORIOLE Free-agent pitcher Mike DeJean agreed Monday to a one-year contract with the Baltimore Orioles, contingent on the right-hander passing a physical exam next week. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH GRAPHIC: Colour Photo: The Associated Press; Kelli White plans to appeal her positive test result. TYPE: Sports Copyright 2003 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 642 of 998 DOCUMENTS The Washington Post December 31, 2003 Wednesday Final Edition USOC Formally Announces Flunked Tests SECTION: Sports; D02 LENGTH: 432 words Sprint champion Kelli White and six other American athletes flunked drug tests this summer, the U.S. Olympic Committee announced yesterday. White and five other track and field athletes tested positive for the banned stimulant modafinil. Hammer thrower John McEwen tested positive for modafinil and the newly discovered steroid THG, and cyclist Adham Sbeih tested positive for the endurance-boosting hormone EPO. The USOC announced the test results after the substances were found in two urine tests from each of the athletes, and following a 30-day review of the tests. All seven athletes are appealing their test results. Any suspensions or other penalties would come only after appeals. White said she was prescribed modafinil for a sleeping disorder -- a claim ridiculed by international track officials after word emerged of other athletes using the banned stimulant. Also testing positive for modafinil at the national track championships were sprinter Chryste Gaines, hurdler Sandra Glover, McEwen, and hurdler Eric Thomas. Hurdler Chris Phillips tested positive for modafinil at the world championships. * SOCCER: Landon Donovan, star of the U.S. team at the 2002 World Cup, was among 25 players selected for the under-23 national training camp leading to Olympic qualifying. Coach Glenn Myernick also chose DaMarcus Beasley, another member of the American team that went to the World Cup quarterfinals, as well as five D.C. United players -- Doug Warren, Bobby Convey, Alecko Eskandarian, David Stokes and Brian Carroll. * WINTER SPORTS: Ronny Ackermann of Germany swept to his fifth World Cup Nordic combined victory . Ackermann finished 53.6 seconds ahead of Austria's Felix Gottwald, with American Todd Lodwick third, 1:06.6 behind, in Oberhof, Germany. . . . Jacob Beste and Rachel Steer won pursuit events at the U.S. biathlon championships in Lake Placid, N.Y. * HOCKEY: Stephen Werner of the University of Massachusetts scored two goals, including the game-winner, as the United States defeated Sweden, 4-3, at the world junior hockey championship in Helsinki. The United States remained undefeated in the under-20 tournament. * AUTO RACING: The CART racing series could win court approval of its proposed sale to a group of team owners by Jan. 28 under a plan an Indianapolis bankruptcy judge approved. U.S. District Judge Frank J. Otte's approval of CART's proposed sales procedures came two weeks after the series filed for Chapter 11 bankruptcy protection as part of an agreement with the series' buyers, Open Wheel Racing Series LLC. -- From News Services LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2003 The Washington Post 643 of 998 DOCUMENTS The Associated Press December 30, 2003, Tuesday, BC cycle USOC releases names of athletes with positive drug tests BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Sports News LENGTH: 382 words Sprint champion Kelli White was among seven American athletes - six in track and field and one in cycling - identified Tuesday by the U.S. Olympic Committee as having flunked drug tests this summer. White and five others tested positive for the banned stimulant modafinil. Hammer thrower John McEwen tested positive for modafinil and the newly discovered steroid THG, and cyclist Adham Sbeih tested positive for the endurance-boosting hormone EPO. The USOC announced the test results after the substances were found in two urine tests from each of the athletes, and following a 30-day review of the tests by the U.S. Anti-Doping Agency. All seven athletes are appealing their test results, the USOC said in a news release from its base in Colorado Springs, Colo., and any suspensions or other sanctions would come only after those appeals are exhausted. White, of Union City, Calif., already faces the loss of her two gold medals at the World Championships because of modafinil use. The USOC said Tuesday that White also tested positive for modafinil at the U.S. track and field championships at Stanford, Calif., in June - where she also swept the 100 and 200 meter titles. By winning at the national meet in June, White qualified for the world meet in August in France. She has claimed she was prescribed modafinil for the sleep disorder narcopelsy - a claim that has been ridiculed by international track officials since word emerged of other athletes using the banned stimulant. Also testing positive for modafinil at the U.S. track and field championships were sprinter Chryste Gaines, of Lithonia, Ga.; 400-meter runner Sandra Glover of Sugarland, Texas; McEwen, of Ashland, Ohio, and hurdler Eric Thomas of Houston. Hurdler Chris Phillips of Little Rock, Ark., tested positive for modafinil at the World Championships. Sbeih of Sacramento, Calif., tested positive for EPO at the U.S. Cycling Federation's Elite Track National Champonships at Trexlertown, Pa., in August. Modafinil use results in disqualification at the event at which a positive test has occurred. THG use could lead to a two-year ban for McEwen. At least three other U.S. track and field athletes tested positive for THG this summer, and their cases are still being considered by USADA. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 644 of 998 DOCUMENTS The Associated Press December 30, 2003, Tuesday, BC cycle World-champion sprinter among seven athletes to fail drug tests BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Domestic News LENGTH: 215 words A world-champion sprinter and six other American athletes flunked drug tests this summer, the U.S. Olympic Committee announced Tuesday. The Olympic Committee announced the results after banned substances were found in two urine tests from each of the athletes, and following a 30-day review of the tests by the U.S. Anti-Doping Agency. All seven athletes are appealing their test results, the USOC said. Any suspensions or other penalties would come only after appeals. The athletes include sprint champion Kelli White, who tested positive for the banned stimulant modafinil along with five other track and field athletes. A hammer thrower tested positive for modafinil and the newly discovered steroid THG, and a cyclist tested positive for the endurance-boosting hormone EPO. White twice tested positive for modafinil during the summer. Officials previously disclosed that she tested positive at the world championships in August. On Tuesday, the USOC said White also tested positive for modafinil at the national championships in June. White won the 100 and 200 meters at both events. White said she was prescribed modafinil for a sleeping disorder - a claim ridiculed by international track officials after word emerged of other athletes using the banned stimulant. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 645 of 998 DOCUMENTS The Associated Press December 30, 2003, Tuesday, BC cycle White among seven athletes to fail drug tests BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Sports News LENGTH: 407 words Sprint champion Kelli White and six other American athletes flunked drug tests this summer, the U.S. Olympic Committee announced Tuesday. White and five other track and field athletes tested positive for the banned stimulant modafinil. Hammer thrower John McEwen tested positive for modafinil and the newly discovered steroid THG, and cyclist Adham Sbeih tested positive for the endurance-boosting hormone EPO. The USOC announced the test results after the substances were found in two urine tests from each of the athletes, and following a 30-day review of the tests by the U.S. Anti-Doping Agency. All seven athletes are appealing their test results, the USOC said in a news release from its base in Colorado Springs, Colo. Any suspensions or other penalties would come only after appeals. White, of Union City, Calif., already faces the loss of two world championship gold medals because of modafinil use. The USOC said Tuesday that White also tested positive for modafinil at the national championships in June, when she also swept the 100 and 200 meters. White said she was prescribed modafinil for a sleeping disorder - a claim ridiculed by international track officials after word emerged of other athletes using the banned stimulant. Also testing positive for modafinil at the national track championships were sprinter Chryste Gaines, hurdler Sandra Glover, McEwen, and hurdler Eric Thomas of Houston. Hurdler Chris Phillips of Little Rock, Ark., tested positive for modafinil at the world championships. White and Gaines are coached by Remy Korchemny, who also coaches British sprinter Dwain Chambers, now facing a two-year suspension for THG. Phillips said Korchemny gave him a modafinil pill at the world championships to help him overcome jet lag. Sbeih of Sacramento, Calif., tested positive for EPO at the U.S. Cycling Federation's Elite Track National Championships in August. Sbeih faces up to a two-year ban. Modafinil use results in disqualification at the event at which a positive test has occurred, but no suspension. THG use can lead to a two-year ban. McEwen's attorney, Howard Jacobs, said McEwen would consider working with the International Association of Athletics Federations, which floated an offer of leniency for drug cheaters who provide valuable information about doping. No such offer has yet been made by the IAAF, Jacobs said in an interview with The Associated Press. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 646 of 998 DOCUMENTS The Associated Press December 30, 2003, Tuesday, BC cycle White among seven U.S. athletes to fail drug tests BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Sports News LENGTH: 462 words Capping a year of sports drug scandals, the U.S. Olympic Committee announced Tuesday that sprint champion Kelli White and six other American athletes tested positive for banned substances. White and five other track and field athletes tested positive for the banned stimulant modafinil. Hammer thrower John McEwen tested positive for modafinil and the newly discovered steroid THG, and cyclist Adham Sbeih became the first U.S. athlete to test positive for the endurance-boosting hormone EPO. The USOC announced the test results after the substances were found in two urine tests from each athlete, and following a review by the U.S. Anti-Doping Agency. All seven are challenging their test results, the USOC said in a news release from its base in Colorado Springs, Colo. Any suspensions or other penalties would come only after an arbitration process. White already faces the loss of two world championship gold medals because of modafinil use. The USOC said Tuesday that White also tested positive for modafinil at the national championships in June, when she swept the 100 and 200 meters. White said she was prescribed modafinil for a sleeping disorder - a claim ridiculed by international track officials after word emerged of other athletes using the banned stimulant. Also testing positive for modafinil at the national track championships were sprinter Chryste Gaines and hurdlers Sandra Glover and Eric Thomas. Another hurdler, Chris Phillips, tested positive for modafinil at the world championships. Modafinil use results in disqualification at the event at which a positive test has occurred, but no suspension. THG use can lead to a two-year ban. Sbeih, who tested positive for EPO at the national cycling championships in August, faces up to a two-year ban. White and Gaines are coached by Remy Korchemny, who also coaches British sprinter Dwain Chambers, now facing a two-year suspension for THG. Phillips said Korchemny gave him a modafinil pill at the world championships to help him overcome jet lag. At least five track and field athletes - including McEwen and Chambers - have tested positive for THG, and a source who requested anonymity has told The Associated Press that four Oakland Raiders also flunked THG tests. The discovery of THG led to a grand jury probe in San Francisco. Athletes from at least five sports - including baseball sluggers Barry Bonds and Jason Giambi - appeared before the panel. McEwen's attorney, Howard Jacobs, said the hammer thrower would consider working with the International Association of Athletics Federations, which floated an offer of leniency for drug cheaters who provide valuable information about doping. Jacobs said Tuesday that no such offer has yet been made by the IAAF. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 647 of 998 DOCUMENTS Associated Press Worldstream December 30, 2003 Tuesday White among seven United States athletes to fail drug tests BYLINE: ROB GLOSTER; AP Sports Writer SECTION: SPORTS LENGTH: 453 words DATELINE: SAN FRANCISCO Capping a year of sports drug scandals, the U.S. Olympic Committee announced that sprint champion Kelli White and six other American athletes tested positive for banned substances. White and five other track and field athletes tested positive for the banned stimulant modafinil. Hammer thrower John McEwen tested positive for modafinil and the newly discovered steroid THG, and cyclist Adham Sbeih became the first U.S. athlete to test positive for the endurance-boosting hormone EPO. The USOC announced the test results after the substances were found in two urine tests from each athlete, and following a review by the U.S. Anti-Doping Agency. All seven are challenging their test results, the USOC said Tuesday in a news release from its base in Colorado Springs, Colorado. Any suspensions or other penalties would come only after an arbitration process. White already faces the loss of two world championship gold medals because of modafinil use. The USOC said Tuesday that White also tested positive for modafinil at the national championships in June, when she swept the 100 and 200 meters. White said she was prescribed modafinil for a sleeping disorder - a claim ridiculed by international track officials after word emerged of other athletes using the banned stimulant. Also testing positive for modafinil at the national track championships were sprinter Chryste Gaines and hurdlers Sandra Glover and Eric Thomas. Another hurdler, Chris Phillips, tested positive for modafinil at the world championships. Modafinil use results in disqualification at the event at which a positive test has occurred, but no suspension. THG use can lead to a two-year ban. Sbeih, who tested positive for EPO at the national cycling championships in August, faces up to a two-year ban. White and Gaines are coached by Remy Korchemny, who also coaches British sprinter Dwain Chambers, now facing a two-year suspension for THG. Phillips said Korchemny gave him a modafinil pill at the world championships to help him overcome jet lag. At least five track and field athletes - including McEwen and Chambers - have tested positive for THG, and a source who requested anonymity has told The Associated Press that four Oakland Raiders also flunked THG tests. The discovery of THG led to a grand jury probe in San Francisco. Athletes from at least five sports - including baseball sluggers Barry Bonds and Jason Giambi - appeared before the panel. McEwen's attorney, Howard Jacobs, said the hammer thrower would consider working with the IAAF, which floated an offer of leniency for drug cheaters who provide valuable information about doping. Jacobs said Tuesday that no such offer has yet been made by the IAAF. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 648 of 998 DOCUMENTS Associated Press Online December 30, 2003 Tuesday Names of Drug-Positive Athletes Released BYLINE: ROB GLOSTER; AP Sports Writer SECTION: SPORTS LENGTH: 460 words Capping a year of sports drug scandals, the U.S. Olympic Committee announced Tuesday that sprint champion Kelli White and six other American athletes tested positive for banned substances. White and five other track and field athletes tested positive for the banned stimulant modafinil. Hammer thrower John McEwen tested positive for modafinil and the newly discovered steroid THG, and cyclist Adham Sbeih became the first U.S. athlete to test positive for the endurance-boosting hormone EPO. The USOC announced the test results after the substances were found in two urine tests from each athlete, and following a review by the U.S. Anti-Doping Agency. All seven are challenging their test results, the USOC said in a news release from its base in Colorado Springs, Colo. Any suspensions or other penalties would come only after an arbitration process. White already faces the loss of two world championship gold medals because of modafinil use. The USOC said Tuesday that White also tested positive for modafinil at the national championships in June, when she swept the 100 and 200 meters. White said she was prescribed modafinil for a sleeping disorder - a claim ridiculed by international track officials after word emerged of other athletes using the banned stimulant. Also testing positive for modafinil at the national track championships were sprinter Chryste Gaines and hurdlers Sandra Glover and Eric Thomas. Another hurdler, Chris Phillips, tested positive for modafinil at the world championships. Modafinil use results in disqualification at the event at which a positive test has occurred, but no suspension. THG use can lead to a two-year ban. Sbeih, who tested positive for EPO at the national cycling championships in August, faces up to a two-year ban. White and Gaines are coached by Remy Korchemny, who also coaches British sprinter Dwain Chambers, now facing a two-year suspension for THG. Phillips said Korchemny gave him a modafinil pill at the world championships to help him overcome jet lag. At least five track and field athletes - including McEwen and Chambers - have tested positive for THG, and a source who requested anonymity has told The Associated Press that four Oakland Raiders also flunked THG tests. The discovery of THG led to a grand jury probe in San Francisco. Athletes from at least five sports - including baseball sluggers Barry Bonds and Jason Giambi - appeared before the panel. McEwen's attorney, Howard Jacobs, said the hammer thrower would consider working with the International Association of Athletics Federations, which floated an offer of leniency for drug cheaters who provide valuable information about doping. Jacobs said Tuesday that no such offer has yet been made by the IAAF. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 649 of 998 DOCUMENTS The Associated Press State & Local Wire December 30, 2003, Tuesday, BC cycle USOC releases names of athletes with positive drug tests BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Sports News LENGTH: 382 words Sprint champion Kelli White was among seven American athletes - six in track and field and one in cycling - identified Tuesday by the U.S. Olympic Committee as having flunked drug tests this summer. White and five others tested positive for the banned stimulant modafinil. Hammer thrower John McEwen tested positive for modafinil and the newly discovered steroid THG, and cyclist Adham Sbeih tested positive for the endurance-boosting hormone EPO. The USOC announced the test results after the substances were found in two urine tests from each of the athletes, and following a 30-day review of the tests by the U.S. Anti-Doping Agency. All seven athletes are appealing their test results, the USOC said in a news release from its base in Colorado Springs, Colo., and any suspensions or other sanctions would come only after those appeals are exhausted. White, of Union City, Calif., already faces the loss of her two gold medals at the World Championships because of modafinil use. The USOC said Tuesday that White also tested positive for modafinil at the U.S. track and field championships at Stanford, Calif., in June - where she also swept the 100 and 200 meter titles. By winning at the national meet in June, White qualified for the world meet in August in France. She has claimed she was prescribed modafinil for the sleep disorder narcopelsy - a claim that has been ridiculed by international track officials since word emerged of other athletes using the banned stimulant. Also testing positive for modafinil at the U.S. track and field championships were sprinter Chryste Gaines, of Lithonia, Ga.; 400-meter runner Sandra Glover of Sugarland, Texas; McEwen, of Ashland, Ohio, and hurdler Eric Thomas of Houston. Hurdler Chris Phillips of Little Rock, Ark., tested positive for modafinil at the World Championships. Sbeih of Sacramento, Calif., tested positive for EPO at the U.S. Cycling Federation's Elite Track National Champonships at Trexlertown, Pa., in August. Modafinil use results in disqualification at the event at which a positive test has occurred. THG use could lead to a two-year ban for McEwen. At least three other U.S. track and field athletes tested positive for THG this summer, and their cases are still being considered by USADA. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 650 of 998 DOCUMENTS The Associated Press State & Local Wire December 30, 2003, Tuesday, BC cycle Two Texans among athletes USOC says had positive drug tests BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Sports News LENGTH: 382 words Sprint champion Kelli White was among seven American athletes - six in track and field and one in cycling - identified Tuesday by the U.S. Olympic Committee as having flunked drug tests this summer. White and five others tested positive for the banned stimulant modafinil. Hammer thrower John McEwen tested positive for modafinil and the newly discovered steroid THG, and cyclist Adham Sbeih tested positive for the endurance-boosting hormone EPO. The USOC announced the test results after the substances were found in two urine tests from each of the athletes, and following a 30-day review of the tests by the U.S. Anti-Doping Agency. All seven athletes are appealing their test results, the USOC said in a news release from its base in Colorado Springs, Colo., and any suspensions or other sanctions would come only after those appeals are exhausted. White, of Union City, Calif., already faces the loss of her two gold medals at the World Championships because of modafinil use. The USOC said Tuesday that White also tested positive for modafinil at the U.S. track and field championships at Stanford, Calif., in June - where she also swept the 100 and 200 meter titles. By winning at the national meet in June, White qualified for the world meet in August in France. She has claimed she was prescribed modafinil for the sleep disorder narcopelsy - a claim that has been ridiculed by international track officials since word emerged of other athletes using the banned stimulant. Also testing positive for modafinil at the U.S. track and field championships were sprinter Chryste Gaines, of Lithonia, Ga.; 400-meter runner Sandra Glover of Sugarland, Texas; McEwen, of Ashland, Ohio, and hurdler Eric Thomas of Houston. Hurdler Chris Phillips of Little Rock, Ark., tested positive for modafinil at the World Championships. Sbeih of Sacramento, Calif., tested positive for EPO at the U.S. Cycling Federation's Elite Track National Championships at Trexlertown, Pa., in August. Modafinil use results in disqualification at the event at which a positive test has occurred. THG use could lead to a two-year ban for McEwen. At least three other U.S. track and field athletes tested positive for THG this summer, and their cases are still being considered by USADA. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 651 of 998 DOCUMENTS The Associated Press State & Local Wire December 30, 2003, Tuesday, BC cycle White among seven athletes to fail drug tests BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Sports News LENGTH: 407 words Sprint champion Kelli White and six other American athletes flunked drug tests this summer, the U.S. Olympic Committee announced Tuesday. White and five other track and field athletes tested positive for the banned stimulant modafinil. Hammer thrower John McEwen tested positive for modafinil and the newly discovered steroid THG, and cyclist Adham Sbeih tested positive for the endurance-boosting hormone EPO. The USOC announced the test results after the substances were found in two urine tests from each of the athletes, and following a 30-day review of the tests by the U.S. Anti-Doping Agency. All seven athletes are appealing their test results, the USOC said in a news release from its base in Colorado Springs, Colo. Any suspensions or other penalties would come only after appeals. White, of Union City, Calif., already faces the loss of two world championship gold medals because of modafinil use. The USOC said Tuesday that White also tested positive for modafinil at the national championships in June, when she also swept the 100 and 200 meters. White said she was prescribed modafinil for a sleeping disorder - a claim ridiculed by international track officials after word emerged of other athletes using the banned stimulant. Also testing positive for modafinil at the national track championships were sprinter Chryste Gaines, hurdler Sandra Glover, McEwen, and hurdler Eric Thomas of Houston. Hurdler Chris Phillips of Little Rock, Ark., tested positive for modafinil at the world championships. White and Gaines are coached by Remy Korchemny, who also coaches British sprinter Dwain Chambers, now facing a two-year suspension for THG. Phillips said Korchemny gave him a modafinil pill at the world championships to help him overcome jet lag. Sbeih of Sacramento, Calif., tested positive for EPO at the U.S. Cycling Federation's Elite Track National Championships in August. Sbeih faces up to a two-year ban. Modafinil use results in disqualification at the event at which a positive test has occurred, but no suspension. THG use can lead to a two-year ban. McEwen's attorney, Howard Jacobs, said McEwen would consider working with the International Association of Athletics Federations, which floated an offer of leniency for drug cheaters who provide valuable information about doping. No such offer has yet been made by the IAAF, Jacobs said in an interview with The Associated Press. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 652 of 998 DOCUMENTS The Associated Press State & Local Wire December 30, 2003, Tuesday, BC cycle White among seven U.S. athletes to fail drug tests BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Sports News LENGTH: 462 words Capping a year of sports drug scandals, the U.S. Olympic Committee announced Tuesday that sprint champion Kelli White and six other American athletes tested positive for banned substances. White and five other track and field athletes tested positive for the banned stimulant modafinil. Hammer thrower John McEwen tested positive for modafinil and the newly discovered steroid THG, and cyclist Adham Sbeih became the first U.S. athlete to test positive for the endurance-boosting hormone EPO. The USOC announced the test results after the substances were found in two urine tests from each athlete, and following a review by the U.S. Anti-Doping Agency. All seven are challenging their test results, the USOC said in a news release from its base in Colorado Springs, Colo. Any suspensions or other penalties would come only after an arbitration process. White already faces the loss of two world championship gold medals because of modafinil use. The USOC said Tuesday that White also tested positive for modafinil at the national championships in June, when she swept the 100 and 200 meters. White said she was prescribed modafinil for a sleeping disorder - a claim ridiculed by international track officials after word emerged of other athletes using the banned stimulant. Also testing positive for modafinil at the national track championships were sprinter Chryste Gaines and hurdlers Sandra Glover and Eric Thomas. Another hurdler, Chris Phillips, tested positive for modafinil at the world championships. Modafinil use results in disqualification at the event at which a positive test has occurred, but no suspension. THG use can lead to a two-year ban. Sbeih, who tested positive for EPO at the national cycling championships in August, faces up to a two-year ban. White and Gaines are coached by Remy Korchemny, who also coaches British sprinter Dwain Chambers, now facing a two-year suspension for THG. Phillips said Korchemny gave him a modafinil pill at the world championships to help him overcome jet lag. At least five track and field athletes - including McEwen and Chambers - have tested positive for THG, and a source who requested anonymity has told The Associated Press that four Oakland Raiders also flunked THG tests. The discovery of THG led to a grand jury probe in San Francisco. Athletes from at least five sports - including baseball sluggers Barry Bonds and Jason Giambi - appeared before the panel. McEwen's attorney, Howard Jacobs, said the hammer thrower would consider working with the International Association of Athletics Federations, which floated an offer of leniency for drug cheaters who provide valuable information about doping. Jacobs said Tuesday that no such offer has yet been made by the IAAF. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 653 of 998 DOCUMENTS Voice of America News December 30, 2003 USOC Announces Sprint Champ Kelli White Failed Doping Test SECTION: SPORTS LENGTH: 213 words Filed: 20:41 UTC The USOC announced Tuesday that White, sprinter Chryste Gaines, hurdlers Sandra Glover, Chris Phillips and Eric Thomas, and hammer-thrower John McEwen tested positive for the banned stimulant modafinil at either the U.S. or World Athletics Championships. John McEwen also tested positive for the newly discovered steroid THG, while cyclist Adham Sbeih tested positive for the endurance-boosting hormone EPO. The USOC announced the results after the substances were found in two urine tests from each of the athletes following a 30-day review of the tests by the U.S. Anti-Doping Agency. All seven athletes will appeal their test results, and any suspensions or other sanctions would come only after those appeals are exhausted. White already faces the loss of her two gold medals at the World Championships because of modafinil use. The USOC said Tuesday that White also tested positive for modafinil at the U.S. track and field championships in June, where she swept the 100- and 200-meter titles. White has claimed she was prescribed modafinil for the sleep disorder narcolepsy. At least three other U.S. track and field athletes tested positive for THG this summer, and their cases are still being considered by the U.S. Anti-Doping Agency. LOAD-DATE: December 31, 2003 LANGUAGE: ENGLISH Copyright 2003 Federal Information and News Dispatch, Inc. 654 of 998 DOCUMENTS Edmonton Journal (Alberta) December 29, 2003 Monday Final Edition Stay-awake drugs high in demand: Despite society's chronic lack of sleep SOURCE: Ottawa Citizen; CanWest News Service BYLINE: Sharon Kirkey SECTION: Body & Health; Pg. B13 LENGTH: 808 words DATELINE: OTTAWA OTTAWA - Psychologist Stanley Coren finds a particular lunacy to our determination to squeeze more minutes out of every day, when science shows not getting enough sleep is putting people at risk. Humans have been hardwired through evolution to require nine, even 10 hours of sleep a night, but the average North American is getting more like seven, says Coren, director of the Human Neuropsychology and Perception Laboratory at the University of British Columbia. "Generally, we're about two hours sleep-deprived every night." Some polls suggest one out of every three Canadians is managing just six hours of sleep a night, or less. But what if you could get the equivalent of a good night's sleep in a pill, a drug that would keep you awake for 40 hours or more with little, if any, of the jitteriness, agitation, anxiety and insomnia associated with other brain stimulants? "Wake-promoting" agents have become one of the hottest fields of drug research, with a vast, mostly untapped market potentially worth billions. One such drug is already here: Modafinil (sold as Alertec in Canada and Provigil in the U.S.) has been available since 1999 for the treatment of narcolepsy, a devastating disorder that affects one out of every 3,000 people and causes uncontrollable sleep attacks at inappropriate times. But now, the U.S. Food and Drug Administration has given preliminary blessing to expanded uses of the drug to treat excessive daytime sleepiness in shift workers as well as for sleep apnea, a condition that causes people to stop breathing at night. Official approval, which is expected soon, will mean Cephalon can start promoting the drug not just to sleep doctors but to family doctors. The company is gearing up to deploy an "expanded sales force" early next year. But the prospect of people swallowing pills to postpone sleep has some critics nervous. When is sleepiness a sickness? Doctors can't even agree whether "shift work sleep disorder" is a true medical illness, and there's evidence people are taking Modafinil for conditions not sanctioned by government regulators. In the U.S. alone, some 250,000 people are using Modafinil, even though only 150,000 Americans are estimated to have narcolepsy. Canadian prescriptions have nearly doubled since 2001. Nearly 28,000 prescriptions were dispensed in Canadian drugstores during the 12 months ending October 2003, compared to 14,648 in 2001, according to Health Canada. People have always searched for ways to get by on less sleep. Coffee has become the second most commonly traded commodity in the world, next to oil. But now athletes and CEOs and college students "and everyone who wants to stay wide awake all day long under minimal sleep are asking their physicians for prescriptions," for Modafinil, says Cornell University psychologist and sleep expert James Maas. "There is this notion that if you sleep a lot, you're lazy and useless," Coren says. Add that to our frenetic lives, the growing numbers of harried, dual-income families trying to cope with the demands of work and home, the seductive all-night allure of the Internet, and it's little wonder we've become a nation "of walking zombies," says Maas. Millions try to catch up by oversleeping on holidays and weekends, but our sleep debts just keep accruing, week after week. Studies have found that people who sleep six hours or less a night have an increased risk of high blood pressure, heart attacks and stroke. Just one bad night's sleep can have a dramatic effect on memory, alertness, concentration and judgment, and chronic sleep deprivation can lead to depression. More worrisome, "when we're really sleep deprived, at some point in time we start to micro-sleep," says Coren. "No matter what we're doing, our brain goes into a sleep state, and it can remain there anywhere from 10 seconds to a minute. "Now suppose that you're tooling down the road in your car at 50 kilometres an hour and you have one of these small little micro-sleeps, and it's the 10-second kind. What that means is that your car will travel more than the length of a football field while you're asleep." Still, Coren worries about using drugs to manipulate the body's need for sleep. "Obviously if you have an individual who is in jeopardy of losing his livelihood if he can't adapt to shift work, you might consider it." But given the huge number of people in the world who work odd hours, from nurses, firefighters, and factory workers to pilots and 911 operators, "we could be talking about a large number of individuals who are going to start to muck up their sleep chemistry." And no matter how safe drugs that beat back sleep become, they will always bump up against the fact that the brain will always find a way to sleep, no matter what we're doing. That, the experts say, is enough to lose sleep over. LOAD-DATE: December 29, 2003 LANGUAGE: ENGLISH TYPE: News Copyright 2003 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 655 of 998 DOCUMENTS Windsor Star (Ontario) December 24, 2003 Wednesday Final Edition 'Wake-promoting' drugs a hot untapped market; Polls say one out of three Canadians getting six hours of sleep or less SOURCE: CanWest News Service BYLINE: Sharon Kirkey CanWest News Service SECTION: NEWS; Pg. C1 LENGTH: 666 words DATELINE: Ottawa Psychologist Stanley Coren finds a particular lunacy in our determination to squeeze more minutes out of every day, when all the science shows not getting enough sleep makes people, as he puts it, clumsy, stupid, unhappy and dead. Humans have been hardwired through evolution to require nine, even 10 hours of sleep a night, but the average North American is getting more like seven, says Coren, director of the Human Neuropsychology and Perception Laboratory at the University of British Columbia. "Generally speaking, we're about two hours sleep-deprived every night." Some polls suggest one out of every three Canadians is managing just six hours of sleep a night, or less. But, what if you could get the equivalent of a good night's sleep in a pill, a drug that would keep you awake for 40 hours or more with little, if any, of the jitteriness, agitation, anxiety and insomnia associated with other brain stimulants, including caffeine? "Wake-promoting" agents have become one of the hottest fields of drug research, with a vast, mostly untapped market potentially worth billions. The patient population for "sleep therapeutics" is bigger than that for depression. One such drug is already here: Modafinil (sold as Alertec in Canada and Provigil in the U.S.) has been available since 1999 for the treatment of narcolepsy, a devastating disorder that affects one out of every 3,000 people and causes uncontrollable sleep attacks in the middle of a conversation, sitting in the drive-through at McDonald's or any other inappropriate time. But now, the U.S. Food and Drug Administration has given its preliminary blessing for expanded uses of the drug to treat excessive daytime sleepiness in shift workers, or so-called "shift work sleep disorder," as well as for sleep apnea, a condition that causes people to stop breathing for a minute or longer up to 100 times a night. Official approval, which is expected soon, will mean Cephalon can start promoting the drug not just to sleep doctors and other specialists, but to the real wellspring for drug sales: family doctors. The company is already gearing up to deploy an "expanded sales force" early next year. But the prospect of people swallowing pills to postpone sleep has some critics nervous. When is sleepiness a sickness? Doctors can't even agree whether "shift work sleep disorder" is a true medical illness and there's already evidence people are getting modafinil "off label," meaning for conditions that haven't been sanctioned by government regulators. In the U.S. alone, some 250,000 people are using modafinil, even though only 150,000 Americans are estimated to have narcolepsy. Canadian prescriptions have nearly doubled since 2001. Nearly 28,000 prescriptions were dispensed in Canadian drugstores during the 12 months ending October 2003, compared to 14,648 in 2001, according to IMS Health Canada. People have always searched for ways to get by on less sleep. Coffee has become the second most commonly traded commodity in the world, next to oil. But now athletes and CEOs and college students "and everyone who wants to stay wide awake all day long under minimal sleep are asking their physicians for prescriptions," for modafinil, says Cornell University psychologist and sleep expert James Maas. ATHLETE'S STIMULANT DU JOUR? Some reports suggest the drug has become the stimulant du jour among track and field athletes. U.S. sprinter Kelli White tested positive for the drug at the world championships in Paris earlier this year. She says she was taking it to treat her narcolepsy. Chris Phillips, another U.S. athlete, also tested positive for modafinil at the same Paris meet, prompting anti-doping officials to muse about the oddly high number of athletes with narcolepsy. But the potential for abuse isn't limited to the playing field. Some fear the pressure for employees to drug themselves to meet employers' demands may be huge. After all, sleep is seen as a luxury, not a need, Coren says. LOAD-DATE: December 24, 2003 LANGUAGE: ENGLISH GRAPHIC: Kelli White TYPE: News Copyright 2003 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 656 of 998 DOCUMENTS XINHUA GENERAL NEWS SERVICE December 24, 2003, Wednesday YEARENDER-Athletics-Modafinil, THG rock track and field SECTION: WORLD NEWS; SPORTS LENGTH: 822 words By Sportswriter Pan Yi BEIJING, Dec. 24 (Xinhua) -- Modafinil, a medical stimulant which can prevent a person from sleepiness, and THG, a newly- detected steroid, have become the two most eye-catching things in this year's world track and field arena which has seen tougher anti-doping hands of IAAF and dim performances by top stars. Attention was drawn to the doping as many top names emerged on the black list. British sprinter Dwain Chambers, the European 100 meters champion and record holder, tested positive for the designer anabolic steroid tetrahydrogestrinone (THG) and is facing a two-year ban and return of the men's 4x100m relay silver medal gained at the Paris World Championships in August. Chambers' training partner American Kelli White, who claimed the titles of women's 100m and 200m in Paris, tested positive for modafinil. Also on the modafinil list were American sprinter Chryste Gaines, a member of the victorious women's 4x100m relay team in the 1996 Atlanta Olympics, hurdler Chris Phillips, who finished sixth in men's 110m hurdles in Paris, and American 400m runner Calvin Harrison, the Olympic and world gold medallist and a member of the American team who won the gold medal in the 4x400m relay in Paris. Obviously, the United States, the world athletics powerhouse, has become the most serious doping-hit area where three shinning stars, middle-distance runner Regina Jacobs, shot put champion Kevin Toth and hammer thrower John McEwan, have also tested positive for THG this year. Coincidentally, Gaines, White, Phillips, Chambers all train with Ukrainian-born coach Remi Korchemny who is under scrutiny for doping abuse. Moreover, White, Chambers, Harrison and Phillips are all clients of a California lab that sells nutritional supplements but is suspected by the U.S. federal grand jury of developing THG. THG is a new kind of anabolic steroids which are synthetic versions of the male hormone testosterone. Athletes use them illegally to bulk up muscle and enhance performance. U.S. drug authorities first learned about THG this summer after an unidentified coach gave them a syringe containing it. THG apparently was designed specifically (molecule structure changed) to be undetectable by the standard test given to athletes. Modafinil, which is marketed under the name Provigil, was not officially banned until after the world championships in August but it qualified as a banned substance because of a broad clause in the anti-doping rules prohibiting substances closely related to banned drugs. As so many athletes were suddenly testing positive for Modafinil, doping experts suspected that they were also taking THG. It is possible they believe that modafinil would act as a masking agent in case laboratories could test for THG. Facing the two new foes of the sport and such an embarrassing situation, the International Association of Athletics Federations (IAAF) took prompt moves and used iron hands to purify the arena. It has decided to retest all urine samples (about 400) from Paris World Championships. Any positive findings would lead to retroactive disqualification, including stripping of any medals, and two-year bans. "The emergence of this new steroid is a matter of great concern and we are taking all steps that we can to investigate how widespread its use has been," IAAF president Lamine Diack said in October. The IAAF also requested the United States, which is at the heart of the doping scandals, to make extensive and intensive investigation into the doping cases. In the war against THG, the IAAF needs the concrete assistance from the United States, the only country having the effective methods to check THG. The United States, which is often blamed for shielding its suspected athletes, has paid great attention to the new situation now. It has identified THG as illegal, put manufacturers on notice that the government will crack down on anyone caught selling it. The U.S. Food and Drug Administration also warned consumers that the use of anything containing THG may risk their health. The U.S. anti-doping agency has retested the samples from the U.S. Championships, and those found guilty have been punished. Partly because of the IAAF anti-doping punches, there were lack of astonishing performances in the world arena this year, especially made by those star athletes. At the Paris World Championships, the highest-level gathering this year, the mark of the champion from the most eye-catching men's 100m was only 10.07 seconds, which was the poorest one in high-level competitions in 20 years. However, the IAAF anti-doping determination has won support from most of the world. People rather want to see no-shinning but real results than shinning but fake ones. Fair play is unshakable norm of sports forever. At the 2004 Olympic Games, people from all over the world are eager to see brilliant and cheat-free performances. LOAD-DATE: December 25, 2003 LANGUAGE: ENGLISH COPYRIGHT 2003 XINHUA NEWS AGENCY 657 of 998 DOCUMENTS Edmonton Journal (Alberta) December 23, 2003 Tuesday Final Edition Cutting back on sleep at your peril: Illness, accidents result from fatigue SOURCE: CanWest News Service BYLINE: Sharon Kirkey SECTION: News; Pg. A1 LENGTH: 784 words DATELINE: OTTAWA OTTAWA - Psychologist Stanley Coren finds a particular lunacy in our determination to squeeze more minutes out of every day, when all the science shows not getting enough sleep makes people, as he puts it, clumsy, stupid, unhappy and dead. Humans have been hard-wired through evolution to require nine, even 10 hours of sleep a night, but the average North American is getting more like seven, says Coren, director of the Human Neuropsychology and Perception Laboratory at the University of British Columbia. "Generally speaking, we're about two hours sleep-deprived every night." Some polls suggest one out of every three Canadians is managing on just six hours of sleep a night, or less. But, what if you could get the equivalent of a good night's sleep in a pill, a drug that would keep you awake for 40 hours or more with little, if any, of the jitteriness, agitation, anxiety and insomnia associated with other brain stimulants, including caffeine? "Wake-promoting" agents have become one of the hottest fields of drug research, with a vast, mostly untapped market potentially worth billions. The patient population for "sleep therapeutics" is bigger than that for depression. One such drug is already here: Modafinil (sold as Alertec in Canada and Provigil in the U.S.) has been available since 1999 for the treatment of narcolepsy, a devastating disorder that affects one out of every 3,000 people and causes uncontrollable sleep attacks in the middle of a conversation, sitting in the drive-through at McDonald's or any other inappropriate time. But now, the U.S. Food and Drug Administration has given its preliminary blessing for expanded uses of the drug to treat excessive daytime sleepiness in shift workers, or so-called "shift work sleep disorder," as well as for sleep apnea, a condition that causes people to stop breathing for a minute or longer up to 100 times a night. Official approval, which is expected soon, will mean Cephalon can start promoting the drug not just to sleep doctors and other specialists, but to the real wellspring for drug sales: family doctors. The company is already gearing up to deploy an "expanded sales force" early next year. But the prospect of people swallowing pills to postpone sleep has some critics nervous. When is sleepiness a sickness? Doctors can't even agree whether "shift work sleep disorder" is a true medical illness, and there's already evidence people are getting modafinil "off label," meaning for conditions that haven't been sanctioned by government regulators. In the U.S. alone, some 250,000 people are using modafinil, even though only 150,000 Americans are estimated to have narcolepsy. Canadian prescriptions have nearly doubled since 2001. People have always searched for ways to get by on less sleep. Coffee has become the second most commonly traded commodity in the world, next to oil. But now athletes and CEOs and college students "and everyone who wants to stay wide awake all day long under minimal sleep are asking their physicians for prescriptions," for modafinil, says Cornell University sleep expert James Maas. "There is this notion somehow or another that if you sleep a lot, you're lazy and useless," Coren says. Add that to our frenetic lives, the growing numbers of harried, dual-income families trying to cope with the demands of work and home, the seductive all-night allure of the Internet, and it's little wonder we've become a nation "of walking zombies," says Maas. Studies have found that people who sleep six hours or less a night have an increased risk of high blood pressure, heart attacks and stroke. Just one bad night's sleep can have a dramatic effect on memory, alertness, concentration and judgment, and chronic sleep deprivation can lead to anxiety and depression. More worrisome, "when we're really sleep deprived, at some point in time we start to micro sleep," says Coren. "No matter what we're doing, our brain goes into a sleep state, and it can remain there anywhere from 10 seconds to a minute." "Now suppose that you're tooling down the road in your car at 50 kilometres an hour and you have one of these small little micro sleeps, and it's the 10-second kind. What that means is that your car will travel more than the length of a football field while you're asleep." In fact, Coren's team has found that traffic accidents in Canada jump seven per cent on the Monday after the switch to daylight time and people lose an hour's worth of sleep. Still, Coren worries about using drugs to manipulate the body's need for sleep. "Obviously if you have an individual who is in jeopardy of losing his livelihood if he can't adapt to shift work, you might consider it." LOAD-DATE: December 23, 2003 LANGUAGE: ENGLISH GRAPHIC: Colour Photo: Ottawa Citizen, Canwest News, File; Drowsy drivers are one symptom of a sleep-deprived society. TYPE: News Copyright 2003 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 658 of 998 DOCUMENTS The Gazette (Montreal, Quebec) December 23, 2003 Tuesday Final Edition Drugs mean you can forfeit 40 winks: Humans have been hardwired to require nine, even 10 hours of sleep a night. But what if you could get a good night's sleep in a pill? SOURCE: CanWest News Service BYLINE: SHARON KIRKEY SECTION: News; Pg. A4 LENGTH: 799 words DATELINE: OTTAWA Psychologist Stanley Coren finds a particular lunacy in our determination to squeeze more minutes out of every day, when most research suggests not getting enough sleep makes people, as he puts it, clumsy, stupid, unhappy and dead. Humans have been hardwired through evolution to require nine, even 10 hours of sleep a night, but the average North American is getting more like seven, says Coren, director of the Human Neuropsychology and Perception Laboratory at the University of British Columbia. "Generally speaking, we're about two hours sleep-deprived every night." Some polls suggest one out of every three Canadians is managing just six hours of sleep a night, or less. But, what if you could get the equivalent of a good night's sleep in a pill, a drug that would keep you awake for 40 hours or more with little, if any, of the jitteriness, agitation, anxiety and insomnia associated with other brain stimulants, including caffeine? "Wake-promoting" agents have become one of the hottest fields of drug research, with a vast, mostly untapped market potentially worth billions. The patient population for "sleep therapeutics" is bigger than that for depression. One such drug is already here: Modafinil (sold as Alertec in Canada and Provigil in the U.S.) has been available since 1999 for the treatment of narcolepsy, a devastating disorder that affects one out of every 3,000 people and causes uncontrollable sleep attacks in the middle of a conversation, sitting in the drive-through at McDonald's or any other inappropriate time. But now, the U.S. Food and Drug Administration has given its preliminary blessing for expanded uses of the drug to treat excessive daytime sleepiness in shift workers, as well as for sleep apnea, a condition that causes people to stop breathing for a minute or longer up to 100 times a night. But the prospect of people swallowing pills to postpone sleep has some critics nervous. People have always searched for ways to get by on less sleep. Coffee has become the second-most commonly traded commodity in the world, next to oil. But now athletes and CEOs and college students "and everyone who wants to stay wide awake all day long under minimal sleep are asking their physicians for prescriptions," for modafinil, says Cornell University psychologist and sleep expert James Maas. Some reports suggest the drug has become the stimulant du jour among track and field athletes. U.S. sprinter Kelli White tested positive for the drug at the world championships in Paris this year. She says she was taking it to treat her narcolepsy. Chris Phillips, another U.S. athlete, also tested positive for modafinil at the same Paris meet, prompting anti-doping officials to muse about the oddly high number of athletes with narcolepsy. But the potential for abuse isn't limited to the playing field. Some fear the pressure for employees to drug themselves to meet employers' demands may be huge. After all, sleep is seen as a luxury, not a need, Coren says. A Microsoft executive once sniffed sleep is "nonproductive downtime." "There is this notion somehow or another that if you sleep a lot, you're lazy and useless," Coren says. Add that to our frenetic lives, the growing numbers of harried, dual-income families trying to cope with the demands of work and home, the seductive all-night allure of the Internet, and it's little wonder we've become a nation "of walking zombies," Maas says. Millions try to catch up by oversleeping on holidays and weekends, but our sleep debts just keep accruing, week after week. Studies have found people who sleep six hours or less a night have an increased risk of high blood pressure, heart attacks and stroke. Just one bad night's sleep can have a dramatic effect on memory, alertness, concentration and judgment, and chronic sleep deprivation can lead to anxiety and depression. More worrisome, "when we're really sleep deprived, at some point in time we start to micro sleep," Coren says. "No matter what we're doing, our brain goes into a sleep state, and it can remain there anywhere from 10 seconds to a minute." In fact, Coren's team has found traffic accidents in Canada jump seven per cent on the Monday after the switch to daylight savings time and people lose an hour's worth of sleep. Still, Coren worries about using drugs to manipulate the body's need for sleep. "We could be talking about a large number of individuals who are going to start to muck up their sleep chemistry," he says, considering the high number of people who work night shifts. And no matter how safe drugs that beat back sleep become, they will always bump up against the fact that the brain will always find a way to sleep, no matter what we're doing. That, the experts say, is enough to lose sleep over. LOAD-DATE: December 23, 2003 LANGUAGE: ENGLISH GRAPHIC: Photo: THE GAZETTE; Modafinil has become the stimulant du jour for some athletes. Copyright 2003 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 659 of 998 DOCUMENTS National Post (Canada) December 23, 2003 Tuesday National Edition Giving sleep a rest: A drug narcoleptics take to stay awake is being promoted for a sleep-deprived public SOURCE: CanWest News Service BYLINE: Sharon Kirkey SECTION: News; Pg. A17 LENGTH: 1270 words Psychologist Stanley Coren finds a particular lunacy in our determination to squeeze more minutes out of every day, when all the science shows not getting enough sleep makes people, as he puts it, clumsy, stupid, unhappy and dead. Humans have been hardwired through evolution to require nine, even 10 hours of sleep a night, but the average North American is getting more like seven, says Coren, director of the Human Neuropsychology and Perception Laboratory at the University of British Columbia. "Generally speaking, we're about two hours sleep-deprived every night." Some polls suggest one out of every three Canadians is managing just six hours of sleep a night, or less. But, what if you could get the equivalent of a good night's sleep in a pill, a drug that would keep you awake for 40 hours or more with little, if any, of the jitteriness, agitation, anxiety and insomnia associated with other brain stimulants, including caffeine? "Wake-promoting" agents have become one of the hottest fields of drug research, with a vast, mostly untapped market potentially worth billions. The patient population for "sleep therapeutics" is bigger than that for depression. One such drug is already here: modafinil (sold as Alertec in Canada and Provigil in the United States) has been available since 1999 for the treatment of narcolepsy, a devastating disorder that affects one out of every 3,000 people and causes uncontrollable sleep attacks in the middle of a conversation, sitting in the drive-through at McDonald's or any other inappropriate time. But now, the U.S. Food and Drug Administration has given its preliminary blessing for expanded uses of the drug to treat excessive daytime sleepiness in shift workers, or so-called "shift work sleep disorder," as well as for sleep apnea, a condition that causes people to stop breathing for a minute or longer up to 100 times a night. Official approval, which is expected soon, will mean the manufacturer, Cephalon, can start promoting the drug not just to sleep doctors and other specialists, but to the real wellspring for drug sales: family doctors. The company is gearing up to deploy an expanded sales force early next year. Meanwhile, Massachusetts-based Hypnion Inc. has wake-alertness compounds in the queue that it claims are superior to modafinil. Researchers in Ottawa are about to start testing a new chemical cousin of modafinil. And a Canadian military-sponsored research facility in Toronto has been testing modafinil in soldiers under different simulated field conditions of "sustained wakefulness." According to Wired Magazine, "continuous alertness could be available over the counter" within 10 years. "These drugs will do for sleep disorders what Prozac did for depression," Dale Edgar, co-founder of Hypnion, told the magazine. But the prospect of people swallowing pills to postpone sleep has some critics nervous. When is sleepiness a sickness? Doctors cannot even agree whether "shift work sleep disorder" is a true medical illness, and there is already evidence people are getting modafinil "off label," meaning for conditions that have not been sanctioned by government regulators. In the United States alone, some 250,000 people are using modafinil, even though only 150,000 Americans are estimated to have narcolepsy. Canadian prescriptions have nearly doubled since 2001. Nearly 28,000 prescriptions were dispensed in Canadian drugstores during the 12 months ending October, 2003, compared to 14,648 in 2001, according to IMS Health Canada. People have always searched for ways to get by on less sleep. Coffee has become the second most commonly traded commodity in the world, next to oil. But now athletes and CEOs and college students "and everyone who wants to stay wide awake all day long under minimal sleep are asking their physicians for prescriptions" for modafinil, says Cornell University psychologist and sleep expert James Maas. "There is this notion somehow or another that if you sleep a lot, you're lazy and useless," Coren says. Add that to our frenetic lives, the growing numbers of harried, dual-income families trying to cope with the demands of work and home, the seductive all-night allure of the Internet, and it is little wonder we have become a nation "of walking zombies," says Maas. Millions try to catch up by oversleeping on holidays and weekends, but our sleep debts just keep accruing, week after week. Children, too, are being increasingly sleep starved, a phenomenon Maas partly pins on parents "who don't know diddly about sleep and sleep requirements" in school-aged children. Old diaries and letters suggest that people were logging about nine hours a night before 1913. Then Thomas Edison invented the light bulb. "Part of the reason he did was that he really felt people were using darkness as an excuse not to work and he wanted to increase our productivity," says Coren, author of the book Sleep Thieves. "I don't know whether we're more productive, but we're certainly more tired." Scientist do not really know why humans need sleep, although most believe it plays a fundamental role in regulating the genes in the brain that are involved in numerous cellular functions. Deprive rats of sleep long enough and they will die, usually within two weeks. Researchers also know that sleep occurs throughout the animal kingdom, right down to the smallest complex animals, such as fruit flies. Shortened sleep can lead to reduced brain levels of leptin, the hormone that controls appetite. Get too little sleep, Maas says, and the brain signals us to eat complex carbohydrates, starches and sugars. U.S. researchers recently discovered that "short sleepers" produce more cytokines, molecules that normally fight germs and other invaders. "Except there are no germs, you just slept too little, but they have to attack something, so they start to eat the arterial walls," Maas says. Studies have found that people who sleep six hours or less a night have an increased risk of high blood pressure, heart attacks and stroke. Just one bad night's sleep can have a dramatic effect on memory, alertness, concentration and judgment, and chronic sleep deprivation can lead to anxiety and depression. More worrisome, "when we're really sleep deprived, at some point in time we start to micro sleep," Coren says. "No matter what we're doing, our brain goes into a sleep state, and it can remain there anywhere from 10 seconds to a minute." "Now suppose that you're tooling down the road in your car at 50 kilometres an hour and you have one of these small little micro sleeps, and it's the 10-second kind. What that means is that your car will travel more than the length of a football field while you're asleep." In fact, Coren's team has found that traffic accidents in Canada jump 7% on the Monday after the switch to daylight savings time and people lose an hour's sleep. Still, Coren worries about using drugs to manipulate the body's need for sleep. "Obviously if you have an individual who is in jeopardy of losing his livelihood if he can't adapt to shift work, you might consider it." But given the huge number of people in the world who work odd hours, from nurses, firefighters and factory workers to pilots and 911 operators, "we could be talking about a large number of individuals who are going to start to muck up their sleep chemistry." And no matter how safe drugs that beat back sleep become, they will always bump up against the fact that the brain will always find a way to sleep, no matter what we're doing. That, the experts say, is enough to lose sleep over. LOAD-DATE: December 23, 2003 LANGUAGE: ENGLISH GRAPHIC: Black & White Photo: Carlo Allegri, National Post; Researchers say few people get the sleep their bodies require. One solution would be to remove the need for rest. TYPE: News Copyright 2003 National Post, All Rights Reserved 660 of 998 DOCUMENTS Ottawa Citizen December 23, 2003 Tuesday Final Edition Sleep-deprived Canadians make enticing market for alertness drugs SOURCE: The Ottawa Citizen BYLINE: Sharon Kirkey SECTION: News; Pg. A1 LENGTH: 1523 words Psychologist Stanley Coren finds a particular lunacy in our determination to squeeze more minutes out of every day, when all the science shows not getting enough sleep makes people, as he puts it, clumsy, stupid, unhappy and dead. Humans have been hardwired through evolution to require nine, even 10, hours of sleep a night, but the average North American is getting more like seven, says Mr. Coren, director of the Human Neuropsychology and Perception Laboratory at the University of British Columbia. "Generally speaking, we're about two hours sleep-deprived every night." Some polls suggest one out of every three Canadians is managing just six hours of sleep a night or less. But, what if you could get the equivalent of a good night's sleep in a pill, a drug that would keep you awake for 40 hours or more with little, if any, of the jitteriness, agitation, anxiety and insomnia associated with other brain stimulants, including caffeine? "Wake-promoting" agents have become one of the hottest fields of drug research, with a vast, mostly untapped market potentially worth billions. The patient population for "sleep therapeutics" is bigger than that for depression. One such drug is already here: Modafinil (sold as Alertec in Canada and Provigil in the U.S.) has been available since 1999 for the treatment of narcolepsy, a devastating disorder that affects one out of every 3,000 people and causes uncontrollable sleep attacks in the middle of a conversation, sitting in the drive-through at McDonald's or any other inappropriate time. But now, the U.S. Food and Drug Administration has given its preliminary blessing for expanded uses of the drug to treat excessive daytime sleepiness in shift workers, or so-called "shift work sleep disorder," as well as for sleep apnea, a condition that causes people to stop breathing for a minute or longer up to 100 times a night. Official approval, which is expected soon, will mean Cephalon can start promoting the drug not just to sleep doctors and other specialists, but to the real wellspring for drug sales: family doctors. The company is already gearing up to deploy an "expanded sales force" early next year. Meanwhile, Massachusetts-based Hypnion Inc. has wake-alertness compounds in the queue that it claims are superior to modafinil. Researchers in Ottawa are about to start testing a new chemical cousin of modafinil. And a Canadian military-sponsored research facility in Toronto has been testing modafinil in soldiers under different simulated field conditions of "sustained wakefulness." According to Wired magazine, "continuous alertness could be available over the counter" within 10 years. "These drugs will do for sleep disorders what Prozac did for depression," Dale Edgar, cofounder of Hypnion, told the magazine. But the prospect of people swallowing pills to postpone sleep has some critics nervous. When is sleepiness a sickness? Doctors can't even agree whether "shift work sleep disorder" is a true medical illness, and there's already evidence people are getting modafinil "off-label," meaning for conditions that haven't been sanctioned by government regulators. In the U.S. alone, some 250,000 people are using modafinil, even though only 150,000 Americans are estimated to have narcolepsy. Canadian prescriptions have nearly doubled since 2001. Nearly 28,000 prescriptions were dispensed in Canadian drugstores during the 12 months ending October 2003, compared to 14,648 in 2001, according to IMS Health Canada. People have always searched for ways to get by on less sleep. Coffee has become the second most commonly traded commodity in the world, next to oil. But now athletes and CEOs and college students "and everyone who wants to stay wide awake all day long under minimal sleep are asking their physicians for prescriptions," for modafinil, says Cornell University psychologist and sleep expert James Maas. Some reports suggest the drug has become the stimulant du jour among track and field athletes. U.S. sprinter Kelli White tested positive for the drug at the world championships in Paris earlier this year. She says she was taking it to treat her narcolepsy. Chris Phillips, another U.S. athlete, also tested positive for modafinil at the same Paris meet, prompting anti-doping officials to muse about the oddly high number of athletes with narcolepsy. But the potential for abuse isn't limited to the playing field. Some fear the pressure for employees to drug themselves to meet employers' demands may be huge. After all, sleep is seen as a luxury, not a need, Mr. Coren says. A Microsoft executive once sniffed that sleep is "nonproductive downtime." "There is this notion somehow or another that if you sleep a lot, you're lazy and useless," Mr. Coren says. Add that to our frenetic lives, the growing numbers of harried, dual-income families trying to cope with the demands of work and home, the seductive all-night allure of the Internet, and it's little wonder we've become a nation "of walking zombies," says Mr. Maas. Millions try to catch up by oversleeping on holidays and weekends, but our sleep debts just keep accruing, week after week. Children too are being increasingly sleep starved, a phenomenon Mr. Maas partly pins on parents "who don't know diddly about sleep and sleep requirements" in school-aged children. Old diaries and letters suggest that people were logging about nine hours a night before 1913. Then Thomas Edison invented the light bulb. "Part of the reason he did was that he really felt people were using darkness as an excuse not to work and he wanted to increase our productivity," says Mr. Coren, author of the book Sleep Thieves. "I don't know whether we're more productive, but we're certainly more tired." Scientist don't really know why humans need sleep, although most believe it plays a fundamental role in regulating the genes in the brain that are involved in numerous cellular functions. Deprive rats of sleep long enough and they will die, usually within two weeks. Researchers also know that sleep occurs throughout the animal kingdom, right down to the smallest complex animals, such as fruit flies. Shortened sleep can lead to reduced brain levels of leptin, the hormone that controls appetite. Get too little sleep, Mr. Maas says, and the brain signals us to eat complex carbohydrates, starches and sugars. U.S. researchers recently discovered that "short sleepers" produce more cytokines, molecules that normally fight germs and other invaders. "Except there are no germs, you just slept too little, but they have to attack something so they start to eat the arterial walls," Mr. Maas says. Studies have found that people who sleep six hours or less a night have an increased risk of high blood pressure, heart attacks and stroke. Just one bad night's sleep can have a dramatic effect on memory, alertness, concentration and judgment, and chronic sleep deprivation can lead to anxiety and depression. More worrisome, "when we're really sleep-deprived, at some point in time we start to microsleep," says Mr. Coren. "No matter what we're doing, our brain goes into a sleep state, and it can remain there anywhere from 10 seconds to a minute." "Now suppose that you're tooling down the road in your car at 50 kilometres an hour and you have one of these small little microsleeps, and it's the 10-second kind. What that means is that your car will travel more than the length of a football field while you're asleep." In fact, Mr. Coren's team has found that traffic accidents in Canada jump seven per cent on the Monday after the switch to daylight savings time, when people lose an hour's worth of sleep. Modafinil, for its part, appears safer than traditional stimulants at conquering sleepiness. Researchers at the Ottawa Hospital have found more complaints of nausea and nervousness in patients taking 400 mg of modafinil a day versus those on a placebo, though the side-effects disappeared after a week. Some studies have shown a significant increase in "pounding, pulsating" headaches, reports Ottawa sleep expert Dr. Roger Broughton, usually also during the first several days of treatment. "But the rates of side-effects are really quite low." The drug doesn't cause the hangover effects amphetamines do, and you can't get high from it. There is also a lower risk of abuse. (It can, however, interfere with some forms of birth control.) Still, Mr. Coren worries about using drugs to manipulate the body's need for sleep. "Obviously, if you have an individual who is in jeopardy of losing his livelihood if he can't adapt to shift work, you might consider it." But given the huge number of people in the world who work odd hours, from nurses, firefighters, and factory workers to pilots and 911 operators, "we could be talking about a large number of individuals who are going to start to muck up their sleep chemistry." And no matter how safe drugs that beat back sleep become, they will always bump up against the fact that the brain will always find a way to sleep, no matter what we're doing. That, the experts say, is enough to lose sleep over. LOAD-DATE: December 23, 2003 LANGUAGE: ENGLISH TYPE: News Copyright 2003 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 661 of 998 DOCUMENTS The Vancouver Sun (British Columbia) December 23, 2003 Tuesday Final Edition Take this pill, stay awake all day and all night, too: Go 40 hours without sleep with no side effects SOURCE: CanWest News Services BYLINE: Sharon Kirkey SECTION: News; Pg. A1 LENGTH: 1520 words DATELINE: OTTAWA OTTAWA -- Psychologist Stanley Coren finds a particular lunacy in our determination to squeeze more minutes out of every day, when all the science shows not getting enough sleep makes people, as he puts it, clumsy, stupid, unhappy and dead. Humans have been hardwired through evolution to require nine, even 10 hours of sleep a night, but the average North American is getting more like seven, says Coren, director of the Human Neuropsychology and Perception Laboratory at the University of British Columbia. "Generally speaking, we're about two hours sleep-deprived every night," he says. Some polls suggest one out of every three Canadians is managing just six hours of sleep a night, or less. But, what if you could get the equivalent of a good night's sleep in a pill, a drug that would keep you awake for 40 hours or more with little, if any, of the jitteriness, agitation, anxiety and insomnia associated with other brain stimulants, including caffeine? "Wake-promoting" agents have become one of the hottest fields of drug research, with a vast, mostly untapped market potentially worth billions. The patient population for "sleep therapeutics" is bigger than that for depression. One such drug is already here: Modafinil (sold as Alertec in Canada and Provigil in the U.S.) has been available since 1999 for the treatment of narcolepsy, a devastating disorder that affects one out of every 3,000 people and causes uncontrollable sleep attacks in the middle of a conversation, sitting in the drive-through at McDonald's or any other inappropriate time. But now, the U.S. Food and Drug Administration has given its preliminary blessing for expanded uses of the drug to treat excessive daytime sleepiness in shift workers, or so-called "shift work sleep disorder," as well as for sleep apnea, a condition that causes people to stop breathing for a minute or longer up to 100 times a night. Official approval, which is expected soon, will mean Cephalon can start promoting the drug not just to sleep doctors and other specialists, but also to the real wellspring for drug sales: family doctors. The company is already gearing up to deploy an "expanded sales force" early next year. Meanwhile, Massachusetts-based Hypnion Inc. has wake-alertness compounds in the queue that it claims are superior to modafinil. Researchers in Ottawa are about to start testing a new chemical cousin of modafinil. And a Canadian military-sponsored research facility in Toronto has been testing modafinil in soldiers under different simulated field conditions of "sustained wakefulness." According to Wired Magazine, "continuous alertness could be available over the counter" within 10 years. "These drugs will do for sleep disorders what Prozac did for depression," Dale Edgar, cofounder of Hypnion, told the magazine. But the prospect of people swallowing pills to postpone sleep has some critics nervous. When is sleepiness a sickness? Doctors can't even agree whether "shift work sleep disorder" is a true medical illness, and there's already evidence people are getting modafinil "off label," meaning for conditions that haven't been sanctioned by government regulators. In the U.S. alone, some 250,000 people are using modafinil, even though only 150,000 Americans are estimated to have narcolepsy. Canadian prescriptions have nearly doubled since 2001. Nearly 28,000 prescriptions were dispensed in Canadian drugstores during the 12 months ending October 2003, compared with 14,648 in 2001, according to IMS Health Canada. People have always searched for ways to get by on less sleep. Coffee has become the second most commonly traded commodity in the world, next to oil. But now athletes and CEOs and college students "and everyone who wants to stay wide awake all day long under minimal sleep are asking their physicians for prescriptions," for modafinil, says Cornell University psychologist and sleep expert James Maas. Some reports suggest the drug has become the stimulant du jour among track and field athletes. U.S. sprinter Kelli White tested positive for the drug at the world championships in Paris earlier this year. She says she was taking it to treat her narcolepsy. Chris Phillips, another U.S. athlete, also tested positive for modafinil at the same Paris meet, prompting anti-doping officials to muse about the oddly high number of athletes with narcolepsy. But the potential for abuse isn't limited to the playing field. Some fear the pressure for employees to drug themselves to meet employers' demands may be huge. After all, sleep is seen as a luxury, not a need, Coren says. A Microsoft executive once sniffed that sleep is "nonproductive downtime." "There is this notion somehow or another that if you sleep a lot, you're lazy and useless," Coren says. Add that to our frenetic lives, the growing numbers of harried, dual-income families trying to cope with the demands of work and home, the seductive all-night allure of the Internet, and it's little wonder we've become a nation "of walking zombies," says Maas. Millions try to catch up by oversleeping on holidays and weekends, but our sleep debts just keep accruing, week after week. Children too are being increasingly sleep starved, a phenomenon Maas partly pins on parents "who don't know diddly about sleep and sleep requirements" in school-aged children. Old diaries and letters suggest that people were logging about nine hours a night before 1913. Then Thomas Edison invented the light bulb. "Part of the reason he did was that he really felt people were using darkness as an excuse not to work and he wanted to increase our productivity," says Coren, author of the book Sleep Thieves. "I don't know whether we're more productive, but we're certainly more tired." Scientists don't really know why humans need sleep, although most believe it plays a fundamental role in regulating the genes in the brain that are involved in numerous cellular functions. Deprive rats of sleep long enough and they will die, usually within two weeks. Researchers also know that sleep occurs throughout the animal kingdom, right down to the smallest complex animals, such as fruit flies. Shortened sleep can lead to reduced brain levels of leptin, the hormone that controls appetite. Get too little sleep, Maas says, and the brain signals us to eat complex carbohydrates, starches and sugars. U.S. researchers recently discovered that "short sleepers" produce more cytokines, molecules that normally fight germs and other invaders. "Except there are no germs, you just slept too little, but they have to attack something so they start to eat the arterial walls," Maas says. Studies have found that people who sleep six hours or less a night have an increased risk of high blood pressure, heart attacks and stroke. Just one bad night's sleep can have a dramatic effect on memory, alertness, concentration and judgment, and chronic sleep deprivation can lead to anxiety and depression. More worrisome, "when we're really sleep deprived, at some point in time we start to micro sleep," says Coren. "No matter what we're doing, our brain goes into a sleep state, and it can remain there anywhere from 10 seconds to a minute." "Now suppose that you're tooling down the road in your car at 50 kilometres an hour and you have one of these small little micro sleeps, and it's the 10-second kind. What that means is that your car will travel more than the length of a football field while you're asleep." In fact, Coren's team has found that traffic accidents in Canada jump seven per cent on the Monday after the switch to daylight savings time and people lose an hour's worth of sleep. Modafinil, for its part, appears safer than traditional stimulants at conquering sleepiness. Researchers at the Ottawa Hospital have found more complaints of nausea and nervousness in patients taking 400 mg of modafinil a day versus those on a placebo, though the side effects disappeared after a week. Some studies have shown a significant increase in "pounding, pulsating" headaches, reports Ottawa sleep expert Dr. Roger Broughton, usually also during the first several days of treatment. "But the rates of side effects are really quite low." The drug doesn't cause the hangover effects amphetamines do, and you can't get high from it. There is also a lower risk of abuse. (It can, however, interfere with some forms of birth control.) Still, Coren worries about using drugs to manipulate the body's need for sleep. "Obviously if you have an individual who is in jeopardy of losing his livelihood if he can't adapt to shift work, you might consider it." But given the huge number of people in the world who work odd hours, from nurses, firefighters, and factory workers to pilots and 911 operators, "we could be talking about a large number of individuals who are going to start to muck up their sleep chemistry." And no matter how safe drugs that beat back sleep become, they will always bump up against the fact that the brain will always find a way to sleep, no matter what we're doing. That, the experts say, is enough to lose sleep over. LOAD-DATE: December 23, 2003 LANGUAGE: ENGLISH TYPE: News Copyright 2003 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 662 of 998 DOCUMENTS The Leader-Post (Regina, Saskatchewan) November 22, 2003 Saturday Final Edition New drug fools the brain into being alert SOURCE: Special to The Leader-Post BYLINE: Ed Willett SECTION: Weekender; Science; Pg. G3 LENGTH: 524 words There were lots of bleary-eyed people around Regina this week, following the Grey Cup revelry. But then, there are always lots of bleary-eyed people around, since very few of us get enough sleep. So wouldn't it be great if you could just take a pill and feel alert? I'm not talking about amphetamines, but about eugeroics (the name means "good arousal"), a new class of drugs which currently has only two members, adrafinil and its successor, modafinil, developed in France and available in Canada since 1999 as Alertec. Currently approved only for narcolepsy it's beginning to find its way into the hands of other people who need to stay awake, from soldiers to stockbrokers. Eugeroics differ significantly from amphetamines. Amphetamines stimulate the entire central nervous system, essentially by fooling the brain into thinking it's being threatened. They raise your pulse rate, give you jolts of adrenaline, interfere with normal sleep, and can be addictive. You also have to to take larger and larger doses to get the same effect until, inevitably, you crash. Modafinil, on the other hand, somehow (the precise mechanism isn't known) targets a part of the hypothalamus called the suprachiasmatic nuclei. In the late 1980s, researchers discovered this part of the brain controls wakefulness, quite separately from the mechanism that makes us feel sleepy. Modafinil keeps the wakefulness centre active long after it would normally have shut down. As a result, the rest of the brain thinks it's well-rested, even when it's not. Modafinil doesn't produce the "wired" sensation of amphetamines or caffeine. It also doesn't interfere with normal sleep -- you can take it, stay alert until bedtime, then go to sleep as usual. Modafinil also shows no signs of being addictive and only rarely causes minor side effects like headache and nausea. So will it be available over-the-counter? Not in the short term. Side-effects from long-term use might still crop up. As well, experts worry people would use it to avoid sleep to the point that their health would suffer -- besides keeping us mentally alert, sleep helps regulate our hormonal and immune systems. There is also concern about unknown interactions with other drugs. However, tests are underway for its use to help sufferers of chronic fatigue syndrome and sleep apnea, multiple sclerosis, and depression. It's being tested on Chicago shift workers who find themselves too sleepy to work in the middle of the night. And it's apparently already in use, in a limited and somewhat unofficial fashion, by the U.S. forces in Iraq. More effective drugs, both to help people stay awake and to help them fall asleep more quickly and sleep better are now under development. We may eventually be able to schedule sleep when we want it, and avoid it when it's inconvenient. What that means to society, no one can yet say. For now, at least, the age-old solution to drowsiness remains the best: take a nap. - Edward Willett is a Regina freelance writer. E-mail comments or questions to edward@edwardwillett.com. Read a longer version of this column online at www.edwardwillett.com LOAD-DATE: November 22, 2003 LANGUAGE: ENGLISH TYPE: Column Copyright 2003 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 663 of 998 DOCUMENTS The Daily Telegraph (Sydney, Australia) November 20, 2003 Thursday Hot on the trail of the THG cheats SOURCE: MATP BYLINE: MIKE HURST SECTION: SPORTTABLE; Pg. 73 LENGTH: 1222 words SEPARATE investigations into seemingly unrelated drug busts for designer anabolic steroids appear to be converging as America finally responds to calls to get tougher on sports doping. A US grand jury has called many high-profile sports champions, including 100m world record-holder Tim Montgomery and fellow Sydney Olympic sprint gold medallist Marion Jones, to testify under oath at an inquiry into the use of tetrahydrogestrinone (THG) -- a body-building steroid previously unidentified by drug testers. There is no suggestion Montgomery or Jones used or supplied THG or any other drug. The grand jury is also questioning witnesses about the endurance-enhancing drug EPO, HGH (human growth hormone) and other anabolic agents. Another investigation by the US Attorney's Office in the Central District of Illinois has been running since March this year when track cyclist Tammy Thomas became the first person known to have failed a test for the obscure anabolic steroid Norbolethone. Thomas, 33, won a sprint silver medal at the 2001 world championships in Antwerp, Belgium. She has received a life ban from USA Cycling. US anti-doping officials believe prominent dietary supplement designer, Patrick Arnold, may have made Norbolethone. Arnold is said to be the first chemist outside of the former East Germany to make androstenedione, a legal steroid in the US where it is used in food supplements. He is also credited with inventing 1-testosterone, another steroid legal used in US supplements. Arnold and Thomas deny knowing each other. Also known as Genabol, powerfully acting Norbolethone was designed in 1964 at Wyeth Laboratories in Philadelphia and studied until 1972 when the company decided not to trade the product. Nothing was heard in public about Norbolethone until in 2001 Canadian athletics coach Charlie Francis wrote: "In a review of the negative tests after the Sydney Olympics, the drug testers saw a suspicious compound on many of their tests and began to investigate. Some months later they identified the compound as Genabol [also called Norbolethone]. "By the time a test was developed, the word was out and the athletes moved on to newer products."  One of those newer products may have been the fore-runner to THG, which appears to have been this year's most favoured model. Five track and field athletes have so far tested positive to THG. They include Europe's top sprinter Dwain Chambers of England and Americans Regina Jacobs (1500m, 5000m), Kevin Toth (shot put) and John McEwen (hammer throw). The identity of a fifth athlete who competed at the recent world championships in Paris has not been made public. The fifth athlete is understood to be a low-profile thrower, possibly an American male hammer thrower. Another investigation into the use of a stimulant, Modafinil, has been running concurrent with the THG inquiry and there appears to be some overlapping. Kelli White, the world 100m and 200m champion, claims after she was busted in the Paris championships in August that she took Modafinil to treat narcolepsy, which is a sleep-disorder. White's training partner, Chryste Gaines, also tested positive for Modafinil. Fellow Americans, the Paris world championship 400m hurdles silver medallist Sandra Glover, Eric Thomas, Calvin Harrison and Chris Phillips were also caught for Modafinil. They dispensed with the narcolepsy excuse. The common denominator between most of these athletes is 71-year-old Remy Korchemny, a famous coach of the Soviet Union's 1972 Munich Olympic sprint double winner Valeriy Borzov. He is now based at Berkeley, California, where he coaches White, Gaines and Chambers. Korchemny admits giving Modafinil to Phillips. He also coaches Harrison's twin brother Alvin, both of whom won Olympic 4x400m relay gold medals in Sydney. The Daily Telegraph has been told by a source close to the grand jury proceedings that an as yet unnamed but high-profile athlete has talked under immunity of receiving THG and using it on assurances that it could not be found. She did not fail a test for THG. She allegedly nominated Victor Conte as having provided her with THG and gave Conte a $US10,000 bonus out of her winnings at the end of the European season. Conte denies being the source of THG. CONTE and Korchemny formed a track club called ZMA, short for Zinc-Magnesium, two common minerals Conte developed into a sports formula to reap a small fortune. Arnold and Conte know each other, but deny doing business with each other. Conte is the owner of the Bay Area Laboratory Co-Operative (BALCO). Conte does not have a college degree or professional background in health or science, but runs a lucrative nutritional and testing business near San Francisco airport. BALCO was raided on September 3 by agents from the San Mateo County Narcotics Task Force and Internal Revenue Service (taxation) authorities who confiscated numerous boxes of files. This followed the case-breaking delivery in mid-June, allegedly by an anonymous whistleblower athletics coach, of a syringe containing a "designer" steroid to the United States Anti Doping Agency. USADA claims to have passed the syringe to the UCLA Olympic Analytical Laboratory where the lab chief of 21 years, Don Catlin, a molecular pharmacologist and endocrinologist, drew together a team of chemists who "reverse engineered" the substance and identified it as THG. THE STORY SO FAR * United States Anti-Doping Agency (USADA) claim to receive a syringe containing a "designer steroid" from an anonymous athletics coach in mid-June. * UCLA Olympic lab sleuths "reverse engineer" the mystery compound and named it THG (tetrahydrogestrinone). * Europe's top sprinter Dwain Chambers returns positive result for THG from test taken on August 1 * New world sprint double champion Kelli White tests positive for stimulant Modafinil on August 30 in Paris. * Narcotics agents and IRS raid the California sports food supplements laboratory, BALCO, on September 3. * USADA reveals existence of THG on October 16. * Worldwide investigation involving re-testing of samples across the globe and from athletics and swimming world championships and winter olympics * American grand jury convened to investigate doping in US sport. THE ATHLETES * Positive to Modafinil Americans: Kelli White (world champion 100m, 200m), Chryste Gaines (world's second fastest 100m runner), Calvin Harrison (world champion 4x400m), Chris Phillips (world finalist 110m hurdles), Sandra Glover (world 400m hurdles silver medallist), Eric Thomas (world championships semi-finalist). * Positive to THG Britain's Dwain Chambers (Goodwill Games and European Championships 100m winner), and Americans Regina Jacobs (at 39, set world record indoor 1500m this year), Kevin Toth (this year threw longest shot put mark since 1990), John McEwen (runner-up hammer throw at US titles). WHAT NEXT * WADA to expand influence into communist China, specifically targeting the Thinker Chemical lab in Hangzhou. * Revelations about other designer drugs, dating back to 1984 LA Olympics * Increased funding to develop tests for HGH (human growth hormone) * Legal challenges by athletes busted in re-testing Legal challenges to the EPO (erythropoietin) test. Resurgence of the drug culture LOAD-DATE: November 19, 2003 LANGUAGE: ENGLISH JOURNAL-CODE: DTM Copyright 2003 Nationwide News Pty Limited 664 of 998 DOCUMENTS The Times (London) November 13, 2003, Thursday White's second positive serves only to muddy waters BYLINE: Peter Nichols SECTION: Sport; 42 LENGTH: 590 words KELLI WHITE could miss out on the Olympic Games next year after recording a second positive drugs test. The United States sprinter's 100 metres and 200 metres world titles were already under threat after the sample given after the 100 metres final in Paris three months ago showed evidence of Modafinil, a drug variously described as a "mild stimulant" and a "wake-promoter". The second positive, also for Modafinil, has come after the re-examination by the US Anti-Doping Agency (Usada) of samples taken at the US Track and Field Championships at Stanford, California, in June. The rules of the International Association of Athletics Federations (IAAF) state that the penalty for a first offence is a warning and disqualification from the championships in question; for a second offence, the penalty is a two-year ban. Should the IAAF apply the letter of the law, White will lose not just her world titles, but be banned until 2005. If, that is, Modafinil is definitively identified as a banned substance. When the story broke in Paris in August, Arne Lundqvist, chairman of the IAAF Medical Commission, stated that he had no doubt that Modafinil was a banned substance, even though it was not on either the IAAF list nor that of the World Anti Doping Authority (Wada). Yet when questioned as to which group it fell into or which of the drugs on the list it related to, Lundqvist was unable to answer. Even though the drug could not be properly classified, the US team, for fear of being disqualified later, withdrew White from the 4 x 100 metres relay team. The IAAF subsequently determined that Modafinil was a "mild stimulant" and fell within the category of substances similar to those listed. However, while the definition given by the Wada list is a distinctly loose one, stating that any "related substances" are banned, the IAAF list is much more precise, listing 36 examples and adding substances that are "pharmacologically or chemically related". Within a fortnight of the World Championships, Robert Wagner, White's agent, handed a 25-page statement to Lundqvist which argued that Modafinil could not be considered a banned substance. Later that month, Cephalon, the worldwide manufacturers of the drug, sent a submission to Dick Pound, chief executive of Wada. Paul Blake, senior vice-president of Cephalon, argued that Modafinil was not a stimulant, but a "wake-promoter" and could not be related to any stimulant on the list. "It is a separate pharmacological entity," Blake said. Olivier Rabin, the science director of Wada, accepted that Modafinil was not related chemically to any of the drugs on the list and could only be classified as pharmacologically related because there was some evidence that it "stimulated the central nervous system". Rabin agreed that Wada's information on the drug was minimal. "It is not the typical profile of a stimulant...the full mechanism of this substance remains unknown," he said, adding that the final decision may be made in the US Courts. Usada must determine not whether White was seeking to claim an advantage - Modafinil has been used in sailing and rallying to promote wakefulness -but whether a doping offence has been committed. The Usada Anti-Doping Review Board should reach a decision soon but, having ordered the wholesale retesting of samples, it may have argued itself into a corner. Should it decide that no offence has been committed, the case reverts back to the IAAF, which could itself decide to take further action. LOAD-DATE: November 13, 2003 LANGUAGE: ENGLISH Copyright 2003 Times Newspapers Limited 665 of 998 DOCUMENTS The Sun Herald (Sydney, Australia) November 9, 2003 Sunday Late Edition Drug crisis tai nts all: Fortune; ATHLETICS BYLINE: JAMES MacSMITH SECTION: SPORT; Pg. 106 LENGTH: 348 words ONE of Australia's leading coaches says he is worried about the future of athletics and the reputations of its star performers, if the drugs crisis continues to gain momentum. Peter Fortune, best known as Cathy Freeman's former coach, said if the spate of positive tests to designer steroid tetrahydrogestrinone and banned stimulant modafinil grew, an increasingly sceptical public might consider coaches and athletes guilty of doping simply because they were involved in the sport. Five world-class athletes have tested positive to using THG, and six top runners have been caught taking modafinil. "I'm not necessarily surprised at the extent of it [the doping] as much as it does seem to be confined to a group or an area," Fortune said. "One of the interesting things is that it's come about through jealousy [a coach anonymously sending in a sample of THG to drug testing authorities in the US]. "It's disturbing and very negative for the sport. And it shows the extent that some people are prepared to go to cheat." Fortune said one of the good things to take out of the crisis was that the US appeared to be getting serious in the fight against doping in track and field. "It seems that at last authorities in the US are taking a much stronger approach, where they have been a bit soft before, and that can only be good for the sport," he said. Athletics has been plunged into its biggest drugs crisis since Ben Johnson tested positive to a steroid at the 1988 Olympic Games. It began when THG was detected in the urine samples of athletes including British sprinter Dwain Chambers. Others, including Sandra Glover, who finished second in the 400-metres hurdles at the world championships in August, and double world sprint champion Kelli White, tested positive to modafinil. Fortune warned that clean athletes and coaches might be unfairly grouped with those guilty of using, or promoting the use of performance-enhancing substances. But the responsibility for drug use rested with athletes. "They shouldn't be taking anything unless they know exactly what it is and where it came from," he said. LOAD-DATE: June 20, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2003 John Fairfax Publications Pty Ltd All Rights Reserved 666 of 998 DOCUMENTS The San Francisco Chronicle NOVEMBER 4, 2003, TUESDAY, FINAL EDITION PROFILE; Remi Korchemny; Caught in a tempest SOURCE: Chronicle Staff Writer BYLINE: John Crumpacker SECTION: SPORTS; Pg. C1 LENGTH: 1822 words If Remi Korchemny isn't quite in the eye of the storm, he's close enough to find himself swept up in a widening sports-doping scandal. For more than three decades, the Ukrainian-born Korchemny built a reputation as an astute and analytical track and field coach, specializing in the sprints and hurdles. His runners include some of the world's fastest men and women, as well as some Union City teenagers who dream of becoming elite athletes themselves. But now, at age71, this man -- whose father was executed by a Stalinist firing squad and whose mother was imprisoned when he was a boy -- is being drawn toward the center of an international sports-drug scandal that involves his clients and a Burlingame laboratory. Dwain Chambers, Great Britain's fastest man, said Korchemny sent him to Victor Conte, the owner of the Bay Area Laboratory Co-Operative (BALCO), for nutritional supplements last year. Now, Chambers said through his lawyer that he tested positive for THG, the newly discovered designer steroid that the U.S. Anti-Doping Agency (USADA) says came from BALCO. Kelli White, the Union City champion sprinter who has worked with Korchemny since her pre-teen years, tested positive for the stimulant modafinil during the World Championships in Paris last August. Dr. Brian Goldman, once BALCO's medical director, said he prescribed the drug for White to counter symptoms of narcolepsy. White is among the scores of top athletes subpoenaed to testify before a federal grand jury in San Francisco that is investigating Conte and BALCO. USADA said when it retested urine samples of athletes who competed in the June U.S. Track and Field Championships at Stanford -- looking for THG -- it also discovered several competitors who tested positive for modafinil. Hurdler Chris Phillips, who coaches himself, reportedly told the International Association of Athletics Federations after he tested positive for using modafinil at the Stanford meet that he got the drug from Korchemny. The Washington Post quoted the coach as saying he'd given Phillips one pill -- for sleeping problems, not to make him run faster. Olympic relay gold medalist and Stanford grad Chryste Gaines, another sprinter coached by Korchemny, also tested positive for modafinil at Stanford. So did Olympic gold-medal relay winner Calvin Harrison of Salinas, another Korchemny client. Korchemny denies giving any of his athletes a drug to enhance performance, but colleagues in the world of track and field say his reputation is being tarnished by the scandal. Reputation will take hit "He's going to be the collateral damage for this whole thing, that's for sure," said track coach Randy Huntington, who works at the U.S. Olympic Training Center in Chula Vista (San Diego County). "I feel bad for Remi. He probably feels he was doing something OK. The athletes will suffer from it and he'll suffer from it." Korchemny, standing alongside the track at James Logan High School in Union City, where he volunteers to work with prep sprinters and hurdlers, agreed. "Yes, it is going to affect my reputation as a coach," he said in an interview with The Chronicle. "People think my success is not a result of my work, but a stimulant. My success is a result of my hard work and knowledge." It's knowledge gleaned from nearly a half-century of working with sprinters, starting in his native Ukraine, where an early pupil was the schoolboy Valery Borzov, who would win gold medals in the 100- and 200-meter dashes for the Soviet Union at the 1972 Munich Olympics. All told, Korchemny has coached three athletes who went on to win eight Olympic medals, including Gaines in 1996 and 2000 and Harrison in 2000. Arrived in '75 Korchemny came to the United States in 1975, following brief stays in Israel and Italy, after being allowed to leave the former Soviet Union. Having a Jewish mother (who spent four years -- 1937-41 -- in a work camp) facilitated his departure. His father, a suspected dissident, was executed by a Stalinist firing squad in 1937 in a dockside labor dispute when Remi was 5. "Too many stories," Korchemny said with a sigh. "The most important thing was to get to the free world. The most difficult thing was to establish yourself in another country, with a new culture." Korchemny's interest in sprinting sprung from need. After his father was executed and his mother sent to a work camp, young Remi went to live with grandparents. With money and food in short supply, he took to racing boys at his school for bread and sandwiches. Lose, and he'd have to carry the winner on his shoulders in front of the school. "I never lost," he said in a 2002 interview in American Track & Field magazine. Eventually, Korchemny became a very good sprinter, running 100 meters in 10.4 seconds. He became an even better coach. Korchemny molded the early career of fellow Ukrainian Borzov. Borzov was regarded as a technically perfect sprinter, at least in part because of the coaching he received as a teenager from Korchemny. Korchemny unfailingly points out that he was not Borzov's personal coach when he won at Munich in 1972. Korchemny "is one of the best," Huntington said. "He's taught many coaches in this country a lot about sprint mechanics and hurdle mechanics. ... This is like everyone's grandfather: gentle, sweet, caring. To see him go through this hurts a lot of us." BALCO link unclear Korchemny's link to BALCO and Conte and the sports-doping scandal swirling around them is not entirely clear, but the fact of the link is as evident as the floppy hat the coach wore to shade the sun on a recent afternoon at James Logan High. Above the hat's brim are stitched the letters ZMA. It's a promotion for Conte's signature product, a zinc magnesium supplement that athletes from the Giants' Barry Bonds to Raiders linebacker Bill Romanowski swear by. Korchemny remains a supporter of Conte and his nutritional supplement products, despite the controversy. The coach and Conte reportedly formed the ZMA Track Club several years ago, featuring clients of BALCO. "It's just a company that makes the supplement, Korchemny said. "It (the track club) doesn't exist as an organization. Somebody made it up. It's much easier to call USA Track & Field (and ask) if they have registered ZMA as a club." There was a ZMA Track Club registered with USA Track & Field in 2001, but it is no longer in existence, according to that organization's records. As for Conte, Korchemny said: "I still believe in what he's doing. I still believe he provides excellent services for people. Not just good -- excellent. I still use his product. I still recommend to people to use ZMA." Korchemny says he learned of Conte "three or four years ago" from a professional football player he was training. Though he would not say who the player was, Korchemny did work with Romanowski when he was with the Denver Broncos. Romanowski got some of his supplements from Conte at BALCO and recommended the lab to other athletes. Chambers, the champion sprinter from Great Britain who said Korchemny sent him to BALCO, seemed to blame Conte after testing positive for the steroid THG. "Dwain had never heard of this substance and he immediately challenged Mr. Conte on this finding and was categorically assured that all the supplements he had been given were within the rules of the International Association of Athletics Federations (IAAF)," Chambers' British lawyer, Graham Shear, said. "In his eight years in international athletics, he has never been tempted to succumb to illegal methods of enhancing a performance." Korchemny, who said he introduced Chambers to Conte last year, said his client doesn't know where the THG in his system came from "and I don't know where it came from." Athletes caught using a steroid such as THG can be banned from competition for two years. Use of modafinil, the stimulant for which some of Korchemny's other clients tested positive, results in a public warning and disqualification from the competition in which the athlete tested positive. Korchemny told The Chronicle he never gave or recommended modafinil to an athlete to make the athlete run faster. 'No scientific evidence' "It doesn't improve their performance," he said. "There's no scientific evidence or proof it improves performance. As a stimulant, it's very mild. It's not on the list of prohibited substances. There's no evidence that this substance can change athletic performance. "They found it only affects your sleeping. When you travel a lot and don't have a whole night's sleep and have to practice the next day, you feel sleepy. I don't feel anyone did anything wrong with this substance." Noting that two other stimulants, caffeine and over-the-counter cold medications such as Sudafed, recently were removed from the list of banned substances, Korchemny said, ruefully, "Better to have a cup of coffee than one modafinil." Huntington and another coach, former Stanford head man Brooks Johnson, both said Korchemny told them he gave his athletes modafinil to combat the effects of plane travel. "He told me he only gave it to the kids to beat jet lag," said Johnson, now director of the U.S. Olympic Training Center. "It had nothing to do with performance ..." Skirting culpability However, standing on Logan High's rubberized track in the meager shade of a baking afternoon, Korchemny skirted the issue of culpability. "I did not make a statement that I gave it to them," he said. "I don't know where it came from." White, for one, said earlier the modafinil was prescribed to her by her doctor, Goldman, of Walnut Creek, to counteract the effects of narcolepsy, which she said runs in her family. The modafinil findings have brought stress and accusations to Korchemny at an age when he should be enjoying the tag end of his long career in coaching. He has many supporters in the sport of track and field who said they don't want to see the man's reputation tarnished by one act for which he might bear some responsibility. "He was a fantastic coach and the kids loved him," Johnson said of Korchemny's time (1983-87) on his staff at Stanford. "He really earned their trust because he was basically selfless. Remi was the most modest, non-ego-driven person of any magnitude in the sport I've seen." With accusations flying about him, Korchemny appears to seek pleasure, as well as refuge, from the storm by volunteering as a coach at Logan High, not far from his home in Castro Valley. One of his young charges, Logan junior Kevin Craddock, is among the best prep hurdlers in the country and could develop into an elite competitor one day. "I enjoy my life," Korchemny said. "I enjoy working with kids. I enjoy passing my knowledge to the younger generation. My nature is as a teacher. I love to teach." E-mail John Crumpacker at jcrumpacker@sfchronicle.com. LOAD-DATE: November 4, 2003 LANGUAGE: ENGLISH GRAPHIC: PHOTO (4), (1) These days, Remi Korchemny spends time as a volunteer track coach at James Logan High in Union City. / Kurt Rogers / The Chronicle, (2) Sprinters Kelli White (front) and Dwain Chambers both have connections with Korchemny. / Darryl Bush / The Chronicle, (3) Athletes on the track team at Logan High chat with Remi Korchemny (with hat), who is a volunteer coach at the Union City school. / Kurt Rogers / The Chronicle, (4) Valery Borzov, a student of Korchemny's, won the 100- and 200-meter dashes at the 1972 Olympics. / Associated Press 1972 Copyright 2003 The Chronicle Publishing Co. 667 of 998 DOCUMENTS Sunday Times (South Africa) November 2, 2003 Dwain's coach takes heat as list of drugs cheats grows BYLINE: DAVID MILLER SECTION: Sport; Pg. 3 LENGTH: 593 words Dwain's coach takes heat as list of drugs cheats grows TOM KNIGHT and THE focus in the escalating American doping scandal shifted to Dwain Chambers's coach, Remi Korchemny, this week, as yet another of his athletes was reported to have tested positive for a banned substance. According to the Washington Post, American sprinter Chryste Gaines is the latest athlete to have tested positive for modafinil, a stimulant. Istvan Gyulai, general secretary of the International Association of Athletics Federations, said Korchemny could become the first coach to face sanctions - possibly a life ban - in a doping case. It is understood modafinil was found in Gaines's urine sample at the US Championships in June. The samples were recently retested when the US Anti-Doping Agency uncovered the existence of a new, designer steroid called tetrahydrogestrinone, or THG. Gaines, 33, who won the 100m at the World Athletics Finals in Monte Carlo, would be the fourth athlete connected to Korchemny to have failed a drugs test. Chambers has tested positive for THG and Americans Kelli White, Chris Phillips and Calvin Harrison for modafinil, a drug banned by the IAAF because it is categorised as being related to the family of stimulants. Phillips and Harrison said they were given modafinil by Korchemny. Phillips, who along with White tested positive at the world championships, told the IAAF that he was given the drug just before his 110m hurdles semifinal. Gyulai said: "If what Phillips said is true, we will investigate, because it is unacceptable for coaches to encourage athletes to take prohibited substances." Robert Wagner, Phillips's agent, said: "Everybody is taking something to be alert and awake. I've seen sprinters drink lots of coffee because it makes you sharper." Korchemny remained defiant. He said: "Modafinil is the same as aspirin or coffee - big deal. It was not on the list of banned substances." * Countries that fail to help fund the World Anti-Doping Agency (Wada) will not have their national anthem played if they win gold at next year's Olympic Games in Athens. In addition, they will not be able to display their national flag at the opening and closing ceremonies, and their officials will not be given accreditation to attend any Olympic event or function. They will also lose out on funding for coaches. Wada are hoping the potential embarrassment of such sanctions will force into line those governments which have yet to pay their subscription to the agency. Dick Pound, chairman of Wada, is determined his organisation should be properly funded in order to tackle the growing problem of drugs in sport. "We are prepared to take the gloves off," warned Pound, who was in London this week for an informal meeting with sports minister Richard Caborn. However, the threat will alarm leading athletes, according to Stephanie Cook, who won gold for Britain in the women's modern pentathlon at the 2000 Olympics in Sydney. "Watching the flag being raised and hearing the music is what it's all about," Cook said. "To not have that because your country has not contributed to fighting the drugs problem would be like not recognising what you've achieved." According to Pound, the main offenders are from Central/South America and Africa - the latter including Senegal, the country of Lamine Diack, president of the IAAF. Funding by governments is arranged on a continental basis - Europe 47.5%, America 29%, Asia 20% and Africa 0.5%. © The Telegraph, London LOAD-DATE: November 5, 2003 LANGUAGE: ENGLISH PUB-TYPE: Paper Copyright 2003 Times Media Limited 668 of 998 DOCUMENTS The Washington Times November 2, 2003, Sunday, Final Edition More athletes use anti-sleep drug BYLINE: By Steve Nearman, THE WASHINGTON TIMES SECTION: SPORTS; WEEKEND ATHLETE: RUNNING; Pg. C13 LENGTH: 761 words Has track and field in America become so boring that even its athletes need to take modafinil to keep from falling asleep during competition? Just wait until they start busting track and field writers for taking the stimulant. Three U.S. athletes have tested positive for the eugeroic drug, which in medical terms simply means "good arousal." More positive tests may follow. The drug's revelation hit the track circuit shortly after the Track & Field World Championships in Paris in late August. World 100/200 double champ Kelli White was the first athlete exposed, saying she took modafinil on prescription from her physician to combat narcolepsy. The International Association of Athletics Federations charged her with a doping offense. True, modafinil, a k a provigil, is used to improve wakefulness in people with excessive daytime sleepiness associated with narcolepsy. But now we have two other U.S. athletes who competed at the worlds - Chris Phillips who finished fifth in the 110-meter hurdles and Calvin Harrison who ran the opening leg of the gold-medal 1,600-meter relay - who admitted they took modafinil. While modafinil was not on the banned substance list at the time of the world championships, caffeine and amphetamines were. Just recently, caffeine was taken off the list. An interesting question came out of research conducted in 1991 by T.J. Lyons and J. French for the U.S. Air Force School of Aerospace Human Systems Division at Brooks Air Force Base in Texas: "The development of modafinil brings to light a crucial social question. What would be the impediment for its use, if a compound such as modafinil is more like caffeine than amphetamine in terms of safety, and yet, as effective as the amphetamines?" Marine Corps magic - No performance in the 28-year history of the Marine Corps Marathon was as dominating as Heather Hanscom's triumph this year. The 25-year-old Alexandria resident's margin of victory last weekend was 20 minutes and 47 seconds over runner-up Lindsey Gannon. The next largest win, including both the men's and women's 28 races, was approximately six minutes, according to historian George Banker. Only Olga Markova of Russia had a faster winning time for women at Marine Corps, covering the 1990 course 59 ticks faster than Hanscom did a week ago. Even more significant for Hanscom, in her marathon debut, is that she qualified with an "A" standard for the U.S. Women's Olympic Trials in St. Louis on April 3. Her time has her ranked in the top 20 of nearly 125 American women to qualify thus far for the trials. That "A" standard - a time of 2:39:59 or faster - will get her travel expenses to the trials paid by the race organizers. And this is just the beginning for Hanscom. The Marine Corps win launched Markova's career. She traveled from Russia as an unknown, had lodging arranged with a couple living on Capitol Hill and went on to triumphs at Boston in 1992 and 1993. The Marine Corps Marathon also spring-boarded a career in the marathon for 1987 titlist Mary Robertson. The then-Richmond resident's 2:44 qualified her for the 1988 U.S. Women's Olympic marathon trials. Today, she is Mary Wittenberg, executive vice president and chief operating officer of the New York Road Runners Club, organizers of today's New York City Marathon. Olympic marathon trials fever - When the Chicago Marathon had a few last-minute cancellations, a chunk of money was freed up. So organizers offered cash incentives of $2,500 and $3,500 to each U.S. athlete running a "B" or an "A" Olympic trials qualifying standard. The marathon paid out $115,000 to 39 U.S. marathoners in its Oct. 12 event. There were 21 men, including area runners Edmund Burke of Burtonsville and Nick Gramsky of McLean, as well as 18 women. There goes your amateur status, boys. Today for the first time at New York, organizers have hired U.S. marathon record-holder Deena Kastor [formerly Drossin] to pace, for at least 25 kilometers, a group of approximately six American women to break the 2:40 Olympic trials "A" standard. Meanwhile, 2003 USA Marathon champion Sara Wells will lead a large group of athletes toward the 2:48 "B" standard. +++++ EVENTS * Ivymount School 5K Race for Excellence - Today, 8 a.m., Potomac, Md. Information: 301/871-0400. * Halloween Young Run - Today, 9 a.m., Rockville. Ages 12-and-under run quarter-, half- or full mile. Information: 301/353-0200. * United We Stand 5K - Saturday, 1 p.m., Bon Air Park, Arlington. LOAD-DATE: November 3, 2003 LANGUAGE: ENGLISH Copyright 2003 The Washington Times LLC All Rights Reserved 669 of 998 DOCUMENTS Contra Costa Times October 31, 2003 Friday FINAL EDITION ATHLETES WARY OF GROCERY LIST OF BANNED DRUGS; OVERSIGHTS OCCUR FROM THE VOLUMINOUS EDUCATIONAL INFORMATION AVAILABLE BYLINE: ANN TATKO, TIMES STAFF WRITER SECTION: SPORTS; Pg. B06 LENGTH: 697 words Three years ago, a simple case of bronchitis wasn't so simple for Cal grad Jason Han. As a member of the U.S. Taekwondo team, Han hesitated before taking an antibiotic prescribed by his doctor. Antibiotics were listed as acceptable medication under the International Olympic Committee's guidelines for prohibited substances, but Han decided to check with a national team trainer, just to be safe. This cautious approach is how most aspiring Olympic athletes live because of the IOC's lengthy list of performance-enhancing drugs and costly ramifications of taking one, even accidentally. Recently, five track and field athletes tested positive for a previously undetected designer steroid, tetrahydrogestrinone, also known as THG. Three of them have denied knowingly taking any banned substance. In a separate case, six track athletes reportedly tested positive for modafinil, a stimulant used to treat sleep disorders. Those athletes include former El Sobrante resident Kelli White and ex-Stanford star Chryste Gaines. White said she didn't know modafinil was a banned substance when her doctor prescribed it for narcolepsy, a sleep disorder that runs in her family. At the time, modafinil was included on the IOC list as a "related substance," making it a prohibited mild stimulant. She failed a drug test at the world track and field championships in August and may lose the gold medals she won in the 100- and 200-meter races. "I've never taken any performance enhancing drugs and I certainly didn't believe I was taking one (at worlds)," she said. "I was on the medicine all summer and never tested positive once." Ignorance rarely passes as a defense when athletes fail drug tests these days because educational information is so readily available, said Terry Madden, chief executive officer of the U.S. Anti-Doping Agency. In the United States, Madden's agency handles dispersing such information and drug testing athletes from the country's 39 Olympic sport organizations. USADA provides athletes with a 37-page guidebook listing more than 100 banned generic stimulants and anabolic agents. It also operates a toll-free drug reference phone line to answer athletes' questions. But having information doesn't make it necessarily easy to assimilate. "Generic drugs go by so many different (pharmaceutical) names; you may think it's safe to take a medicine that's actually prohibited," Han said. "That's why I always double check. I don't want to jeopardize my career because of an oversight." Oversights could occur easily considering the amount of information athletes are expected to know. USADA provides "wallet cards," via its Web site, that list a condensed version of some allowed medications and prohibited substances. The cards completely fill two letter-size pages with small type, and even then, not all drugs are included. Also, some permissible medications include warnings that they are allowed only in certain forms, such as decongestants only in nasal sprays, or that some may contain prohibited substances, such as in certain cold medicines. "It's like reading through a warranty for something you buy - a lot of mind-numbing fine print," said skier Daron Rahlves, a native of Clayton and former world champion. "But you have to do it, because even one inadvertent slip-up could cost you everything." Rahlves witnessed just such an example at the 2002 Olympics in Salt Lake City, where Great Britain's Alain Baxter won his country's first Olympic alpine skiing medal with a bronze in slalom. He later lost that medal when he tested positive for methamphetamine because of a Vicks inhaler he used. In some cases, perhaps even White's, an athlete could avoid failing a drug test by seeking permission to take a banned prescription medication. If an athlete needs it because of a diagnosed condition, he can fill out a medical notification form and wait for approval from USADA. "Filling out paperwork and drug testing may be inconvenient, but it's how the system works," said biathlete Rachel Steer, a USADA athlete ambassador. "Everyone wants fair competition, and this is the best system we have to accomplish that." LOAD-DATE: November 10, 2005 LANGUAGE: ENGLISH Copyright 2003 Contra Costa Times All Rights Reserved 670 of 998 DOCUMENTS THE DAILY TELEGRAPH(LONDON) October 31, 2003, Friday US gold still under threat BYLINE: By Scott Purchase SECTION: Pg. 06 LENGTH: 410 words THE United States could lose the 4 x 400 metre relay gold medal from this summer's World Championships due to a second drug violation by Calvin Harrison, the sport's top anti-doping official said yesterday. Harrison confirmed last week that he tested positive for the stimulant modafinil at the United States track championships at Stanford in June. Under international rules the penalty for stimulants is a public warning and disqualification from the event where the test took place, but no ban. The International Association of Athletics Federations had said that, despite the positive test in June, Harrison remained eligible for the World Championships in Paris in August, but Arne Ljungqvist, head of the IAAF medical commission, pointed to an earlier offence. Ljungqvist confirmed that Harrison tested positive for the stimulant pseudoephedrine at the 1993 US junior indoor championships and served a three-month suspension. This second offence at Stanford in June should have attracted a two-year ban, and Harrison should not have been eligible for the World Championships, according to Ljungqvist. The athlete could be retroactively disqualified. Harrison, who finished sixth in the individual 400 metres, ran the opening leg in the relay final in Paris. The other runners were Tyree Washington, Derrick Brew and Jerome Young. It was Young who failed a doping test in 1999. Ljungqvist said Harrison's case must first be investigated by the US Anti-Doping Agency. USADA have not announced the names of athletes who tested positive for modafinil or the designer steroid THG, pending the analysis of backup 'B' samples. Under IAAF rules the American relay team face being stripped of the gold medal if Harrison is found guilty of the second doping offence by USADA and the ruling is upheld through appeal. Ljungqvist said: "That is our interpretation, but it will be a matter for the legal people to debate. It's a little tricky because he was properly entered. At the time it was not know he was had an earlier test for modafinil." If the United States team lose the relay medal, the French team - anchored by Marc Raquil - would move up to the gold. USADA retested urine samples from the US championships after the UCLA doping control laboratory devised a test for previously undetectable THG. Six Americans have been identified as testing positive for modafinil, which is prescribed for narcolepsy. [PS]Sport: [ES] Yachting: LOAD-DATE: October 31, 2003 LANGUAGE: ENGLISH Copyright 2003 Telegraph Group Limited 671 of 998 DOCUMENTS The Age (Melbourne, Australia) October 30, 2003 Thursday Late Edition Pittman rival tests positive BYLINE: Jacquelin Magnay, Len Johnson SECTION: SPORT; Pg. 16 LENGTH: 445 words One of Jana Pittman's main rivals in the 400 metres hurdles, American champion Sandra Glover, has tested positive to the banned stimulant modafinil. The 34-year-old athlete, who calls herself the "grandma" of the track, was named by the Los Angeles Times as testing positive to the drug during re-testing of the US Track and Field trial samples for the steroid THG. Glover is the latest big name athlete to have been caught in the biggest drugs scandal since Ben Johnson was stripped of his 100 metres gold medal in 1988. Her fast finishing burst at the Paris world championships in August snared her the silver medal to relegate the world-record holder Yuliya Pechonkina into third place, as Sydneysider Pittman triumphed. In the last event of the season, the world grand prix final, Glover won the 400 metres hurdles in the absence of Pittman and Pechonkina. Glover is likely to face the loss of her US trial title but she will be able to keep the world championships silver medal under IAAF rules. But the humiliation will not sit easily with Glover, a primary school teacher, and she might retire. Sprinters Chryste Gaines and Kelli White, another 400 metres hurdler Eric Thomas, 400 runner Calvin Harrison and 110 hurdler Chris Phillips have already tested positive to modafinil. Doctors say modafinil is taken to regulate sleeping patterns but bodybuilders believe it also promotes the production of growth hormone in the body. World governing body, the IAAF, has said it will punish any coaches directly connected to the spate of positive tests for modafinil. Meanwhile, a key element of the defence mounted by the coach and the nutritional supplement company linked to the designer steroid scandal has been knocked out with the declaration by the US Food and Drug Administration that the drug involved is potentially harmful and not a nutritional supplement. A statement in Washington said the FDA had completed an analysis of THG and determined it is "an unapproved new drug," which makes its use for any reason illegal in the US. "Rather, it is a purely synthetic `designer' steroid derived by simple chemical modification from another anabolic steroid that is explicitly banned by the US Anti-Doping Agency," the statement said. THG is also a banned substance in Australia. The Therapeutic Goods Administration said yesterday it fell under the Schedule Eight, Customs (Prohibited Imports) regulations entry for "anabolic or androgenic substances". It appears unlikely that any Australian-based athlete will be found to have used THG. The Customs Department has confirmed that there has been no commercial importation of Balco products into Australia in the past five years. LOAD-DATE: June 18, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2003 The Age Company Limited All Rights Reserved 672 of 998 DOCUMENTS Associated Press Worldstream October 30, 2003 Thursday Harrison had previous doping offense; US could lose world relay gold BYLINE: STEPHEN WILSON; AP Sports Writer SECTION: SPORTS LENGTH: 687 words DATELINE: LONDON The United States could lose its 1,600-meter relay gold medal from this summer's World Championships due to a second drug violation by Calvin Harrison, the sport's top anti-doping official said Thursday. Harrison confirmed last week that he tested positive for the stimulant modafinil at the U.S. track championships at Stanford in June. Under international rules, the penalty for stimulants is a public warning and disqualification from the event where the test took place - but no ban. The International Association of Athletics Federations had said that, despite the positive test in June, Harrison remained eligible for the World Championships in Paris in August. But IAAF medical commission chief Arne Ljungqvist told The Associated Press on Thursday that he has since confirmed that Harrison tested positive for the stimulant pseudoephedrine at the 1993 U.S. junior indoor championships and served a three-month suspension. Jill Geer, spokeswoman of USA Track & Field, confirmed the 1993 positive. "This would be a second offense," Ljungqvist said in a phone interview. "The second offense for a mild stimulant would be a two-year ban." In that case, Harrison should not have been eligible for the world meet and he could be retroactively disqualified, Ljungqvist said. Harrison ran the opening leg in the relay final in Paris. The other runners were Tyree Washington, Derrick Brew and Jerome Young, who is engulfed in controversy over a failed doping test in 1999. Harrison also finished sixth in the individual 400-meter final in Paris. Ljungqvist said Harrison's case must first be investigated by the U.S. Anti-Doping Agency. USADA has not announced the names of athletes who tested positive for modafinil or the designer steroid THG, pending the analysis of backup B samples. Under IAAF rules, the U.S. relay team faces being stripped of the gold medal if Harrison is found guilty of the second doping offense by USADA and the ruling is upheld through the appeals process. "That is our interpretation but it will be a matter for the legal people to debate," Ljungqvist said. "It's a little tricky because he was properly entered. At the time it was not know he was had an earlier test for modafinil." If the U.S. team loses the relay medal, the French team - anchored by Marc Raquil - would move up to the gold. USADA retested urine samples from the U.S. championships after the UCLA doping control laboratory devised a test for previously undetectable THG. Six Americans have been identified as testing positive for modafinil, which is prescribed for treatment of the sleeping disorder narcolepsy. Harrison and Young were both members of the winning U.S. 1,600 relay squad at the 2000 Sydney Olympics. The team was anchored by Michael Johnson. Young tested positive for the steroid nandrolone in 1999, but was exonerated on appeal by USA Track & Field officials. The IOC and IAAF are investigating whether Young was improperly cleared and should have been ineligible for the Olympics. The probe could lead to the team being stripped of the gold. Young, who won golds in the 400 meters and 1,600 relay at the Paris championships, said he never committed a doping offense. In a column in Thursday's Daily Telegraph, Johnson said he can't see how he could lose one of his five Olympic gold medals because of the positive tests of Young and Harrison. "The only way the medals could be taken away now, since neither athlete tested positive during the games, is if one of them were to admit having taken performance enhancing drugs during the games," he said. "Personally I don't like the rules and think they should be changed. But as they stand now I don't think Young should be targeted, and his medals threatened, for a positive test four years ago for which he was exonerated." World Anti-Doping Agency chairman Dick Pound scoffed at Johnson's position. "He's trying to keep his medal," he told the AP. "There was clearly a very goofy internal process ... The worst thing is USA Track & Field knew it and still put (Young) in the event and put Michael Johnson at risk as well." LOAD-DATE: October 31, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 673 of 998 DOCUMENTS The Daily Telegraph (Sydney, Australia) October 30, 2003 Thursday Athletes' mentors to face punishment SOURCE: MATP BYLINE: STEPHEN WILSON SECTION: SPORT; Pg. 61 LENGTH: 323 words THE International Association of Athletics Federation plans to punish any coaches directly connected to the spate of positive tests among US athletes for the stimulant modafinil. Six Americans have been identified as testing positive for the substance, which is prescribed for treatment of the sleeping disorder narcolepsy. Some were coached by Ukrainian-born coach Remi Korchemny, who is based in the San Francisco area. IAAF general secretary Istvan Gyulai said yesterday that coaches involved in drug cases should face sanctions. "If it proved that they incite or promote the use of drugs or substances which are not permitted, they are considered to have committed a doping offence themselves," he said. IAAF rules do not specify penalties for non-athletes in doping cases. But Gyulai said the IAAF could consider banning a coach or refusing accreditation for major events. Three more US athletes were cited in newspaper reports yesterday for positive modafinil tests. The Washington Post reported that 1996 Olympic 4x100m gold medallist Chryste Gaines tested positive at the US championships in Stanford in July. The Los Angeles Times also cited Gaines along with hurdlers Sandra Glover and Eric Thomas. Glover is a four-time US 400m hurdles champion and won silver at the World Championships in Paris in August. Thomas is the US men's 400m hurdles champion. Olympic and world relay gold medallist Calvin Harrison had already confirmed he has tested positive for modafinil, while Kelli White -- who won gold in both 100m and 200m in Paris -- and hurdler Chris Phillips tested positive at the world championships. White could be stripped of her medals. Modafinil wasn't named on the sport's banned drug list, but the IAAF said it fell under the category of related substances and classified it as a "minor stimulant". It has now been placed by name on the World Anti-Doping Agency's banned list. LOAD-DATE: October 29, 2003 LANGUAGE: ENGLISH JOURNAL-CODE: DTM Copyright 2003 Nationwide News Pty Limited 674 of 998 DOCUMENTS Sydney Morning Herald (Australia) October 30, 2003 Thursday Late Edition Pittman rival shows positive to vogue drug in mass retesting of US track team; ATHLETICS BYLINE: Jacquelin Magnay, AP for the last two paragraphs only. SECTION: SPORT; Pg. 38 LENGTH: 607 words One of Jana Pittman's key rivals in the 400-metre hurdles, the American champion Sandra Glover , has tested positive to the banned stimulant modafinil . The 34-year-old, who calls herself the "grandma" of the track, was named by the Los Angeles Times as having tested positive during mass retesting of the US track-and-field trial drug samples for the other vogue steroid drug tetrahydrogestrinone (THG). The religious Glover is the latest big-name athlete to have been caught in the biggest drugs scandal since Ben Johnson in 1988. Her fast-finishing burst at the Paris world championships in August snared her the silver medal to relegate world-record-holder Yuliya Pechonkina to third place, as Sydneysider Pittman triumphed. And in the last event of the season, the world grand prix final, Glover won the 400m hurdles as Pittman partied and Pechonkina was sick with bronchitis. Glover is likely to face the loss of her US trial title but she will be able to keep the world championships silver medal because under current IAAF rules the modafinil sanction involves the stripping of results from the competition in which the stimulant was found, as well as a public warning. But the humiliation will not sit easily with Glover, a primary school teacher. She may elect to retire. Glover's US colleague Kelli White is battling to keep her two sprint gold medals from the world championships because she tested positive to modafinil at that Paris competition. Those caught taking modafinil now include sprinter Chryste Gaines , another 400m hurdler Eric Thomas , 400m runner Calvin Harrison , 110m hurdler Chris Phillips , Glover and White. Doctors say modafinil is taken to regulate sleeping patterns but bodybuilders believe it also promotes the production of growth hormone in the body. Meanwhile, the US Food and Drug Administration yesterday banned the sale and use of THG, to which British sprinter Dwain Chambers ; hammer-thrower John McEwen; shot-putter Kevin Toth ; distance-runner Regina Jacobs and another unnamed US athlete have tested positive in the past fortnight after retesting of stored urine samples. The drug administration ruled the drug was not a dietary supplement, but a synthetic designer steroid and warned its use may pose considerable risk to health. The administration's associate commissioner, John Taylor, told US Congress that THG was derived from gestrinone . Gestrinone is often used in Europe to treat endometriosis, an extremely painful condition where part of the womb grows into the abdomen. Taylor also said THG was chemically linked to the veterinary steroid trenbolone , which is favoured by US cattle ranchers to beef up the size of their cows. The classification of THG as a controlled substance similar to that of morphine, runs contrary to the claims by the man accused of supplying THG to athletes, BALCO president Victor Conte , that it was a dietary supplement. Conte is facing a US grand jury over tax fraud and dozens of his clients, including high-profile athlete Marion Jones and baseballers Barry Bonds and Jason Giambi have been subpoenaed to appear. In a news release, the administration said it was working with other federal law enforcement agencies to aggressively engage, enforce, and prosecute those firms or individuals who manufacture, distribute or market THG. * Phoenix: Olympic sprint champion Gail Devers , 37, will return to competition next season hoping to show young athletes and fans there can be success without performance-enhancing drugs, AP reports. In a telephone interview from Japan, Devers said she was motivated to come back by the recent controversy over the designer steroid THG. LOAD-DATE: July 17, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2003 John Fairfax Publications Pty Ltd All Rights Reserved 675 of 998 DOCUMENTS The Times (London) October 30, 2003, Thursday White's case strengthened by claims of drugs company BYLINE: Peter Nichols SECTION: Sport; 50 LENGTH: 394 words KELLI WHITE, who tested positive for the stimulant modafinil at the World Championships in August, has been given hope in her battle to retain the 100 and 200 metres titles that she won in Paris. Speaking to The Times, Dr Paul Blake, a senior vice-president of Cephalon, the company that manufactures the drug, has cast serious doubt on the claims of the IAAF that it could be regarded as a banned substance at the time of the World Championships. Modafinil was not identified by name on the list of banned stimulants and the disqualification of White hinges on the fact that the drug falls into the catch-all category of "chemically and pharmacologically related compounds". However, Blake insists that modafinil is not related to the stimulants on the list. "It is clearly a very different chemical, having a different pharmacological structure. It is a separate pharmacological entity," he said. Modafinil was developed more than 20 years ago in France at Lafon Laboratories, a company that is now part of the Cephalon group. Company literature describes modafinil as a "wake promoter" rather than a stimulant and states that the drug belongs to its own class, which it has called Eugeroics, of which there is just one other related drug, also manufactured by Cephalon. The Food and Drug Administration first ratified modafinil's limited use in the United States in 1998 and recently a more extended approval has been given for the drug, which is generally used to treat sleeping disorders. Blake expressed surprise that, when the positive test for the drug surfaced in Paris, the IAAF did not contact the company immediately. "We eventually contacted WADA (the World Anti-Doping Agency) after it had gone on their lists and asked if we could present a submission," Blake said. That review of the status of the drug has yet to take place, but Blake's comments will provide ammunition for White, whose hearing is expected soon, although the US Anti-Doping Agency (USADA) would not give a date. If the USADA cannot classify modafinil in the "related compounds" grouping and it will be all too aware of the threat of legal action if there are any doubts - then White would keep both the 100 metres and 200 metres titles that she won in Paris and also collect $ 120,000 (about £70,000) in prize-money that has so far been withheld. LOAD-DATE: October 30, 2003 LANGUAGE: ENGLISH Copyright 2003 Times Newspapers Limited 676 of 998 DOCUMENTS USA TODAY October 30, 2003, Thursday, FINAL EDITION Athletes reported with positive tests SECTION: SPORTS; Pg. 16C LENGTH: 129 words There have been a rash of positive drug tests recently for the previously undetectable steroid THG and the stimulant modafinil. Athletes are entitled to appeals. The THG penalty is a two-year ban from competition. Modafinil carries a penalty of disqualification for the meet in which the athlete was tested but no further competition ban. Athletes identified as testing positive: THG 1. Regina Jacobs, USA, middle-distance runner 2. Kevin Toth, USA, shot put 3. John McEwen, USA, hammer thrower 4. Dwain Chambers, Britain, sprinter Modafinil 1. Kelli White, USA, sprinter 2. Chris Phillips, USA, hurdler 3. Calvin Harrison, USA, sprinter 4. Sandra Glover, USA, hurdler 5. Eric Thomas, USA, hurdler 6. Chryste Gaines, USA, sprinter LOAD-DATE: October 30, 2003 LANGUAGE: ENGLISH Copyright 2003 Gannett Company, Inc. 677 of 998 DOCUMENTS The Advertiser October 29, 2003 Wednesday IAAF wakes up to drug pattern BYLINE: By STEPHEN WILSON in London SECTION: SPORT; Pg. 102 LENGTH: 324 words TWO drugs under scrutiny in sports - modafinil and THG - are part of a pattern of doping abuse in the United States, according to Arne Ljungqvist, the IAAF's medical commission chief. Evidence suggests a link between Modafinil - the drug sprinter Kelli White says she took for a sleep disorder - and Tetrahydrogestrinone, or THG, a previously undetectable designer steroid that has turned up in the samples of several track and field athletes. "What emerges now is a pattern," Ljungqvist said. "People have taken THG for obvious reasons - it's been designed with the intent not to be discovered. "And modafinil seems to have become a fashionable stimulant among certain athletes as well. It's a pattern I've seen before, where drugs have become popular and we find them." The Washington Post, citing unidentified international sources with knowledge of the results, reported on its Web site Monday night that American sprinter Chryste Gaines tested positive for modafinil at the US track and field championships in July. Calvin Harrison, an Olympic and world relay gold medallist, also tested positive for the stimulant this past summer, a source close to a US doping investigation said. Harrison, still awaiting the result of his backup B sample, was tested at the US national championships in June at Stanford, California. Modafinil first came to prominence in August when White tested positive for the drug at the world championships in Paris. She stands to be stripped of her 100m and 200m titles. White said she took modafinil on prescription from her personal doctor to combat narcolepsy. The International Association of Athletics Federations charged her with a doping offence and submitted her case to U.S. authorities for disciplinary action. Referring to White's narcolepsy defence, Ljungqvist said: "It comes into a different sort of light when it becomes known that modafinil has been taken by a number of athletes." LOAD-DATE: October 28, 2003 LANGUAGE: ENGLISH JOURNAL-CODE: ADV Copyright 2003 Nationwide News Pty Limited 678 of 998 DOCUMENTS DAILY MAIL (London) October 29, 2003 Narcolepsy drug used by seven, say IAAF BYLINE: NEIL WILSON SECTION: ED_2ND; Pg. 77 LENGTH: 301 words SEVEN athletes have recently tested positive for the new stimulant modafinil, the head of the International Association of Athletics Federations, Istvan Gyulai, revealed yesterday. 'We have been informed about the number, it's a maximum of seven, but I can't name them,' he said. Modafinil, normally used to treat narcolepsy, does not appear on the IAAF's banned list but is closely related to other drugs that do. One of the seven is the US sprinter Chryste Gaines, 33, the Washington Post claimed yesterday. Gaines is coached by Remi Korchemny, the Ukrainian who also numbers Kelli White, winner of the 100m and 200m titles at this year's World Championships, and Britain's 100metres European champion Dwain Chambers in his stable of athletes. Chambers tested positive for the designer steroid THG in August, while White stands to lose her sprint titles after also showing positive for modafinil in the summer. Meanwhile, one of the athletes subpoenaed to testify before the U.S. federal grand jury investigating the California laboratory BALCO, which allegedly manufactured THG, is suing the American scientist who unmasked it. Tammy Thomas, a former world track cycling record holder before she was banned for life last year, has accused Dr Don Catlin and his Los Angeles university laboratory of unethical conduct in identifying her in its published research, a federal offence. What makes Thomas of interest to prosecutors may be Catlin's claim that the steroid he caught her using on two occasions, norbolethone, could have come from an illicit laboratory, possibly BALCO. Yesterday, the US Food and Drug Administration declared THG illegal. It is not a dietary supplement, they say, but a designeer steroid which could have serious effects on longterm health. END LOAD-DATE: October 30, 2003 LANGUAGE: English PUB-TYPE: Paper Copyright 2003 Associated Newspapers Ltd. 679 of 998 DOCUMENTS THE DAILY TELEGRAPH(LONDON) October 29, 2003, Wednesday Chambers coach in new link BYLINE: By Tom Knight SECTION: Pg. 05 LENGTH: 325 words THE focus in the escalating American doping scandal shifted to Dwain Chambers's coach, Remi Korchemny, yesterday, as yet another of his athletes was reported to have tested positive for a banned substance. According to the Washington Post the American sprinter Chryste Gaines is the latest athlete to have tested positive for the stimulant, modafinil. Istvan Gyulai, general- secretary of the International Association of Athletics Federations, said Korchemny could become the first coach to face sanctions - possibly a life ban - in a doping case. It is understood modafinil was found in the urine sample provided by Gaines at the US Championships in June. The samples collected at those championships were recently re-tested when the US Anti-Doping Agency uncovered the existence of a new, designer steroid called tetrahydrogestrinone, or THG. Gaines, 33, who enjoyed a late run of form during the season to win the 100 metres at the World Athletics Finals in Monte Carlo, would be the fourth athlete connected to Korchemny to have failed a drugs test. Chambers has tested positive for THG and the Americans Kelli White, Chris Phillips and Calvin Harrison for modafinil, a drug banned by the IAAF because it is categorised as being related to the family of stimulants. Phillips and Harrison said they were given modafinil by Korchemny. Phillips, who along with White tested positive at the World Championships, told the IAAF that he was given the drug just before his 110m hurdles semi-final. Korchemny remained defiant. He said: "Modafinil is the same as aspirin or coffee - big deal. It was not on the list of banned substances." In a later development, the Los Angeles Times reported that two other American athletes had tested positive for modafinil - Sandra Glover, a four-time US champion in the 400m hurdles and runner-up in August at the World Championships in Paris, and Eric Thomas, the reigning US 400m hurdles champion. LOAD-DATE: October 29, 2003 LANGUAGE: ENGLISH Copyright 2003 Telegraph Group Limited 680 of 998 DOCUMENTS Edmonton Journal (Alberta) October 29, 2003 Wednesday Final Edition IAAF threatens to nab drug-pushing coaches SOURCE: The Associated Press SECTION: Sports; Pg. D4 / LENGTH: 422 words DATELINE: LONDON LONDON - Track and field's world governing body plans to punish any coaches directly connected to the spate of positive tests among U.S. athletes for the stimulant modafinil. Six Americans have been identified as testing positive for the substance, which is prescribed for treatment of the sleeping disorder narcolepsy. Istvan Gyulai, general secretary of the International Association of Athletics Federations, said Tuesday that any coaches or trainers involved in the use of modafinil should face sanctions. "If it proved that they incite or promote the use of drugs or substances which are not permitted, they are considered to have committed a doping offence themselves," he said. "This has to be investigated. We cannot just turn a blind eye to this." IAAF rules do not specify penalties for non-athletes in doping cases. But Gyulai said the IAAF could consider banning a coach or refusing accreditation for major events. Three more U.S. athletes were cited in newspaper reports Tuesday for positive modafinil tests. The Washington Post reported that sprinter Chryste Gaines -- a relay gold medallist at the 1996 Olympics --tested positive at the U.S. championships in Stanford, Calif., in July. The Los Angeles Times said hurdlers Sandra Glover and Eric Thomas also tested positive for the drug. Calvin Harrison, an Olympic and world relay gold medallist, had previously confirmed he tested positive for modafinil at the U.S. meet. Sprinter Kelli White and hurdler Chris Phillips tested positive at the World Championships. White, who said she took modafinil for narcolepsy, risks losing her gold medals from the 100 and 200 metres. Modafinil wasn't named on the sport's banned drug list, but the IAAF said it fell under the category of related substances and classified as a "minor stimulant." Gyulai stressed that modafinil should not be viewed in the same light as the designer steroid THG, which has turned up in the samples of several track and field athletes. The sanction for steroids is a two-year ban. "THG was invented, produced and masterminded to cheat," Gyulai said. "There is a major difference with modafinil. The athletes may have thought this is not forbidden. They should have checked more carefully." DEVERS RETURNS - Olympic champion sprinter Gail Devers will return to competition next season, hoping to show young athletes and track fans that there can be success without performance-enhancing drugs. - Devers says she was motivated to come back by the recent controversy over THG. LOAD-DATE: October 29, 2003 LANGUAGE: ENGLISH TYPE: Sports Copyright 2003 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 681 of 998 DOCUMENTS The Guardian - Final Edition October 29, 2003 Football: Chambers coach under scrutiny BYLINE: Vivek Chaudhary SECTION: Guardian Sport Pages, Pg. 34 LENGTH: 678 words Track and field's world governing body, the International Association of Athletics Federations (IAAF), yesterday announced plans to punish any coaches directly connected to the spate of positive tests among US athletes for the stimulant modafinil. Six Americans have been identified as testing positive for the substance, which is prescribed for treatment of the sleeping disorder narcolepsy. Istvan Gyulai, the IAAF's general secretary, said that any coaches or trainers involved in the use of modafinil would face sanctions. iIf it is proved that they incite or promote the use of drugs or substances which are not permitted, they are considered to have committed a doping offence themselves,i he said. The announcement came on the day that the American sprinter Chryste Gaines became the fourth athlete trained by the Ukrainian-borncoach Remi Korchemny to test positive for banned drugs. The IAAF confirmed that Gaines had tested positive for modafinil and that it would launch an investigation into the links between Korchemny, who also coaches Britain's Dwain Chambers, and the positive drugs tests of some of his athletes. Gaines, 33, was a member of the victorious women's 4x100 metres relay team in the 1996 Atlanta Olympics. Gaines, her fellow sprinter Kelli White and the hurdler Chris Phillips, who all train with Korchemny, have all tested positive for modafinil. Chambers has tested positive for the designer steroid tetrahydrogestrinone (THG). Gyulai revealed that up to seven athletes had tested positive for modafinil. iOf course modafinil is a concern for us. We have been informed about the number (of positive tests). It's a maximum of seven but I can't name them.i He said that the links between the athletes and Korchemny was a matter of concern. iIf it's proven that this coach was offering anything that is not a permissible substance to athletes, that is the biggest concern to the IAAF.i White, Gaines and Chambers train frequently with Korchemny in the San Francisco area. Phillips coaches himself, but he told the IAAF that Korchemny gave him a modafinil pill before the 110 metres hurdles semi-finals in the world championships in Paris because he was having trouble sleeping. Korchemny told the Washington Post yesterday that he gave Phillips the modafinil to help him sleep and not to improve his performance. He denied giving modafinil to Gaines and said that he did not know how she had tested positive. Modafinil, which is marketed under the name Provigil, was not officially banned until after the world championships in August but drug-testingofficials said that it qualified as a banned substance because of a broad clause in the antidoping rules prohibiting substances closely related to banned drugs. Referring to the White and Phillips cases, Korchemny said: iI had in my package one pill because Kelli took only one pill. I'm sorry I did it . . . but it was not prohibited (under anti-doping rules) . . . I was 100% sure everything was legal.i Commenting on Gaines's positive test, he said: iI don't know anything about her case. She is my student, but I don't know anything about her. I didn't give her modafinil.i White's agent Robert Wagner, who also represents Phillips, claimed that there was a grey area in the use of modafinil that had left manyathletes confused. Wagner said: iAthletes travel a lot; they come from different time zones. They can't just drink five or six cups of coffee so they need to find something similar that's not on the banned list. Modafinil was not on the banned list; it is still not on the banned list.i After the positive test of Chambers' A sample, his lawyer Graham Shear claimed that Korchemny made all the arrangements for his nutritional supplements and that he had no idea he was taking a banned steroid when he consumed THG. Three Americans, the middle-distance runner Regina Jacobs, the US shot put champion Kevin Toth and the hammer thrower John McEwan, have also tested positive for THG this year. LOAD-DATE: October 30, 2003 LANGUAGE: ENGLISH Copyright 2003 Guardian Newspapers Limited 682 of 998 DOCUMENTS The Guardian - Final Edition October 29, 2003 Football: Drugs coaches to face charges BYLINE: Vivek Chaudhary SECTION: Guardian Sport Pages, Pg. 34 LENGTH: 420 words The International Association of Athletics Federations (IAAF) yesterday announced plans to punish any coaches directly connected to the spate of positive tests among US athletes for the stimulant modafinil. Six Americans have been identified as testing positive for the substance, which is prescribed for treatment of the sleeping disorder narcolepsy. Istvan Gyulai, the IAAF's general secretary, said that any coaches or trainers involved in the use of modafinil would face sanctions. "If it is proved that they incite or promote the use of drugs or substances which are not permitted, they are considered to have committed a doping offence themselves," he said. The announcement came on the day that the American sprinter Chryste Gaines became the fourth athlete trained by the Ukrainian-born coach Remi Korchemny to test positive for banned drugs. The IAAF confirmed that Gaines, 33, had tested positive for modafinil and that it would launch an investigation into the links between Korchemny, who also coaches Britain's Dwain Chambers, and the positive tests of some of his athletes. Gaines, her fellow sprinter Kelli White and the hurdler Chris Phillips, who all train with Korchemny, have all tested positive for modafinil. Chambers has tested positive for the designer steroid tetrahydrogestrinone (THG). Gyulai said: "We have been informed about the number (of positive tests for madafinil). It's a maximum of seven but I can't name them." White, Gaines and Chambers train with Korchemny in the San Francisco area. Phillips coaches himself, but he told the IAAF that Korchemny gave him a modafinil pill before the 110 metres hurdles semi- finals in the world championships in Paris because he was having trouble sleeping. Korchemny denied giving modafinil to Gaines and said that he did not know how she had tested positive. "She is my student, but I don't know anything about her. I didn't give her modafinil." Referring to the White and Phillips cases, he said: "I had in my package one pill because Kelli took only one pill. I'm sorry I did it . . . but it was not prohibited (under anti-doping rules) . . . I was 100% sure everything was legal." White's agent Robert Wagner, who also represents Phillips, said: "Athletes travel a lot; they come from different time zones. They can't just drink five or six cups of coffee so they need to find something similar that's not on the banned list. Modafinil was not on the banned list; it is still not on the banned list." LOAD-DATE: October 30, 2003 LANGUAGE: ENGLISH Copyright 2003 Guardian Newspapers Limited 683 of 998 DOCUMENTS The Herald (Glasgow) October 29, 2003 Fresh scare for Chambers;Steroid 'a health risk' warns US food and drug administration BYLINE: Doug Gillon SECTION: Pg. 32 LENGTH: 494 words THE American Food and Drug Administration yesterday said that users of an anabolic steroid specifically designed to evade detection face a health risk. This is a new concern for the British sprinter Dwain Chambers, who faces a ban despite claims that he took the drug unwittingly. Since development of a test for the previously undetectable substance, competitors are running scared as their stored urine samples await re -examination. The US authority has classified tetrahydrogestrinone (THG) as an illegal drug, and not a dietary supplement. As such it poses serious health risks to users, said the FDA associate commissioner John Taylor. He said THG would require clearance to be sold in the US. Consequently its use there is illegal. Side effects of steroid-use include tumours, liver damage, heart disease, anxiety and rage. Little is known about the specific effects of THG, as it is so new, but Taylor added that it is likely to pose similar risks. The European 100 metres champion, Chambers, the world No.1 shot-putter Kevin Toth, the world indoor 1500m record-holder Regina Jacobs, and the US hammer No.2 John McEwan have been named as having tested positive for THG. The world athletics body expect more to be identified. Their general secretary, Istvan Gyulai, confirmed yesterday that up to seven athletes have tested positive for the stimulant Modafinil, but declined to name them. However a US newspaper yesterday identified the sprinter Chryste Gaines as being among them. Gaines, who was a member of the gold medal 4 x 100m US relay squad at the 1996 Olympics and 2001 world championships, was also in their quartet in Paris at the world event in August. The favourites were beaten into second by France after Kelli White was withdrawn from the US team. White is likely to forfeit world 100 and 200m gold, having given a sample which showed she used the same stimulant. She, Gaines, and Chambers worked with the same coach, Remi Korchemny, as did the sprint hurdler Chris Phillips, who was fifth in the Paris final. He, too, has tested positive for Modafinil. White said that she and her mother use Modafinil to treat a sleeping disorder called narcolepsy, but the condition seems to have reached epidemic proportions in athletics. Professor Arne Ljungqvist, head of the medical commision at the International Association of Athletics Federations, said evidence suggests a link between modafinil and THG. "It's a pattern I've seen before, where drugs have become popular and we find them." White's defence of a family condition seems compromised. As Ljungqvist said: "It comes into a different sort of light when it becomes known that modafinil has been taken by a number of athletes." l The French Sports Ministry are to screen 10,200 promising young athletes for drugs next year. This will be in addition to the 7300 already tested on national teams. The UK does some 6000 tests annually. LOAD-DATE: October 29, 2003 LANGUAGE: English GRAPHIC: WAKE-UP CALL: Chryste Gaines is lastest champion to test positive for stimulant. Picture: Getty Images PUB-TYPE: Paper Copyright 2003 Scottish Media Newspapers Limited 684 of 998 DOCUMENTS The San Francisco Chronicle OCTOBER 29, 2003, WEDNESDAY, FINAL EDITION FDA outlaws designer steroid; Burlingame firm allegedly the source of controversial drug SOURCE: Chronicle Staff Writer BYLINE: Mark Fainaru-Wada SECTION: NEWS; Pg. A10 LENGTH: 548 words The designer steroid linked by Olympic drug-testing officials to a Burlingame supplement lab being investigated by a federal grand jury is illegal, the Food and Drug Administration announced Tuesday. The FDA issued a statement saying it had determined that tetrahydrogestrinone (THG) is an unapproved drug, and the agency said it is working with other federal agencies to "aggressively engage, enforce and prosecute those firms or individuals who manufacture, distribute or market THG." Two weeks ago, the U.S. Anti-Doping Agency (USADA), a nonprofit that oversees drug testing of Olympic sports, announced the discovery of THG as part of a doping scandal and named Victor Conte and the Bay Area Laboratory Co-Operative (BALCO) as the source of the drug. Conte has denied in repeated e-mails to The Chronicle and other media outlets that he is the source of the substance, and he also has questioned whether it is anabolic in nature. Anabolic steroids stimulate muscle development. That question is moot to the FDA, which said in its statement that unapproved new drugs can't be marketed without undergoing the agency's approval process. Because that has not been done with THG, an FDA spokesperson said anyone marketing or providing the drug would be in violation of the Food, Drug and Cosmetic Act. The FDA said that although THG might be marketed by some as a dietary supplement, it is, indeed, a "designer" steroid that is "closely and structurally related" to gestrinone and trenbolone, two synthetic anabolic steroids. Conte and his company have been thrust into the middle of what has become an international doping scandal, details of which continue to trickle out daily. More athletes were reported to have tested positive for the stimulant modafinil, which had previously showed up in a test of Union City sprinter and BALCO client Kelli White at the World Championships in Paris this summer. White's doctor, Brian Goldman, once a BALCO medical director, said she used the drug to combat narcolepsy. When the USADA announced its news about THG, it also said re-testing of samples from the U.S. National Track and Field Championships at Stanford revealed several other athletes testing positive for modafinil. The Washington Post and Los Angeles Times, citing sources, said BALCO client and U.S. sprinter Chryste Gaines had tested positive for the substance, and the Times also named hurdlers Eric Thomas and Sandra Glover. Salinas sprinter Calvin Harrison and U.S. hurdler Chris Phillips also have been identified as having tested positive for modafinil. Also Tuesday, the Associated Press reported that track's international governing body would pursue punishment of coaches as well as athletes directly connected to use of prohibited substances. The organization's medical commission chief, Arne Ljungqvist, was quoted as saying the revelations about THG and modafinil were part of a "pattern" of abuse in the United States. Several other sports associations have announced additional testing since USADA first discussed THG publicly. Swimming's world governing body said Tuesday it would retest hundreds of urine samples from this summer's world championships for the designer steroid.E-mail Mark Fainaru-Wada at mfainaru-wada@sfchronicle.com LOAD-DATE: October 29, 2003 LANGUAGE: ENGLISH Copyright 2003 The Chronicle Publishing Co. 685 of 998 DOCUMENTS San Jose Mercury News (California) October 29, 2003 Wednesday MORNING FINAL EDITION POSITIVE DRUG TESTS REVEALED; BAY AREA TRACK COACH HAS TIES TO SOME WHO USED STIMULANT BYLINE: PETE CAREY, Mercury News SECTION: SPORTS; Pg. 2D LENGTH: 615 words A secondary track and field drug scandal involving the use of the narcolepsy drug modafinil grew Tuesday with disclosures that a half-dozen top athletes have tested positive for it. The agent for the American 110-meter hurdler Chris Phillips said Phillips told the International Association of Athletics Federations that he was given a modafinil tablet by Castro Valley track coach Remi Korchemny, who assured him it was not a banned substance. Also Tuesday, the Food and Drug Administration declared that the designer steroid THG, or tetrahydrogestrinone, is an unapproved new drug and cannot legally be marketed. A representative said the FDA would "prosecute those firms or individuals who manufacture, distribute or market THG." THG is a steroid derivative identified this summer after someone anonymously mailed a used syringe to the U.S. Anti-Doping Agency, saying it came from nutritionist Victor Conte Jr. and his Burlingame company, Balco Laboratories. Several athletes with ties to Conte have since tested positive for THG. Modafinil is not a steroid, but a treatment for sleep disorders approved in 1998. The continuing positive tests are an indication that athletes were telling one another that there were benefits from taking it. Four of the athletes reported to have tested positive for modafinil are linked to Korchemny through his coaching, consulting or a track club he helped found -- Phillips; Union City sprinter Kelli White; sprinter Chryste Gaines, and Salinas native Calvin Harrison. The Los Angeles Times, citing "sources familiar with the inquiry," reported that four-time U.S. Outdoor champion Sandra Glover and 400-meter hurdles champion Eric Thomas also tested positive. A leading authority on sprint events, Korchemny has also used Balco products with his athletes. The coach couldn't be reached for comment Tuesday, but he has repeatedly told the Mercury News he does not provide performance-enhancing drugs to his athletes. A longtime friend, Bill Alston, said he spoke to Korchemny recently and "he sounds really depressed. He's really hurting." "He's so adamant against drugs," Alston said. "He just fumes when he thinks about that. To have him in that position, it just doesn't fit." Sold under the brand name Provigil, modafinil is used in treating narcolepsy but has several "off label" uses, from treating multiple sclerosis symptoms to keeping soldiers alert in battle. Track federations have classified modafinil as a mild stimulant. An athlete found using it at a meet would be disqualified and would forfeit any medals. White won two gold medals in August at the world championships in Paris and then tested positive. She said the drug was prescribed for narcolepsy by Balco's former medical director. Sports organizations say modafinil is performance-enhancing, while sleep experts doubt that. Even if it has only a small positive effect, said Dr. Gary Wadler, a New York University School of Medicine professor and sports doping expert, "it could be the difference between a gold and a silver medal, or a silver and bronze." Robert Wagner, the agent for Phillips, White and Glover, told the Associated Press his athletes were taking the drug all summer. None of them thought it was a prohibited substance, he said. "When Americans come to Europe, they take it to get over the jet lag," he said. "It's not a stimulant. It wasn't on the list." Also Tuesday, the world governing organization for swimming said it would retest athletes' urine samples from the world championships in July for THG. David Howman, director general of the World Anti-Doping Agency, said this could prompt other sports to do the same. LOAD-DATE: August 17, 2005 LANGUAGE: ENGLISH Copyright 2003 San Jose Mercury News All Rights Reserved 686 of 998 DOCUMENTS Sydney Morning Herald (Australia) October 29, 2003 Wednesday Early Edition US star and Chinese the latest to test positive; DRUGS IN SPORT BYLINE: Jacquelin Magnay SECTION: SPORT; Pg. 38 LENGTH: 402 words The drip-feed of athletes testing positive to banned drugs continues, the latest being US sprinter Chryste Gaines , ranked No.3 in the world in the 100 metres. Gaines tested positive to the same modafinil stimulant that has jeopardised the two world championship gold medals won by her San Francisco training partner, Kelli White . But the biggest surprise is the news of positive drug tests to erythropoietin (EPO) in China, which has so far escaped the ignominy of tetrahydrogestrinone (THG) or modafinil. Chinese runners Zheng Yongji and Li Huiquan were expelled from the fifth Chinese City Games at the weekend after testing positive for the blood boosting hormone. So quickly is the drugs issue moving that EPO, which has been around for nearly 20 years but testing for which has been refined only in the past three years, seems rather passe. Zheng Yongji finished second in qualification for the men's 3000m steeplechase, while Li Huiquan won the men's 800m qualification. Chinese authorities have promised that the cases will be investigated promptly. But it is Gaines's test result that has confirmed the strong links between those caught in the latest drugs scandal, the coach Remi Korchemny , his San Francisco training group and the vitamin and supplement company BALCO. The IAAF medical commission chairman Arne Ljungqvist said there might be six to eight modafinil cases being processed at the moment, damaging White's defence that she had a genuine medical excuse. He said the drug was the latest fashionable stimulant among athletes. "It's a little odd to find an epidemic of narcolepsy in top athletes," he said. Gaines has made no comment about how modafinil came to be in her urine sample taken at the July US track and field trials. "She is my student, but I don't know anything about her," Korchemny told The Washington Post. "I didn't give her modafinil." White reckoned she took the substance to treat narcolepsy after it was prescribed by Brian Goldman, a doctor who used to be BALCO's medical director. White has trained under Korchemny for the past three years, and last season European champion sprinter Dwain Chambers joined the squad. Chambers is one of four top athletes to have tested positive to THG. Chambers was introduced to BALCO by Korchemny. The IAAF officials have started their own investigations and are likely to impose a sanction on Korchemny within their rules, but seldom applied. LOAD-DATE: July 17, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2003 John Fairfax Publications Pty Ltd All Rights Reserved 687 of 998 DOCUMENTS Sydney Morning Herald (Australia) October 29, 2003 Wednesday Late Edition US star and Chinese the latest to fall; DRUGS IN SPORT BYLINE: Jacquelin Magnay SECTION: SPORT; Pg. 38 LENGTH: 395 words The drip-feed of athletes testing positive to banned drugs continues, the latest being US sprinter Chryste Gaines , ranked No.3 in the world in the 100 metres. Gaines tested positive to the same modafinil stimulant that has jeopardised the two world championship gold medals won by her San Francisco training partner, Kelli White . But the biggest surprise is the news of positive drug tests to erythropoietin (EPO) in China, which has so far escaped the ignominy of tetrahydrogestrinone (THG) or modafinil. Chinese runners Zheng Yongji and Li Huiquan were expelled from the fifth Chinese City Games at the weekend after testing positive for the blood boosting hormone. So quickly is the drugs issue moving that EPO, which has been around for nearly 20 years but testing for which has been refined only in the past three years, seems rather passe. Zheng Yongji finished second in qualification for the men's 3000m steeplechase, while Li Huiquan won the men's 800m qualification. Chinese authorities have promised that the cases will be investigated promptly. But it is Gaines's test result that has confirmed the strong links between those caught in the latest drugs scandal, the coach Remi Korchemny , his San Francisco training group and the vitamin and supplement company BALCO. The IAAF medical commission chairman Arne Ljungqvist said there might be six to eight modafinil cases being processed at the moment, damaging White's defence that she had a genuine medical excuse. He said the drug was the latest fashionable stimulant among athletes. "It's a little odd to find an epidemic of narcolepsy in top athletes," he said. Gaines has made no comment about how modafinil came to be in her urine sample taken at the July US track and field trials. "She is my student, but I don't know anything about her," Korchemny told The Washington Post. "I didn't give her modafinil." White reckoned she took the substance to treat narcolepsy after it was prescribed by Brian Goldman, a doctor who used to be BALCO's medical director. White has trained under Korchemny for the past three years, and last season European champion sprinter Dwain Chambers joined the squad. Chambers is one of four top athletes to have tested positive to THG. Chambers was introduced to BALCO by Korchemny. The IAAF officials have started their own investigations and are likely to impose a sanction on Korchemny. LOAD-DATE: July 17, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2003 John Fairfax Publications Pty Ltd All Rights Reserved 688 of 998 DOCUMENTS Tampa Tribune (Florida) October 29, 2003, Wednesday, FINAL EDITION FDA Classifies Steroid THG As An Illegal Drug BYLINE: A Tribune staff, wire report; BILL WARD, TRIBUNE WIRES SECTION: SPORTS, Pg. 2 LENGTH: 561 words WASHINGTON - The newly detected steroid that is casting a shadow on Olympic and professional sports is an illegal drug that may pose considerable health risks, the government warned Tuesday. THG has been sold in the guise of a dietary supplement when it is in fact a drug that lacks federal permission for sale in this country, the Food and Drug Administration said. It is a drug derived from another steroid long banned in athletics, the agency said. The FDA's official designation of THG as illegal, which had been anticipated since the scandal about the previously undetectable steroid emerged, puts manufacturers on notice that the government will crack down on anyone caught selling it. It also is the strongest warning yet that using THG is risky. Anabolic steroids can have dangerous side effects, including liver damage, heart disease, anxiety and rage. While little is known about THG's specific effects because it is new, its close chemical similarity to other well-known steroids means it poses the same risks, FDA Associate Commissioner John Taylor said. "The greatest importance is preventing exposure and trying to nip this in the bud," he said. U.S. drug authorities first learned about THG, or tetrahydrogestrinone, this summer after an unidentified coach gave them a syringe containing it. THG apparently was designed specifically to be undetectable by the standard test given to athletes. Now armed with a test, sports organizations are scrambling to re-examine athletes and to decide what penalties to impose for THG use. Four U.S. track and field athletes have tested positive for THG, and Europe's top sprinter has admitted taking it in nutritional supplements that he says he thought were allowed. Anabolic steroids are synthetic versions of the male hormone testosterone. Some are approved by FDA for prescription-only sale to treat certain diseases; athletes use them illegally to bulk up muscle and enhance performance. ATHLETES TEST POSITIVE: The Washington Post reported that U.S. sprinter Chryste Gaines, the 2001 U.S. champion at 100 meters and a two-time Olympic medalist in the 4x100 relay, tested positive for the banned stimulant modafinil. Quoting "international officials with knowledge of the results," the Post said Gaines tested positive for modafinil, which is often used to treat the sleep disorder narcolepsy, at the U.S. Track and Field Championships in July. Gaines is the fourth athlete connected to Ukrainian-born coach Remi Korchemny to test positive for banned drugs this summer. International Association of Athletics Federations General Secretary Istvan Gyulai called the matter a "concern" and said the IAAF planned to conduct an investigation. "This has to be investigated," he said. "We cannot just turn a blind eye to this." Gaines, 100/200 world champion Kelli White and seven-time NCAA All-America hurdler Chris Phillips - all with ties to Korchemny - have tested positive for modafinil. Another of Korchemny's athletes, former European 100 champion Dwain Chambers of England, tested positive for THG. Meanwhile, The Los Angeles Times, citing unnamed sources, said hurdlers Sandra Glover and Eric Thomas also tested positive for modafinil. Calvin Harrison, an Olympic and world relay gold medalist, had previously confirmed he tested positive for modafinil at the U.S. meet. LOAD-DATE: October 30, 2003 LANGUAGE: ENGLISH NOTES: TRACK AND FIELD Copyright 2003 The Tribune Co. Publishes The Tampa Tribune 689 of 998 DOCUMENTS The Toronto Star October 29, 2003 Wednesday Ontario Edition Narcolepsy outbreak among top athletes? BYLINE: Randy Starkman, Toronto Star SECTION: SPORTS; Pg. C07 LENGTH: 504 words HIGHLIGHT: Four U.S. runners test positive for new drug All of them 'can't have a sleep problem' Narcolepsy is a disease affecting about one in every 2,000 Americans, but there appears to be an epidemic among top U.S. track athletes. At least four of them have now tested positive for a drug created to treat the sleep disorder. Modafinil first came to prominence in sports when double gold medallist Kelli White of the U.S. tested positive for it in August at the world track and field championships in Paris. White, who stands to lose her gold medals from the women's 100 and 200 metres, claimed she was using the medication to treat narcolepsy, which is characterized by sudden and uncontrollable episodes of deep sleep. But top anti-doping officials say the rash of positive tests - sprinter Chryste Gaines is the fourth American reported to have tested positive for it - demonstrates that athletes are using modafinil as a stimulant. Track officials say there have been as many as seven positive tests for the drug. "All the athletes can't be narcoleptic and have a sleep problem," said Dr. Christiane Ayotte of the IOC-accredited testing laboratory in Montreal. "This is enough now. They thought they had a stimulant that was not detectable and was not being tested by the lab." Ayotte said the first positive modafinil finding was made in the Paris lab during the world championships because of pressure applied by the French government to test for such substances. Modafinil was not officially listed as a banned substance, but is considered a "like substance" in the banned stimulant category. Dr. Leonid Kayumov, professor of psychiatry at the University of Toronto and director of the sleep disorders clinic at Toronto Western Hospital, said modafinil has proved to be a good treatment for narcolepsy because it has fewer side effects than previously used medications. He said it would likely improve motor skills and motor reaction if taken by a healthy athlete. "It has an alerting effect, a boosting of energy," Kayumov said. "It has a life of about 10 hours and then it would be eliminated from the bloodstream. It's very disconcerting that people in sport would take this. It's inappropriate." Kayumov also finds it hard to believe someone could be narcoleptic and a world-class athlete. "It's (the disease) incompatible with sport," he said. Modafinil is a controlled substance both here and in the U.S. and illegal to distribute without a prescription. Under present rules, a positive test calls for disqualification from the event but no additional ban, meaning the athletes can compete at next year's Athens Olympics. The four reported positives for the drug include Alvin Harrison, an Olympic and world gold medallist in the men's 4x400-metre relay, and Chris Phillips, who tested positive after finishing fifth in the men's 110-metre hurdles at Paris. White, Gaines and Phillips are coached by 71-year-old Ukrainian Remy Korchemney, who is associated with Victor Conte, owner of Balco Laboratories, which is the subject of a U.S. federal grand jury investigation. LOAD-DATE: October 29, 2003 LANGUAGE: ENGLISH Copyright 2003 Toronto Star Newspapers, Ltd. 690 of 998 DOCUMENTS USA TODAY October 29, 2003, Wednesday, FINAL EDITION Developments come quick in drug issue BYLINE: Dick Patrick SECTION: SPORTS; Pg. 10C LENGTH: 424 words The drugs in sport issue continued on different fronts Tuesday. In a Senate Commerce Committee hearing, chairman John McCain (R-Ariz.) was disturbed over a statistic cited in a hearing on a bill seeking to reclassify the popular steroid precursor androstenedione, which is banned by the Olympics, the NFL and NCAA but is available over the counter in the USA. The CEO of the U.S. Anti-Doping Agency, Terry Madden, reported a study of 624 dietary supplements determined that 41% of the products by U.S. companies contained either a steroid precursor or banned substance not disclosed on the label. "It's very worrisome to athletes," Madden told McCain. Meanwhile, the list of U.S. track athletes with positive drug tests grew. Sprinter Chryste Gaines and 400-meter hurdlers Sandra Glover and Eric Thomas have tested positive for the stimulant modafinil, according to the Los Angeles Times and Washington Post. The penalty for modafinil calls for disqualification from the meet in which the violation occurs but carries no further competition ban. If Glover and Thomas don't win appeals, they'll lose titles won at June's USA Track & Field Championships. U.S. sprinter Calvin Harrison has acknowledged a positive test for modafinil, and officials from the international track federation (IAAF) have indicated there could be six to eight U.S. positives from re-evaluations of drug tests at the U.S. championships. In August's world track and field championships, sprinter Kelli White and hurdler Chris Phillips, both Americans, tested positive for modafinil. White, who says it was prescribed for the sleep disorder narcolepsy, faces loss of her 100- and 200-meter titles. There are connections between some of the modafinil-positive athletes, including White, and the man being investigated by a federal grand jury for his activities at BALCO Laboratories. USADA has linked BALCO owner Victor Conte to the designer steroid THG, undetectable until recently when it resulted in at least five positive tests, four from Americans. Conte denies he's the source of THG and also contends THG is not a steroid. The search for THG keeps expanding. The world swimming federation (FINA) plans to retest hundreds of urine samples from July's world championships. The IAAF and the NFL already said they would retest. Another link is Remi Korchemny, who coaches White, Gaines, THG-positive British sprinter Dwain Chambers and Phillips. The IAAF has revived talk of suspending coaches found to promote drug use. LOAD-DATE: October 29, 2003 LANGUAGE: ENGLISH GRAPHIC: PHOTO, B/W, 2000 photo by Jack Gruber, USA TODAY; Troubling trend: Hurdler Eric Thomas and two other U.S. athletes are the latest to test positive for modafinil, a stimulant. The penalty for using modafinil does not include suspension. Copyright 2003 Gannett Company, Inc. 691 of 998 DOCUMENTS Agence France Presse -- English October 28, 2003 Tuesday Reports say Gaines among US modafinil dope positives SECTION: Sports LENGTH: 525 words DATELINE: LOS ANGELES, Oct 28 Olympic gold medal winner Chryste Gaines is among three athletes who tested positive for the banned stimulant modafinil at June's United States athletics championship, according to US newspaper reports. The Los Angeles Times and Washington Post, both citing unnamed sources, reported Tuesday that Gaines, a member of the triumphant US 4x100m relay at the 1996 Olympics, failed a doping test at the US meet. Sandra Glover, a four-time US champion in the 400m hurdles and runner-up in August at the World Championship in Paris, and Eric Thomas, the reigning US 400 hurdles champion, also tested positive at the US meet, the Times reported. At least six US athletes are believed to have tested positive for modafinil, with 2000 Olympic triumphant US 4x400 relay member Calvin Harrison admitting a positive test for a substance, used to combat the sleep disorder narcolepsy. A drug scandal has swirled around US athletics since United States Anti-Doping Agency chief executive Terry Madden disclosed that a designer steroid, tetrahydrogestrinone (THG), was being taken by US athletes. Madden linked the previously undectable substance to BALCO Labs, a nutritional supplement firm near San Francisco run by Victor Conte, who has denied wrongdoing. Harrison's positive test for modafinil touched off yet another firestorm over modafinil a key figure being Ukranian-born coach Remi Korchemny, also living in the San Francisco area. Gaines became the fourth athlete with ties to Korchemny to test positive for banned drugs this summer, following US sprinter Kelli White, hurdler Chris Phillips and British sprinter Dwain Chambers, the Post reported. "If it is proven that this coach was offering anything that is not a permissible substance to athletes, that is the biggest concern to the IAAF," Istvan Gyulai, general secretary for the world governing body, told the Post. Chambers, Gaines and White train with Korchemny. Robert Wagner, the agent for Phillips and White, told the Post that Korchemny gave Phillips a modafinil pill before the 110m semi-finals at the world championships in Paris because he was having trouble sleeping. Korchemny told the Post he gave Phillips modafinil and White also. "I'm sorry I did it ... but it was not prohibited," Korchemny told the Post. "I was 100 percent sure everything was legal." Korchemny said he knew nothing about Chambers' arrangements with BALCO for supplements and that he did not give Gaines modafinil, adding, "She is my student, but I don't know anything about her." Modafinil was not banned until after the world championships but comes under anti-doping jurisdictions, drug-test officials told the Post, because of rule provisions regarding substances closely related to banned drugs. "They were all under the impression modafinil was OK," Wagner told the Post. US athletics officials say four Americans would join Chambers with positive doping tests for THG. Various US newspaper accounts have identified three of them as middle-distance runner Regina Jacobs, US shot put champion Kevin Toth and hammer thrower John McEwan. js/ea03 Athletics-USA-doping LOAD-DATE: October 29, 2003 LANGUAGE: ENGLISH Copyright 2003 Agence France Presse 692 of 998 DOCUMENTS Alameda Times-Star (Alameda, CA) October 28, 2003 Tuesday Hot Gordon grabs second win in row BYLINE: WIRE REPORTS SECTION: SPORTS NEWS & COLUMNS LENGTH: 809 words Jeff Gordon is back to his old winning ways, holding off a challenge from Tony Stewart on Monday at Atlanta Motor Speedway to earn his second straight victory. The Bass Pro Shops MBNA 500, halted by rain Sunday after just 39 of 325 laps, was completed Monday under a caution after pole-winner Ryan Newman was sent spinning into the wall with a tap on the rear bumper by Dale Earnhardt Jr. four laps from the end. Gordon had gone 22 races without a win before taking the checkered flag Oct.19 at Martinsville. The four-time Winston Cup champion now has three wins this season and 64 in his career. "Never count us out," Gordon said. "I know we haven't won a lot this year, but we're strong finishers." The two latest wins followed four straight fifth-place finishes and have helped Gordon move to fifth in the season points, only 38 points behind third-place Kevin Harvick. On Monday, Gordon passed six-time Atlanta winner Bobby Labonte for the lead on lap 277 and stayed out front the rest of the way to earn his second victory in as many weeks. Jimmie Johnson, who finished second to his car owner and Hendrick Motorsports teammate at Martinsville, was third. He was followed by Bill Elliott and Labonte, who faded after the final pit stops. Series leader Matt Kenseth, who came into the race with a 240-point lead over Harvick, finished 11th. Earnhardt's sixth-place finish Monday, combined with a 20th-place run by Harvick, moved Earnhardt to second in the points race. TRACK AND FIELD Two drugs under scrutiny in sports -- modafinil and THG -- are part of a pattern of doping abuse in the United States, a top track and field executive said. Arne Ljungqvist, the IAAF's medical commission chief, said the evidence suggests a link between the substances. Modafinil is the drug sprinter Kelli White of Union City says she took for a sleep disorder. Tetrahydrogestrinone, or THG, is a previously undetectable designer steroid that has turned up in the samples of several track and field athletes. The Washington Post, citing unidentified international sources with knowledge of the results, reported on its Web site Monday night that former Stanford sprinter Chryste Gaines tested positive for modafinil at the U.S. track and field championships in July. "What emerges now is a pattern," Ljungqvist told The Associated Press by phone from Sweden. "People have taken THG for obvious reasons -- it's been designed with the intent not to be discovered. "And modafinil seems to have become a fashionable stimulant among certain athletes as well. It's a pattern I've seen before, where drugs have become popular and we find them." FOOTBALL Florida State moved to the top of the one-loss crowd. The Seminoles are third in the new Bowl Championship Series standings, trailing only unbeaten Oklahoma and Miami in the race to play for the national championship. Southern California, third in both the AP and coaches polls, is fourth in the BCS standings, followed by Georgia and Ohio State. Georgia cornerback Decory Bryant had neck surgery Sunday morning that will end his season and leaves his NFL future in doubt, the seventh starter or top backup lost to a season-ending injury for the Bulldogs this season. SOCCER Mia Hamm, Joy Fawcett and Shannon Boxx, all World Cup all-stars, were selected to the U.S. team that will play Mexico on Sunday at the Cotton Bowl. U.S. coach April Heinrichs chose 19 players as the national team wraps up a 2003 season in which it has a 16-2-4 record and finished third at the World Cup. Among the others chosen by Heinrichs were defender Brandi Chastain, goalkeepers Brianna Scurry and Siri Mullinix; defender Danielle Slaton of Santa Clara; midfielder Tiffany Roberts of San Ramon and Aly Wagner from Santa Clara. Mexico's popular Chivas team and Major League Soccer reached an agreement in principal for the Gudalajara-based team to acquire an expansion franchise. Chivas, one of Mexico's most popular clubs, probably won't operate the team until 2005. MLS and Chivas officials are leaning toward putting the team in San Diego. TENNIS Albert Costa of Spain defeated Mariano Zabaleta of Argentina 6-7 [4], 6-4, 7-5 to reach the second round of the Paris Masters. BOXING Former lightweight champion Paul Spadafora was arraigned in Pittsburgh on Monday on charges of attempted homicide and aggravated assault for allegedly shooting his girlfriend after an argument over flat tires. HOCKEY Marc Savard and Jeff Cowan scored 24 seconds apart in the third period, and Savard scored again with 15 seconds left in overtime as the Atlanta Thrashers rallied for a 3-2 victory over host Toronto. John LeClair had a goal and an assist in his first game of the season, and Robert Esche earned his sixth career shutout, leading Philadelphia to a 5-0 win over visiting Montreal. LOAD-DATE: October 28, 2003 LANGUAGE: ENGLISH Copyright 2003 MediaNews Group, Inc. and ANG Newspapers 693 of 998 DOCUMENTS The Associated Press October 28, 2003, Tuesday, BC cycle AP Interview: Top track official sees pattern of doping abuse BYLINE: By STEPHEN WILSON, AP Sports Writer SECTION: Sports News LENGTH: 575 words DATELINE: LONDON Two drugs under scrutiny in sports - modafinil and THG - are part of a pattern of doping abuse in the United States, a top track and field executive said Monday. Arne Ljungqvist, the IAAF's medical commission chief, said the evidence suggests a link between the substances. Modafinil is the drug sprinter Kelli White says she took for a sleep disorder. Tetrahydrogestrinone, or THG, is a previously undetectable designer steroid that has turned up in the samples of several track and field athletes. "What emerges now is a pattern," Ljungqvist told The Associated Press by phone from Sweden. "People have taken THG for obvious reasons - it's been designed with the intent not to be discovered. "And modafinil seems to have become a fashionable stimulant among certain athletes as well. It's a pattern I've seen before, where drugs have become popular and we find them." The Washington Post, citing unidentified international sources, reported Tuesday that American sprinter Chryste Gaines tested positive for modafinil at the U.S. track and field championships in July. The Los Angeles Times also cited Gaines along with hurdlers Sandra Glover and Eric Thomas as testing positive for modafinil. The Times based its report on unidentified sources. Calvin Harrison, an Olympic and world relay gold medalist, also tested positive for the stimulant this past summer, a source close to a U.S. doping investigation, told the AP on Saturday on condition of anonymity. Harrison, still awaiting the result of his backup B sample, was tested at the U.S. national championships in June at Stanford, Calif. Modafinil first came to prominence in August when White tested positive for the drug at the world championships in Paris. She stands to be stripped of her 100-meter and 200 titles. White said she took modafinil on prescription from her personal doctor to combat narcolepsy. The International Association of Athletics Federations charged her with a doping offense and submitted her case to U.S. authorities for disciplinary action. Another U.S. athlete, Chris Phillips, who finished fifth in the 110 hurdles at the worlds, also tested positive for modafinil at the Paris meet. Harrison ran the opening leg of the 1,600 relay at the worlds. Ljungqvist said the IAAF's penalty for modafinil is a public warning and disqualification from the competition where the test took place - but no ban. Samples from the U.S. championships were retested after the UCLA doping control laboratory, acting on a tip, devised a test for THG. While retesting, U.S. officials discovered several positives for modafinil. Ljungqvist said the IAAF had been "directly or indirectly" informed of six to eight modafinil cases. Referring to White's narcolepsy defense, he said: "It comes into a different sort of light when it becomes known that modafinil has been taken by a number of athletes." On another drug issue, Ljungqvist said USA Track & Field still has not provided the required documents on Jerome Young's 1999 positive steroid test - a case that could cost the United States an Olympic relay gold medal. Ljungqvist set a deadline of Nov. 21 for USATF to comply. Young tested positive for the steroid nandrolone but was cleared on appeal by USATF officials. He went on to win a 1,600 relay gold medal at the 2000 Olympics. USATF officials have declined to provide the information, citing confidentiality rules at the time. LOAD-DATE: October 29, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 694 of 998 DOCUMENTS The Associated Press October 28, 2003, Tuesday, BC cycle IAAF to go after coaches in modafinil cases BYLINE: By STEPHEN WILSON, AP Sports Writer SECTION: Sports News LENGTH: 613 words DATELINE: LONDON Track and field's world governing body plans to punish any coaches directly connected to the spate of positive tests among U.S. athletes for the stimulant modafinil. Six Americans have been identified as testing positive for the substance, which is prescribed for treatment of the sleeping disorder narcolepsy. Istvan Gyulai, general secretary of the International Association of Athletics Federations, said Tuesday that any coaches or trainers involved in the use of modafinil should face sanctions. "If it proved that they incite or promote the use of drugs or substances which are not permitted, they are considered to have committed a doping offense themselves," he told The Associated Press in a telephone interview. "This has to be investigated," Gyulai added. "We cannot just turn a blind eye to this." IAAF rules do not specify penalties for non-athletes in doping cases. But Gyulai said the IAAF could consider banning a coach or refusing accreditation for major events. Three more U.S. athletes were cited in newspaper reports Tuesday for positive modafinil tests. The Washington Post, citing unidentified sources, reported that sprinter Chryste Gaines - a relay gold medalist at the 1996 Olympics -tested positive at the U.S. championships in Stanford, Calif., in July. The Los Angeles Times, citing unnamed sources, said hurdlers Sandra Glover and Eric Thomas also tested positive for the drug. Calvin Harrison, an Olympic and world relay gold medalist, had previously confirmed he tested positive for modafinil at the U.S. meet. Sprinter Kelli White and hurdler Chris Phillips tested positive at the World Championships. White, who said she took modafinil for narcolepsy, risks losing her gold medals from the 100 and 200 meters. Modafinil wasn't named on the sport's banned drug list, but the IAAF said it fell under the category of related substances and classified as a "minor stimulant." It has since been placed by name on the World Anti-Doping Agency's banned list. Gyulai said it's possible the athletes all believed modafinil wasn't prohibited. "This is an option, but it has been determined that it is a stimulant and was a stimulant at the time as well," he said. "It's up to USA Track & Field to take the necessary action." The IAAF's penalty for use of minor stimulants is a public warning and disqualification from the event where the test took place - but no ban. Some of the athletes have been coached by Ukrainian-born coach Remi Korchemny, who is based in the San Francisco area. He did not return repeated messages left by the AP this week. Robert Wagner, the agent for White, Phillips and Glover, said Phillips told the IAAF that Korchemny gave him a modafinil tablet at the worlds because he was having trouble sleeping. "None of these athletes thought this was a prohibited substance, they were taking it all summer," Wagner told the AP by telephone from Austria. "It's like melatonin. When Americans come to Europe, they take it to get over the jet lag. It's not a stimulant. It wasn't on the list." Gyulai stressed that modafinil should not be viewed in the same light as the designer steroid THG, which has turned up in the samples of several track and field athletes. The sanction for steroids is a two-year ban. "THG was invented, produced and masterminded to cheat," Gyulai said. "There is a major difference with modafinil. The athletes may have thought this is not forbidden. They should have checked more carefully." Gyulai said he had read or heard reports of a total of seven modafinil cases, but stressed the IAAF had received no official notification of the tests or names involved. LOAD-DATE: October 29, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 695 of 998 DOCUMENTS Associated Press Worldstream October 28, 2003 Tuesday IAAF to go after coaches in modafinil cases BYLINE: STEPHEN WILSON; AP Sports Writer SECTION: SPORTS LENGTH: 710 words DATELINE: LONDON Track and field's world governing body plans to punish any coaches directly connected to the spate of positive tests among U.S. athletes for the stimulant modafinil. Six Americans have been identified as testing positive for the substance, which is prescribed for treatment of the sleeping disorder narcolepsy. Some of the athletes have been coached by Ukrainian-born coach Remi Korchemny, who is based in the San Francisco area. Istvan Gyulai, general secretary of the International Association of Athletics Federations, said Tuesday that any coaches or trainers involved in the use of modafinil should face sanctions. "If it proved that they incite or promote the use of drugs or substances which are not permitted, they are considered to have committed a doping offense themselves," he told The Associated Press in a telephone interview. "This has to be investigated," Gyulai added. "We cannot just turn a blind eye to this." IAAF rules do not specify penalties for non-athletes in doping cases. But Gyulai said the IAAF could consider banning a coach or refusing accreditation for major events. Three more U.S. athletes were cited in newspaper reports Tuesday for positive modafinil tests. The Washington Post, citing unidentified international sources, reported that sprinter Chryste Gaines - a relay gold medalist at the 1996 Olympics -tested positive at the U.S. championships in Stanford in July. The Los Angeles Times also cited Gaines along with hurdlers Sandra Glover and Eric Thomas. The Times based its report on unidentified sources. Glover is a four-time U.S. champ in the 400 hurdles and won the silver medal at the World Championships in Paris in August. Thomas is the U.S. men's 400 hurdles champion. He did not win a medal in Paris. Calvin Harrison, an Olympic and world relay gold medalist, had previously confirmed that he tested positive for modafinil at the U.S. meet. Sprinter Kelli White and hurdler Chris Phillips tested positive at the World Championships. White, who said she took modafinil for narcolepsy, risks losing her gold medals from the 100 and 200 meters. Modafinil wasn't named on the sport's banned drug list, but the IAAF said it fell under the category of related substances and classified as a "minor stimulant." It has since been placed by name on the World Anti-Doping Agency's banned list. Gyulai said it's possible the athletes all believed modafinil wasn't prohibited. "This is an option, but it has been determined that it is a stimulant and was a stimulant at the time as well," he said. "It's up to USA Track & Field to take the necessary action." The IAAF's penalty for use of minor stimulants is a public warning and disqualification from the event where the test took place - but no ban. Gyulai reiterated the IAAF's position that athletes who tested positive for modafinil at the U.S. championships remained eligible for the world meet. Robert Wagner, the agent for White, Phillips and Glover, said Phillips told the IAAF that Korchemny gave him a modafinil tablet at the worlds because he was having trouble sleeping. "None of these athletes thought this was a prohibited substance, they were taking it all summer," Wagner told the AP by telephone from Austria. "It's like melatonin. When Americans come to Europe, they take it to get over the jet lag. It's not a stimulant. It wasn't on the list. Why weren't all the labs testing for it?" Gyulai stressed that modafinil should not be viewed in the same light as the designer steroid THG, which has turned up in the samples of several track and field athletes. The sanction for steroids is a two-year ban. Urine samples from the U.S. championships were retested after the UCLA doping control laboratory, acting on a tip, devised a test for THG. While retesting, U.S. officials discovered several modafinil cases as well as four THG positives. "THG was invented, produced and masterminded to cheat," Gyulai said. "There is a major difference with modafinil. The athletes may have thought this is not forbidden. They should have checked more carefully." Gyulai said he had read or heard reports of a total of seven modafinil cases, but stressed the IAAF had received no official notification of the tests or names involved. LOAD-DATE: October 29, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 696 of 998 DOCUMENTS The Associated Press State & Local Wire October 28, 2003, Tuesday, BC cycle IAAF to go after coaches in modafinil cases BYLINE: By STEPHEN WILSON, AP Sports Writer SECTION: Sports News LENGTH: 613 words DATELINE: LONDON Track and field's world governing body plans to punish any coaches directly connected to the spate of positive tests among U.S. athletes for the stimulant modafinil. Six Americans have been identified as testing positive for the substance, which is prescribed for treatment of the sleeping disorder narcolepsy. Istvan Gyulai, general secretary of the International Association of Athletics Federations, said Tuesday that any coaches or trainers involved in the use of modafinil should face sanctions. "If it proved that they incite or promote the use of drugs or substances which are not permitted, they are considered to have committed a doping offense themselves," he told The Associated Press in a telephone interview. "This has to be investigated," Gyulai added. "We cannot just turn a blind eye to this." IAAF rules do not specify penalties for non-athletes in doping cases. But Gyulai said the IAAF could consider banning a coach or refusing accreditation for major events. Three more U.S. athletes were cited in newspaper reports Tuesday for positive modafinil tests. The Washington Post, citing unidentified sources, reported that sprinter Chryste Gaines - a relay gold medalist at the 1996 Olympics - tested positive at the U.S. championships in Stanford, Calif., in July. The Los Angeles Times, citing unnamed sources, said hurdlers Sandra Glover and Eric Thomas also tested positive for the drug. Calvin Harrison, an Olympic and world relay gold medalist, had previously confirmed he tested positive for modafinil at the U.S. meet. Sprinter Kelli White and hurdler Chris Phillips tested positive at the World Championships. White, who said she took modafinil for narcolepsy, risks losing her gold medals from the 100 and 200 meters. Modafinil wasn't named on the sport's banned drug list, but the IAAF said it fell under the category of related substances and classified as a "minor stimulant." It has since been placed by name on the World Anti-Doping Agency's banned list. Gyulai said it's possible the athletes all believed modafinil wasn't prohibited. "This is an option, but it has been determined that it is a stimulant and was a stimulant at the time as well," he said. "It's up to USA Track & Field to take the necessary action." The IAAF's penalty for use of minor stimulants is a public warning and disqualification from the event where the test took place - but no ban. Some of the athletes have been coached by Ukrainian-born coach Remi Korchemny, who is based in Castro Valley, Calif. He did not return repeated messages left by the AP this week. Robert Wagner, the agent for White, Phillips and Glover, said Phillips told the IAAF that Korchemny gave him a modafinil tablet at the worlds because he was having trouble sleeping. "None of these athletes thought this was a prohibited substance, they were taking it all summer," Wagner told the AP by telephone from Austria. "It's like melatonin. When Americans come to Europe, they take it to get over the jet lag. It's not a stimulant. It wasn't on the list." Gyulai stressed that modafinil should not be viewed in the same light as the designer steroid THG, which has turned up in the samples of several track and field athletes. The sanction for steroids is a two-year ban. "THG was invented, produced and masterminded to cheat," Gyulai said. "There is a major difference with modafinil. The athletes may have thought this is not forbidden. They should have checked more carefully." Gyulai said he had read or heard reports of a total of seven modafinil cases, but stressed the IAAF had received no official notification of the tests or names involved. LOAD-DATE: October 29, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 697 of 998 DOCUMENTS Associated Press Online October 28, 2003 Tuesday AP Interview: Track Head Discusses Doping BYLINE: STEPHEN WILSON; AP Sports Writer SECTION: SPORTS LENGTH: 610 words DATELINE: LONDON Track and field's world governing body plans to punish any coaches directly connected to the spate of positive tests among U.S. athletes for the stimulant modafinil. Six Americans have been identified as testing positive for the substance, which is prescribed for treatment of the sleeping disorder narcolepsy. Istvan Gyulai, general secretary of the International Association of Athletics Federations, said Tuesday that any coaches or trainers involved in the use of modafinil should face sanctions. "If it proved that they incite or promote the use of drugs or substances which are not permitted, they are considered to have committed a doping offense themselves," he told The Associated Press in a telephone interview. "This has to be investigated," Gyulai added. "We cannot just turn a blind eye to this." IAAF rules do not specify penalties for non-athletes in doping cases. But Gyulai said the IAAF could consider banning a coach or refusing accreditation for major events. Three more U.S. athletes were cited in newspaper reports Tuesday for positive modafinil tests. The Washington Post, citing unidentified sources, reported that sprinter Chryste Gaines - a relay gold medalist at the 1996 Olympics -tested positive at the U.S. championships in Stanford, Calif., in July. The Los Angeles Times, citing unnamed sources, said hurdlers Sandra Glover and Eric Thomas also tested positive for the drug. Calvin Harrison, an Olympic and world relay gold medalist, had previously confirmed he tested positive for modafinil at the U.S. meet. Sprinter Kelli White and hurdler Chris Phillips tested positive at the World Championships. White, who said she took modafinil for narcolepsy, risks losing her gold medals from the 100 and 200 meters. Modafinil wasn't named on the sport's banned drug list, but the IAAF said it fell under the category of related substances and classified as a "minor stimulant." It has since been placed by name on the World Anti-Doping Agency's banned list. Gyulai said it's possible the athletes all believed modafinil wasn't prohibited. "This is an option, but it has been determined that it is a stimulant and was a stimulant at the time as well," he said. "It's up to USA Track & Field to take the necessary action." The IAAF's penalty for use of minor stimulants is a public warning and disqualification from the event where the test took place - but no ban. Some of the athletes have been coached by Ukrainian-born coach Remi Korchemny, who is based in the San Francisco area. He did not return repeated messages left by the AP this week. Robert Wagner, the agent for White, Phillips and Glover, said Phillips told the IAAF that Korchemny gave him a modafinil tablet at the worlds because he was having trouble sleeping. "None of these athletes thought this was a prohibited substance, they were taking it all summer," Wagner told the AP by telephone from Austria. "It's like melatonin. When Americans come to Europe, they take it to get over the jet lag. It's not a stimulant. It wasn't on the list." Gyulai stressed that modafinil should not be viewed in the same light as the designer steroid THG, which has turned up in the samples of several track and field athletes. The sanction for steroids is a two-year ban. "THG was invented, produced and masterminded to cheat," Gyulai said. "There is a major difference with modafinil. The athletes may have thought this is not forbidden. They should have checked more carefully." Gyulai said he had read or heard reports of a total of seven modafinil cases, but stressed the IAAF had received no official notification of the tests or names involved. LOAD-DATE: October 29, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 698 of 998 DOCUMENTS Calgary Herald (Alberta, Canada) October 28, 2003 Tuesday Final Edition Track official detects pattern in doping tests SOURCE: The Associated Press SECTION: Sports; Pg. F4 LENGTH: 167 words DATELINE: LONDON Two drugs under scrutiny in sports -- modafinil and THG -- are part of a pattern of doping abuse in the United States, a top track and field executive said Monday. Arne Ljungqvist, the IAAF's medical commission chief, said the evidence suggests a link between the substances. Modafinil is the drug sprinter Kelli White says she took for a sleep disorder. Tetrahydrogestrinone, or THG, is a previously undetectable designer steroid that has turned up in the samples of several track and field athletes. "What emerges now is a pattern," Ljungqvist said via phone from Sweden. "People have taken THG for obvious reasons -- it's been designed with the intent not to be discovered. "And modafinil seems to have become a fashionable stimulant among certain athletes as well. It's a pattern I've seen before, where drugs have become popular and we find them." Ljungqvist spoke after 400-metre runner Calvin Harrison became the latest athlete identified as having tested positive for modafinil. LOAD-DATE: October 28, 2003 LANGUAGE: ENGLISH TYPE: Sports Copyright 2003 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 699 of 998 DOCUMENTS Edmonton Journal (Alberta) October 28, 2003 Tuesday Final Edition Narcolepsy the new excuse for drug use among athletes: Narcolepsy drug has ties with designer steroid SOURCE: The Associated Press SECTION: Sports; Pg. D4 LENGTH: 417 words DATELINE: LONDON LONDON - Two drugs under scrutiny in sports -- modafinil and THG -- are part of a pattern of doping abuse in the United States, a top track and field executive said Monday. Arne Ljungqvist, medical commission chief of track and field's governing body, said the evidence suggests a link between the substances. Modafinil is the drug sprinter Kelli White says she took for a sleep disorder. Tetrahydrogestrinone, or THG, is a previously undetectable designer steroid that has turned up in the samples of several track and field athletes. "What emerges now is a pattern," Ljungqvist said via phone from Sweden. "People have taken THG for obvious reasons -- it's been designed with the intent not to be discovered. "And modafinil seems to have become a fashionable stimulant among certain athletes as well. It's a pattern I've seen before, where drugs have become popular and we find them." Ljungqvist spoke after 400-metre runner Calvin Harrison became the latest athlete identified as having tested positive for modafinil. Harrison, an Olympic and world relay gold medallist, tested positive for modafinil this past summer, according to an anonymous source. Harrison, still awaiting the result of his backup B sample, was tested at the U.S. national championships in June at Stanford, Calif. Modafinil first came to prominence in August when White tested positive for the drug at the World Championships in Paris. She stands to be stripped of her 100- and 200-metre titles. White said she took modafinil on prescription from her personal doctor to combat narcolepsy. The International Association of Athletics Federations charged her with a doping offence and submitted her case to U.S. authorities for disciplinary action. The drug has become the "fashionable" stimulant of choice among certain American athletes, track and field's top anti-doping official said Monday. "It's a little odd to find an epidemic of narcolepsy in top athletes," said Ljungqvist. "The disorder of narcolepsy is not that frequent." Another U.S. athlete, Chris Phillips, who finished fifth in the 110-metre hurdles at the Worlds, also tested positive for modafinil at the Paris meet. Ljungqvist said the IAAF's penalty for modafinil is a public warning and disqualification from the competition where the test took place -- but no ban. Referring to White's narcolepsy defence, he said: "It comes into a different sort of light when it becomes known that modafinil has been taken by a number of athletes." LOAD-DATE: October 28, 2003 LANGUAGE: ENGLISH TYPE: News Copyright 2003 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 700 of 998 DOCUMENTS Hamilton Spectator (Ontario, Canada) October 28, 2003 Tuesday Final Edition Drug use ridiculed; Claims modafinil taken to combat narcolepsy SOURCE: The Canadian Press BYLINE: Stephen Wilson SECTION: SPORTS; Pg. SP09 LENGTH: 487 words DATELINE: LONDON Modafinil, the drug which sprinter Kelli White claims she took for a sleep disorder, has become the "fashionable" stimulant of choice among certain American athletes, track and field's top anti-doping official said yesterday. "It's a little odd to find an epidemic of narcolepsy in top athletes," said Arne Ljungqvist, medical commission chief of track and field's governing body. "The disorder of narcolepsy is not that frequent." Ljungqvist spoke after 400-metre runner Calvin Harrison became the latest athlete identified as having tested positive for the drug. In an interview with The Associated Press, Ljungqvist said a spate of positive tests for modafinil suggests the substance is part of a pattern of doping abuse in the United States along with the designer steroid THG. On another drug issue, Ljungqvist said USA Track & Field still has not provided the required documents on Jerome Young's 1999 positive steroid test -- a case which could cost the U.S. an Olympic relay gold medal. Ljungqvist set a deadline of Nov. 21 for the U.S. association to comply. Harrison, an Olympic and world relay gold medallist, tested positive for modafinil last summer, a source told the AP on Saturday. Harrison, still awaiting the result of his backup B sample, was tested at the U.S. national championships in June at Stanford. Modafinil first came to prominence in August when White tested positive for the drug at the world championships in Paris. She stands to be stripped of her 100-metre and 200-metre titles. White said she took modafinil on prescription from her personal doctor to combat narcolepsy. The International Association of Athletics Federations charged her with a doping offence and submitted her case to U.S. authorities for disciplinary action. Another U.S. athlete, Chris Phillips, who finished fifth in 110-metre hurdles at the worlds, also tested positive for modafinil at the Paris meet. Harrison ran the opening leg of the 1,600-relay at the world championships. Ljungqvist disputed reports that Harrison's relay gold could be stripped because of his positive test in June. He said IAAF's penalty for modafinil is a public warning and disqualification from the competition where the test took place -- but no ban. "He was eligible in our rules for the world championships," Ljungqvist said. Samples from the U.S. championships were retested after the UCLA doping control laboratory, acting on a tip-off, devised a test for the previously unknown and undetectable steroid tetrahydrogestrinone, or THG. While retesting for THG, U.S. officials discovered several positives for modafinil.Ljungqvist said the IAAF had been "directly or indirectly" informed of between six and eight modafinil cases. Referring to White's narcolepsy defence, he said, "It comes into a different sort of light when it becomes known that modafinil has been taken by a number of athletes." LOAD-DATE: October 28, 2003 LANGUAGE: ENGLISH GRAPHIC: Photo: Paul Sakuma, the Associated Press; Victor Conte has been accused of supplying athletes a new designer drug that's rocked track and field world. TYPE: News Copyright 2003 Metroland Media Group Ltd 701 of 998 DOCUMENTS The Independent (London) October 28, 2003, Tuesday ATHLETICS: MODAFINIL IS DRUG OF CHOICE, SAYS IAAF CHIEF BYLINE: MIKE ROWBOTTOM SECTION: SPORT; Pg. 26 LENGTH: 419 words MODAFINIL, THE drug which the world 100 metres champion, Kelli White, claims she took for a sleep disorder, has become the "fashionable" stimulant of choice among certain American athletes, the sport's top anti- doping official said yesterday. "It's a little odd to find an epidemic of narcolepsy in top athletes," Arne Ljungqvist, the head of the International Association of Athletics Federations' medical commission, said. "The disorder of narcolepsy is not that frequent." Ljungqvist was speaking after the American 400m runner Calvin Harrison became the latest athlete identified as having tested positive for the substance, although Harrison's comments about his case appeared to make it clear that the stimulant had not been recommended to him for any other reason than to keep him, in his own words, "up". The Olympic and world gold medallist, who has trained with Dwain Chambers in the group supervised by the Ukrainian coach, Remy Korchemny, confirmed he had tested positive for modafinil at this summer's American Championships. "I did have modafinil in my system," Harrison said. He added that he was given the substance by a coach in California, stressing that he had never been given an illegal substance by his current coach, Trevor Graham. "He the coach in California had given me this pill and I had taken it. He told me it was not a steroid and that it would just keep you up' so you wouldn't be so fatigued," Harrison said. "He emphasised that it was not on the banned substance list and assured me that it was not an illegal substance." Ljungqvist said a spate of positive tests for modafinil suggests the substance is part of a pattern of doping abuse in the United States along with the designer steroid THG. Chambers, who tested positive for THG at an out-of-competition sampling on 1 August, will find out within the next fortnight whether his test is confirmed through an analysis of the B sample. Three other US athletes have now been named as testing positive for THG but await B sample test results: Kevin Toth, the world's leading shot putter this year; Regina Jacobs, the 39-year-old who broke the world indoor 1500m record this year before beating Kelly Holmes to gold at the World Indoor Championships in Birmingham; and the hammer thrower John McEwen. Two other US athletes who have tested positive for THG have yet to be named. Ljungqvist said the IAAF had been "directly or indirectly" informed of between six and eight modafinil cases. LOAD-DATE: October 28, 2003 LANGUAGE: ENGLISH Copyright 2003 Independent Print Ltd 702 of 998 DOCUMENTS Times Colonist (Victoria, British Columbia) October 28, 2003 Tuesday Final Edition Anti-doping officials focus on modafinil SOURCE: Associated Press SECTION: Sports; Pg. C2 LENGTH: 566 words DATELINE: LONDON LONDON (AP) -- Modafinil, the drug which sprinter Kelli White claims she took for a sleep disorder, has become the "fashionable" stimulant of choice among certain American athletes, track and field's top anti-doping official said Monday. "It's a little odd to find an epidemic of narcolepsy in top athletes," said Arne Ljungqvist, medical commission chief of track and field's governing body. "The disorder of narcolepsy is not that frequent." Ljungqvist spoke after 400-metre runner Calvin Harrison became the latest athlete identified as having tested positive for the drug. In an interview with The Associated Press, Ljungqvist said a spate of positive tests for modafinil suggests the substance is part of a pattern of doping abuse in the United States along with the designer steroid THG. On another drug issue, Ljungqvist said USA Track & Field still has not provided the required documents on Jerome Young's 1999 positive steroid test -- a case which could cost the U.S. an Olympic relay gold medal. Ljungqvist set a deadline of Nov. 21 for the U.S. association to comply. Harrison, an Olympic and world relay gold medallist, tested positive for modafinil last summer, a source told the AP on Saturday. Harrison, still awaiting the result of his backup B sample, was tested at the U.S. national championships in June at Stanford. Modafinil first came to prominence in August when White tested positive for the drug at the world championships in Paris. She stands to be stripped of her 100-metre and 200-metre titles. White said she took modafinil on prescription from her personal doctor to combat narcolepsy. The International Association of Athletics Federations charged her with a doping offence and submitted her case to U.S. authorities for disciplinary action. Another U.S. athlete, Chris Phillips, who finished fifth in the 110-metre hurdles at the worlds, also tested positive for modafinil at the Paris meet. Harrison ran the opening leg of the 1,600-relay at the world championships. Ljungqvist disputed reports that Harrison's relay gold could be stripped because of his positive test in June. He said the IAAF's penalty for modafinil is a public warning and disqualification from the competition where the test took place -- but no ban. "He was eligible in our rules for the world championships," Ljungqvist said. Samples from the U.S. championships were retested after the UCLA doping control laboratory, acting on a tip-off, devised a test for the previously unknown and undetectable steroid tetrahydrogestrinone, or THG. While retesting for THG, U.S. officials discovered several positives for modafinil. Ljungqvist said the IAAF had been "directly or indirectly" informed of between six and eight modafinil cases. Referring to White's narcolepsy defence, he said, "It comes into a different sort of light when it becomes known that modafinil has been taken by a number of athletes." Ljungqvist, who is also head of the IOC's medical commission, said the evidence suggests a link between THG and modafinil. "What emerges now is a pattern," he said by phone from Sweden. "People have taken THG for obvious reasons -- it's been designed with the intent not to be discovered. And modafinil seems to have become a fashionable stimulant among certain athletes as well. It's a pattern I've seen before, where drugs have become popular and we find them." LOAD-DATE: October 28, 2003 LANGUAGE: ENGLISH TYPE: Sports Copyright 2003 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 703 of 998 DOCUMENTS The Times (London) October 28, 2003, Tuesday Harrison to keep medal despite his positive test BYLINE: Peter Nichols SECTION: Sport; 42 LENGTH: 246 words CALVIN HARRISON, the United States 400 metres runner who has admitted taking the stimulant modafinil, will not be stripped of his World Championships relay gold medal, according to Arne Ljungqvist, the head of the International Association of Athletics Federations (IAAF) Medical Commission. "He was eligible in our rules for the World Championships," Ljungqvist said. Ljungqvist was citing the rule that, for stimulants in modafinil's class, the athlete is disqualified from the competition only where the positive test has taken place and receives a public warning. Since Harrison's positive came from the re-test of samples taken at the US trials in California in June, IAAF sanctions, according to Ljungqvist's interpretation, allow him to be disqualified only from that championship. Representatives of the US Anti-Doping Agency that re-tested the samples would make no comment yesterday, but the ruling effectively undermines the re-analysis of samples for stimulants in the modafinil class because, in many cases, the only retrospective sanction available is a public warning. Nor will it seem like justice to Kelli White, the American who tested positive for modafinil at the World Championships in Paris. The ruling does allow White to be stripped of the 100 and 200 metres titles. To date, three athletes have tested positive for the drug: Harrison, White and Chris Phillips, who was fifth in the 110 metres hurdles in Paris. Debate, page 35 LOAD-DATE: October 28, 2003 LANGUAGE: ENGLISH Copyright 2003 Times Newspapers Limited 704 of 998 DOCUMENTS The Washington Post October 28, 2003 Tuesday Final Edition Gaines Took Banned Drug; She Is 4th Athlete Tied to Korchemny BYLINE: Amy Shipley, Washington Post Staff Writer SECTION: Sports; D01 LENGTH: 901 words U.S. sprinter Chryste Gaines, who trains with Ukrainian-born coach Remi Korchemny, tested positive for modafinil, a stimulant used to treat narcolepsy, at the U.S. Track and Field Championships in July, according to international officials with knowledge of the results. Gaines is the fourth athlete connected to Korchemny to test positive for banned drugs this summer. International Association of Athletics Federations General Secretary Istvan Gyulai called the matter a "concern" and said the IAAF planned to conduct an investigation. Gaines, fellow sprinter Kelli White and hurdler Chris Phillips, all U.S. athletes with ties to Korchemny, have tested positive for modafinil, a prescription drug said to promote wakefulness that is commonly used to treat sleep disorders. Another of Korchemny's athletes, British sprinter Dwain Chambers, tested positive for the designer steroid tetrahydrogestrinone (THG). "If it is proven that this coach was offering anything that is not a permissible substance to athletes, that is the biggest concern to the IAAF," Gyulai said yesterday. The developments are the latest in a drug scandal that has enveloped track and field since U.S. Anti-Doping Agency CEO Terry Madden publicly identified THG about 10 days ago, saying the steroid was part of a "conspiracy" among coaches, chemists and athletes to defraud the American public. IAAF rules permit -- but do not define -- sanctions against anyone who assists or incites a doping offense, Gyulai said. White, Gaines and Chambers train frequently with Korchemny in the San Francisco area. Phillips coaches himself, but he told the IAAF Korchemny gave him a modafinil pill before the 110-meter hurdle semifinals at the August world championships in Paris because he was having trouble sleeping, his agent Robert Wagner said yesterday. Phillips finished fifth in the final. Korchemny told The Post that he gave Phillips the modafinil, but only to resolve his sleeping problem, not for performance enhancement. He said he had one pill available because White had taken only one of the two she had at the world championships. Because modafinil is a Schedule IV controlled substance, it is illegal to distribute it without a prescription in the United States. "I had in my package one pill because Kelli took only one pill," Korchemny said. "I'm sorry I did it . . . but it was not prohibited [under anti-doping rules]. . . . I was 100 percent sure everything was legal." Korchemny said he did not give modafinil to Gaines. He said he did not know she had tested positive until informed by a reporter. "I don't know anything about her [case]," Korchemny said. "She is my student, but I don't know anything about her. I didn't give her" modafinil. Gaines and her agent, Renaldo Nehemiah, have not returned repeated phone messages in the last week. Modafinil, marketed under the name Provigil, was not officially banned until after the world championships, but drug-testing officials said it qualified as a banned drug because of a broad clause in the anti-doping rules prohibiting substances closely related to banned drugs. Wagner, who also represents White, said it was "ridiculous" that the IAAF would punish athletes for using substances not specifically banned. He said Phillips and White had no idea they were consuming prohibited substances. "The explanation Chris gave the IAAF was that Remi gave him a tablet in Paris because he had problems sleeping," Wagner said. " . . . Everybody is taking something to be alert and awake. . . . Some people drink five or six cups of coffee, others people take modafinil. They were all under the impression modafinil was okay." Chambers's lawyer, Graham Shear, alleged in a statement that Korchemny made all arrangements for Chambers's nutritional supplements through Bay Area Laboratory Co-Operative (BALCO) and that Chambers had no idea that he was taking a banned steroid when he consumed THG. Korchemny said last week that Chambers made his own supplement arrangements with BALCO and that he had never heard of THG before the positive tests were revealed about 10 days ago. After White tested positive for modafinil at the world championships, she said she took the stimulant to treat the sleep disorder narcolepsy. She said a sample of Provigil was given to her by her physician, Brian Goldman. She told The Post she was informed by the USADA that she also tested positive for the substance at the U.S. championships. If White is found guilty of a doping offense, she is subject to losing the four gold medals she won at both championships. USADA officials allege that BALCO is the source of the designer steroid THG, for which Chambers, middle-distance runner Regina Jacobs, U.S. shot put champion Kevin Toth and hammer thrower John McEwan have tested positive this summer. McEwan's positive was first reported by the Chicago Tribune. One unidentified U.S. track and field athlete has also tested positive for THG. BALCO is also the subject of a federal grand jury investigation. Noted BALCO clients including Barry Bonds, Jason Giambi, White and Toth have been subpoenaed to appear before the grand jury. USADA officials said several U.S. athletes tested positive for modafinil this summer, but declined to release their names. The positives were uncovered during re-testing of some 350 samples from the U.S. championships and about 200 additional out-of-competition tests. LOAD-DATE: October 28, 2003 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2003 The Washington Post 705 of 998 DOCUMENTS The Associated Press October 27, 2003, Monday, BC cycle AP Interview: Top track official sees pattern of doping abuse BYLINE: By STEPHEN WILSON, AP Sports Writer SECTION: Sports News LENGTH: 534 words DATELINE: LONDON Two drugs under scrutiny in sports - modafinil and THG - are part of a pattern of doping abuse in the United States, a top track and field executive said Monday. Arne Ljungqvist, the IAAF's medical commission chief, said the evidence suggests a link between the substances. Modafinil is the drug sprinter Kelli White says she took for a sleep disorder. Tetrahydrogestrinone, or THG, is a previously undetectable designer steroid that has turned up in the samples of several track and field athletes. "What emerges now is a pattern," Ljungqvist told The Associated Press by phone from Sweden. "People have taken THG for obvious reasons - it's been designed with the intent not to be discovered. "And modafinil seems to have become a fashionable stimulant among certain athletes as well. It's a pattern I've seen before, where drugs have become popular and we find them." Ljungqvist spoke after 400-meter runner Calvin Harrison became the latest athlete identified as having tested positive for modafinil. Harrison, an Olympic and world relay gold medalist, tested positive for modafinil this past summer, a source close to a U.S. doping investigation, told the AP on Saturday on condition of anonymity. Harrison, still awaiting the result of his backup B sample, was tested at the U.S. national championships in June at Stanford, Calif. Modafinil first came to prominence in August when White tested positive for the drug at the world championships in Paris. She stands to be stripped of her 100-meter and 200-meter titles. White said she took modafinil on prescription from her personal doctor to combat narcolepsy. The International Association of Athletics Federations charged her with a doping offense and submitted her case to U.S. authorities for disciplinary action. Another U.S. athlete, Chris Phillips, who finished fifth in the 110-meter hurdles at the worlds, also tested positive for modafinil at the Paris meet. Harrison ran the opening leg of the 1,600-relay at the worlds. Ljungqvist said the IAAF's penalty for modafinil is a public warning and disqualification from the competition where the test took place - but no ban. Samples from the U.S. championships were retested after the UCLA doping control laboratory, acting on a tip, devised a test for THG. While retesting, U.S. officials discovered several positives for modafinil. Ljungqvist said the IAAF had been "directly or indirectly" informed of six to eight modafinil cases. Referring to White's narcolepsy defense, he said: "It comes into a different sort of light when it becomes known that modafinil has been taken by a number of athletes." On another drug issue, Ljungqvist said USA Track & Field still has not provided the required documents on Jerome Young's 1999 positive steroid test - a case that could cost the United States an Olympic relay gold medal. Ljungqvist set a deadline of Nov. 21 for USATF to comply. Young tested positive for the steroid nandrolone but was cleared on appeal by USATF officials. He went on to win a 1,600-meter relay gold medal at the 2000 Olympics. USATF officials have declined to provide the information, citing confidentiality rules at the time. LOAD-DATE: October 28, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 706 of 998 DOCUMENTS Associated Press Worldstream October 27, 2003 Monday AP Interview: IAAF official scoffs at 'narcolepsy epidemic' BYLINE: STEPHEN WILSON; AP Sports Writer SECTION: SPORTS LENGTH: 736 words DATELINE: LONDON Modafinil, the drug which sprinter Kelli White claims she took for a sleep disorder, has become the "fashionable" stimulant of choice among certain American athletes, the sport's top anti-doping official said Monday. "It's a little odd to find an epidemic of narcolepsy in top athletes," said Arne Ljungqvist, medical commission chief of track and field's governing body. "The disorder of narcolepsy is not that frequent." Ljungqvist spoke after 400-meter runner Calvin Harrison became the latest athlete identified as having tested positive for the drug. In an interview with The Associated Press, Ljungqvist said a spate of positive tests for modafinil suggests the substance is part of a pattern of doping abuse in the United States along with the designer steroid THG. On another drug issue, Ljungqvist said USA Track & Field still has not provided the required documents on Jerome Young's 1999 positive steroid test - a case which could cost the United States an Olympic relay gold medal. Ljungqvist set a deadline of Nov. 21 for USATF to comply. Harrison, an Olympic and world relay gold medalist, tested positive for modafinil last summer, a source told the AP on Saturday. Harrison, still awaiting the result of his backup B sample, was tested at the U.S. national championships in June at Stanford. Modafinil first came to prominence in August when White tested positive for the drug at the World Championships in Paris. She stands to be stripped of her 100-meter and 200-meter titles. White said she took modafinil on prescription from her personal doctor to combat narcolepsy. The International Association of Athletics Federations charged her with a doping offense and submitted her case to U.S. authorities for disciplinary action. Another U.S. athlete, Chris Phillips, who finished fifth in the 110-meter hurdles at the worlds, also tested positive for modafinil at the Paris meet. Harrison ran the opening leg of the 1,600-relay at the World Championships. Ljungqvist disputed reports that Harrison's relay gold could be stripped because of his positive test in June. He said the IAAF's penalty for modafinil is a public warning and disqualification from the competition where the test took place - but no ban. "He was eligible in our rules for the World Championships," Ljungqvist said. Samples from the U.S. championships were retested after the UCLA doping control laboratory, acting on a tip-off, devised a test for the previously unknown and undetectable steroid tetrahydrogestrinone, or THG. While retesting for THG, U.S. officials discovered several positives for modafinil. Ljungqvist said the IAAF had been "directly or indirectly" informed of between six and eight modafinil cases. Referring to White's narcolepsy defense, he said, "It comes into a different sort of light when it becomes known that modafinil has been taken by a number of athletes." Ljungqvist, who is also head of the IOC's medical commission, said the evidence suggests a link between THG and modafinil. "What emerges now is a pattern," he said by phone from Sweden. "People have taken THG for obvious reasons - it's been designed with the intent not to be discovered. And modafinil seems to have become a fashionable stimulant among certain athletes as well. It's a pattern I've seen before, where drugs have become popular and we find them." Meanwhile, Ljungqvist said the IAAF has sent a second letter to USATF requesting explanation for Young's exoneration in 1999. Young tested positive for the steroid nandrolone, but was cleared on appeal by USATF officials and went on to win a 1,600-meter relay gold medal at the 2000 Sydney Olympics. The International Olympic Committee started disciplinary proceedings last month which could result in Young and the rest of the team losing the gold medal. USATF officials have declined to provide the information, citing confidentiality rules in place at the time and an arbitration court ruling upholding their right not to disclose details of 13 positive cases from 1996-2000. Ljungqvist said the IAAF had received some documents from the USOC but "one crucial piece" was still missing - a witness statement upon which the USATF appeals board based its decision to clear Young. The IAAF must have the information before the Nov. 21-23 meeting of its decision-making Council in Berlin or else "we will have a big new problem," Ljungqvist said. LOAD-DATE: October 28, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 707 of 998 DOCUMENTS Associated Press Online October 27, 2003 Monday AP Interview: Track Chief Discusses Doping BYLINE: STEPHEN WILSON; AP Sports Writer SECTION: SPORTS LENGTH: 531 words DATELINE: LONDON Two drugs under scrutiny in sports - modafinil and THG - are part of a pattern of doping abuse in the United States, a top track and field executive said Monday. Arne Ljungqvist, the IAAF's medical commission chief, said the evidence suggests a link between the substances. Modafinil is the drug sprinter Kelli White says she took for a sleep disorder. Tetrahydrogestrinone, or THG, is a previously undetectable designer steroid that has turned up in the samples of several track and field athletes. "What emerges now is a pattern," Ljungqvist told The Associated Press by phone from Sweden. "People have taken THG for obvious reasons - it's been designed with the intent not to be discovered. "And modafinil seems to have become a fashionable stimulant among certain athletes as well. It's a pattern I've seen before, where drugs have become popular and we find them." Ljungqvist spoke after 400-meter runner Calvin Harrison became the latest athlete identified as having tested positive for modafinil. Harrison, an Olympic and world relay gold medalist, tested positive for modafinil this past summer, a source close to a U.S. doping investigation, told the AP on Saturday on condition of anonymity. Harrison, still awaiting the result of his backup B sample, was tested at the U.S. national championships in June at Stanford, Calif. Modafinil first came to prominence in August when White tested positive for the drug at the world championships in Paris. She stands to be stripped of her 100-meter and 200-meter titles. White said she took modafinil on prescription from her personal doctor to combat narcolepsy. The International Association of Athletics Federations charged her with a doping offense and submitted her case to U.S. authorities for disciplinary action. Another U.S. athlete, Chris Phillips, who finished fifth in the 110-meter hurdles at the worlds, also tested positive for modafinil at the Paris meet. Harrison ran the opening leg of the 1,600-relay at the worlds. Ljungqvist said the IAAF's penalty for modafinil is a public warning and disqualification from the competition where the test took place - but no ban. Samples from the U.S. championships were retested after the UCLA doping control laboratory, acting on a tip, devised a test for THG. While retesting, U.S. officials discovered several positives for modafinil. Ljungqvist said the IAAF had been "directly or indirectly" informed of six to eight modafinil cases. Referring to White's narcolepsy defense, he said: "It comes into a different sort of light when it becomes known that modafinil has been taken by a number of athletes." On another drug issue, Ljungqvist said USA Track & Field still has not provided the required documents on Jerome Young's 1999 positive steroid test - a case that could cost the United States an Olympic relay gold medal. Ljungqvist set a deadline of Nov. 21 for USATF to comply. Young tested positive for the steroid nandrolone but was cleared on appeal by USATF officials. He went on to win a 1,600-meter relay gold medal at the 2000 Olympics. USATF officials have declined to provide the information, citing confidentiality rules at the time. LOAD-DATE: October 28, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 708 of 998 DOCUMENTS The Australian October 27, 2003 Monday All-round Country Edition Stimulant cloud over Harrison SOURCE: Reuters, The Times SECTION: SPORT-BIOG- CALVIN HARRISON; Pg. 24 LENGTH: 538 words * Drugs IN the latest in a series of scandals to rock athletics, Olympic 4x400m relay gold medallist Calvin Harrison admitted yesterday he had tested positive for the banned stimulant modafinil. Harrison's positive test comes in the wake of revelations that four US athletes and Britain's European 100m champion Dwain Chambers had tested positive to the previously undetectable designer steroid tetrahydrogestrinone. Dozens of other athletes, including Marion Jones and Tim Montgomery, have been engulfed in the THG scandal through their links to Victor Conte, the head of the company that has been identified as the drug's source. "Yes, I tested positive for modafinil at the (US) nationals," Harrison said. "I was notified that they (the US Anti-Doping Agency) had tested my A sample and that they would test my B sample, which they probably have by now. "I did have modafinil in my system. However, I am not in the least advocating the taking of any illegal substances because I strongly believe in fair play." Harrison, 29, is alleged to be one of up to 12 athletes who have tested positive for the stimulant in re-tests from the meeting in Stanford, California. He said he was given the substance by a coach in California. But the athlete stressed he had never been given an illegal substance by his current coach, Trevor Graham. "He (the coach in California) had given me this pill and I had taken it," Harrison said. "He told me it was not a steroid and that it would just keep you up so you wouldn't be so fatigued. "He emphasised that it was not on the banned substance list and assured me that it was not an illegal substance." Modafinil is the same stimulant to which double world sprint champion Kelli White of the US tested positive at the world championships in Paris in August. While not specified by name on the banned list at the time, modafinil was covered under the stimulants category of "related substances", the International Association of Athletics Federations said. Modafinil has since been added to the list. White, who is also a client of Conte, owner of the Bay Area Laboratory Co-operative (BALCO), has said she was prescribed the drug for a sleeping disorder. Her case is under review by the US Anti-Doping Agency. If she is found to have committed a doping offence, she could lose her Paris gold medals. Harrison's positive, if confirmed by the testing of his B urine sample, could also put in jeopardy the 4x400m relay gold medal the US won at the world championships, as he ran the opening leg. He was also a member of the victorious 2000 Olympics 4x400m relay team, who could have their gold medal taken away because Jerome Young ran in the early rounds after failing a 1999 doping test. The International Olympic Committee has called for an investigation into why Young was allowed to run. The four US athletes to have tested positive to THG include US shot put champion Kevin Toth, world indoor 1500m champion Regina Jacobs and US hammer thrower John McEwen. The fourth athlete is yet to be identified. A group of 40 athletes and sports stars have been subpoenaed to give evidence to a US federal grand jury investigation into BALCO's finances. LOAD-DATE: October 26, 2003 LANGUAGE: ENGLISH JOURNAL-CODE: AUS Copyright 2003 Nationwide News Pty Limited 709 of 998 DOCUMENTS The Daily Telegraph (Sydney, Australia) October 27, 2003 Monday Now US Olympic gold sprinter tests positive SOURCE: MATP BYLINE: GENE CHERRY SECTION: SPORT-BIOG- CALVIN HARRISON; Pg. 29 LENGTH: 290 words AMERICAN sprinter Calvin Harrison has tested positive for banned stimulant modafinil, he revealed yesterday. "I tested positive for modafinil at the [US] nationals," the US Sydney Olympics 4x400m relay gold medallist said. "I was notified [the US Anti-Doping Agency] had tested my A sample and that they would test my B sample."  Harrison's modafinil positive is the latest in a series of drug shocks that have rocked track and field and could leave next year's Athens Olympics missing a host of big names. It follows the discovery of the previously undetectable designer steroid THG, or tetrahydrogestrinone. American officials say four US athletes have tested positive for THG, as has Britain's 100m star Dwain Chambers. "I did have modafinil in my system," Harrison said. "However, I am not advocating the taking of any illegal substances because I strongly believe in fair play."  Harrison said he was given the substance by a former coach in California. "He had given me this pill and I had taken it. He told me it was not a steroid and would just keep you 'up' so you wouldn't be so fatigued. "He emphasised that it was not on the banned substance list and assured me that it was not an illegal substance."  Modafinil is the stimulant for which US double world sprint champion Kelli White tested positive at the world championships in Paris in August. It is not specifically named on the banned list, but the International Association of Athletics Federations (IAAF) has said it falls into the category of "related substances". If Harrison's positive test is confirmed, the US could be stripped of its 4x400 metres relay gold medal at this year's world championships, where he ran the opening leg. LOAD-DATE: October 26, 2003 LANGUAGE: ENGLISH JOURNAL-CODE: DTM Copyright 2003 Nationwide News Pty Limited 710 of 998 DOCUMENTS Gold Coast Bulletin (Australia) October 27, 2003 Monday Positive test for US star SECTION: SPORT; Pg. 33 LENGTH: 249 words Athletics US Olympic 4x400m relay gold medallist Calvin Harrison has tested positive for the banned stimulant modafinil.    "Yes, I tested positive for modafinil at the (US) nationals," said Harrison.    "I was notified they (the US Anti-Doping Agency) had tested my A sample and they would test my B sample, which they probably have by now."    Harrison's modafinil positive is the latest in a series of positive tests which have rocked track and field on both sides of the Atlantic and could leave next year's Athens Olympics missing a host of banned big-name athletes.    It also follows the discovery of the previously undetectable designer steroid tetrahydrogestrinone THG.    Four US athletes have tested positive for the steroid, American officials have said, as has Britain's European 100m champion Dwain Chambers, who said through his lawyer if he did take the drug it was unwittingly.    "I did have modafinil in my system," said Harrison.    "However, I am not in the least advocating the taking of any illegal substances because I strongly believe in fair play."    Harrison said he was given the substance by a coach in California.    But the athlete stressed he had never been given an illegal substance by his current coach, Trevor Graham.    "He (the coach in California) had given me this pill and I had taken it. He told me it was not a steroid and it would just keep you 'up' so you wouldn't be so fatigued," said Harrison. LOAD-DATE: October 27, 2003 LANGUAGE: ENGLISH JOURNAL-CODE: GCB Copyright 2003 Nationwide News Pty Limited 711 of 998 DOCUMENTS The Guardian - Final Edition October 27, 2003 Athletics: Harrison blames controversial coach for positive test BYLINE: Duncan Mackay SECTION: Guardian Sport Pages, Pg. 26 LENGTH: 402 words The Olympic and world gold medallist Calvin Harrison, an occasional training partner of Britain's Dwain Chambers, has admitted he is the latest top American athlete to have tested positive for banned performance-enhancing drugs. Harrison has confirmed that he has failed a test for modafinil, the stimulant prescribed to treat narcolepsy. Sources close to the case claim that Harrison has alleged he was given the banned substance by Remi Korchemny, the San Francisco-based coach whom Chambers was working under when he tested positive for the banned designer anabolic steroid tetrahydrogestrinone (THG). Harrison's positive test is the latest in a series of positive tests that have rocked the sport on both sides of the Atlantic and could leave next year's Athens Olympic Games missing a number of banned big-name athletes. "I did have modafinil in my system," Harrison said. "However, I am not in the least advocating the taking of any illegal substances because I strongly believe in fair play." Modafinil is the drug that has put Kelli White's 100 and 200m titles from the world championships at risk. Like Harrison, White claims she took modafinil for narcolepsy. Korchemny is her coach. Harrison said a coach in California gave him the substance. But he stressed he had never been given an illegal substance by his current coach, Trevor Graham, who has previously worked with the world's leading female and male sprinters Marion Jones and Tim Montgomery. "He (the coach in California) had given me this pill and I had taken it. He told me it was not a steroid and that it would just keep you 'up' so you wouldn't be so fatigued," said Harrison. "He emphasised that it was not on the banned substance list and assured me it was not an illegal substance." Harrison, who rose to prominence in track and field with his twin brother Alvin in the late 1990s, was a member of the American team who won the 4x400 metres relay in the 2000 Sydney Olympics and the world championships in Paris. His positive test came to light after 350 samples from the US championships in Stanford in June were retested after American anti-doping officials were given a used syringe by an unidentified track coach containing the previously undetectable THG. Sources have warned that more major names from America may come out this week as having tested positive for THG and modafinil. LOAD-DATE: October 27, 2003 LANGUAGE: ENGLISH Copyright 2003 Guardian Newspapers Limited 712 of 998 DOCUMENTS Illawarra Mercury (Australia) October 27, 2003 Monday Late Edition US sprinter admits positive test SECTION: SPORT MONDAY; Pg. 37 LENGTH: 175 words RALEIGH, North Carolina.- US Olympic 4x400m relay gold medallist Calvin Harrison has tested positive for the banned stimulant modafinil. "Yes, I tested positive for modafinil at the (US) nationals," Harrison said in a telephone interview from his North Carolina home. "I was notified that they (the US Anti-Doping Agency) had tested my A sample and that they would test my B sample, which they probably have by now." Harrison's modafinil positive is the latest in a series of positive tests which have rocked track and field on both sides of the Atlantic and could leave next year's Athens Olympics missing a host of banned big-name athletes. It also follows the discovery of the previously undetectable designer steroid tetrahydrogestrinone THG. Four US athletes have tested positive for the steroid, American officials have said, as has Britain's European 100m champion Dwain Chambers. "I did have modafinil in my system," Harrison said. "However, I am not in the least advocating the taking of any illegal substances because I strongly believe in fair play." LOAD-DATE: June 19, 2007 LANGUAGE: ENGLISH GRAPHIC: Illus: CALVIN HARRISON PUBLICATION-TYPE: Newspaper Copyright 2003 Illawarra Newspapers Holdings Pty Ltd All Rights Reserved 713 of 998 DOCUMENTS The Straits Times (Singapore) Champion tests positive October 27, 2003 Monday RALEIGH (North Carolina) - Calvin Harrison has tested positive for the banned stimulant modafinil, the US Olympic and world 4x400 metres relay gold medallist told Reuters on Saturday. 'Yes, I tested positive for modafinil at the US nationals,' he said in a telephone interview. He said he was notified that the US Anti-Doping Agency had tested his A sample and that they would test his B sample. This is the latest in a series of positive drugs tests which have rocked track and field on both sides of the Atlantic. It also follows the discovery of the previously undetectable designer steroid tetrahydrogestrinone THG. Harrison said he was given the substance by a coach - 'who emphasised it was not on the banned substance list' - in California. But the runner stressed he had never been given an illegal substance by current coach Trevor Graham. Modafinil is the same stimulant that American double world sprint champion Kelli White tested positive for at the World Championships in Paris last August. While not specified by name on the banned list, modafinil is covered under the stimulants category of 'related substances'. Harrison's positive, if confirmed by the testing of his B urine sample, could put in jeopardy the 4x400m gold won in Paris, as he ran the opening leg. SECTION: WHATS IN; Sports LENGTH: 216 words LOAD-DATE: October 26, 2003 LANGUAGE: ENGLISH Copyright 2003 Singapore Press Holdings Limited 714 of 998 DOCUMENTS The Times (London) October 27, 2003, Monday Harrison a sample of things to come SECTION: Sport; 35 LENGTH: 263 words THE positive test for modafinil that has shown up on the re-tested sample of Calvin Harrison, the United States 400 metres runner, could be the first of many. Harrison's sample was just one of about 350 taken at the US Trials at Stanford in June, all of which are being re-tested. The re-testing programme was initiated by the US Anti-Drug Agency after the development of new protocols to identify tetrahydrogestrinone (THG), the designer steroid. But there was no test for modafinil, so that procedure was added. Modafinil came to light in athletics circles only at the World Championships in Paris in August, when Kelli White, the US sprinter and winner of the 100 metres and 200 metres, tested positive for the drug. White, like Harrison and Dwain Chambers, the British sprinter, has been advised by Remi Korchemny, the coach with links to the Bay Area Laboratory Co-operative (Balco), at present the subject of a Grand Jury investigation in San Francisco. White claimed that she was prescribed the drug for a sleeping disorder, but even if her story is accepted, the sprinter still stands to lose both titles. Harrison also won gold in Paris, leading off the US relay team in the 4 x 400m final, and, if his positive test is confirmed, he and his team-mates stand to be disqualified. Harrison, 29 was also part of the gold-medal winning US relay squad at the 2000 Olympic Games, and that medal could be lost if the International Olympic Committee decides that Jerome Young, who failed a drugs test in 1999, should not have been allowed to compete. LOAD-DATE: October 27, 2003 LANGUAGE: ENGLISH Copyright 2003 Times Newspapers Limited 715 of 998 DOCUMENTS Townsville Bulletin/Townsville Sun (Australia) October 27, 2003 Monday Harrison positive SECTION: SPORT; Pg. 18 LENGTH: 185 words RALEIGH, North Carolina -- Calvin Harrison has tested positive for the banned stimulant modafinil, the US Olympic 4x400m relay gold medallist said yesterday. "Yes, I tested positive for modafinil at the (US) nationals," Harrison said. "I was notified that they (the US Anti-Doping Agency) had tested my A sample and that they would test my B sample, which they probably have by now." Harrison's result is the latest in a series of positive tests which have rocked track and field on both sides of the Atlantic and could leave next year's Athens Olympics missing a host of banned big-name athletes. It also follows the discovery of the previously undetectable designer steroid tetrahydrogestrinone THG. Four US athletes have tested positive for the steroid, American officials have said, as has Britain's European 100m champion Dwain Chambers, who said through his lawyer that if he did take the drug it was unwittingly. "I did have modafinil in my system," Harrison said. "However, I am not in the least advocating the taking of any illegal substances because I strongly believe in fair play." LOAD-DATE: October 27, 2003 LANGUAGE: ENGLISH JOURNAL-CODE: BUL Copyright 2003 Nationwide News Pty Limited 716 of 998 DOCUMENTS Associated Press Worldstream October 26, 2003 Sunday Correction Appended Source: Relay gold medalist flunked test for modafinil BYLINE: ROB GLOSTER; AP Sports Writer SECTION: SPORTS LENGTH: 410 words DATELINE: SAN FRANCISCO Olympic and world relay gold medalist Calvin Harrison tested positive for a banned stimulant, a source told The Associated Press. Harrison, a member of the winning U.S. 1,600-meter relay team at the 2000 Olympics and this summer's world championships, tested positive for the stimulant modafinil, a source close to a U.S. anti-doping investigation said Saturday, speaking on the condition of anonymity. The Los Angeles Times reported Saturday that Harrison's flunked drug test was believed to be from a urine sample taken at the U.S. track and field championships in June at Stanford, California. Harrison finished second in the 400 meters at that meet, making the U.S. team for the world championships and qualifying for a spot on the relay squad. Harrison, who rose to prominence in track and field with his twin brother, Alvin, in the late 1990s, could not immediately be reached for comment. Some 350 samples from the Stanford meet were retested after U.S. anti-doping officials were given a used syringe by an unidentified track coach containing a substance that turned out to be the previously undetectable designer steroid THG. While retesting for THG, officials discovered several positive tests for modafinil, U.S. Anti-Doping Agency chief executive Terry Madden said last week. The names of those athletes have not been released by the USADA. Harrison tested positive on his "A" sample, but results of his "B" sample were not yet available, the source said. If confirmed as a positive test, Harrison could face a two-year suspension and miss the 2004 Athens Olympics. Modafinil is the same drug that has put Kelli White's 100 and 200 titles from the world championships at risk. White claims she took modafinil for the sleep disorder narcolepsy. White is coached by Remi Korchemny, who has also worked with Harrison. Korchemny is the coach of British sprinter Dwain Chambers, the only athlete to publicly announce he tested positive for THG. Harrison ran the first leg of the 1,600 relay at the world championships. The anchor leg was run by Jerome Young, who is engulfed in controversy because of a failed doping test in 1999. At the 2000 Olympics, Harrison ran the third leg of the winning U.S. 1,600 squad that was anchored by Michael Johnson. Young ran in the preliminary and semifinal rounds for that squad, just weeks after being cleared by U.S. officials in a process now under scrutiny by international sports authorities. LOAD-DATE: October 27, 2003 LANGUAGE: ENGLISH CORRECTION-DATE: October 28, 2003 Tuesday CORRECTION: In an Oct. 25 story about runner Calvin Harrison testing positive for the stimulant modafinil, The Associated Press reported erroneously that Harrison could face a two-year suspension and miss the 2004 Athens Olympics. The penalty for modafinil use is disqualification from the competition where the test took place, not a two-year ban. Copyright 2003 Associated Press All Rights Reserved 717 of 998 DOCUMENTS The Associated Press State & Local Wire October 26, 2003, Sunday, BC cycle Correction Appended Source: Relay gold medalist flunked test for modafinil BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Sports News LENGTH: 421 words DATELINE: SAN FRANCISCO Olympic and world relay gold medalist Calvin Harrison tested positive for a banned stimulant, a source told The Associated Press on Saturday. Harrison, a member of the winning U.S. 1,600-meter relay team at the 2000 Olympics and this summer's world championships, tested positive for the stimulant modafinil, a source close to a U.S. anti-doping investigation said, speaking on the condition of anonymity. The Los Angeles Times reported Saturday that Harrison's flunked drug test was believed to be from a urine sample taken at the U.S. track and field championships in June at Stanford, Calif. Harrison, who graduated from North Salinas High School in 1993, finished second in the 400 meters at that meet, making the U.S. team for the world championships and qualifying for a spot on the relay squad. Harrison, who rose to prominence in track and field with his twin brother, Alvin, in the late 1990s, could not immediately be reached for comment. Some 350 samples from the Stanford meet were retested after U.S. anti-doping officials were given a used syringe by an unidentified track coach containing a substance that turned out to be the previously undetectable designer steroid THG. While retesting for THG, officials discovered several positive tests for modafinil, U.S. Anti-Doping Agency chief executive Terry Madden said last week. The names of those athletes have not been released by the USADA. Harrison tested positive on his "A" sample, but results of his "B" sample were not yet available, the source said. If confirmed as a positive test, Harrison could face a two-year suspension and miss the 2004 Athens Olympics. Modafinil is the same drug that has put Kelli White's 100 and 200 titles from the world championships at risk. White claims she took modafinil for the sleep disorder narcolepsy. White is coached by Remi Korchemny, who has also worked with Harrison. Korchemny is the coach of British sprinter Dwain Chambers, the only athlete to publicly announce he tested positive for THG. Harrison ran the first leg of the 1,600 relay at the world championships. The anchor leg was run by Jerome Young, who is engulfed in controversy because of a failed doping test in 1999. At the 2000 Olympics, Harrison ran the third leg of the winning U.S. 1,600 squad that was anchored by Michael Johnson. Young ran in the preliminary and semifinal rounds for that squad, just weeks after being cleared by U.S. officials in a process now under scrutiny by international sports authorities. LOAD-DATE: October 27, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved CORRECTION-DATE: October 28, 2003, Tuesday CORRECTION: In an Oct. 25 story about runner Calvin Harrison testing positive for the stimulant modafinil, The Associated Press reported erroneously that Harrison could face a two-year suspension and miss the 2004 Athens Olympics. The penalty for modafinil use is disqualification from the competition where the test took place, not a two-year ban. 718 of 998 DOCUMENTS Associated Press Online October 26, 2003 Sunday Correction Appended Source: Runner Harrison Flunked Drug Test BYLINE: ROB GLOSTER; AP Sports Writer SECTION: SPORTS LENGTH: 410 words DATELINE: SAN FRANCISCO Olympic and world relay gold medalist Calvin Harrison tested positive for a banned stimulant, a source told The Associated Press on Saturday. Harrison, a member of the winning U.S. 1,600-meter relay team at the 2000 Olympics and this summer's world championships, tested positive for the stimulant modafinil, a source close to a U.S. anti-doping investigation said, speaking on the condition of anonymity. The Los Angeles Times reported Saturday that Harrison's flunked drug test was believed to be from a urine sample taken at the U.S. track and field championships in June at Stanford, Calif. Harrison finished second in the 400 meters at that meet, making the U.S. team for the world championships and qualifying for a spot on the relay squad. Harrison, who rose to prominence in track and field with his twin brother, Alvin, in the late 1990s, could not immediately be reached for comment. Some 350 samples from the Stanford meet were retested after U.S. anti-doping officials were given a used syringe by an unidentified track coach containing a substance that turned out to be the previously undetectable designer steroid THG. While retesting for THG, officials discovered several positive tests for modafinil, U.S. Anti-Doping Agency chief executive Terry Madden said last week. The names of those athletes have not been released by the USADA. Harrison tested positive on his "A" sample, but results of his "B" sample were not yet available, the source said. If confirmed as a positive test, Harrison could face a two-year suspension and miss the 2004 Athens Olympics. Modafinil is the same drug that has put Kelli White's 100 and 200 titles from the world championships at risk. White claims she took modafinil for the sleep disorder narcolepsy. White is coached by Remi Korchemny, who has also worked with Harrison. Korchemny is the coach of British sprinter Dwain Chambers, the only athlete to publicly announce he tested positive for THG. Harrison ran the first leg of the 1,600 relay at the world championships. The anchor leg was run by Jerome Young, who is engulfed in controversy because of a failed doping test in 1999. At the 2000 Olympics, Harrison ran the third leg of the winning U.S. 1,600 squad that was anchored by Michael Johnson. Young ran in the preliminary and semifinal rounds for that squad, just weeks after being cleared by U.S. officials in a process now under scrutiny by international sports authorities. LOAD-DATE: October 27, 2003 LANGUAGE: ENGLISH CORRECTION-DATE: October 28, 2003 Tuesday CORRECTION: In an Oct. 25 story about runner Calvin Harrison testing positive for the stimulant modafinil, The Associated Press reported erroneously that Harrison could face a two-year suspension and miss the 2004 Athens Olympics. The penalty for modafinil use is disqualification from the competition where the test took place, not a two-year ban. Copyright 2003 Associated Press All Rights Reserved 719 of 998 DOCUMENTS Calgary Herald (Alberta, Canada) October 26, 2003 Sunday Final Edition Olympic champion Harrison fails drug test SOURCE: The Associated Press SECTION: Sports; Pg. B2 LENGTH: 428 words Olympic and world relay gold medallist Calvin Harrison tested positive for a banned stimulant, a source told The Associated Press on Saturday. Harrison, a member of the winning U.S. 4x400-metre relay team at the 2000 Olympics and this summer's world championships, tested positive for the stimulant modafinil, a source close to a U.S. anti-doping investigation said, speaking on the condition of anonymity. The Los Angeles Times reported Saturday that Harrison's flunked drug test was believed to be from a urine sample taken at the U.S. track and field championships in June at Stanford, Calif. Harrison finished second in the 400 metres at that meet, making the U.S. team for the world championships and qualifying for a spot on the relay squad. Harrison, who rose to prominence in track and field with his twin brother, Alvin, in the late 1990s, could not immediately be reached for comment. Some 350 samples from the Stanford meet were retested after U.S. anti-doping officials were given a used syringe by an unidentified track coach containing a substance that turned out to be the previously undetectable designer steroid THG. While retesting for THG, officials discovered several positive tests for modafinil, U.S. Anti-Doping Agency chief executive Terry Madden said last week. The names of those athletes have not been released by the USADA. Harrison tested positive on his "A" sample, but results of his "B" sample were not yet available, the source said. If confirmed as a positive test, Harrison could face a two-year suspension and miss the 2004 Athens Olympics. Modafinil is the same drug that has put Kelli White's 100 and 200 titles from the world championships at risk. White claims she took modafinil for the sleep disorder narcolepsy. White is coached by Remi Korchemny, who has also worked with Harrison. Korchemny is the coach of British sprinter Dwain Chambers, the only athlete to publicly announce he tested positive for THG. Meanwhile, the National Football League is rechecking players' drug tests to look for the newly identified steroid THG. The USADA received a used syringe containing the designer steroid from an anonymous coach and then began retesting samples of track and field athletes. NFL spokesman Greg Aiello said Saturday "as soon as the report came out about THG, we said we would be testing for it and we are." That includes previously taken urine samples that were tested by the NFL for other drugs. An NFL player testing positive for steroids receives a four-game suspension for the first offence. LOAD-DATE: October 26, 2003 LANGUAGE: ENGLISH TYPE: Sports Copyright 2003 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 720 of 998 DOCUMENTS San Jose Mercury News (California) October 26, 2003 Sunday MORNING FINAL EDITION DRUG SCANDAL INVOLVES SALINAS' CALVIN HARRISON BYLINE: MARK EMMONS, Mercury News SECTION: FRONT; Pg. 27A LENGTH: 220 words Another prominent track-and-field name has surfaced in the sport's "other" drug scandal. U.S. Olympic 4x400-meter relay gold medalist Calvin Harrison reportedly has tested positive for the banned stimulant modafinil. The positive test came from a drug test conducted during the summer, sources told Reuters. Harrison becomes the third American to test for modafinil. Union City sprinter Kelli White, who tested positive in August, risks losing two gold medals she won at the World Championships in Paris. White, who trains with East Bay coach Remi Korchemny, claims that she was given the drug to combat the sleeping disorder narcolepsy. American hurdler Chris Phillips, who uses Korchemny as a consultant, also tested positive. Harrison, according the various track Web sites, has been a member of ZMA Track Club -- which was formed by Korchemny and Victor Conte, the nutritionist and owner the Burlingame laboratory that is currently under investigation as the possible source of a new designer steroid. Calvin Harrison and his twin brother Alvin both were track stars at North Salinas High. The positive test, if confirmed by a second sample, could put in jeopardy the United States' 4x400 gold medal at the World Championships because Calvin Harrison ran the opening leg on the Americans' winning team. LOAD-DATE: August 17, 2005 LANGUAGE: ENGLISH NOTES: RELATED STORY, PAGE 1A GRAPHIC: Photo; PHOTO: KAREN T. BORCHERS -- MERCURY NEWS ARCHIVES Calvin Harrison reportedly tested positive for the banned stimulant modafinil this summer. Copyright 2003 San Jose Mercury News All Rights Reserved 721 of 998 DOCUMENTS The Times Union (Albany, NY) October 26, 2003 Sunday THREE STAR EDITION Tests find new stimulant BYLINE: Combined Wire Services SECTION: SPORTS, Pg. C2 LENGTH: 506 words Sprinter Calvin Harrison, a gold medalist in the relays at the Sydney Olympic Games, tested positive this summer for the stimulant modafinil, sources told the Los Angeles Times, adding that at least half a dozen U.S. athletes might have tested positive for the same stimulant. The positive testing for modafinil showed up when the U.S. Anti-Doping Agency reviewed tests taken at the U.S. national track championships at Stanford in June and after the agency learned of a new designer steroid, tetrahydrogestrinone, or THG. Modafinil was recently added to the list of banned performance-enhancing substances. Track's worldwide governing body, the International Assn. of Athletics Federations, has said it plans to retest about 400 samples from the world championships in August in Paris for THG. FIGURE SKATING     Tanith Belbin and Benjamin Agosto became the first U.S. ice dance team to take a Grand Prix event in six years when they won Skate America in Reading, Pa.  Belbin and Agosto, ranked seventh in the world, easily won the free dance with a rousing performance to "West Side Story." They edged Ukraine's Elena Grushina and Ruslan Goncharov, who won the compulsories. Belbin and Agosto finished with 212.08 points. Grushina and Goncharov were at 197.66. TRIATHLON Rasmus Henning of Denmark won the triathlon World Cup by 0.03 seconds in Vouliagmeni, Greece, when Cedric Fleureton of France stumbled at the finish of the 10-kilometer run. Michellie Jones of Australia won the women's division of the competition, which served as an Olympic test event. Henning, who edged Cedric Fleureton of France in a photo finish, completed the 1.5-kilometer swim, 40-kilometer cycle and the closing run in 1 hour, 52 minutes, 41.93 seconds. Among the women, Jones, the Olympic silver medalist, beat Britain's Jodie Swallow by 1.30 seconds, finishing in 2:06:47.02. TENNIS Top-seeded Andy Roddick was knocked off by David Nalbandian 7-5, 7-5 in the semifinals of the Swiss Indoors in Basel. It was a rematch from the U.S. Open semifinals, where Roddick overcame a two-set deficit and a match point to win en route to his first Grand Slam title. Nalbandian will play Guillermo Coria in an all-Argentine final today. Coria eliminated Ivan Ljubicic 6-4, 6-4.     Kim Clijsters overwhelmed 16-year-old Maria Sharapova 6-0, 6-3 in the SEAT Open semifinals in Luxembourg. Clijsters, who will regain the No. 1 ranking next week, will play Chanda Rubin in the final.   SKIING     Martina Ertl of Germany opened the World Cup ski season by winning a giant slalom in Soelden, Austria, for her first victory in three years. She had a two-run time of 2 minutes, 31.86 seconds in recording her 14th World Cup victory.  Veikko Hakulinen, a Finnish cross-country skier who won three Olympic gold medals, died after being hit by a car in Helsinki, police said. He was 78. Hakulinen's victories began with the 50-kilometer race at the 1952 Oslo Olympics. In all, he won three golds, three silvers and one bronze at Olympics. LOAD-DATE: October 27, 2003 LANGUAGE: ENGLISH Copyright 2003 The Hearst Corporation 722 of 998 DOCUMENTS The Washington Post October 26, 2003 Sunday Final Edition U.S.'s Harrison Tests Positive for Stimulant BYLINE: From News Services SECTION: Sports; E02 LENGTH: 574 words Calvin Harrison has tested positive for the banned stimulant modafinil, the U.S. Olympic 4x400-meter relay gold medalist told Reuters yesterday. "Yes, I tested positive for modafinil at the [U.S.] nationals," Harrison said in a telephone interview. "I was notified that they [the U.S. Anti-Doping Agency] had tested my A sample and that they would test my B sample, which they probably have by now." Harrison's modafinil positive test is the latest in a series of positive tests that have rocked track and field on both sides of the Atlantic and could leave next year's Athens Olympics missing a number of banned big-name athletes. It also follows the discovery of the previously undetectable designer steroid tetrahydrogestrinone (THG). "I did have modafinil in my system," Harrison said. "However, I am not in the least advocating the taking of any illegal substances because I strongly believe in fair play." Skiing Martina Ertl of Germany opened the World Cup season by winning a giant slalom in Soelden, Austria, her first victory in three years. "This is absolutely sensational," Ertl said. "I've been waiting so long." She had a two-run time of 2 minutes 31.86 seconds in recording her 14th World Cup victory. Anja Paerson of Sweden, the World Cup champion and reigning world championship gold medalist, was second in 2:32.06. Maria Jose Rienda Contreras was third in 2:32.25, giving Spain its first top-three finish since Carolina Ruiz Castillo in 2000. Sarah Schleper of the United States was seventh in 2:34.30. "I'm psyched," Schleper said. "The atmosphere on our team is getting better and better." Teammate Kirsten Clark was 23rd and Caroline Lalive was 28th. Ertl's last World Cup victory was a giant slalom on the same site in October 2000. She has struggled since a series of knee injuries in that season. The German was third in the 2002 Olympic combined event, which adds the downhill and slalom times. "It's been two years that I've been injury-free, but it has been a long road back to the top," Ertl said. "I am lucky that I am a person who has a lot of energy and determination and I really wanted to fight." Schleper was tied for 13th after the first run, then rose to seventh after posting the fifth-fastest second run. "I'm believing more and more in myself," she said. The men's World Cup season opens today with a giant slalom. . . . In Duesseldorf, Germany, Sweden's Peter Larsson and Italy's Gabriela Paruzzi won the opening races of the World Cup cross-country season. Larsson was first in the one-kilometer sprint for the second straight year. Martin Koukal of the Czech Republic was second, followed by Thobias Fredriksson of Sweden. Swedish men captured five of the top eight places. Among the women, Russians Olena Sidko and Yevgenia Chachina were second and third. German biathlon star Uschi Disl was a surprising fourth. Tennis David Nalbandian upset top-seeded Andy Roddick, 7-5, 7-5, in the semifinals of the Swiss Indoors in Basel. It was a rematch from the U.S. Open semifinals, in which Roddick overcame a two-set deficit and a match point to win en route to his first Grand Slam title. Nalbandian will play Guillermo Coria in an all-Argentine final today. Coria eliminated Ivan Ljubicic, 6-4, 6-4. Both finalists are playing in their first tournament since the U.S. Open, having taken time off because of injuries. Nalbandian beat Roddick with impressive returns and passing shots. LOAD-DATE: October 26, 2003 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2003 The Washington Post 723 of 998 DOCUMENTS XINHUA GENERAL NEWS SERVICE October 26, 2003, Sunday American Harrison tests positive for stimulant SECTION: WORLD NEWS; SPORTS LENGTH: 216 words WASHINGTON, Oct. 25 (Xinhua) -- American Calvin Harrison, winning member of the U.S. Olympic 4x400 meters relay team, has tested positive for stimulant modafinil, sources close to the anti-doping program said on Saturday. Harrison's A sample tested positive this summer, but he ran the opening leg on the US 4x400m winning team at the world championships in Paris last August. If his positive is confirmed by the B sample, the United States might be stripped of its world and Olympic titles in the 4x400m relay as Jerome Young also ran in the early Olympic rounds of relay after failing a 1999 doping test. World 100 and 200m woman champion Kelli White also tested positive for the same stimulant at the world championships, and her case is under review by the U.S. Anti-Doping Agency. Harrison's modafinil positive is the latest in the doping scandal that has rocked the track and field world, followed the discovery of designer steroid tetrahydrogestrinone (THG). Four positives for THG and a number for the stimulant modafinil were found at the re-testing of urine samples from the U.S. championships in June, the sources said. Britain's European 100m champion Dwain Chambers, and US world indoor 1,500m record holder Regina Jacobs also tested positive for the THG. LOAD-DATE: October 27, 2003 LANGUAGE: ENGLISH COPYRIGHT 2003 XINHUA NEWS AGENCY 724 of 998 DOCUMENTS The Associated Press October 25, 2003, Saturday, BC cycle Correction Appended Source: Relay gold medalist flunked test for modafinil BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Sports News LENGTH: 412 words DATELINE: SAN FRANCISCO Olympic and world relay gold medalist Calvin Harrison tested positive for a banned stimulant, a source told The Associated Press on Saturday. Harrison, a member of the winning U.S. 1,600-meter relay team at the 2000 Olympics and this summer's world championships, tested positive for the stimulant modafinil, a source close to a U.S. anti-doping investigation said, speaking on the condition of anonymity. The Los Angeles Times reported Saturday that Harrison's flunked drug test was believed to be from a urine sample taken at the U.S. track and field championships in June at Stanford, Calif. Harrison finished second in the 400 meters at that meet, making the U.S. team for the world championships and qualifying for a spot on the relay squad. Harrison, who rose to prominence in track and field with his twin brother, Alvin, in the late 1990s, could not immediately be reached for comment. Some 350 samples from the Stanford meet were retested after U.S. anti-doping officials were given a used syringe by an unidentified track coach containing a substance that turned out to be the previously undetectable designer steroid THG. While retesting for THG, officials discovered several positive tests for modafinil, U.S. Anti-Doping Agency chief executive Terry Madden said last week. The names of those athletes have not been released by the USADA. Harrison tested positive on his "A" sample, but results of his "B" sample were not yet available, the source said. If confirmed as a positive test, Harrison could face a two-year suspension and miss the 2004 Athens Olympics. Modafinil is the same drug that has put Kelli White's 100 and 200 titles from the world championships at risk. White claims she took modafinil for the sleep disorder narcolepsy. White is coached by Remi Korchemny, who has also worked with Harrison. Korchemny is the coach of British sprinter Dwain Chambers, the only athlete to publicly announce he tested positive for THG. Harrison ran the first leg of the 1,600 relay at the world championships. The anchor leg was run by Jerome Young, who is engulfed in controversy because of a failed doping test in 1999. At the 2000 Olympics, Harrison ran the third leg of the winning U.S. 1,600 squad that was anchored by Michael Johnson. Young ran in the preliminary and semifinal rounds for that squad, just weeks after being cleared by U.S. officials in a process now under scrutiny by international sports authorities. LOAD-DATE: October 26, 2003 LANGUAGE: ENGLISH CORRECTION-DATE: October 28, 2003, Tuesday CORRECTION: In an Oct. 25 story about runner Calvin Harrison testing positive for the stimulant modafinil, The Associated Press reported erroneously that Harrison could face a two-year suspension and miss the 2004 Athens Olympics. The penalty for modafinil use is disqualification from the competition where the test took place, not a two-year ban. Copyright 2003 Associated Press All Rights Reserved 725 of 998 DOCUMENTS The Associated Press State & Local Wire October 25, 2003, Saturday, BC cycle Correction Appended Source: Relay gold medalist flunked test for modafinil BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Sports News LENGTH: 412 words DATELINE: SAN FRANCISCO Olympic and world relay gold medalist Calvin Harrison tested positive for a banned stimulant, a source told The Associated Press on Saturday. Harrison, a member of the winning U.S. 1,600-meter relay team at the 2000 Olympics and this summer's world championships, tested positive for the stimulant modafinil, a source close to a U.S. anti-doping investigation said, speaking on the condition of anonymity. The Los Angeles Times reported Saturday that Harrison's flunked drug test was believed to be from a urine sample taken at the U.S. track and field championships in June at Stanford, Calif. Harrison finished second in the 400 meters at that meet, making the U.S. team for the world championships and qualifying for a spot on the relay squad. Harrison, who rose to prominence in track and field with his twin brother, Alvin, in the late 1990s, could not immediately be reached for comment. Some 350 samples from the Stanford meet were retested after U.S. anti-doping officials were given a used syringe by an unidentified track coach containing a substance that turned out to be the previously undetectable designer steroid THG. While retesting for THG, officials discovered several positive tests for modafinil, U.S. Anti-Doping Agency chief executive Terry Madden said last week. The names of those athletes have not been released by the USADA. Harrison tested positive on his "A" sample, but results of his "B" sample were not yet available, the source said. If confirmed as a positive test, Harrison could face a two-year suspension and miss the 2004 Athens Olympics. Modafinil is the same drug that has put Kelli White's 100 and 200 titles from the world championships at risk. White claims she took modafinil for the sleep disorder narcolepsy. White is coached by Remi Korchemny, who has also worked with Harrison. Korchemny is the coach of British sprinter Dwain Chambers, the only athlete to publicly announce he tested positive for THG. Harrison ran the first leg of the 1,600 relay at the world championships. The anchor leg was run by Jerome Young, who is engulfed in controversy because of a failed doping test in 1999. At the 2000 Olympics, Harrison ran the third leg of the winning U.S. 1,600 squad that was anchored by Michael Johnson. Young ran in the preliminary and semifinal rounds for that squad, just weeks after being cleared by U.S. officials in a process now under scrutiny by international sports authorities. LOAD-DATE: October 26, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved CORRECTION-DATE: October 28, 2003, Tuesday CORRECTION: In an Oct. 25 story about runner Calvin Harrison testing positive for the stimulant modafinil, The Associated Press reported erroneously that Harrison could face a two-year suspension and miss the 2004 Athens Olympics. The penalty for modafinil use is disqualification from the competition where the test took place, not a two-year ban. 726 of 998 DOCUMENTS Associated Press Online October 25, 2003 Saturday Source: Runner Harrison Flunked Drug Test BYLINE: ROB GLOSTER; AP Sports Writer SECTION: SPORTS LENGTH: 410 words DATELINE: SAN FRANCISCO Olympic and world relay gold medalist Calvin Harrison tested positive for a banned stimulant, a source told The Associated Press on Saturday. Harrison, a member of the winning U.S. 1,600-meter relay team at the 2000 Olympics and this summer's world championships, tested positive for the stimulant modafinil, a source close to a U.S. anti-doping investigation said, speaking on the condition of anonymity. The Los Angeles Times reported Saturday that Harrison's flunked drug test was believed to be from a urine sample taken at the U.S. track and field championships in June at Stanford, Calif. Harrison finished second in the 400 meters at that meet, making the U.S. team for the world championships and qualifying for a spot on the relay squad. Harrison, who rose to prominence in track and field with his twin brother, Alvin, in the late 1990s, could not immediately be reached for comment. Some 350 samples from the Stanford meet were retested after U.S. anti-doping officials were given a used syringe by an unidentified track coach containing a substance that turned out to be the previously undetectable designer steroid THG. While retesting for THG, officials discovered several positive tests for modafinil, U.S. Anti-Doping Agency chief executive Terry Madden said last week. The names of those athletes have not been released by the USADA. Harrison tested positive on his "A" sample, but results of his "B" sample were not yet available, the source said. If confirmed as a positive test, Harrison could face a two-year suspension and miss the 2004 Athens Olympics. Modafinil is the same drug that has put Kelli White's 100 and 200 titles from the world championships at risk. White claims she took modafinil for the sleep disorder narcolepsy. White is coached by Remi Korchemny, who has also worked with Harrison. Korchemny is the coach of British sprinter Dwain Chambers, the only athlete to publicly announce he tested positive for THG. Harrison ran the first leg of the 1,600 relay at the world championships. The anchor leg was run by Jerome Young, who is engulfed in controversy because of a failed doping test in 1999. At the 2000 Olympics, Harrison ran the third leg of the winning U.S. 1,600 squad that was anchored by Michael Johnson. Young ran in the preliminary and semifinal rounds for that squad, just weeks after being cleared by U.S. officials in a process now under scrutiny by international sports authorities. LOAD-DATE: October 26, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 727 of 998 DOCUMENTS CTV Television, Inc. 23:00:00 - 23:30:00 Eastern Time SHOW: CTV NEWS October 25, 2003, Saturday New pill makes weary persons alert ANCHOR: SANDIE RINALDO LENGTH: 478 words    SANDIE RINALDO: Sunday at 2:00 a.m., much of the country says good-bye to daylight saving time. Most of us will set our clocks back an hour and it seems many could use the extra sleep. A poll commissioned by the Better Sleep Council of Canada says more than one-third of us gets less than six hours of sleep a night. Soon, there will be a pill on the US market that could help the weary stay alert. But as CTV's Genevieve Beauchemin shows us, Canadian experts warn it is not for everyone. GENEVIEVE BEAUCHEMIN [Reporter]: For twenty-three years, nurse Inge Decastris has helped moms deliver their babies day and night. INGE DECASTRIS [St. Mary's Hospital Nurse]: During the night, around three o'clock, you're ready, your eyes start to droop if you're not really busy and active. BEAUCHEMIN: But a pill promises to perk up the sleep deprived. The US Food and Drug Administration and Health Canada approved Modafinil for the treatment of narcolepsy in the late 1990s. Now the United States is set to approve it for wider use, including for shift workers desperate to stay alert. And that has caused controversy over whether that should happen in Canada too. Dr. Ross Pigeau studied Modafinil's effects for the Department of National Defence. He kept soldiers up for 64 hours, gave them the drug and tested their performance. DR. ROSS PIGEAU [Defence Research and Development Canada]: Modafinil would be, from my research, a good alternative to, for instance, amphetamine. BEAUCHEMIN: Amphetamines and other stimulants including coffee cause side effects, including jitteriness and heart palpitations. Modafinil doesn't. But experts warn it is not a magic pill. They fear expanding its use could lead to abuse. But it may be a licence for many to try to do more on less sleep. Sleep depravity leads to increased risk of diabetes, heart problems and shorter lifespans. DR. DIANE BOIVIN [Sleep Expert]: The only real treatment for sleep deprivation is sleep itself. BEAUCHEMIN: Dr. Diane Boivin researched shift workers' sleep troubles. She says the Modafinil is a good drug that could help emergency workers who need to work nights, but few others. BOIVIN: There is a choice of society to be made, and we should try to limit as much as possible this twenty-four hour society because it's still not normal to work nights. BEAUCHEMIN: The company that sells Modafinil in Canada says it has not started the process of having it approved for any other use than in the treatment of narcolepsy. The Canadian Sleep Society says it hopes there will be further studies into the drug's long-term effects before that happens. Genevieve Beauchemin, CTV News, Montreal. RINALDO: Thank you for joining us here at CTV News this Saturday. Good night. Enjoy that extra hour. I'm Sandie Rinaldo. We'll see you tomorrow. LOAD-DATE: November 3, 2003 LANGUAGE: ENGLISH Copyright 2003 CTV Television, Inc. 728 of 998 DOCUMENTS San Jose Mercury News (California) October 19, 2003 Sunday MORNING FINAL EDITION STEROID FLAP OVERSHADOWS ANOTHER DRUG; MANY ATHLETES TEST POSITIVE FOR MILD STIMULANT MODAFINIL BYLINE: MARK EMMONS AND PETE CAREY, Mercury News SECTION: FRONT; Pg. 25A LENGTH: 1095 words When sprinter Kelli White tested positive for a mild stimulant called modafinil at the World Championships in Paris in August, she had an explanation. She told officials that she suffers from narcolepsy and that her doctor prescribed the drug to combat her excessive fatigue. But now that extensive laboratory sleuthing by the U.S. Anti-Doping Agency has found several other American track athletes, so far unnamed, who tested positive for modafinil this summer, one of two conclusions can be drawn: * There is an epidemic of sleep disorders among the U.S. track elite. * At least some athletes believe the drug enhances performance. Thursday, the anti-doping agency said it was "fairly certain" that Balco Laboratories of Burlingame was the source of a sample of a previously unknown "designer" steroid, tetrahydrogestrinone, for which several athletes at the national championships at Stanford University tested positive. Balco and its president, Victor Conte Jr., also are targets of a federal grand jury that has subpoenaed dozens of athletes to testify. Another drug But almost lost in the steroid controversy is the anti-doping agency's announcement Thursday that track athletes may be using another banned drug to aid them on the track: modafinil. Asked Thursday if modafinil improves performance, the agency's chief executive, Terry Madden, said bluntly: "Absolutely." Yet sleep experts who prescribe the drug to patients sharply disagree. "If I was an athlete, I sure wouldn't pick modafinil," said Dr. Thomas Scammell of Beth Israel Deaconess Medical Center in Boston. White, of Union City, is facing the loss of two gold medals and $120,000 that she won in Paris. She denies that she took modafinil, sold under the brand name Provigil, to give her an extra boost. Last week European newspapers reported that a second U.S. athlete, hurdler Chris White, also tested positive for modafinil. He finished sixth in the 110-meter hurdles in Paris. Sprinter's defense White says she didn't know the International Association of Athletics Federations considered modafinil a "related substance" to other stimulants on the official banned list. But she also didn't disclose, on a form that all athletes must complete listing the medications they are ingesting, that she was taking Provigil. Dr. Brian Goldman, an East Bay physician who at one time was Balco's medical director, said he prescribed the drug for White when she showed symptoms of narcolepsy, including fatigue and depression, before the World Championships. Goldman said White's mother and maternal aunt also have the ailment. Sleep experts respond Goldman said that he had "no idea" athletes were using the drug when he gave White some samples of Provigil. He believes White, at least, had a legitimate reason to take it. He also remains convinced that the drug doesn't do anything to improve athletic performance. But he does note that because athletes may have been convinced that it would help them, a "placebo effect" could have helped their performance. "Athletes are very prone to a placebo effect," Goldman said. "So maybe they believe it works, so it does." But several sleep disorder experts say they don't understand how international sports organizations can consider modafinil a substance that would make track athletes faster. They say it does not act like a traditional stimulant, a main reason prescriptions for it have grown sharply in recent years. "I don't know what their issue is," said Joyce A. Walsleben, director at the New York University School of Medicine's Sleep Disorders Center. "It's not a stimulant as we know the word stimulant. "It is a wake promoter, working in the area of the brain that wakes people up. It does not stimulate the cardiovascular system or muscle system as amphetamines do." Dr. James Wyatt of Chicago's Rush University Medical Center said, "It is actually one of the less potent medications available. That's one of the reasons why it is preferred by sleep disorder specialists." A representative for Cephalon, the West Chester, Pa., company that makes Provigil, said reports of athletes using the drug are mystifying. "We heard Kelli White had narcolepsy, so it wasn't surprising that she was taking Provigil, because that's the standard of care for excessive sleep," Sheryl Williams said. "The whole situation with the IAAF is something that we weren't expecting and prepared for because we make a pharmaceutical product for sick people." Other uses Although the Food and Drug Administration approved Provigil in 1998 for narcolepsy treatment, Williams said only about 20 percent of prescriptions concern sleep disorders. She said it also is used to treat fatigue associated with multiple sclerosis, depression, Parkinson's disease and chronic fatigue syndrome, among other conditions. In fact, physicians have found plenty of "off-label" uses for Provigil. People who need to stay awake for long periods of time, such as truck drivers, use it. The U.S. military is testing Provigil on pilots. Dr. Frank Baldino, Cephalon's chief executive, recently told Fortune magazine that some of the off-label uses of Provigil make him slightly uncomfortable. "In some sense, physicians are way ahead of us," he said. The question is whether athletes think they're way ahead, too. When the anti-doping agency began its steroid investigation, it re-examined 350 urine samples taken at the USA Outdoor Track & Field Championships at Stanford University and took 200 additional out-of-competition samples from athletes in track and other Olympic sports. 'Really frustrating' While the stunning news was the discovery of the designer steroid in some samples, the agency said "several" positive tests for modafinil also were found. Those who test positive for steroids risk a minimum two-year ban from competition. The penalty for using modafinil is disqualification from the meet where an athlete tested positive. Goldman said that whether other athletes were taking it to gain an advantage, White was taking it legitimately. Contacted last week at her East Bay home, White sounded weary. She has been subpoenaed to testify before a grand jury in the federal investigation of Balco. She adamantly denied being one of the athletes who tested positive for THG. "I've already got enough stuff to deal with," White said, referring to the modafinil case. Then, after a deep sigh, she added: "This is really frustrating and it's probably going to get even more frustrating over the next few weeks." LOAD-DATE: August 17, 2005 LANGUAGE: ENGLISH NOTES: RELATED STORY: page 1A. Copyright 2003 San Jose Mercury News All Rights Reserved 729 of 998 DOCUMENTS SUNDAY TELEGRAPH(LONDON) October 19, 2003, Sunday Doping scandal could cost White more gold Simon Hart reports on the gathering drugs scandal which has been sparked by the detection of a new steroid BYLINE: by Simon Hart SECTION: Pg. 16 LENGTH: 624 words KELLI WHITE, the American sprint star who faces being stripped of the two gold medals she won at the World Championships in Paris after failing a drug test, could also lose the two golds she won at this summer's US Championships after testing positive for the same banned substance. White has admitted that the urine sample she gave at the US Championships in Palo Alto, California, in June has revealed traces of modafinil - the same drug that was discovered in the sample taken two months later after her 100 metres triumph in Paris. The American claims the drug was prescribed for an hereditary sleeping disorder but admits she failed to notify the anti-doping authorities in advance because she had no idea it was a banned drug. The reason that the earlier drug test failure has only recently come to light is because at the time of the US Championships the US Anti-Doping Agency (USADA) did not test for modafinil. However, all 350 samples provided at the championships have recently been re-examined following an anonymous tip-off that a new, hitherto undetectable anabolic called tetrahydrogestrinone, or THG, was being widely abused. Tests for modafinil were also carried out as part of the investigation. White faces a disciplinary hearing in the United States which is likely to result in the loss of the two gold medals she won in Paris in the 100m and 200m, and she expects the US Championships case to be dealt with at the same time. However, her claims that the drug, a mild stimulant, was used to treat a narcolepsy condition have been thrown into doubt by the revelation that several more modafinil 'positives' have been detected among other samples. Unless sleeping disorders are rife among American athletes, the likelihood seems to be that it is being used as a performance enhancer. White, who insists she has not tested positive for THG, has also confirmed that she is one of 40 American sports stars who have been subpoenaed to give evidence to a Federal Grand Jury in San Francisco investigating the activities of the Bay Area Laboratory Cooperative (BALCO) in California, a company producing nutritional supplements that has been named as the source of THG, a so-called "designer" or artificially produced steroid that was previously unknown to drug-testers. USADA were alerted to the drug by a tip-off in May but have only recently discovered a reliable test to detect it. Up to 20 stars are said to have tested positive for the steroid in what could be one of the biggest doping scandals in history, though anti-doping officials are refusing to reveal their identities until tests on second 'B' samples have been carried out. The only athlete to have been named is American shot put champion Kevin Toth, one of dozens of sportsmen mentioned on BALCO's website. His agent, John Nubani, has confirmed THG was part of his supplement package but said his client had no idea it was a banned anabolic steroid. USADA have confirmed that 100 out-of-competition samples were also being re-analysed as part of the THG investigation, though it is unclear whether any foreign athletes are involved. The THG scandal, which anti-doping officials in America have described as an "international doping conspiracy", is threatening to bring down the country's governing body of athletics, USA Track and Field. Yesterday, the US Olympic Committee gave athletics officials one month to regain control of their sport or face being wound up following a series of controversies including Jon Drummond's histrionics against a false start in Paris and the revelation that world 400m champion Jerome Young was cleared to compete at the Sydney Olympics despite testing positive for nandrolone in 1999. [PS]Sport: [ES] GOLF: LOAD-DATE: October 19, 2003 LANGUAGE: ENGLISH Copyright 2003 The Telegraph Group Limited 730 of 998 DOCUMENTS The Washington Post October 18, 2003 Saturday Final Edition White Says She Passed THG Test; But Sprinter Flunked 2nd Modafinil Screening BYLINE: Amy Shipley, Washington Post Staff Writer SECTION: Sports; D01 LENGTH: 920 words U.S. sprinter Kelli White said yesterday she is not among the handful of U.S. track and field athletes who have tested positive for the newly discovered anabolic steroid tetrahydrogestrinone (THG), but she acknowledged flunking a second drug test for the stimulant modafinil at the U.S. Track and Field Championships this summer, a development that could cost her the two gold medals she won there. Meantime, NFL spokesman Greg Aiello said yesterday that the league plans to include THG on its banned list and will begin testing for the drug shortly. He added that league officials would consider retroactive testing, which officials of the U.S. Anti-Doping Agency undertook this summer after discovering the new steroid. USADA officials announced Thursday that several track and field athletes had tested positive in retroactive testing for THG. White, notified of the second positive test for modafinil in recent days, is already facing a public warning and the loss of the two gold medals she won at the August world championships as a result of her first positive test for modafinil. White emerged this summer as the top female sprinter in the world in the absence of five-time Olympic medalist Marion Jones. White, who said she took modafinil to treat narcolepsy, said she expected the two cases to be adjudicated together this fall. USADA officials, who are handling the case, declined to comment. White also said she has been subpoenaed to appear before a federal grand jury looking into activities at the Bay Area Laboratory Co-Operative (BALCO), a nutrition company run by Victor Conte that USADA officials alleged Thursday was the source of the new steroid. USADA CEO Terry Madden said he believed THG was distributed by Conte and BALCO as part of an international conspiracy to beat standard drug tests. He declined to name the athletes who flunked drug tests, but called it the biggest anabolic steroid bust in sports history. U.S. shot put champion Kevin Toth is among those who have tested positive, according to several sources with knowledge of the investigation. John Nubani, Toth's agent, said yesterday Toth likely was unaware that THG was an anabolic steroid because it was not on the International Olympic Committee's list of banned substances and had never -- until now -- triggered a positive test. Toth, who finished fourth at the world championships, has used nutrition products from Conte and has credited him for helping turn his career around. Toth is among the dozens of athletes mentioned in BALCO's Web site. Nubani said Toth, 35, of Hudson, Ohio, had never tested positive for any other substance during his career. He won his first U.S. indoor and outdoor titles this year. "All I know is what he told me: He said part of his supplement package included whatever this is," Nubani said, referring to the THG. "I don't know if he ingested it, took shots, drops, or what . . . . I don't think he was aware of it [being a steroid] . . . . Guys are always looking for a better edge, better vitamins." Toth, who Nubani said also has been summoned to appear before the grand jury, did not return calls seeking comment. Conte denied Thursday being the source of the drug in an e-mail sent to a number of news outlets, saying the charges against him were motivated by politics and jealousy. In other e-mails yesterday, he said it was "outrageous" for anti-doping officials to describe THG as a powerful anabolic steroid. "USADA is really making a scientific stretch by suggesting that [THG] is closely related to an anabolic steroid. . . . " Conte wrote in one e-mail, adding in another that, "my understanding from what I have been told by experts in this field, is that a very small alteration in the molecular structure of an anabolic steroid can cause it to become totally ineffective. THG may not even reach the androgen receptor at all and there may be absolutely no anabolic effects." Also yesterday, the executive committee of the U.S. Olympic Committee met for more than four hours in Cleveland to discuss the latest drug testing scandal involving track and field athletes. "The United States Olympic Committee has to take the responsibility and leadership to solve this problem because we are not satisfied with the action that has been taken to date by USA Track and Field," USOC acting president Bill Martin said in a news conference afterward. "This is a problem rooted in both perception and reality, and it is a problem related to doping, athlete conduct and the credibility of the sport." Martin appointed a three-person panel to work with USA Track & Field on a plan, to be submitted by Nov. 17 to the USOC, detailing how it will deal with doping issues, athlete conduct and restoring the credibility within USATF. Later, in a news conference of his own, USATF chief executive officer Craig Masback said "we welcome ideas from the USOC or anyone on how we can be better at doing what we're doing, on how we can have a higher profile on these issues and how we can play a more positive role on this issue. "What the developments of the last few days tell us is there's a problem out there. That there is a small number of people, perhaps in pockets around the country, that seem to be under the influence of some gurus who say they can help people get away with something. That they are preying on athletes and they are taking advantage of people who are weak, and who are willing to listen to such arguments." Staff writer Thomas Heath contributed to this report from Cleveland. LOAD-DATE: October 18, 2003 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2003 The Washington Post 731 of 998 DOCUMENTS The Associated Press State & Local Wire October 17, 2003, Friday, BC cycle U.S. Anti-Doping Agency says it has uncovered steroid conspiracy BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Sports News LENGTH: 850 words DATELINE: SAN FRANCISCO The U.S. Anti-Doping Agency has uncovered a widespread drug conspiracy involving coaches, chemists and several track athletes who tested positive for a previously undetectable steroid and now face suspensions that could bar them from the 2004 Athens Olympics. USADA chief executive officer Terry Madden said Thursday that the U.S. athletes had tested positive for the steroid, known as tetrahydrogestrinone, or THG. He said the ongoing inquiry began in June with an anonymous tip and has expanded to include U.S. professional sports. "I know of no other drug bust that is larger than this involving the number of athletes involved," said Madden, who refused to reveal the names or genders of the athletes, or to be more specific about how many had tested positive. Olympic athletes face drug tests at major competitions, as well as random testing between events. Their samples are divided in two and stored for future reference. The athletes whose "A" samples revealed THG have been notified and will now have their "B" samples tested. If those also are positive, a review process will begin. Appeals could last for months. Track athletes found to have used steroids would face two-year bans. "What we have uncovered appears to be intentional doping of the worst sort," Madden said in a conference call from USADA headquarters in Colorado Springs, Colo. "This is a far cry from athletes accidentally testing positive as a result of taking contaminated nutritional supplements. "Rather, this is a conspiracy involving chemists, coaches and certain athletes using what they developed to be 'undetectable' designer steroids to defraud their fellow competitors and the American and world public who pay to attend sports events." THG has a chemical structure similar to the banned anabolic steroids gestrinome and trenbolone, Madden said. Though THG is not specifically named as a banned substance in world track, it would be considered a related substance outlawed under the sport's doping rules. Madden said the USADA received a call from a man in early June claiming to be a track coach and naming athletes whom he claimed were using an undetectable designer steroid. He then sent the agency, by overnight courier, a used syringe containing some of the substance, Madden said. The anti-doping laboratory at UCLA run by Don Catlin determined that the syringe contained THG, leading the USADA to retest 350 urine samples taken from athletes at the U.S. track and field championships in late June at Stanford, as well as 100 samples from random out-of-competition tests. Madden said USADA contacted federal authorities with the findings. He wouldn't say how many of the samples tested positive for THG. Madden said the anonymous tipster identified the source of the THG as Victor Conte, founder of BALCO laboratory of Burlingame. Madden would not say whether he had independent proof the substance came from Conte or BALCO. "Everything that the coach has identified to us up to this time is true. We are fairly certain this substance came from Victor Conte and BALCO labs," said Madden, refusing to provide more specifics about what made him so certain. In an e-mail sent to The Associated Press and other news organizations Thursday, Conte denied BALCO was the source of the substance. "In my opinion, this is about jealous competitive coaches and athletes that all have a history of promoting and using performance enhancing agents being 'completely hypocritical' in their actions," Conte wrote. Madden said he had not spoken with Conte. BALCO, which supplies nutritional guidance and supplements to athletes ranging from Barry Bonds to Bill Romanowski to Marion Jones, was the subject of a visit last month by agents from the Internal Revenue Service and a San Mateo County narcotics task force. No arrests were made, and IRS spokesman Mark Lessler said at the time he could not comment on the purpose of the unannounced visit. Sprinter Kelli White, whose failed drug test for the stimulant modafinil at this summer's track and field World Championships could cost her a pair of sprint gold medals, also is associated with BALCO. Her case is being considered by USADA. White was prescribed modafinil by Dr. Brian Goldman, a psychiatrist who worked with Conte for nearly 20 years. White's coach, Remi Korchemny, joined with Conte to form a track club. As part of the retesting of the 350 samples from the U.S. track championships, Madden said, officials discovered several positive tests for modafinil - which White claims she was taking for the sleep disorder narcolepsy. "Information we gathered showed athletes were using modafinil as a stimulant," Madden said. He said there's no chemical link between modafinil and THG. Dick Pound, chairman of the World Anti-Doping Agency, applauded USADA's work in a statement released at WADA headquarters in Montreal. "This is a serious warning for cheaters," Pound said. "It shows that supposedly undetectable substances can be detected as new tests are developed." On the Net: www.usantidoping.org LOAD-DATE: October 18, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 732 of 998 DOCUMENTS The Orange County Register (California) October 17, 2003 Friday Designer steroid exposed; Widespread use of THG among track and field athletes is uncovered. BYLINE: By SCOTT M. REID , The Orange County Register SECTION: SPORTS LENGTH: 480 words The U.S. Anti-Doping Agency said Thursday it has uncovered a widespread doping ring involving U.S. and international track and field athletes, coaches and a prominent Bay area laboratory. ``Several'' track athletes tested positive for tetrahydrogestrinone, or THG, a previously undetectable steroid, said Terry Madden, chief executive director of the anti-doping agency, but he refused to name the athletes or say how many tested positive. Madden said the names might not be made public until the completion of an appeals process in December. Athletes who test positive for anabolic steroids face two-year suspensions that would keep them out of the 2004 Olympic Games in Athens. ``I know of no other drug bust that is larger than this,'' Madden said. ``This is a far cry from athletes accidentally testing positive as a result of taking contaminated nutritional supplements,'' Madden said. ``Rather, this is a conspiracy involving chemists, coaches and certain athletes using what they developed to be `undetectable' designer steroids to defraud their fellow competitors and the American and world public who pay to attend sports events.'' The first break in the case came in early June, Madden said, when an anonymous source describing himself as a ``top-flight track coach,'' contacted the anti-doping agency. Madden said Thursday agency officials still do not know the source's identity. The source provided a syringe containing a designer steroid, undetectable by previous drug tests, Madden said. According to the source, the steroid came from Victor Conte of the BALCO Laboratory in Burlingame, Madden said. Conte and BALCO have supplied supplements and nutritional consultation to slugger Barry Bonds, sprinter Marion Jones and a number of NFL stars. Citing the potentially illegal activity by a distributor of a controlled substance, the agency contacted the Department of Justice, Madden said. The IRS raided BALCO facilities last month. The IRS also searched the offices of Bonds' personal trainer. The UCLA drug lab was able to come up with a test to detect TGH in mid-June. The anti-doping agency re-tested 350 in-competition samples tests from the 2003 U.S. Track & Field Championships. The organization also ordered 100 out-of-competition drug tests of U.S. track athletes and another 100 tests of athletes in other Olympic sports. Madden also said the agency found a number of positive test results for modafinil, a stimulant. Sprinter Kelli White tested positive for modafinil after winning two gold medal at the World Championships in August. White was prescribed modafinil by Dr. Brian Goldman, a psychiatrist who has worked with Conte for nearly 20 years. The athletes have recently been notified of their positive test results, Madden said. If the initial result is confirmed by a second lab test, the athlete will be considered positive and face suspension. sreid@ocregister.com LOAD-DATE: October 28, 2003 LANGUAGE: ENGLISH DOCUMENT-TYPE: Story PUBLICATION-TYPE: Newspaper Copyright 2003 Orange County Register 733 of 998 DOCUMENTS The Associated Press State & Local Wire October 16, 2003, Thursday, BC cycle U.S. Anti-Doping Agency says it has uncovered steroid conspiracy; Byline: 1/8 By ROB GLOSTER BYLINE: AP Sports Writer SECTION: Sports News LENGTH: 775 words DATELINE: SAN FRANCISCO The U.S. Anti-Doping Agency has uncovered a widespread drug conspiracy involving coaches, chemists and several track athletes who tested positive for a previously undetectable steroid and now face suspensions that could bar them from the 2004 Athens Olympics. USADA chief executive officer Terry Madden said Thursday that both American and international athletes had tested positive for the steroid, known as tetrahydrogestrinone, or THG. He said the ongoing inquiry began with an anonymous tip and has expanded to include U.S. professional sports. "I know of no other drug bust that is larger than this involving the number of athletes involved," said Madden, who refused to reveal the names, genders or nationalities of the athletes, or to be more specific about how many had tested positive. Olympic athletes face drug tests at major competitions, as well as random testing between events. Their samples are divided in two and stored for future reference. The athletes whose "A" samples revealed THG have been notified and will now have their "B" samples tested. If those also are positive, a review process will begin. Appeals could last for months. Track athletes found to have used steroids would face two-year bans. "What we have uncovered appears to be intentional doping of the worst sort," Madden said in a conference call from USADA headquarters in Colorado Springs, Colo. "This is a far cry from athletes accidentally testing positive as a result of taking contaminated nutritional supplements. "Rather, this is a conspiracy involving chemists, coaches and certain athletes using what they developed to be 'undetectable' designer steroids to defraud their fellow competitors and the American and world public who pay to attend sports events." THG has a chemical structure similar to the banned anabolic steroids gestrinome and trenbolone, Madden said. Though THG is not specifically named as a banned substance in world track, it would be considered a related substance outlawed under the sport's doping rules. Madden said the USADA received a call from a man in early June claiming to be a track coach and naming athletes whom he claimed were using an undetectable designer steroid. He then sent the agency, by overnight courier, a used syringe containing some of the substance, Madden said. The anti-doping laboratory at UCLA run by Don Catlin determined that the syringe contained THG, leading the USADA to retest 350 urine samples taken from athletes at the U.S. track and field championships in late June at Stanford, as well as 100 samples from random out-of-competition tests. Madden said USADA contacted federal authorities with the findings. He wouldn't say how many of the samples tested positive for THG. Madden said the anonymous tipster identified the source of the THG as Victor Conte, founder of BALCO laboratory of Burlingame. Madden would not say whether he had independent proof the substance came from Conte or BALCO. "Everything that the coach has identified to us up to this time is true. We are fairly certain this substance came from Victor Conte and BALCO labs," said Madden, refusing to provide more specifics about what made him so certain. Madden said he had not spoken with Conte, and Conte did not immediately respond Thursday to an e-mail inquiry from The Associated Press. A message left by phone at BALCO went unanswered. BALCO, which supplies nutritional guidance and supplements to athletes ranging from Barry Bonds to Bill Romanowski to Marion Jones, was the subject of enforcement action last month by the Internal Revenue Service and a San Mateo County narcotics task force. No arrests were made, and IRS spokesman Mark Lessler said he could not comment on the purpose of the unannounced visit to BALCO. Sprinter Kelli White, whose failed drug test for the stimulant modafinil at this summer's track and field World Championships could cost her a pair of sprint gold medals, also is associated with Conte. Her case currently is being considered by USADA. White was prescribed modafinil by Dr. Brian Goldman, a psychiatrist who has worked with Conte for nearly 20 years. And White's coach, Remi Korchemny, joined with Conte to form a track club. As part of the retesting of the 350 samples from the U.S. track championships, Madden said, officials discovered several positives for modafinil - which White claims she was taking for the sleep disorder narcolepsy. "Information we gathered showed athletes were using modafinil as a stimulant," Madden said. He said there's no chemical link between modafinil and THG. On the Net: www.usantidoping.org LOAD-DATE: October 17, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 734 of 998 DOCUMENTS The Associated Press State & Local Wire October 16, 2003, Thursday, BC cycle U.S. Anti-Doping Agency says it has uncovered steroid conspiracy BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Sports News LENGTH: 868 words DATELINE: SAN FRANCISCO The U.S. Anti-Doping Agency has uncovered a widespread drug conspiracy involving coaches, chemists and several track athletes who tested positive for a previously undetectable steroid and now face suspensions that could bar them from the 2004 Athens Olympics. USADA chief executive officer Terry Madden said Thursday that the U.S. athletes had tested positive for the steroid, known as tetrahydrogestrinone, or THG. He said the ongoing inquiry began in June with an anonymous tip and has expanded to include U.S. professional sports. "I know of no other drug bust that is larger than this involving the number of athletes involved," said Madden, who refused to reveal the names or genders of the athletes, or to be more specific about how many had tested positive. Olympic athletes face drug tests at major competitions, as well as random testing between events. Their samples are divided in two and stored for future reference. The athletes whose "A" samples revealed THG have been notified and will now have their "B" samples tested. If those also are positive, a review process will begin. Appeals could last for months. Track athletes found to have used steroids would face two-year bans. "What we have uncovered appears to be intentional doping of the worst sort," Madden said in a conference call from USADA headquarters in Colorado Springs, Colo. "This is a far cry from athletes accidentally testing positive as a result of taking contaminated nutritional supplements. "Rather, this is a conspiracy involving chemists, coaches and certain athletes using what they developed to be 'undetectable' designer steroids to defraud their fellow competitors and the American and world public who pay to attend sports events." THG has a chemical structure similar to the banned anabolic steroids gestrinome and trenbolone, Madden said. Though THG is not specifically named as a banned substance in world track, it would be considered a related substance outlawed under the sport's doping rules. Madden said the USADA received a call from a man in early June claiming to be a track coach and naming athletes whom he claimed were using an undetectable designer steroid. He then sent the agency, by overnight courier, a used syringe containing some of the substance, Madden said. The anti-doping laboratory at UCLA run by Don Catlin determined that the syringe contained THG, leading the USADA to retest 350 urine samples taken from athletes at the U.S. track and field championships in late June at Stanford, as well as 100 samples from random out-of-competition tests. Madden said USADA contacted federal authorities with the findings. He wouldn't say how many of the samples tested positive for THG. Madden said the anonymous tipster identified the source of the THG as Victor Conte, founder of BALCO laboratory of Burlingame. Madden would not say whether he had independent proof the substance came from Conte or BALCO. "Everything that the coach has identified to us up to this time is true. We are fairly certain this substance came from Victor Conte and BALCO labs," said Madden, refusing to provide more specifics about what made him so certain. In e-mails to several newspapers Thursday, Conte denied BALCO was the source of the substance. "In my opinion, this is about jealous competitive coaches and athletes that all have a history of promoting and using performance enhancing agents being 'completely hypocritical' in their actions," Conte said. Madden said he had not spoken with Conte, and Conte did not immediately respond Thursday to an e-mail inquiry from The Associated Press. A message left by phone at BALCO went unanswered. BALCO, which supplies nutritional guidance and supplements to athletes ranging from Barry Bonds to Bill Romanowski to Marion Jones, was the subject of a visit last month by agents from the Internal Revenue Service and a San Mateo County narcotics task force. No arrests were made, and IRS spokesman Mark Lessler said at the time he could not comment on the purpose of the unannounced visit. Sprinter Kelli White, whose failed drug test for the stimulant modafinil at this summer's track and field World Championships could cost her a pair of sprint gold medals, also is associated with BALCO. Her case is being considered by USADA. White was prescribed modafinil by Dr. Brian Goldman, a psychiatrist who worked with Conte for nearly 20 years. White's coach, Remi Korchemny, joined with Conte to form a track club. As part of the retesting of the 350 samples from the U.S. track championships, Madden said, officials discovered several positive tests for modafinil - which White claims she was taking for the sleep disorder narcolepsy. "Information we gathered showed athletes were using modafinil as a stimulant," Madden said. He said there's no chemical link between modafinil and THG. Dick Pound, chairman of the World Anti-Doping Agency, applauded USADA's work in a statement released at WADA headquarters in Montreal. "This is a serious warning for cheaters," Pound said. "It shows that supposedly undetectable substances can be detected as new tests are developed." On the Net: www.usantidoping.org LOAD-DATE: October 17, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 735 of 998 DOCUMENTS Edmonton Journal (Alberta) October 10, 2003 Friday Final Edition White's second test shows stimulant: IAAF leaves it up to USA Track & Field to decide next move SOURCE: The Associated Press SECTION: Sports; Pg. D5 LENGTH: 316 words DATELINE: PARIS PARIS - A second drug test indicates U.S. sprinter Kelli White used a stimulant during the world championships this summer when she won two gold medals, track's world governing body said Thursday. The results confirmed an earlier test that found modafinil, a medication used to treat a sleep disorder, in White's urine, according to Nick Davies, a spokesman for the International Association of Athletics Federations. The latest test was conducted on a second sample taken from White during the August meet, but not tested until now. U.S. officials must now decide whether the case constitutes a doping offence. The results go to USA Track & Field officials, who are expected to refer the case to the U.S. Anti-Doping Agency, Davies said. White will lose her 100- and 200-metre gold medals if U.S. officials determine she committed a doping offence. USA Track & Field spokeswoman Jill Geer wouldn't comment Thursday other than to say the results from the second test weren't surprising. "Remember, Kelli said the day the story broke that she was taking modafinil, so she's never said it wasn't in her system," she said. After she tested positive for modafinil at the championships in France, White said she used the medication for a sleep disorder and didn't know it contained banned substances. The IAAF said modafinil was covered under the category of "related substances." If White is stripped of her medals, Torri Edwards of the United States would be awarded the 100 gold medal while Zhanna Block of Ukraine would take the silver and Chandra Sturrup of Bahamas the bronze. The new 200 champion would be Russia's Anastaiya Kapachinskaya. Edwards would take the silver and France's Muriel Hurtis the bronze. Also Thursday, the IAAF said a second sample from American 110-metre hurdler Chris Phillips, who finished fifth at the worlds, also tested positive for modafinil. LOAD-DATE: October 10, 2003 LANGUAGE: ENGLISH GRAPHIC: Photo: The Associated Press, File; U.S. sprinter Kelli White TYPE: Sports Copyright 2003 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 736 of 998 DOCUMENTS Espicom Business Intelligence October 10, 2003 Modafinil approved for expanded use in Germany and Republic of Ireland LENGTH: 275 words Cephalon has received authorisation from the Federal Institute for Drugs and Devices and the Irish Medicines Board to market modafinil tablets in Germany and the Republic of Ireland, respectively, for the treatment of excessive daytime sleepiness associated with obstructive sleep apnoea/hypopnoea syndrome (OSA/HS). Both approvals include the adjunctive use of modafinil in patients who are receiving adequate treatment for their OSA/HS with standard therapy continuous positive airway pressure (CPAP). Modafinil is marketed under the trade name, Vigil, in Germany and as Provigil in Ireland. Modafinil is the first in a new class of wake-promoting agents believed to work selectively through the sleep/wake centres to activate the cortex of the brain. The drug is currently approved in more than 20 countries for the treatment of excessive daytime sleepiness associated with narcolepsy. In December of 2002, Provigil was approved to treat excessive daytime sleepiness in patients with OSA/HS in the UK. On 25th September 2003, the Peripheral and Central Nervous System Advisory Committee of the FDA recommended to expand the label for Provigil beyond its current indication for excessive daytime sleepiness associated with narcolepsy. The FDA is expected to determine the precise language of the modified label for Provigil by year-end. In controlled clinical trials, modafinil has been found to be generally well tolerated with a low incidence of adverse events relative to placebo. The most commonly observed adverse events associated with the use of modafinil were headache, infection, nausea, nervousness, anxiety and insomnia. LOAD-DATE: October 13, 2003 LANGUAGE: ENGLISH Copyright 2003 ESPICOM Business Intelligence Ltd. 737 of 998 DOCUMENTS Philadelphia Daily News OCTOBER 10, 2003 Friday 4STAR EDITION Kelli White's positive test confirmed BYLINE: Daily News Wire Services SECTION: SPORTS; Pg. 126 LENGTH: 288 words A second drug test indicates U.S. sprinter Kelli White used a stimulant during the World Championships this summer, when she won two gold medals, track's world governing body said yesterday in Paris. The results confirmed an earlier test that found modafinil, a medication used to treat a sleep disorder, in White's urine, said Nick Davies, a spokesman for the International Association of Athletics Federations. The latest test was conducted on a second sample taken from White during the August meet, but not tested until now. The results go to USA Track & Field officials, who are expected to refer the case to the U.S. Anti-Doping Agency, Davies said. White will lose her 100- and 200-meter gold medals if U.S. officials determine she committed a doping offense. After she tested positive for modafinil at the championships in France, White said she used the medication for a sleep disorder and didn't know it contained banned substances. The IAAF said modafinil was covered under the category of "related substances." Olympics * About 1,200 employees at the Olympic Village in Athens staged a 24-hour strike, a day after a construction worker was killed after being hit by a vehicle. * Olympic skating champion Alexei Yagudin applied for an alcohol education program that would clear his record of a drunken driving charge. Yagudin, 23, was pulled over Aug. 31 while driving in a Hartford, Conn., suburb. Sport Stops * Scott Verplank shot a second-round 62 to tie Steve Flesch for the lead at the Las Vegas Invitational. * South Carolina basketball center Rolando Howell pleaded no contest to domestic-violence charges and was ordered to pay a $50 fine and complete a counseling program. * LOAD-DATE: August 17, 2005 LANGUAGE: ENGLISH Copyright 2003 Philadelphia Newspapers, LLC All Rights Reserved 738 of 998 DOCUMENTS The Associated Press October 9, 2003, Thursday, BC cycle Second drug test shows U.S. sprinter Kelli White used a stimulant, IAAF says BYLINE: By ANGELA DOLAND, Associated Press Writer SECTION: Sports News LENGTH: 316 words DATELINE: PARIS A second drug test indicates U.S. sprinter Kelli White used a stimulant during the World Championships this summer, when she won two gold medals, track's world governing body said Thursday. The results confirmed an earlier test that found modafinil, a medication used to treat a sleep disorder, in White's urine, according to Nick Davies, a spokesman for the International Association of Athletics Federations. The latest test was conducted on a second sample taken from White during the August meet, but not tested until now. U.S. officials must now decide whether the case constitutes a doping offense. The results go to USA Track & Field officials, who are expected to refer the case to the U.S. Anti-Doping Agency, Davies said. White will lose her 100 and 200 meter gold medals if U.S. officials determine she committed a doping offense. USA Track & Field spokeswoman Jill Geer wouldn't comment Thursday other than to say the results from the second test weren't surprising. "Remember, Kelli said the day the story broke that she was taking modafinil, so she's never said it wasn't in her system," she said. After she tested positive for modafinil at the championships in France, White said she used the medication for a sleep disorder and didn't know it contained banned substances. The IAAF said modafinil was covered under the category of "related substances." If White is stripped of her medals, Torri Edwards of the United States would be awarded the 100 gold medal while Zhanna Block of Ukraine would take the silver and Chandra Sturrup of Bahamas the bronze. The new 200 champion would be Russia's Anastaiya Kapachinskaya. Edwards would take the silver and France's Muriel Hurtis the bronze. Also Thursday, the IAAF said a second sample from American 110-meter hurdler Chris Phillips, who finished fifth at the worlds, also tested positive for modafinil. LOAD-DATE: October 10, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 739 of 998 DOCUMENTS Associated Press Worldstream October 9, 2003 Thursday URGENT Second drug test shows U.S. sprinter Kelli White used a stimulant at world championships BYLINE: ANGELA DOLAND; Associated Press Writer SECTION: SPORTS LENGTH: 278 words DATELINE: PARIS A second urine sample showed that U.S. sprinter Kelli White used a stimulant during the August world championships, where she won two gold medals, the IAAF said Thursday. The results of a B Sample confirmed an earlier test that indicated White had ingested modafinil, a medication used to treat a sleep disorder, said Nick Davies, spokesman for the International Association of Athletics Federations. L'Equipe newspaper reported that the second test was done earlier in the week. U.S. officials must now decide whether the case constitutes a doping offense. The results go to USA Track & Field officials, who are expected to refer the case to the U.S. Anti-Doping Agency, Davies said. White will lose both her 100 and 200 meter gold medals if U.S. officials determine she committed a doping offense. After she tested positive for modafinil at the world championships in France, White said she used the medication for a sleep disorder and didn't know it contained banned substances because it didn't appear on the list. The IAAF said modafinil was covered under the category of "related substances." It rejected White's explanation. If White is stripped of her medals, Torri Edwards of the United States would be awarded the 100 gold medal while Zhanna Block of Ukraine would take the silver and Chandra Sturrup of Bahamas the bronze. In the possible shake-up, the new 200 champion would be Russia's Anastaiya Kapachinskaya. Edwards would take the silver and France's Muriel Hurtis the bronze. The IAAF spokesman also said a B Sample from American 110-meter hurdler Chris Phillips, who finished fifth at the worlds, also tested positive for modafinil. LOAD-DATE: October 10, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 740 of 998 DOCUMENTS The Associated Press State & Local Wire October 9, 2003, Thursday, BC cycle Second drug test shows Kelli White used stimulant, IAAF says BYLINE: By ANGELA DOLAND, Associated Press Writer SECTION: Sports News LENGTH: 328 words DATELINE: PARIS A second drug test indicates U.S. sprinter Kelli White used a stimulant during the World Championships this summer, when she won two gold medals, track's world governing body said Thursday. The results confirmed an earlier test that found modafinil, a medication used to treat a sleep disorder, in White's urine, according to Nick Davies, a spokesman for the International Association of Athletics Federations. The latest test was conducted on a second sample taken from White during the August meet, but not tested until now. White grew up in Oakland, Calif., and now lives nearby in Union City. U.S. officials must now decide whether the case constitutes a doping offense. The results go to USA Track & Field officials, who are expected to refer the case to the U.S. Anti-Doping Agency, Davies said. White will lose her 100 and 200 meter gold medals if U.S. officials determine she committed a doping offense. USA Track & Field spokeswoman Jill Geer wouldn't comment Thursday other than to say the results from the second test weren't surprising. "Remember, Kelli said the day the story broke that she was taking modafinil, so she's never said it wasn't in her system," she said. After she tested positive for modafinil at the championships in France, White said she used the medication for a sleep disorder and didn't know it contained banned substances. The IAAF said modafinil was covered under the category of "related substances." If White is stripped of her medals, Torri Edwards of the United States would be awarded the 100 gold medal while Zhanna Block of Ukraine would take the silver and Chandra Sturrup of Bahamas the bronze. The new 200 champion would be Russia's Anastaiya Kapachinskaya. Edwards would take the silver and France's Muriel Hurtis the bronze. Also Thursday, the IAAF said a second sample from American 110-meter hurdler Chris Phillips, who finished fifth at the worlds, also tested positive for modafinil. LOAD-DATE: October 10, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 741 of 998 DOCUMENTS Associated Press Online October 9, 2003 Thursday IAAF: 2nd Test Shows White Used Stimulant BYLINE: ANGELA DOLAND; Associated Press Writer SECTION: SPORTS LENGTH: 314 words DATELINE: PARIS A second drug test indicates U.S. sprinter Kelli White used a stimulant during the World Championships this summer, when she won two gold medals, track's world governing body said Thursday. The results confirmed an earlier test that found modafinil, a medication used to treat a sleep disorder, in White's urine, according to Nick Davies, a spokesman for the International Association of Athletics Federations. The latest test was conducted on a second sample taken from White during the August meet, but not tested until now. U.S. officials must now decide whether the case constitutes a doping offense. The results go to USA Track & Field officials, who are expected to refer the case to the U.S. Anti-Doping Agency, Davies said. White will lose her 100 and 200 meter gold medals if U.S. officials determine she committed a doping offense. USA Track & Field spokeswoman Jill Geer wouldn't comment Thursday other than to say the results from the second test weren't surprising. "Remember, Kelli said the day the story broke that she was taking modafinil, so she's never said it wasn't in her system," she said. After she tested positive for modafinil at the championships in France, White said she used the medication for a sleep disorder and didn't know it contained banned substances. The IAAF said modafinil was covered under the category of "related substances." If White is stripped of her medals, Torri Edwards of the United States would be awarded the 100 gold medal while Zhanna Block of Ukraine would take the silver and Chandra Sturrup of Bahamas the bronze. The new 200 champion would be Russia's Anastaiya Kapachinskaya. Edwards would take the silver and France's Muriel Hurtis the bronze. Also Thursday, the IAAF said a second sample from American 110-meter hurdler Chris Phillips, who finished fifth at the worlds, also tested positive for modafinil. LOAD-DATE: October 10, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 742 of 998 DOCUMENTS Midnight Trader This content is provided to LexisNexis by Comtex News Network, Inc. October 9, 2003 Thursday Cephalon Gets German, Irish Oks for Expanded Use of Modafinil Sleep Disorder Drug LENGTH: 107 words DATELINE: Boston Cephalon (CEPH) said today the company has received authorization from the Federal Institute for Drugs and Devices and the Irish Medicines Board to market modafinil tablets in Germany and the Republic of Ireland, respectively, for the treatment of excessive daytime sleepiness associated with obstructive sleep apnea/hypopnea syndrome. Both approvals include the adjunctive use of modafinil in patients who are receiving adequate treatment for their OSA/HS with standard therapy continuous positive airway pressure. Stock should see continued movement into the after-hours. http://www.midnighttrader.com LOAD-DATE: October 10, 2003 LANGUAGE: ENGLISH Copyright 2003 Comtex News Network, Inc. All Rights Reserved Copyright 2003 MidnightTrader.com. All rights reserved. Unauthorized reproduction is strictly prohibited. 743 of 998 DOCUMENTS PR Newswire October 9, 2003 Thursday Cephalon Receives Approval for Expanded Use of Modafinil in Germany and the Republic of Ireland SECTION: FINANCIAL NEWS LENGTH: 984 words Market Authorization Received for the Treatment of Excessive Daytime Sleepiness Associated with Obstructive Sleep Apnea/Hypopnea Syndrome WEST CHESTER, Pa., Oct. 9 /PRNewswire-FirstCall/ -- Cephalon, Inc. (Nasdaq: CEPH) announced today that the company has received authorization from the Federal Institute for Drugs and Devices (BfArM) and the Irish Medicines Board (IMB) to market modafinil tablets in Germany and the Republic of Ireland, respectively, for the treatment of excessive daytime sleepiness associated with obstructive sleep apnea/hypopnea syndrome (OSA/HS). Both approvals include the adjunctive use of modafinil in patients who are receiving adequate treatment for their OSA/HS with standard therapy continuous positive airway pressure (CPAP). Modafinil is marketed under the trade name VIGIL(R) in Germany and under the trade name PROVIGIL(R) in Ireland. "Modafinil is an important component of our European business, and these approvals and our label expansion strategy will contribute to our growing presence in the European market," said John Dawson, Vice President, Pharmaceutical Operations Europe. Modafinil Modafinil is the first in a new class of wake-promoting agents believed to work selectively through the sleep/wake centers to activate the cortex of the brain. The drug is currently approved in more than 20 countries for the treatment of excessive daytime sleepiness associated with narcolepsy. In December of 2002, PROVIGIL was approved to treat excessive daytime sleepiness in patients with obstructive sleep apnea/hypopnea syndrome in the UK. On September 25, 2003, the Peripheral and Central Nervous System Advisory Committee of the U.S. Food and Drug Administration recommended to expand the label for PROVIGIL (modafinil) $(C-IV$) beyond its current indication for excessive daytime sleepiness associated with narcolepsy. The FDA is expected to determine the precise language of the modified label for PROVIGIL by year-end. In controlled clinical trials, modafinil has been found to be generally well tolerated with a low incidence of adverse events relative to placebo. The most commonly observed adverse events associated with the use of modafinil were headache, infection, nausea, nervousness, anxiety and insomnia. Obstructive Sleep Apnea/Hypopnea Syndrome Obstructive sleep apnea/hypopnea syndrome is a serious and potentially life-threatening sleep disorder affecting four percent of middle-aged men and two percent of middle-aged women. Individuals with obstructive sleep apnea/hypopnea syndrome experience frequent awakenings throughout the night as a result of blockage of the airway during sleep. This disruption of sleep leads to excessive daytime sleepiness causing many people to doze off repeatedly throughout the day -- at their jobs and at home. The most commonly used standard treatment is continuous positive airway pressure (CPAP). A nasal CPAP device can prevent airway closure while in use and therefore is used to treat the underlying disorder. Despite treatment of the underlying disorder, many patients continue to experience residual excessive sleepiness and may be candidates for modafinil. Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products to treat sleep and neurological disorders, cancer and pain. Cephalon currently employs approximately 1,400 people in the United States and Europe. U.S. sites include the company's headquarters in West Chester, Pennsylvania, and offices and manufacturing facilities in Salt Lake City, Utah. Cephalon's major European offices are located in Guildford, England, Martinsried, Germany, and at Maisons-Alfort, France. The company currently markets three proprietary products in the United States: PROVIGIL, GABITRIL(R) (tiagabine hydrochloride) and ACTIQ(R) (oral transmucosal fentanyl citrate) $(C-II$) and more than 20 products internationally. Further information about Cephalon and full prescribing information on its U.S. products is available at www.cephalon.com or by calling 1-800-896-5855. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding the timing of FDA action on Cephalon's sNDA, the opportunity created by an expanded PROVIGIL label, anticipated scientific progress on its research programs, development of potential pharmaceutical products, interpretation of clinical results, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, sales and earnings guidance, and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. SOURCE Cephalon, Inc. CONTACT: Media: Robert Grupp, +1-610-738-6402, rgrupp@cephalon.com; or Investor: Chip Merritt, +1-610-738-6376, cmerritt@cephalon.com, both of Cephalon URL: http://www.prnewswire.com LOAD-DATE: October 10, 2003 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS AND MEDICAL EDITORS PUBLICATION-TYPE: Newswire Copyright 2003 PR Newswire Association, Inc. 744 of 998 DOCUMENTS PR Newswire Europe October 9, 2003 Thursday Cephalon receives approval for expanded use of Modafinil in Germany and the Republic of Ireland LENGTH: 1018 words - Market authorization received for the treatment of excessive daytime sleepiness associated with obstructive sleep Apnea/Hypopnea Syndrome Cephalon, Inc. announced today that the company has received authorization from the Federal Institute for Drugs and Devices [BfArM] and the Irish Medicines Board [IMB] to market modafinil tablets in Germany and the Republic of Ireland, respectively, for the treatment of excessive daytime sleepiness associated with obstructive sleep apnea/hypopnea syndrome [OSA/HS]. Both approvals include the adjunctive use of modafinil in patients who are receiving adequate treatment for their OSA/HS with standard therapy continuous positive airway pressure [CPAP]. Modafinil is marketed under the trade name VIGIL[R] in Germany and under the trade name PROVIGIL[R] in Ireland. "Modafinil is an important component of our European business, and these approvals and our label expansion strategy will contribute to our growing presence in the European market," said John Dawson, Vice President, Pharmaceutical Operations Europe. Modafinil Modafinil is the first in a new class of wake-promoting agents believed to work selectively through the sleep/wake centers to activate the cortex of the brain. The drug is currently approved in more than 20 countries for the treatment of excessive daytime sleepiness associated with narcolepsy. In December of 2002, PROVIGIL was approved to treat excessive daytime sleepiness in patients with obstructive sleep apnea/hypopnea syndrome in the UK. On September 25, 2003, the Peripheral and Central Nervous System Advisory Committee of the U.S. Food and Drug Administration recommended to expand the label for PROVIGIL [modafinil] [C-IV] beyond its current indication for excessive daytime sleepiness associated with narcolepsy. The FDA is expected to determine the precise language of the modified label for PROVIGIL by year-end. In controlled clinical trials, modafinil has been found to be generally well tolerated with a low incidence of adverse events relative to placebo. The most commonly observed adverse events associated with the use of modafinil were headache, infection, nausea, nervousness, anxiety and insomnia. Obstructive Sleep Apnea/Hypopnea Syndrome Obstructive sleep apnea/hypopnea syndrome is a serious and potentially life-threatening sleep disorder affecting four percent of middle-aged men and two percent of middle-aged women. Individuals with obstructive sleep apnea/hypopnea syndrome experience frequent awakenings throughout the night as a result of blockage of the airway during sleep. This disruption of sleep leads to excessive daytime sleepiness causing many people to doze off repeatedly throughout the day -- at their jobs and at home. The most commonly used standard treatment is continuous positive airway pressure [CPAP]. A nasal CPAP device can prevent airway closure while in use and therefore is used to treat the underlying disorder. Despite treatment of the underlying disorder, many patients continue to experience residual excessive sleepiness and may be candidates for modafinil. Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products to treat sleep and neurological disorders, cancer and pain. Cephalon currently employs approximately 1,400 people in the United States and Europe. U.S. sites include the company's headquarters in West Chester, Pennsylvania, and offices and manufacturing facilities in Salt Lake City, Utah. Cephalon's major European offices are located in Guildford, England, Martinsried, Germany, and at Maisons-Alfort, France. The company currently markets three proprietary products in the United States: PROVIGIL, GABITRIL[R] [tiagabine hydrochloride] and ACTIQ[R] [oral transmucosal fentanyl citrate] [C-II] and more than 20 products internationally. Further information about Cephalon and full prescribing information on its U.S. products is available at http://www.cephalon.com/ or by calling 1-800-896-5855. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding the timing of FDA action on Cephalon's sNDA, the opportunity created by an expanded PROVIGIL label, anticipated scientific progress on its research programs, development of potential pharmaceutical products, interpretation of clinical results, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, sales and earnings guidance, and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. Web site: http://www.cephalon.com/Cephalon CONTACT: Media: Robert Grupp, +1-610-738-6402, rgrupp@cephalon.com; or Investor: Chip Merritt, +1-610-738-6376, cmerritt@cephalon.com, both of Cephalon/ First Call Analyst: Robert S. Merritt/ Company News On-Call: http://www.prnewswire.com/comp/134563.html LOAD-DATE: October 10, 2003 LANGUAGE: ENGLISH Copyright 2003 PR Newswire Europe Limited 745 of 998 DOCUMENTS The Independent (London) October 4, 2003, Saturday SPORT LETTERS: HEALTHY CASE BYLINE: HANS NAERT SECTION: SPORT; Pg. 9 LENGTH: 150 words Sir: It would be an unacceptable mistake to disqualify Kelli White as the world champion in the 100 and 200 metres dash. The IAAF wants that because they found Modafinil in her urine after the 100m. Modafinil is not, however, on the list of banned products. The IAAF's statement that it is a "light stimulant" and a "related product" is extremely vague and subjective. Modafinil is a kind of anti-sleeping pill, the best medicine to fight the symptoms of narcolepsy, a disease from which White suffers. Narcolepsy is a form of brain damage that makes her fall asleep without being tired. White needs Modafinil for her health, not to run faster. This makes it a medicine, not a doping product. She is clearly a victim of false accusations. She should take legal action against the IAAF. An athlete doesn't have to accept this kind of treatment. HANS NAERT Berchem, Netherlands LOAD-DATE: October 6, 2003 LANGUAGE: ENGLISH Copyright 2003 Independent Print Ltd 746 of 998 DOCUMENTS Agence France Presse -- English September 24, 2003 Wednesday Anti-doping body place 'Kelli White drug' on banned list SECTION: Sports LENGTH: 392 words DATELINE: MONTREAL, Sept 23 The World Anti-Doping Agency (WADA) added Modafinil, the stimulant which may cost American sprinter Kelli White her two world sprint titles, to its list of banned substances here on Tuesday. Caffeine and pseudoephedrine were however taken off the list, which will be published on WADA's website on October 1. "Changes to the list this year include the removal of caffeine and pseudoephedrine. Some substances, such as modafinil, have been added," said a statement after the final day of the global anti-drugs body's Executive Committee. Modafinil, known in the United States by the brand name Provigil, was found in White's urine sample after her 100 metres victory at last month's World Championships in Paris. White claimed she took the drug to combat narcolepsy, or extreme tiredness, but the International Association of Athletics Federations rejected her explanation and passed the case on to the US Anti-Doping Agency (USADA). Although White is likely to lose her titles, she will not be banned because Modafinil was not on the banned list although it was considered related to drugs that were. By adding it to the list, WADA will hope to eliminate a troublesome grey area. WADA said it had examined a number of reprisals for countries who fail to pay their fees to the Agency, which has collected less than 63 percent of dues owned for 2003. Major contributors such as the United States and Italy are among those late in paying up. In a statement, WADA said it was considering "removing members from the Executive Committee or Board whose countries or regions have not paid their dues. It will also be recommended to the Board that no laboratory receive accreditation or re-accreditation from WADA until the country in which the lab is situated has met its financial commitments to the Agency." It said WADA would ask for support from the International Olympic Committee on the matter. WADA President Dick Pound said he still hoped the World Anti-Doping Code would be adopted by all sports federations in time for next year's Athens Olympics. "The speed with which governments and sports organizations are adopting the Code is very encouraging," Pound said in a statement. "I believe we are well on our way to implementation of the Code by the sports world prior to Athens". pjl/gj Sport-doping-WADA-Athletics LOAD-DATE: September 24, 2003 LANGUAGE: ENGLISH Copyright 2003 Agence France Presse 747 of 998 DOCUMENTS Contra Costa Times September 24, 2003 Wednesday FINAL EDITION WHITE PONDERING HANGING UP SPIKES BYLINE: ANN TATKO, TIMES COLUMNIST SECTION: SPORTS; Pg. B03 LENGTH: 782 words SPRINTER KELLI WHITE said next season likely will be her last as a track athlete. Since testing positive for a stimulant at the world championships last month, White said, she has struggled to deal with physical and emotional strain. She intimated before last week's Moscow Challenge that retirement may come sooner rather than later. She said Tuesday by phone that sooner probably means after next summer's Olympics. "What I'm going through now has forced me to re-evaluate how much longer I want to be in this sport," White, 26, said. "I have other options. I'd like to start a few businesses, and a family, eventually. This situation has been very difficult and I'm not sure if (competing) is worth it any more." White, a former El Sobrante resident, tested positive for modafinil after winning the 100-meter world title Aug. 24. White said she was prescribed modafinil for a sleeping disorder. She no longer takes the medication, she said, which has led to her feeling weak and tired. Although she wasn't suspended from competition, White may lose the two gold medals she won at the championships. The U.S. Anti-Doping Agency is reviewing her case. On Tuesday in Montreal, a two-day meeting of the World Anti-Doping Agency executive committee made modafinil a banned stimulant for the first time. (At the same time, the committee removed caffeine and pseudoephedrine, an ingredient in over-the-counter cold remedies such as Sudafed, from the list of banned substances for international sports.) White said she was hit hardest by the boos she has received from fans at three meets since worlds. "I know next year will be difficult, too," she said. "But I intend to stick it out. After that, it probably will be time to move on." SILVER ALL AROUND: M.J. McColgan of Danville and David Bueche of Concord won silver medals at last week's National Special Olympics Golf Championships in Port St. Lucie, Fla. McColgan competed in the level 3 tournament - an 18-hole Ryder Cup format - with his father, Mike. He shot a three-day total of 270 to finish second by five strokes behind Mike and John Higgs of Michigan. McColgan also won silver last year. He bettered his score this year by seven strokes. Competing at level 5, in an 18-hole individual stroke play, Bueche seemed headed for gold after shooting 36 on the front nine. He finished the day at 81, two strokes behind winner Kevin Erickson of Wisconsin. The championship was open to 158 of the nation's top golfers who have some form of disability. HAWAIIAN DEBUT: Brent Descalopoulis, 35, of Pleasanton will join about 1,500 competitors at next month's Ironman World Championships in Kailua Kona, Hawaii. Descalopoulis, an air traffic controller, is making his first trip to the world championships, which will be held Oct. 18. The ironman triathlon features a 2.4-mile swim, 112-mile bike ride and 26.2-mile marathon. Athletes have 17 hours to complete the competition. ONE DOWN: Logan Tom of Stanford helped the U.S. women's volleyball team secure a spot in the first Olympic qualifier. Team USA defeated three-time defending Olympic champion Cuba at the NORCECA Zone Championship in Santo Domingo, Dominican Republic, last week. Tom scored 12 points in the match. Both teams advance to the World Cup, to be held Nov. 1 to 15 in Japan. The top three finishers at the World Cup earn a berth to next summer's Olympics. ROSTER SELECTIONS: USA Baseball officials will announce today the 32 players who will attend next week's USA team trials in Phoenix. They will make the announcement live on MLB.com Radio at 9 a.m. The trials will determine the 25-man roster for an Olympic qualifying event that begins Oct. 30 in Panama. College and minor-league baseball players are eligible to compete, but major-league players are not. Montreal Expos manager Frank Robinson will manage the U.S. national team, USA Baseball announced. QUICK HITS: Sayaka Matsumoto of Richmond failed to place at the World Judo Championships in Osaka, Japan, last week. Competing at 48 kilograms, Matsumoto lost to eventual silver medalist Frederick Jossinet of France in the first round and to Danieska Carrion of Cuba in the first repechage (a second-chance match.) n Former Cal star Holly McPeak and Elaine Youngs lost in a first-round playoff at the women's U.S. Grand Slam beach volleyball tournament last week in Los Angeles. McPeak and Youngs won their three pool play matches before falling 22-20, 21-17 to Tian Jia and Wang Fei of China in the first round. The PGA, USA Volleyball, U.S. Judo, U.S. Sailing and USA Baseball contributed information for this article. Contact Ann Tatko at atatko@cctimes.com. LOAD-DATE: November 10, 2005 LANGUAGE: ENGLISH Copyright 2003 Contra Costa Times All Rights Reserved 748 of 998 DOCUMENTS The New York Times September 24, 2003 Wednesday Late Edition - Final Sports Briefing SECTION: Section D; Column 1; Sports Desk; Pg. 7 LENGTH: 830 words INTERNATIONAL SPORTS Caffeine and a Cold Medication No Longer Banned; Modafinil Is Caffeine and pseudoephedrine, an ingredient in over-the-counter cold remedies like Sudafed, were removed from the list of banned substances for international sports. The World Anti-Doping Agency said yesterday in Montreal that it wanted to prevent the suspensions of athletes who took common cold remedies or drank cola or coffee. A two-day meeting of W.A.D.A.'s executive committee also made modafinil a banned stimulant for the first time. That is the medication that could cost the American sprinter Kelli White two gold medals from the world championships last month. Last week, Arne Ljungqvist, the head of W.A.D.A.'s medical research committee, said the list would be changed to reflect changing times. The agency has set a deadline of Oct. 1 for final ratification of the list, which would take effect globally Jan. 1. The list applies to all sports and all countries covered by W.A.D.A.'s global anti-doping code. It would be in force for next year's Athens Olympics. (AP) SWIMMING Champion's Suspension Reduced The Olympic freestyle champion Claudia Poll's suspension for testing positive for a banned steroid was cut to two years, allowing her to compete next year in the Athens Games. FINA, swimming's world governing body, said yesterday in Geneva that Poll, a 30-year-old Costa Rican swimmer, was benefiting from its new doping code, applied retroactively. Poll, the 200-meter freestyle champion at the 1996 Atlanta Games, tested positive for the banned steroid norandrosterone in an out-of-competition test in 2002 and was suspended for four years. FINA also said that the Greek swimmer Vasileios Demetis, barred for life after testing positive for norandrosterone and lidocaine two years ago, would also be allowed to return to competition because of the new rule, adopted Sept. 11. (AP) FIGURE SKATING Yagudin and Slutskaya Pull Out The Olympic champion Aleksei Yagudin and the 2002 world champion Irina Slutskaya withdrew yesterday from next week's International Figure Skating Classic at Madison Square Garden. Yagudin, a four-time world champion from Russia attempting to come back from a severe hip injury that sidelined him last season, is still not fully fit. Scott Smith of the United States will replace Yagudin. Smith won the silver medal at the Nebelhorn Trophy earlier this month in the first event tested under the International Skating Union's new judging system. Slutskaya withdrew with an illness. The American Jennifer Kirk will replace Slutskaya. (AP) COLLEGE FOOTBALL F.S.U.'s Rix Is Ticketed Again Florida State quarterback Chris Rix was ticketed again yesterday for a parking violation, this time for leaving his vehicle in a spot reserved for patients at the university's regional rehabilitation center in Tallahassee. Rix was ticketed last week for parking in a handicapped-only spot and was fined $100. Yesterday's offense was reported by a student who took several photos of Rix's vehicle, university officials said. Team officials imposed a punishment of extra running drills against Rix this week in response to the handicapped-spot ticket. More team-imposed penalties against Rix are possible, Coach Bobby Bowden said yesterday. Rix refused to comment. (AP) PRO BASKETBALL Lobo Retires from W.N.B.A. Rebecca Lobo retired yesterday after a career in which she led Connecticut to its first N.C.A.A. basketball championship and helped launch the W.N.B.A. Lobo, 30, who spent last season with the Connecticut Sun, was plagued by knee injuries during her seven years in the W.N.B.A. "While I still love playing the game, in my heart, I know it's time to move on to a new phase of my life," the 6-foot-4 Lobo said. Lobo led UConn to the national championship in 1995, when the team went 35-0. She was one of the W.N.B.A.'s original players in 1997, assigned to the Liberty. She spent the first five years of her pro career in New York, missing almost two full seasons because of knee injuries. Lobo averaged 6.7 points and 4.1 rebounds in 121 W.N.B.A. games. (AP) Shaw Retiring From Lakers Los Angeles Lakers guard Brian Shaw, 37, is retiring after 14 N.B.A. seasons to join the team's front office. He won three N.B.A. titles in four seasons with the Lakers, and averaged 6.9 points in 943 N.B.A. games with seven teams. (AP) Coles Returns to Heat The free-agent point guard Bimbo Coles returned to the team where he started his career, signing with the Miami Heat yesterday. The 6-foot-2 Coles, a 13-year N.B.A. veteran, played for Cleveland and Boston last season and averaged 4.4 points. (AP) SOCCER New Owner for M.L.S.'s Rapids Stan Kroenke, owner of basketball's Denver Nuggets and hockey's Colorado Avalanche, bought Major League Soccer's Colorado Rapids and plans to build them a soccer-only stadium. Kroenke purchased the Rapids from Phil Anschutz, who still owns 5 of the league's 10 teams. Financial terms of the sale were not disclosed. (Bloomberg News) URL: http://www.nytimes.com LOAD-DATE: September 24, 2003 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2003 The New York Times Company 749 of 998 DOCUMENTS Associated Press Worldstream September 12, 2003 Friday IAAF confirms White's entry in sprints at Final SECTION: SPORTS LENGTH: 250 words DATELINE: MONTE CARLO, Monaco American sprinter Kelli White, under investigation for testing positive for a minor stimulant at the Paris worlds, will attempt a sprint double at the inaugural World Athletics Final this weekend, the sport's governing body said Friday. White was originally only entered in the 100 meters in Monaco. "Kelli White is scheduled to run in both 100 and 200 meters," IAAF spokesman Nick Davis told The Associated Press by telephone. White tested positive for modafinil after winning the 100 meters at the World Championships on August 24, and four days later won the 200 meters. She set personal best times in both races. Because modafinil is considered a minor stimulant, the IAAF did not suspend White. She won the 100 meters at a Golden League meeting in Brussels on September 5. But the IAAF rejected a doctor's report explaining why she needed to take modafinil. White had claimed she used it to treat a sleep-related disorder called narcolepsy. The IAAF has now asked U.S. track officials to begin disciplinary measures against her. If found guilty of doping, White will be stripped of both her world championship gold medals. White is now scheduled to compete in Saturday's 200 meters and in the 100 on Sunday. She joins some 30 world champions and 250 other athletes competing in the event. The World Athletics Final is the last event of the season before the male and female World Athletes of the Year are crowned. Points gained over the weekend count toward the overall rankings. LOAD-DATE: September 13, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 750 of 998 DOCUMENTS XINHUA GENERAL NEWS SERVICE September 12, 2003, Friday White says she will fight to maintain two gold medals SECTION: WORLD NEWS; SPORTS LENGTH: 174 words LONDON, Sept. 12 (Xinhua) -- American double world sprint champion Kelli White, who tested positive for modafinil at the Paris world championships, said on Friday she would fight to keep her gold medals. The International Association of Athletics Federations(IAAF) said early this week that it did not accept White's explanation for her positive test for modafinil and had referred the matter to the U.S. anti-doping agency. White, who tested positive after winning the 100 meters on August 24, said she took the prescribed medication to combat narcolepsy. A second test after the 200 final was clean. If she is found guilty of a doping offence then she would be disqualified and forced to give up both her gold medals. "No way. No way. I'm still going to fight to keep the medals," White told CNN on Friday. "I still think there is a chance that I will be able to keep my medals. Modafinil is not yet on the IAAF's banned list, therefore, White is still able to compete at this weekend's IAAF Grand Prix Final in Monaco. LOAD-DATE: September 13, 2003 LANGUAGE: ENGLISH COPYRIGHT 2003 XINHUA NEWS AGENCY 751 of 998 DOCUMENTS Herald Sun (Melbourne, Australia) September 11, 2003 Thursday IAAF rejects White's drug defence SOURCE: REUTERS SECTION: SPORT; Pg. 60 LENGTH: 281 words THE International Association of Athletics Federations has rejected double world sprint champion Kelli White's explanation of why she tested positive for the stimulant modafinil at the world championships in Paris last month. IAAF spokesman Nick Davies said her explanation had not been accepted and, in accordance with the normal disciplinary procedures, her case had been referred to the US anti-doping agency for a hearing. White, the first American to win the 100m-200m sprint double, has not been suspended pending her hearing and can run at this weekend's inaugural World Athletics Final at Monaco's Stade Louis II. However, if she was found guilty of a doping offence she would be stripped of the individual gold medals she won in Paris. The 26-year-old White tested positive for modafinil, which is not on the IAAF banned list, after winning the 100m final on August 24. A urine sample taken after she won the 200m four days later was clean. The sprinter said at the time that she had been prescribed modafinil to combat narcolepsy, or sleepiness, and had not sought exemption or entered it on her doping control form because it was not on the banned list. The IAAF said last week that modafinil, which is related to prohibited drugs, will be classified as a weaker stimulant and placed on the World Anti-Doping Agency's banned list next year. White has until September 29 to ask for the B sample to be examined, which she is expected to do, and the US anti-doping agency then has up to three months to hear her case. If the IAAF does not then agree with the result of that hearing it can take the case to the Court of Arbitration for Sport in Switzerland. LOAD-DATE: September 10, 2003 LANGUAGE: ENGLISH JOURNAL-CODE: DHS Copyright 2003 Nationwide News Pty Limited 752 of 998 DOCUMENTS The Associated Press State & Local Wire September 10, 2003, Wednesday, BC cycle IAAF rules Kelli White guilty of doping offense BYLINE: By STEPHEN WILSON, AP Sports Writer SECTION: Sports News LENGTH: 622 words DATELINE: LONDON Track and field's governing body wants American sprinter Kelli White stripped of her two gold medals from the World Championships. Now it's up to U.S. anti-doping officials. The International Association of Athletics Federations ruled Tuesday that White committed a doping offense when she tested positive for a stimulant and should lose her world titles in the 100 and 200 meters. The IAAF rejected White's explanation that she took the stimulant for a sleep disorder and sent the case to the U.S. Anti-Doping Agency for a hearing and disciplinary action. Rich Wanninger, a spokesman for the U.S. Anti-Doping Agency, said his organization had not received any information from the IAAF as of Tuesday afternoon. Once that information is received, Wanninger said, the agency will begin a review process that could last months. The IAAF made clear it expects U.S. authorities to remove White's medals. "The proper sanction under IAAF rules will be a public warning and disqualification from the competition concerned," IAAF general secretary Istvan Gyulai said. If the IAAF isn't satisfied with the U.S. action, the international body would take the case to the Court of Arbitration for Sport in Lausanne, Switzerland. "She is disqualified only at the end of the procedure because further legal issues need to be exhausted," Gyulai told The Associated Press by phone from IAAF headquarters in Monaco. "This can only happen after she has been given a hearing by her national federation." White, the first American woman to sweep the sprint events at the worlds, tested positive for modafinil after winning the 100 on Aug. 24. She passed a drug test after winning the 200 four days later. The IAAF gave White until Tuesday to produce medical documents explaining her use of the drug. She said her personal doctor prescribed the medication for narcolepsy. "The explanation has been studied and turned down," Gyulai said. "Our experts have determined the stimulant is performance-enhancing." White was unavailable for comment Tuesday. She said last week she will fight to keep her medals. "Whatever I have to do to keep them, I will do that," she said. Modafinil is not on the sport's list of banned drugs, but the IAAF says it falls under the category of "related substances." White denied taking the medication to enhance performance and said she didn't know it contained a banned substance. However, she did not declare modafinil on her doping control form as required or apply for a medical exemption to use the product. The IAAF ruled last Wednesday that modafinil was a minor stimulant, similar to ephedrine, and carries a penalty of a public warning and disqualification. The decision allowed White to continue competing. Had modafinil - sold in the United States under the brand name Provigil - been classified as a stronger stimulant, White also would have faced a two-year ban and been ineligible for the 2004 Athens Olympics. Although White tested clean after the 200, the IAAF considers one positive test enough for disqualification from the entire championships. If White loses the medals, the golds would go to fellow American sprinter Torri Edwards in the 100 and Russia's Anastasiya Kapachinskaya in the 200. White would also lose the $120,000 in prize money she won at the worlds. Under the sport's policy of strict liability, athletes are considered guilty of a doping violation if banned substances are found in their bodies, regardless of the circumstances. White competed at the Golden League meet in Brussels, Belgium, last Friday and won the 100 in 10.87 seconds. She is to run in the Grand Prix final in Monaco this weekend and a meet in Moscow on Sept. 20. LOAD-DATE: September 11, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 753 of 998 DOCUMENTS Birmingham Post September 10, 2003, Wednesday ATHLETICS: WHITE FACING US DRUG HEARING SECTION: SPORT; Pg. 24 LENGTH: 300 words The International Association of Athletics Federations (IAAF) has rejected double world sprint champion Kelli White's explanation of why she tested positive for a stimulant at the world championships. 'The IAAF has received the athlete's explanation for testing positive for modafinil at the world championships in Paris last month,' IAAF spokesman Nick Davies said yesterday. 'Following careful examination, the explanation has not been accepted. 'The matter has now be referred to the United States anti-doping agency for a hearing.' White (pictured), the first American to win the 100-200 metres sprint double, has not been suspended pending her hearing before the US antidoping agency and can therefore run at this weekend's inaugural World Athletics Final at Monaco's Stade Louis II. However, if she is found guilty of a doping offence, White would be stripped of the individual gold medals she won in Paris last month. 'The IAAF has already announced that if it is confirmed after the hearing that the athlete has committed a doping offence, the sanction under IAAF rules will be a public warning and disqualification from the competition,' said Davies. The 26-year-old White tested positive for modafinil, which is not at present on the IAAF banned list, after winning the 100m final on August 24. A urine sample taken after she won the 200 four days later was found to be clean. The sprinter said at the time that she had been prescribed modafinil to combat narcolepsy sleepiness and had not sought exemption, or entered it on her doping control form, because it was not on the banned list. The IAAF said last week that modafinil is now to be classified as a weaker stimulant and will be placed on the World Anti-Doping Agency's banned list next year. LOAD-DATE: September 10, 2003 LANGUAGE: ENGLISH PUB-TYPE: PAPER Copyright 2003 Midland Independent Newspapers plc 754 of 998 DOCUMENTS Birmingham Post September 10, 2003, Wednesday ATHLETICS: WHITE FACING US DRUG HEARING SECTION: SPORT; Pg. 24 LENGTH: 300 words The International Association of Athletics Federations (IAAF) has rejected double world sprint champion Kelli White's explanation of why she tested positive for a stimulant at the world championships. 'The IAAF has received the athlete's explanation for testing positive for modafinil at the world championships in Paris last month,' IAAF spokesman Nick Davies said yesterday. 'Following careful examination, the explanation has not been accepted. 'The matter has now be referred to the United States anti-doping agency for a hearing.' White (pictured), the first American to win the 100-200 metres sprint double, has not been suspended pending her hearing before the US antidoping agency and can therefore run at this weekend's inaugural World Athletics Final at Monaco's Stade Louis II. However, if she is found guilty of a doping offence, White would be stripped of the individual gold medals she won in Paris last month. 'The IAAF has already announced that if it is confirmed after the hearing that the athlete has committed a doping offence, the sanction under IAAF rules will be a public warning and disqualification from the competition,' said Davies. The 26-year-old White tested positive for modafinil, which is not at present on the IAAF banned list, after winning the 100m final on August 24. A urine sample taken after she won the 200 four days later was found to be clean. The sprinter said at the time that she had been prescribed modafinil to combat narcolepsy sleepiness and had not sought exemption, or entered it on her doping control form, because it was not on the banned list. The IAAF said last week that modafinil is now to be classified as a weaker stimulant and will be placed on the World Anti-Doping Agency's banned list next year. LOAD-DATE: September 10, 2003 LANGUAGE: ENGLISH PUB-TYPE: PAPER Copyright 2003 Midland Independent Newspapers plc 755 of 998 DOCUMENTS Contra Costa Times September 10, 2003 Wednesday FINAL EDITION SPRINTER WHITE SUFFERS SETBACK; IAAF RULES THE WORLD CHAMPION IS GUILTY OF A DOPING VIOLATION BYLINE: ANN TATKO, TIMES STAFF WRITER SECTION: SPORTS; Pg. B01 LENGTH: 563 words Track and field's governing body on Tuesday found sprinter Kelli White guilty of a doping violation, but she plans to fight any disciplinary action that results in the loss of her gold medals from the world championships. The International Association of Athletics Federation ruled White committed a doping offense when she tested positive for a stimulant after her 100-meter victory at last month's meet in Paris. Four days later, she passed a drug test after winning the 200. The case now moves to the U.S. Anti-Doping Agency to determine what disciplinary action should be taken. Rich Wanninger, a spokesman for the USADA, said the IAAF had not turned the case over to his organization as of Tuesday afternoon. Once the information is received, USADA will hold a hearing that could last several months, Wanninger said by phone from Colorado Springs, Colo. Cases such as these usually end with an athlete receiving a public warning and disqualification from the entire championships. That would cost White both of her gold medals. "I'm very disappointed by the finding," White said by phone Tuesday from Monte Carlo, Monaco. "I have never taken any performance-enhancing drug. (The IAAF officials) have called my reputation into question. Of course, I am going to fight that." White, a former El Sobrante resident, said her doctor prescribed the stimulant, modafinil, for a sleeping disorder. Although not on the banned list of drugs, modafinil is classified as a "related substance." Because the drug was not on the banned list, White said she didn't seek a medical waiver or list taking the medication on doping control forms, as required, at the world championships. IAAF general secretary Istvan Gyulai said that was not a viable excuse. "Her explanation was rejected," Gyulai said by phone Tuesday from IAAF headquarters in Monaco. "Athletes must take responsibility for knowing the rules and following them. Our experts have determined this medication is a performance-enhancing stimulant; therefore, it is a doping violation." Understanding what results in a doping violation, however, is complex considering the number of banned drugs and related substances. The USADA provides a list that covers more than 50 pages. White's doctor, Brian Goldman, argued that modafinil has no performance-enhancing value but added that he should have checked the drug more thoroughly against the list provided by the USADA. White said she also shares some of the responsibility. "I realize in hindsight that I should have done some things differently," she said. "But I didn't win the medals because I took (modafinil). I've won races all year without once testing positive." White avoided the harshest discipline when the IAAF last week ruled modafinil is a light stimulant as opposed to strong stimulant, which would have resulted in a two-year suspension from competition. An appeal is expected regardless of how the USADA's hearing concludes. White said she will not give up her medals -- and the $120,000 prize money she won because of them -- without a fight. Should the USADA decide she can keep the medals, Gyulai said, IAAF officials will send the case to the Court of Arbitration for Sport in Lausanne, Switzerland. That court has the final ruling in all doping violation cases. The Associated Press contributed to this story. LOAD-DATE: November 10, 2005 LANGUAGE: ENGLISH GRAPHIC: Photo 1, Kelli White mug. Photo 2, Kelli White. (Yves Logghe, AP) Copyright 2003 Contra Costa Times All Rights Reserved 756 of 998 DOCUMENTS Deseret Morning News (Salt Lake City) September 10, 2003, Wednesday U.S. sprinter accused of doping BYLINE: Associated Press SECTION: SPORTS; Pg. D06 LENGTH: 406 words U.S. sprinter Kelli White committed a doping offense at the World Championships and should be stripped of her two gold medals, track and field's governing body ruled Tuesday. The International Association of Athletics Federations sent White's case to U.S. track officials for disciplinary action. A final ruling could take months. White should be disqualified and stripped of the medals she won in the 100 and 200 meters last month in France, IAAF general secretary Istvan Gyulai said. A final ruling could take months. The U.S. Anti-Doping Agency must schedule a hearing with White. If it decides not to disqualify White and remove the medals, the IAAF would take the case to the Court of Arbitration for Sport in Lausanne, Switzerland. White, the first American woman to sweep the two sprints at the worlds, tested positive for modafinil after winning the 100 on Aug. 24. She passed a drug test after winning the 200 four days later. The IAAF gave White until Tuesday to produce medical documents explaining her use of the drug. She said her personal doctor prescribed the medication for the sleep disorder narcolepsy. "The explanation has been studied and turned down," Gyulai told The Associated Press. "Our experts have determined the stimulant is performance-enhancing." Modafinil is not on the sport's list of banned drugs, but the IAAF says it falls under the category of "related substances." White denied taking the medication to enhance performance and said she did not know it contained a banned substance. However, she did not declare modafinil on her doping control form as required, or apply for a medical exemption to use the product. White has vowed to fight to keep her medals. The IAAF ruled Sept. 4 that modafinil was a minor stimulant, similar to ephedrine, and carries a penalty of a public warning and disqualification. The decision allowed White to continue competing. Had modafinil -- sold in the United States under the brand name Provigil -- been classified as a stronger stimulant, White also would have faced a two-year ban and been ineligible for the 2004 Athens Olympics. Although White passed a drug test after the 200, the IAAF considers one positive test enough for disqualification from the entire championships. Under track and field rules, athletes are considered guilty of a doping violation if banned substances are found in their bodies, regardless of the circumstances. LOAD-DATE: September 10, 2003 LANGUAGE: ENGLISH Copyright 2003 The Deseret News Publishing Co. 757 of 998 DOCUMENTS Edmonton Journal (Alberta) September 10, 2003 Wednesday Final Edition IAAF wants White stripped of her medals but leaves it up to U.S. Anti-Doping Agency to take action SOURCE: The Associated Press BYLINE: Stephen Wilson SECTION: Sports; Pg. D1 LENGTH: 621 words DATELINE: LONDON LONDON - Track and field's governing body wants American sprinter Kelli White stripped of her two gold medals from the World Championships. Now it's up to U.S. anti-doping officials. The International Association of Athletics Federations ruled Tuesday that White committed a doping offence when she tested positive for a stimulant and should lose her world titles in the 100 and 200 metres. The IAAF rejected White's explanation that she took the stimulant for a sleep disorder and sent the case to the U.S. Anti-Doping Agency for a hearing and disciplinary action. Rich Wanninger, a spokesman for the U.S. Anti-Doping Agency, said his organization had not received any information from the IAAF as of Tuesday afternoon. Once that information is received, Wanninger said, the agency will begin a review process that could last months. The IAAF made clear it expects U.S. authorities to remove White's medals. "The proper sanction under IAAF rules will be a public warning and disqualification from the competition concerned," IAAF general secretary Istvan Gyulai said. If the IAAF isn't satisfied with the U.S. action, the international body would take the case to the Court of Arbitration for Sport in Lausanne, Switzerland. "She is disqualified only at the end of the procedure because further legal issues need to be exhausted," Gyulai told The Associated Press by phone from IAAF headquarters in Monaco. "This can only happen after she has been given a hearing by her national federation." White, the first American woman to sweep the sprint events at the worlds, tested positive for modafinil after winning the 100 on Aug. 24. She passed a drug test after winning the 200 four days later. The IAAF gave White until Tuesday to produce medical documents explaining her use of the drug. She said her personal doctor prescribed the medication for narcolepsy. "The explanation has been studied and turned down," Gyulai said. "Our experts have determined the stimulant is performance-enhancing." White was unavailable for comment Tuesday. She said last week she will fight to keep her medals. "Whatever I have to do to keep them, I will do that," she said. Modafinil is not on the sport's list of banned drugs, but the IAAF says it falls under the category of "related substances." White denied taking the medication to enhance performance and said she didn't know it contained a banned substance. However, she did not declare modafinil on her doping control form as required or apply for a medical exemption to use the product. The IAAF ruled last Wednesday that modafinil was a minor stimulant, similar to ephedrine, and carries a penalty of a public warning and disqualification. The decision allowed White to continue competing. Had modafinil -- sold in the United States under the brand name Provigil -- been classified as a stronger stimulant, White also would have faced a two-year ban and been ineligible for the 2004 Athens Olympics. Although White tested clean after the 200, the IAAF considers one positive test enough for disqualification from the entire championships. If White loses the medals, the golds would go to fellow American sprinter Torri Edwards in the 100 and Russia's Anastasiya Kapachinskaya in the 200. White would also lose the $120,000 US in prize money she won at the Worlds. Under the sport's policy of strict liability, athletes are considered guilty of a doping violation if banned substances are found in their bodies, regardless of the circumstances. White competed at the Golden League meet in Brussels, Belgium, last Friday and won the 100 in 10.87 seconds. She is to run in the Grand Prix final in Monaco this weekend and a meet in Moscow on Sept. 20. LOAD-DATE: September 10, 2003 LANGUAGE: ENGLISH GRAPHIC: Colour Photo: The Associated Press, File; American sprinter Kelli White TYPE: Sports Copyright 2003 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 758 of 998 DOCUMENTS The Guardian (London) September 10, 2003 Athletics: Drug plea by White rejected BYLINE: Michael Phillips SECTION: Guardian Sport Pages, Pg. 27 LENGTH: 202 words Kelli White, the American double world champion who tested positive for the stimulant modafinil, has had her letter of explanation rejected by the International Association of Athletics Federations. The case has been passed on to her governing body, USA Track and Field, and it will be dealt with by the American anti-doping agency. If the sprinter is found guilty she will lose the gold medals she won in the 100m and 200m in last month's World Championships in Paris and the Dollars 120,000 (pounds 76,000) prize money she would have received because she will be disqualified from the competition. White claimed she took modafinil to combat the sleeping disorder narcolepsy and insisted she did not declare it to the IAAF because it was not on the list of banned substances. She tested positive after the 100m. The IAAF has since announced that because modafinil is a minor stimulant she will incur a public warning and disqualification but no ban if found guilty of the offence. On Friday White won the 100m in the Golden League meeting in Brussels and this weekend she is due to compete in the World Athletics Final in Monte Carlo where, ironically, the IAAF has its headquarters. LOAD-DATE: September 10, 2003 LANGUAGE: ENGLISH Copyright 2003 Guardian Newspapers Limited 759 of 998 DOCUMENTS Hamilton Spectator (Ontario, Canada) September 10, 2003 Wednesday Final Edition White will lose golds for using stimulant SOURCE: The Associated Press SECTION: SPORTS; Pg. E03 LENGTH: 457 words DATELINE: LONDON Track and field's governing body wants American sprinter Kelli White stripped of her two gold medals from the World Championships. Now it's up to U.S. anti-doping officials. The International Association of Athletics Federations ruled yesterday that White committed a doping offence when she tested positive for a stimulant and should lose her world titles in the 100 and 200 metres. The IAAF rejected White's explanation that she took the stimulant for a sleep disorder and sent the case to the U.S. Anti-Doping Agency for a hearing and disciplinary action. Rich Wanninger, a spokesman for the U.S. Anti-Doping Agency, said his organization had not received any information from the IAAF as of yesterday afternoon. Once that information is received, he said, the agency will begin a review process that could last months. The IAAF made clear it expects U.S. authorities to remove White's medals. "The proper sanction under IAAF rules will be a public warning and disqualification from the competition concerned," IAAF general secretary Istvan Gyulai said. If the IAAF isn't satisfied with the U.S. action, the international body would take the case to the Court of Arbitration for Sport in Lausanne, Switzerland. "She is disqualified only at the end of the procedure because further legal issues need to be exhausted," Gyulai told The Associated Press by phone from IAAF headquarters in Monaco. "This can only happen after she has been given a hearing by her national federation." White, the first American woman to sweep the sprint events at the worlds, tested positive for modafinil after winning the 100 on Aug. 24. She passed a drug test after winning the 200 four days later. The IAAF gave White until yesterday to produce medical documents explaining her use of the drug. She said her personal doctor prescribed the medication for narcolepsy. "The explanation has been studied and turned down," Gyulai said. "Our experts have determined the stimulant is performance-enhancing." White was unavailable for comment. She said last week she will fight to keep her medals. "Whatever I have to do to keep them, I will do that," she said. Modafinil is not on the sport's list of banned drugs, but the IAAF says it falls under "related substances." White denied taking the medication to enhance performance and said she didn't know it contained a banned substance. However, she did not declare modafinil on her doping control form as required or apply for a medical exemption to use the product. The IAAF ruled last Wednesday that modafinil was a minor stimulant, similar to ephedrine, and carries a penalty of a public warning and disqualification. The decision allowed White to continue competing. LOAD-DATE: September 10, 2003 LANGUAGE: ENGLISH TYPE: News Copyright 2003 Metroland Media Group Ltd 760 of 998 DOCUMENTS The Independent (London) September 10, 2003, Wednesday ATHLETICS: WHITE TO LOSE PARIS MEDALS AS POSITIVE DRUG TEST CONFIRMED BYLINE: MIKE ROWBOTTOM SECTION: SPORT; Pg. 26 LENGTH: 379 words KELLI WHITE'S doping infraction at the recent World Championships in Paris was confirmed yesterday by the sport's international governing body, which intends to disqualify her retrospectively and strip her of the 100 and 200 metres gold medals she won in Paris. She also stands to lose the $ 120,000 (pounds 75,000) prize money she picked up. After examining details of the 26-year-old American's case, the International Association of Athletics Federations found her guilty of taking a minor stimulant. A final ruling could take weeks or months, however, as the case now goes to the US Anti-Doping Agency, which must schedule a hearing with White. If the US body decides not to disqualify White and remove the medals, the IAAF would take the case to the Court of Arbitration for Sport in Lausanne. White, the first American woman to win both sprints at a World Championships, tested positive for modafinil after winning the 100m gold on 24 August. She passed a drug test after winning the 200m four days later. The IAAF gave White until yesterday to produce medical documents explaining her use of modafinil. She said she took the medication on prescription from her personal doctor for the sleep disorder narcolepsy. "The explanation has been studied and turned down," Istvan Gyulai, the IAAF secretary, said. "The IAAF has reached the conclusion she has committed a doping offence. Our experts have determined the stimulant is performance- enhancing." Modafinil is not named on the sport's list of banned drugs, but the IAAF says it falls under the category of "related substances". White denied taking the medication to enhance performance and said she had "no idea" it contained a banned substance. However, she did not declare the substance on her doping control form as required or apply for a medical exemption to use the product. The IAAF ruled last week that modafinil was a minor stimulant, similar to ephedrine, and carried a penalty of a public warning and disqualification. The decision allowed White to continue competing. Had modafinil - sold in the United States under the brand name Provigil - been classified as a stronger stimulant, White also would have faced a two-year ban and ineligibility for the 2004 Athens Olympics. LOAD-DATE: September 10, 2003 LANGUAGE: ENGLISH Copyright 2003 Independent Print Ltd 761 of 998 DOCUMENTS The New York Times September 10, 2003 Wednesday Late Edition - Final Sprinter Likely to Lose Medals SECTION: Section D; Column 5; Sports Desk; Pg. 4 LENGTH: 256 words Track and field's world governing body has rejected the sprinter Kelli White's explanation for taking a stimulant, recommending that she be stripped of the gold medals she won at 100 and 200 meters at the recent world championships in Paris. The International Association of Athletics Federations, which governs the sport, said yesterday it believed that White should receive a public warning for the use of the stimulant modafinil, which means she faces disqualification from the world championships. In addition to losing her medals, she stands to forfeit $160,000 in prize money, but she will not be barred from competition. White will be granted a hearing before the United States Anti-Doping Agency, which will rule on the case. No date for the hearing has been set. If White and the I.A.A.F. accept the eventual ruling by the agency, the case will be closed. If either side disagrees, the final arbiter will be the Court of Arbitration for Sport in Switzerland. White said she took modafinil to combat the fatigue and sleep-inducing affects of narcolepsy. She failed to notify the I.A.A.F. that she was using the stimulant, however, and she did not obtain a waiver. She said she did not know the substance was banned. Modafinil is not listed among prohibited performance-enhancing drugs, but is considered a related substance. "The explanation has been studied and turned down," Istvan Gyulai, general secretary of the I.A.A.F., told The Associated Press. "Our experts have determined the stimulant is performance-enhancing." URL: http://www.nytimes.com LOAD-DATE: September 10, 2003 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2003 The New York Times Company 762 of 998 DOCUMENTS San Jose Mercury News (California) September 10, 2003 Wednesday MORNING FINAL EDITION IAAF: WHITE SHOULD BE STRIPPED OF GOLD MEDALS; RECOMMENDATION SETS OFF DEBATE BYLINE: ELLIOTT ALMOND, Mercury News SECTION: SPORTS; Pg. 1D LENGTH: 913 words In what could spark a protracted debate about doping and sports, track and field officials ruled Tuesday that Kelli White of Union City should be stripped of her world championship gold medals for failing a drug test. The worldwide governing body for track and field rejected White's arguments that the sleeping disorder medication in question -- modafinil -- had no performance benefit. The International Association of Athletics Federations will send the case to the U.S. Anti-Doping Agency, which oversees drug testing for Olympians. A hearing has not been scheduled but White has vowed to fight to keep the medals she won in the 100 meters and 200 meters in France last month. It could take months before it is resolved. The latest episode in Olympic drug testing could have larger ramifications in the complicated world of pharmacology and sports. Olympic leaders are trying to curtail drug abuse at the same time White's supporters are challenging the foundations used to exact punishment. In documents provided to the Mercury News, physicians representing White questioned the IAAF's definition of a banned substance. "Essentially, we support the IAAF's strict enforcement of its rules, but those of us who consult to the athletes would like to know prospectively what is on the 'prohibited substances list,' and not be told retroactively," child psychiatrist Brian Goldman wrote in a Sept. 2 letter to the IAAF. Goldman, a volunteer consultant with Bay Area Laboratories Cooperative, which works with world-class athletes, including White, said he gave the sprinter medication for narcolepsy. He said some Internet information calling modafinil a psycho-stimulant is incorrect. The company that makes the drug also said bad information about modafinil was being distributed. "If anyone says getting someone out of bed is enhancing performance, that would be an interesting debate," said Sheryl Williams of Cephalon, the firm that manufactures the medication. The IAAF ruled that modafinil is a minor stimulant although it is not included on its banned list. It comes under the category of "related substances." The IAAF rejected White's claims because the group's experts determined the stimulant is performance-enhancing, Secretary General Istvan Gyulai told the Associated Press. White's supporters say the IAAF has no basis for its ruling, which would cost the sprinter at least $120,000 in prize money. "They are not defining what is performance-enhancing," said Robert Picker, a Concord psychiatrist who also sent the IAAF a letter on White's behalf. "What is their argument? They are not providing one iota of evidence to show that this drug is performance-enhancing." Larry Bowers of the U.S. Anti-Doping Agency said the performance benefits of modafinil were unclear. Although the drug did not have the properties of amphetamines, Bowers said it could benefit an athlete by changing the perception of fatigue. "One could argue in a 100-meter or 200-meter race it might not be that beneficial -- or it might be," he said last month. Picker wrote to the IAAF: "In Ms. White's case, the only advantage it might give her is not falling asleep at an inappropriate time and missing the bus to the stadium. This is a case of the IAAF simply not keeping up to date on the science involved." White's case likely is headed for the Court of Arbitration for Sport (CAS), a Swiss body of jurists that makes binding decisions about Olympic disputes. IAAF officials said they would appeal the case to the court if U.S. officials reject their recommendations. White seems likely to ask for a CAS ruling should she lose her medals. Goldman, who works at the Amen Clinics in Fairfield, said he gave White two samples of the medication to see if it would help with her sleeping problem. She took the drug on an as-needed basis. "Kelli has complained of falling asleep while talking on the telephone, even if it's during an interesting conversation," Goldman wrote in another correspondence. White's mother, Debra Byfield, and her aunt also suffer from the disorder, the family said. Byfield, a 1972 Olympic runner for Jamaica, said her mother exhibited similar symptoms. White said she took the drug the morning of the 100-meter competition Aug. 24 because she felt "drained" in France. But after the race she did not list it on a doping control form, a requirement almost every world-class athlete understands. Even if she had included it, officials say she needed a medical waiver to take the medication. Olympic athletes face a catch-all phrase known as 'strict liability' when it comes to what they ingest. They are responsible for any substance they take and cannot claim ignorance if it turns up positive. White, who is in Europe, could not be reached. But Byfield said the worst part is the stigma of being viewed a drug cheat. "What it does, it erases the hard work that she put in," Byfield said. Although not related, White's situation has come at the same time as a raid on Bay Area Laboratories Cooperative, a dietary supplement company in Burlingame. Federal and San Mateo county authorities refuse to say why their agents searched the firm of Victor Conte, and the home of Greg Anderson, Barry Bonds' personal trainer. But Olympic drug testers are helping with the investigation, which is ongoing. White is one of the many elite athletes working with Conte, who professes to help performers through natural means. LOAD-DATE: August 16, 2005 LANGUAGE: ENGLISH GRAPHIC: Photos (2), Diagram; DIAGRAM: T.G. TSO -- MERCURY NEWS THE ANATOMY OF A DRUG CASE Source: U.S. Anti-Doping Agency, Mercury News reporting PHOTO: ANJA NIEDRINGHAUS -- ASSOCIATED PRESS Kelli White wins the 200 at the world championships -- one of the gold medals in dispute. PHOTO: MICHEL EULER -- ASSOCIATED PRESS Kelli White's case moves to the U.S. Anti-Doping Agency, which oversees drug testing. Copyright 2003 San Jose Mercury News All Rights Reserved 763 of 998 DOCUMENTS The Times (London) September 10, 2003, Wednesday White likely to lose tarnished gold medals after IAAF ruling BYLINE: David Powell, Athletics Correspondent and John Goodbody SECTION: Sport; 39 LENGTH: 448 words THE sport's world governing body yesterday rejected the evidence from Kelli White in defence of her failed drugs test at the World Championships in Paris two weeks ago and insisted she be stripped of her two gold medals and $ 120,000 (about Pounds 76,000) in prize-money. White tested positive for a mild stimulant after winning the women's 100 metres but returned a negative sample after her 200 metres victory. White, from the United States, remains eligible to compete because the category of drug carries only a warning. The International Association of Athletics Federations (IAAF) will now expect White's national federation, USA Track & Field (USATF), to confirm her punishment. Should it fail to do so, the case will be decided by the Court of Arbitration for Sport. After criticism of its handling of drugs cases up to the 2000 Olympics, USATF agreed to delegate such matters to the United States Anti-Doping Agency, whose first step will be to arrange a hearing with White, 26. White said in Paris that she had taken the drug, modafinil, on prescription from her doctor to counter narcolepsy, a condition that ran in her family, but, having failed either to declare it on her drug-testing form or seek an exemption, her defence is weak. Already back in competition, having won the 100 metres at the Golden League meeting in Brussels on Friday, White said that she would fight to keep her medals and winnings. "Whatever I have to do to keep them, I will do," she said. She stands to lose her 200 metres rewards, as well as those from the 100 metres, because, under IAAF rules, an athlete is disqualified from the meeting in which the offence was committed. Although not named on the banned list, modafinil falls into the "related substances" category, carrying the same penalty as specified drugs. Cephalon, the manufacturer of Provigil, by which modafinil is sold under licence, said that it had not "systematically evaluated" its effect on athletes, but Istvan Gyulai, the IAAF secretary, said: "Our experts have determined (it) is performance-enhancing." Even before the White case, the World Anti-Doping Agency had asked for modafinil to be added to the banned list from next year. Torri Edwards, White's compatriot, who was second in the 100 metres, and Anastasiya Kapachinskaya, from Russia, runner-up in the 200 metres, may have to wait months before the process is exhausted if they are to be crowned champions. Should White's punishment be confirmed, she will lose not only her prize-money and medals but the chance of a lucrative match-up with Marion Jones, the Olympic champion who missed the World Championships after giving birth. LOAD-DATE: September 10, 2003 LANGUAGE: ENGLISH Copyright 2003 Times Newspapers Limited 764 of 998 DOCUMENTS Tulsa World (Oklahoma) September 10, 2003 Wednesday Final Home Edition Sports FYI: White ruled guilty BYLINE: Staff Reports SECTION: SPORTS; General Sports; Pg. B2 LENGTH: 1092 words Last month Kelli White became the first American woman to sweep the 100- and 200-meter dashes at the World Championships. White committed a doping offense at the worlds and the IAAF has recommended she be stripped of her medals. ANJA NIEDRINGHAUS / Associated Press file TRACK U.S. sprinter Kelli White committed a doping offense at the World Championships and should be stripped of her two gold medals, the sport's governing body ruled at Monte Carlo, Monaco, Tuesday. The International Association of Athletics Federations sent White's case to U.S. officials for disciplinary action. White should be disqualified and stripped of the medals she won in the 100 and 200 meters last month in France, IAAF general secretary Istvan Gyulai said. A final ruling could take months. The U.S. Anti-Doping Agency must schedule a hearing with White. If it decides not to disqualify White and remove the medals, the IAAF would take the case to the Court of Arbitration for Sport in Lausanne, Switzerland. White, the first American woman to sweep the two sprints at the worlds, tested positive for modafinil after winning the 100 on Aug. 24. She passed a drug test after winning the 200 four days later. The IAAF gave White until Tuesday to produce medical documents explaining her use of the drug. She said her personal doctor prescribed the medication for the sleep disorder narcolepsy. Modafinil is not on the sport's list of banned drugs, but the IAAF says it falls under the category of "related substances." White denied taking the medication to enhance performance and said she did not know it contained a banned substance. However, she did not declare modafinil on her doping control form as required, or apply for a medical exemption to use the product. White has vowed to fight to keep her medals. The IAAF ruled Sept. 4 that modafinil was a minor stimulant, similar to ephedrine, and carries a penalty of a public warning and disqualification. The decision allowed White to continue competing. Had modafinil -- sold in the United States under the brand name Provigil -- been classified as a stronger stimulant, White also would have faced a two-year ban and been ineligible for the 2004 Athens Olympics. TENNIS Roddick leads U.S. team: U.S. Open champion Andy Roddick will lead an American Davis Cup team that plays at Slovakia this month in a World Group playoff. Roddick is joined by Mardy Fish, James Blake, Brian Vahaly and twins Bob and Mike Bryan. The nominations by the U.S. Tennis Association and captain Patrick McEnroe were submitted to the International Tennis Federation. GOLF Cowgirls ranked No. 4: Golfweek Magazine has ranked Oklahoma State fourth in its preseason women's collegiate poll. Duke was ranked No. 1, followed by UCLA (second) and Ohio State (third). Sophomore Karin Sjodin and junior Annie Thurman were named preseason first-team All-Americans. AUTO RACING Lowe's keeps All-Star race: NASCAR's annual all-star race will remain at Lowe's Motor Speedway in Charlotte, N.C., next season as part of the 36-race, Nextel Cup schedule released. The Nextel All-Star Challenge will be run May 22 at Lowe's, marking the 18th consecutive year the all-star event will be run at the Concord track. The Southern 500 at Darlington will now be run on Nov. 14 and be the penultimate race in the Nextel Cup Series title chase. The switch was all part of NASCAR's "Realignment 2004 and Beyond" plan, designed to move races out of the crowded Southeastern market and into large cities. California Speedway will run its traditional spring event on May 2. Its second race will be Sept. 5, under the lights. The only other change involved the order of the spring races at Talladega Superspeedway and Martinsville Speedway. They will switch their order from the previous year's schedule, with Martinsville being run April 18 and Talladega on April 25. HORSE RACING Jockey suspended: A jockey at Great Lakes Downs in Fruitport Township, Mich., has been suspended after allegations he used an electrical "buzzer" to influence a race he won. A buzzer is a hand-held, battery-operated device that emits an electric shock when pressed against the horse. Jeffrey H. Faul declined to testify at a hearing before track stewards. The stewards will consider the evidence and decide what action to take against Faul, said Dominic Perrone, spokesman for the Michigan Office of Racing Commissioner. Faul denies he cheated in the race, said his agent, Ron Salmon. The state suspended Faul indefinitely pending a decision by the stewards. The suspension decision was made after track stewards ruled there was credible evidence of cheating. The accusations stem from an Aug. 24 claiming race at the Muskegon County track near Muskegon. Faul ran aboard Run for You and was among the leaders before making a move at the top of the stretch, The Muskegon Chronicle reported. HOCKEY Oilers add two: The Tulsa Oilers have signed defenseman Jordon Flodell and forward/defenseman Rob Meanchoff. Flodell is returing for his second season with the Oilers. Meanchoff is a rookie, who recently finished his college career after four years with the University of Ottawa. TENNIS OSU players ranked: Oklahoma State has two individuals ranked in the ITA Top 75 for the first time in coach James Wadley's 32-year tenure. Mark Van Elden and Yevgen Bondarchuk are ranked Nos. 32 and 55, respectively, in the preseason rankings. Van Elden and Bondarchuck went 14-5 and 14-8 last year as the Cowboys' Nos. 1 and 2 singles players. SOCCER Zapata earns honor: Oral Roberts' Hector Zapata was named Mid-Continent Conference Defensive Player of the Week. He posted his ninth career shutout at Drake in a scoreless tie. The host Bulldogs outshot the Golden Eagles 20-7 while Zapata made six saves. Zapata lowered his goals-allowed average to 0.62 by posting his second consecutive shutout. He has allowed only two goals in 290 minutes of work. BASKETBALL No confidence in Sloan: Baylor's faculty senate passed a "no confidence" motion for embattled President Robert Sloan. The 26-6 vote of no confidence came after the faculty senate met for more than three hours. Joe Cox, the faculty senate chairman, said the motion cites the "deeply polarized and relationally paralyzed Baylor community" under Sloan's presidency. The senate, which has no actual authority over Sloan's employment, will forward its recommendation for his ouster to Baylor's 36-member board of regents, which opens a two-day meeting Thursday. LOAD-DATE: September 11, 2003 LANGUAGE: ENGLISH Copyright 2003 The Tulsa World 765 of 998 DOCUMENTS XINHUA GENERAL NEWS SERVICE September 10, 2003, Wednesday White's explanation for positive doping test rejected SECTION: WORLD NEWS; SPORTS LENGTH: 231 words LONDON, Sept. 9 (Xinhua) -- The reason given by American Kelli White, who won women's 100m/200m titles at the Paris athletic worlds in August, for positive test for modafinil was rejected by the International Association of Athletics Federations (IAAF) on Tuesday. "Following careful examination the explanation has not been accepted," IAAF spokesman Nick Davies said. The 26-year-old White tested positive for modafinil, which is not at present on the IAAF banned list, after winning the 100 meters final on August 24. A urine sample taken after she won the 200m four days later was found to be clean. The sprinter said at the time that she had been prescribed modafinil to combat narcolepsy, or sleepiness, and had not sought exemption or entered it on her doping control form because it was not on the banned list. The IAAF said last week that modafinil is now to be classified as a weaker stimulant and will be placed on the World Anti-Doping Agency's banned list next year. "In accordance with the normal disciplinary procedures under our rules the matter has now be referred to the U.S. anti-doping agency for a hearing on a date to be agreed with the athlete." White has not been suspended pending her hearing before the U.S. anti-doping agency and can therefore run at this weekend's inaugural World Athletics Final at Monaco's Stade Louis II. LOAD-DATE: September 11, 2003 LANGUAGE: ENGLISH COPYRIGHT 2003 XINHUA NEWS AGENCY 766 of 998 DOCUMENTS The Associated Press September 9, 2003, Tuesday, BC cycle U.S. sprinter Kelli White guilty of doping offense SECTION: International News; Sports News LENGTH: 402 words DATELINE: MONTE CARLO, Monaco U.S. sprinter Kelli White committed a doping offense at the World Championships and should be stripped of her two gold medals, track and field's governing body ruled Tuesday. The International Association of Athletics Federations sent White's case to U.S. track officials for disciplinary action. White should be disqualified and stripped of the medals she won in the 100 and 200 meters last month in France, IAAF general secretary Istvan Gyulai said. A final ruling could take months. The U.S. Anti-Doping Agency must schedule a hearing with White. If it decides not to disqualify White and remove the medals, the IAAF would take the case to the Court of Arbitration for Sport in Lausanne, Switzerland. White, the first American woman to sweep the two sprints at the worlds, tested positive for modafinil after winning the 100 on Aug. 24. She passed a drug test after winning the 200 four days later. The IAAF gave White until Tuesday to produce medical documents explaining her use of the drug. She said her personal doctor prescribed the medication for the sleep disorder narcolepsy. "The explanation has been studied and turned down," Gyulai told The Associated Press. "Our experts have determined the stimulant is performance-enhancing." Modafinil is not on the sport's list of banned drugs, but the IAAF says it falls under the category of "related substances." White denied taking the medication to enhance performance and said she did not know it contained a banned substance. However, she did not declare modafinil on her doping control form as required, or apply for a medical exemption to use the product. White has vowed to fight to keep her medals. The IAAF ruled Sept. 4 that modafinil was a minor stimulant, similar to ephedrine, and carries a penalty of a public warning and disqualification. The decision allowed White to continue competing. Had modafinil - sold in the United States under the brand name Provigil - been classified as a stronger stimulant, White also would have faced a two-year ban and been ineligible for the 2004 Athens Olympics. Although White passed a drug test after the 200, the IAAF considers one positive test enough for disqualification from the entire championships. Under track and field rules, athletes are considered guilty of a doping violation if banned substances are found in their bodies, regardless of the circumstances. LOAD-DATE: September 10, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 767 of 998 DOCUMENTS The Associated Press September 9, 2003, Tuesday, BC cycle IAAF rules Kelli White guilty of doping offense BYLINE: By STEPHEN WILSON, AP Sports Writer SECTION: Sports News LENGTH: 622 words DATELINE: LONDON Track and field's governing body wants American sprinter Kelli White stripped of her two gold medals from the World Championships. Now it's up to U.S. anti-doping officials. The International Association of Athletics Federations ruled Tuesday that White committed a doping offense when she tested positive for a stimulant and should lose her world titles in the 100 and 200 meters. The IAAF rejected White's explanation that she took the stimulant for a sleep disorder and sent the case to the U.S. Anti-Doping Agency for a hearing and disciplinary action. Rich Wanninger, a spokesman for the U.S. Anti-Doping Agency, said his organization had not received any information from the IAAF as of Tuesday afternoon. Once that information is received, Wanninger said, the agency will begin a review process that could last months. The IAAF made clear it expects U.S. authorities to remove White's medals. "The proper sanction under IAAF rules will be a public warning and disqualification from the competition concerned," IAAF general secretary Istvan Gyulai said. If the IAAF isn't satisfied with the U.S. action, the international body would take the case to the Court of Arbitration for Sport in Lausanne, Switzerland. "She is disqualified only at the end of the procedure because further legal issues need to be exhausted," Gyulai told The Associated Press by phone from IAAF headquarters in Monaco. "This can only happen after she has been given a hearing by her national federation." White, the first American woman to sweep the sprint events at the worlds, tested positive for modafinil after winning the 100 on Aug. 24. She passed a drug test after winning the 200 four days later. The IAAF gave White until Tuesday to produce medical documents explaining her use of the drug. She said her personal doctor prescribed the medication for narcolepsy. "The explanation has been studied and turned down," Gyulai said. "Our experts have determined the stimulant is performance-enhancing." White was unavailable for comment Tuesday. She said last week she will fight to keep her medals. "Whatever I have to do to keep them, I will do that," she said. Modafinil is not on the sport's list of banned drugs, but the IAAF says it falls under the category of "related substances." White denied taking the medication to enhance performance and said she didn't know it contained a banned substance. However, she did not declare modafinil on her doping control form as required or apply for a medical exemption to use the product. The IAAF ruled last Wednesday that modafinil was a minor stimulant, similar to ephedrine, and carries a penalty of a public warning and disqualification. The decision allowed White to continue competing. Had modafinil - sold in the United States under the brand name Provigil - been classified as a stronger stimulant, White also would have faced a two-year ban and been ineligible for the 2004 Athens Olympics. Although White tested clean after the 200, the IAAF considers one positive test enough for disqualification from the entire championships. If White loses the medals, the golds would go to fellow American sprinter Torri Edwards in the 100 and Russia's Anastasiya Kapachinskaya in the 200. White would also lose the $120,000 in prize money she won at the worlds. Under the sport's policy of strict liability, athletes are considered guilty of a doping violation if banned substances are found in their bodies, regardless of the circumstances. White competed at the Golden League meet in Brussels, Belgium, last Friday and won the 100 in 10.87 seconds. She is to run in the Grand Prix final in Monaco this weekend and a meet in Moscow on Sept. 20. LOAD-DATE: September 10, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 768 of 998 DOCUMENTS Associated Press Worldstream September 9, 2003 Tuesday URGENT IAAF rules Kelli White guilty of doping offense SECTION: SPORTS LENGTH: 595 words DATELINE: MONTE CARLO, Monaco U.S. sprinter Kelli White committed a doping offense when she failed a drug test at the World Championships and should lose her two gold medals, track's world governing body said Tuesday. The International Association of Athletics Federations found White guilty of a doping infraction and sent her case to U.S. officials for disciplinary action. IAAF general secretary Istvan Gyulai said White should be disqualified and stripped of the gold medals she won in the 100 and 200 meters at last month's World Championships in the Paris suburb of Saint-Denis. A final ruling could take weeks or months. The matter now goes to the U.S. Anti-Doping Agency, which must schedule a hearing with White. If the U.S. body decides not to disqualify White and remove the medals, the IAAF would take the case to the Court of Arbitration for Sport in Lausanne, Switzerland. White, the first American woman to sweep the two sprint events at a World Championships, tested positive for modafinil after winning the 100 on Aug. 24. She passed a drug test after winning the 200 four days later. The IAAF gave White until Tuesday to produce medical documents explaining her use of modafinil. She said she took the medication on prescription from her personal doctor for the sleep disorder narcolepsy. "The explanation has been studied and turned down," Gyulai told The Associated Press. "The IAAF has reached the conclusion she has committed a doping offense. Our experts have determined the stimulant is performance-enhancing." Modafinil is not named on the sport's list of banned drugs, but the IAAF says it falls under the category of "related substances." White denied taking the medication to enhance performance and said she had "no idea" it contained a banned substance. However, she did not declare modafinil on her doping control form as required or apply for a medical exemption to use the product. The IAAF ruled last Wednesday that modafinil was a minor stimulant, similar to ephedrine, and carries a penalty of a public warning and disqualification. The decision allowed White to continue competing. Had modafinil - sold in the United States under the brand name Provigil - been classified as a stronger stimulant, White also would have faced a two-year ban and ineligibility for the 2004 Athens Olympics. The IAAF said a decision to strip White's medals was not automatic. "She is disqualified only at the end of the procedure because further legal issues need to be exhausted," Gyulai said. "This can only happen after she has been given a hearing by her national federation." Although White tested clean after the 200, the IAAF considers one positive test enough for disqualification from the entire championships. If White loses the medals, the golds would go to fellow American sprinter Torri Edwards in the 100 and Russia's Anastasiya Kapachinskaya in the 200. In addition, White would also lose the US$120,000 in prize money she won at the worlds. Under the sport's policy of strict liability, athletes are considered guilty of a doping violation if banned substances are found in their bodies, regardless of the circumstances. White competed at the Golden League meet in Brussels, Belgium, last Friday and won the 100 in 10.87 seconds, leading a 1-2-3 American sweep ahead of Chryste Gaines and Edwards. White is due to run in the Grand Prix final in Monaco this weekend and an invitatational meet in Moscow on Sept. 20. White said last week she will fight to keep her medals. "Whatever I have to do to keep them, I will do that," she said. LOAD-DATE: September 10, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 769 of 998 DOCUMENTS Associated Press Worldstream September 9, 2003 Tuesday IAAF rules Kelli White guilty of doping offense BYLINE: STEPHEN WILSON; AP Sports Writer SECTION: SPORTS LENGTH: 601 words DATELINE: LONDON Track and field's governing body says American sprinter Kelli White should be stripped of her two gold medals from the World Championships. Now it's up to U.S. anti-doping officials to comply. The International Association of Athletics Federations ruled Tuesday that White committed a doping offense when she tested positive for a stimulant and should lose her world titles in the 100 and 200 meters. The IAAF rejected White's explanation that she took the stimulant for a sleep disorder and sent the case to the U.S. Anti-Doping Agency for a hearing and disciplinary action. The IAAF made clear it expects U.S. authorities to remove White's medals. "The proper sanction under IAAF rules will be a public warning and disqualification from the competition concerned," IAAF general secretary Istvan Gyulai said. If the IAAF isn't satisfied with the U.S. action, the international body would take the case to the Court of Arbitration for Sport in Lausanne, Switzerland. The process could take weeks or months. "She is disqualified only at the end of the procedure because further legal issues need to be exhausted," Gyulai told The Associated Press by phone from IAAF headquarters in Monaco. "This can only happen after she has been given a hearing by her national federation." White, the first American woman to sweep the two sprint events at the worlds, tested positive for modafinil after winning the 100 on Aug. 24. She passed a drug test after winning the 200 four days later. The IAAF gave White until Tuesday to produce medical documents explaining her use of the drug. She said her personal doctor prescribed the medication for narcolepsy. "The explanation has been studied and turned down," Gyulai said. "The IAAF has reached the conclusion she has committed a doping offense. Our experts have determined the stimulant is performance-enhancing." White was unavailable for comment Tuesday. She said last week she will fight to keep her medals. "Whatever I have to do to keep them, I will do that," she said. Modafinil is not on the sport's list of banned drugs, but the IAAF says it falls under the category of "related substances." White denied taking the medication to enhance performance and said she didn't know it contained a banned substance. However, she did not declare modafinil on her doping control form as required or apply for a medical exemption to use the product. The IAAF ruled last Wednesday that modafinil was a minor stimulant, similar to ephedrine, and carries a penalty of a public warning and disqualification. The decision allowed White to continue competing. Had modafinil - sold in the United States under the brand name Provigil - been classified as a stronger stimulant, White also would have faced a two-year ban and been ineligible for the 2004 Athens Olympics. Although White tested clean after the 200, the IAAF considers one positive test enough for disqualification from the entire championships. If White loses the medals, the golds would go to fellow American sprinter Torri Edwards in the 100 and Russia's Anastasiya Kapachinskaya in the 200. In addition, White would also lose the US$120,000 in prize money she won at the worlds. Under the sport's policy of strict liability, athletes are considered guilty of a doping violation if banned substances are found in their bodies, regardless of the circumstances. White competed at the Golden League meet in Brussels, Belgium, last Friday and won the 100 in 10.87 seconds. She is to run in the Grand Prix final in Monaco this weekend and an invitational meet in Moscow on Sept. 20. LOAD-DATE: September 10, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 770 of 998 DOCUMENTS The Associated Press State & Local Wire September 9, 2003, Tuesday, BC cycle IAAF rules Californian Kelli White guilty of doping offense SECTION: Sports News LENGTH: 550 words DATELINE: MONTE CARLO, Monaco U.S. sprinter Kelli White committed a doping offense at the World Championships and should be stripped of her two gold medals, track and field's governing body ruled Tuesday. The International Association of Athletics Federations sent White's case to U.S. track officials for disciplinary action. White, who lives in Union City, Calif., should be disqualified and stripped of the medals she won in the 100 and 200 meters last month in France, IAAF general secretary Istvan Gyulai said. A final ruling could take months. The U.S. Anti-Doping Agency must schedule a hearing with White. If it decides not to disqualify White and remove the medals, the IAAF would take the case to the Court of Arbitration for Sport in Lausanne, Switzerland. White, the first American woman to sweep the two sprints at the worlds, tested positive for modafinil after winning the 100 on Aug. 24. She passed a drug test after winning the 200 four days later. The IAAF gave White until Tuesday to produce medical documents explaining her use of the drug. She said her personal doctor prescribed the medication for the sleep disorder narcolepsy. "The explanation has been studied and turned down," Gyulai told The Associated Press. "Our experts have determined the stimulant is performance-enhancing." Modafinil is not on the sport's list of banned drugs, but the IAAF says it falls under the category of "related substances." White denied taking the medication to enhance performance and said she did not know it contained a banned substance. However, she did not declare modafinil on her doping control form as required or apply for a medical exemption to use the product. White said last week she will fight to keep her medals. "Whatever I have to do to keep them, I will do that," she said. The IAAF ruled last Wednesday that modafinil was a minor stimulant, similar to ephedrine, and carries a penalty of a public warning and disqualification. The decision allowed White to continue competing. Had modafinil - sold in the United States under the brand name Provigil - been classified as a stronger stimulant, White also would have faced a two-year ban and been ineligible for the 2004 Athens Olympics. The IAAF said a decision to strip White's medals was not automatic. "She is disqualified only at the end of the procedure because further legal issues need to be exhausted," Gyulai said. "This can only happen after she has been given a hearing by her national federation." Although White passed a drug test after the 200, the IAAF considers one positive test enough for disqualification from the entire championships. If White loses the medals, the golds would go to fellow American sprinter Torri Edwards in the 100 and Russia's Anastasiya Kapachinskaya in the 200. In addition, White would lose the $120,000 in prize money she won at the worlds. Under track and field rules, athletes are considered guilty of a doping violation if banned substances are found in their bodies, regardless of the circumstances. White competed at the Golden League meet in Brussels, Belgium, on Friday and won the 100 in 10.87 seconds, leading an American sweep of the top three spots. White is to run in the Grand Prix final in Monaco this weekend and a meet in Moscow on Sept. 20. LOAD-DATE: September 10, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 771 of 998 DOCUMENTS The Associated Press State & Local Wire September 9, 2003, Tuesday, BC cycle IAAF rules Kelli White guilty of doping offense BYLINE: By STEPHEN WILSON, AP Sports Writer SECTION: Sports News LENGTH: 629 words DATELINE: LONDON Track and field's governing body wants American sprinter Kelli White stripped of her two gold medals from the World Championships. Now it's up to U.S. anti-doping officials. The International Association of Athletics Federations ruled Tuesday that White, a former University of Tennessee sprinter, committed a doping offense when she tested positive for a stimulant and should lose her world titles in the 100 and 200 meters. The IAAF rejected White's explanation that she took the stimulant for a sleep disorder and sent the case to the U.S. Anti-Doping Agency for a hearing and disciplinary action. Rich Wanninger, a spokesman for the U.S. Anti-Doping Agency, said his organization had not received any information from the IAAF as of Tuesday afternoon. Once that information is received, Wanninger said, the agency will begin a review process that could last months. The IAAF made clear it expects U.S. authorities to remove White's medals. "The proper sanction under IAAF rules will be a public warning and disqualification from the competition concerned," IAAF general secretary Istvan Gyulai said. If the IAAF isn't satisfied with the U.S. action, the international body would take the case to the Court of Arbitration for Sport in Lausanne, Switzerland. "She is disqualified only at the end of the procedure because further legal issues need to be exhausted," Gyulai told The Associated Press by phone from IAAF headquarters in Monaco. "This can only happen after she has been given a hearing by her national federation." White, the first American woman to sweep the sprint events at the worlds, tested positive for modafinil after winning the 100 on Aug. 24. She passed a drug test after winning the 200 four days later. The IAAF gave White until Tuesday to produce medical documents explaining her use of the drug. She said her personal doctor prescribed the medication for narcolepsy. "The explanation has been studied and turned down," Gyulai said. "Our experts have determined the stimulant is performance-enhancing." White was unavailable for comment Tuesday. She said last week she will fight to keep her medals. "Whatever I have to do to keep them, I will do that," she said. Modafinil is not on the sport's list of banned drugs, but the IAAF says it falls under the category of "related substances." White denied taking the medication to enhance performance and said she didn't know it contained a banned substance. However, she did not declare modafinil on her doping control form as required or apply for a medical exemption to use the product. The IAAF ruled last Wednesday that modafinil was a minor stimulant, similar to ephedrine, and carries a penalty of a public warning and disqualification. The decision allowed White to continue competing. Had modafinil - sold in the United States under the brand name Provigil - been classified as a stronger stimulant, White also would have faced a two-year ban and been ineligible for the 2004 Athens Olympics. Although White tested clean after the 200, the IAAF considers one positive test enough for disqualification from the entire championships. If White loses the medals, the golds would go to fellow American sprinter Torri Edwards in the 100 and Russia's Anastasiya Kapachinskaya in the 200. White would also lose the $120,000 in prize money she won at the worlds. Under the sport's policy of strict liability, athletes are considered guilty of a doping violation if banned substances are found in their bodies, regardless of the circumstances. White competed at the Golden League meet in Brussels, Belgium, last Friday and won the 100 in 10.87 seconds. She is to run in the Grand Prix final in Monaco this weekend and a meet in Moscow on Sept. 20. LOAD-DATE: September 10, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 772 of 998 DOCUMENTS Associated Press Online September 9, 2003 Tuesday IAAF Finds Kelli White Guilty of Doping BYLINE: STEPHEN WILSON; AP Sports Writer SECTION: SPORTS LENGTH: 618 words DATELINE: LONDON Track and field's governing body wants American sprinter Kelli White stripped of her two gold medals from the World Championships. Now it's up to U.S. anti-doping officials. The International Association of Athletics Federations ruled Tuesday that White committed a doping offense when she tested positive for a stimulant and should lose her world titles in the 100 and 200 meters. The IAAF rejected White's explanation that she took the stimulant for a sleep disorder and sent the case to the U.S. Anti-Doping Agency for a hearing and disciplinary action. Rich Wanninger, a spokesman for the U.S. Anti-Doping Agency, said his organization had not received any information from the IAAF as of Tuesday afternoon. Once that information is received, Wanninger said, the agency will begin a review process that could last months. The IAAF made clear it expects U.S. authorities to remove White's medals. "The proper sanction under IAAF rules will be a public warning and disqualification from the competition concerned," IAAF general secretary Istvan Gyulai said. If the IAAF isn't satisfied with the U.S. action, the international body would take the case to the Court of Arbitration for Sport in Lausanne, Switzerland. "She is disqualified only at the end of the procedure because further legal issues need to be exhausted," Gyulai told The Associated Press by phone from IAAF headquarters in Monaco. "This can only happen after she has been given a hearing by her national federation." White, the first American woman to sweep the sprint events at the worlds, tested positive for modafinil after winning the 100 on Aug. 24. She passed a drug test after winning the 200 four days later. The IAAF gave White until Tuesday to produce medical documents explaining her use of the drug. She said her personal doctor prescribed the medication for narcolepsy. "The explanation has been studied and turned down," Gyulai said. "Our experts have determined the stimulant is performance-enhancing." White was unavailable for comment Tuesday. She said last week she will fight to keep her medals. "Whatever I have to do to keep them, I will do that," she said. Modafinil is not on the sport's list of banned drugs, but the IAAF says it falls under the category of "related substances." White denied taking the medication to enhance performance and said she didn't know it contained a banned substance. However, she did not declare modafinil on her doping control form as required or apply for a medical exemption to use the product. The IAAF ruled last Wednesday that modafinil was a minor stimulant, similar to ephedrine, and carries a penalty of a public warning and disqualification. The decision allowed White to continue competing. Had modafinil - sold in the United States under the brand name Provigil - been classified as a stronger stimulant, White also would have faced a two-year ban and been ineligible for the 2004 Athens Olympics. Although White tested clean after the 200, the IAAF considers one positive test enough for disqualification from the entire championships. If White loses the medals, the golds would go to fellow American sprinter Torri Edwards in the 100 and Russia's Anastasiya Kapachinskaya in the 200. White would also lose the $120,000 in prize money she won at the worlds. Under the sport's policy of strict liability, athletes are considered guilty of a doping violation if banned substances are found in their bodies, regardless of the circumstances. White competed at the Golden League meet in Brussels, Belgium, last Friday and won the 100 in 10.87 seconds. She is to run in the Grand Prix final in Monaco this weekend and a meet in Moscow on Sept. 20. LOAD-DATE: September 10, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 773 of 998 DOCUMENTS CNN.com September 9, 2003 Tuesday White's drugs explanation rejected SECTION: SPORT LENGTH: 295 words DATELINE: LONDON, England Athletics chiefs have rejected double sprint champion Kelli White's explanation of why she tested positive at the world championships. "The IAAF has received the athlete's explanation for testing positive for (stimulant) modafinil...in Paris last month," IAAF spokesman Nick Davies said on Tuesday. And he confirmed: "Following careful examination the explanation has not been accepted." Davies added: "In accordance with the normal disciplinary procedures under our rules the matter has now be referred to the U.S. anti-doping agency for a hearing on a date to be agreed with the athlete." White, the first American to win the 100-200 sprint double, has not been suspended pending her hearing before the U.S. anti-doping agency and can therefore run at this weekend's inaugural World Athletics Final in Monaco. However, if she is found guilty of a doping offence White would be stripped of the individual gold medals she won in Paris last month. "The IAAF has already announced that if it is confirmed after the hearing that the athlete has committed a doping offence, the sanction under IAAF rules will be a public warning and disqualification from the competition," said Davies. The 26-year-old tested positive for modafinil, which is not at present on the IAAF banned list, after winning the 100m final on August 24. A urine sample taken after she won the 200 four days later was found to be clean. White said at the time she had been prescribed modafinil to combat narcolepsy, or sleepiness, and had not sought exemption or entered it on her doping control form because it was not on the banned list. The IAAF said last week that modafinil is now to be classified as a weaker stimulant and will be placed on the World Anti-Doping Agency's banned list next year. LOAD-DATE: September 26, 2003 LANGUAGE: ENGLISH Copyright 2003 Cable News Network All Rights Reserved 774 of 998 DOCUMENTS The Washington Post September 7, 2003 Sunday Final Edition Testing Positive for Sprinting SECTION: EDITORIAL; Pg. B06 LENGTH: 217 words If Kelli White has narcolepsy, it is unlikely that she could compete in sports without treatment, particularly at a world-class level ["Double Gold Medalist Tests Positive," Sports, Aug. 31]. Untreated, narcolepsy is an incapacitating disability whose effects have been found to be as severe as multiple sclerosis on quality-of-life assessment scales. Does treatment with modafinil provide a competitive edge? Based on the evidence, probably not more than someone else drinking several cups of coffee. Just as people become tolerant of coffee, a person with narcolepsy would have to consume ever greater amounts of modafinil to get any boosting effect. Modafinil is not an amphetamine and is not classified as one by the Drug Enforcement Administration or the Food and Drug Administration. It has not been shown to improve strength, speed or other athletic characteristics -- just to keep people awake and alert enough to function. Rather than condemn Ms. White, we should applaud her motivation for overcoming symptoms that make training difficult. She is competing overseas against the world's best -- and she is winning -- not because she is taking a medication that helps her stay awake but because she is a great athlete. RICHARD L. GELULA Executive Director National Sleep Foundation Washington LOAD-DATE: September 7, 2003 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2003 The Washington Post 775 of 998 DOCUMENTS The Herald (Glasgow) September 5, 2003 IAAF give White Brussels go-ahead BYLINE: Doug Gillon SECTION: Pg. 40 LENGTH: 299 words THE stimulant which double world sprint champion Kelli White took in Paris is considered good enough to fight a war, yet those battling against drugs deem it minor, and have cleared her to run tonight in the Brussels grand prix. International Association of Athletics Federations experts ruled that modafinil, which White used to treat a sleeping disorder, was "in the category of weaker stimulants" and well short of amphetamine strength which would have brought a two-year suspension. As a consequence the American has received a reprimand, though her medals still seem likely to be forfeited. The decision of the IAAF panel to downgrade modafinil seems strange. Professor Michel Jouvet, an authority on sleep, stated at a defence conference in Paris: "Modafinil could keep an army on its feet and fighting for three days and nights with no major side effects." It was used in the Falklands by UK forces, and the Foreign Legion during the Gulf War. The US Aerospace Medical Association reports it as being "as effective as the amphetamines", and the US Air Force Human Systems Division says it is "an ideal replacement for amphetamine in short-term operations". White said she "thoroughly researched" the drug, yet a US pharmacology industry data-base, quoting modafinil literature, warns: "Athletes should be aware one of the main ingredients of this product would produce a positive result in anti -doping tests." It is also listed as a banned stimulant by the International Tennis Federation. White is fighting to keep her medals and endorsements. US Track and Field is due to report by Monday and the case then goes to the US Anti- Doping Agency. If the IAAF is unhappy with the outcome, they will refer the case to the Court of Arbitration for Sport. LOAD-DATE: September 05, 2003 LANGUAGE: English PUB-TYPE: Paper Copyright 2003 Scottish Media Newspapers Limited 776 of 998 DOCUMENTS THE DAILY TELEGRAPH(LONDON) September 04, 2003, Thursday No ban but White may lose medals BYLINE: By Mark Hodgkinson SECTION: Pg. 08 LENGTH: 273 words KELLI WHITE, the American sprinter who had feared a two-year ban covering next year's Olympic Games in Athens, learned yesterday that she would not be suspended from competition after testing positive for a stimulant. However, the 26-year-old Californian, who was the first woman to do the sprint double at a World Championships since 1991, will almost certainly be stripped of the 100 metres and 200m gold medals from Paris. She is now expected to feature at tomorrow's Golden League meeting in Brussels following the announcement by the International Association of Athletic Federations that the offence does not merit suspension. Traces of modafinil - a white, crystalline powder used by soldiers and pilots to stay alert - were found in White's sample after her 100m gold. Had it been classed as a harder stimulant, the penalty would have been disqualification and a two-year ban. However, expert medical advice confirmed that modafinil is a weak stimulant, for which the sanction is disqualification and a public warning. White continues to protest her innocence. She claims that she uses the drug to combat narcolepsy, a condition which causes extreme tiredness. She had "no idea" that her medication contained an illegal substance. Modafinil, though not named on the banned list, falls under the "related substances" clause. The IAAF extended the deadline until Monday for a doctor's report explaining why White needed to take the drug. Istvan Gyulai, the general secretary of the IAAF, said. "Unless the medical explanation casts new light on the matter, she will lose both her medals." [PS]Sport: [ES] Hockey: LOAD-DATE: September 4, 2003 LANGUAGE: ENGLISH Copyright 2003 Telegraph Group Limited 777 of 998 DOCUMENTS The Daily Telegraph (Sydney, Australia) September 4, 2003 Thursday White could lose medals SOURCE: MATP BYLINE: JEROME PUGMIRE SECTION: SPORT-BIOG- KELLI WHITE; Pg. 73 LENGTH: 315 words AMERICAN sprinter Kelli White will not be suspended from future track meets but is still in danger of losing the two gold medals she won at the world championships after testing positive for a minor stimulant. White tested positive for the stimulant modafinil after her victory in the 100 metres on August 24. White said she used the prescription drug for a sleep disorder. The penalty for taking a minor stimulant such as modafinil is disqualification from the tournament where the athlete tested positive -- meaning White could lose the golds she clinched in the 100m and 200m races. Although White passed a drug test after winning the 200m on August 28, the fact that she tested positive once means she could lose both medals. IAAF General-Secretary Istvan Gyulai said from Monaco that his organisation would decide on Monday whether White lost her medals. The IAAF extended the deadline until then for a doctor's report explaining why White needed to take modafinil. The 26-year-old track star said she needed the drug to treat narcolepsy. "Kelli White and the US federation tried to explain to us that she was ordered by her doctor to take modafinil, so the IAAF will wait to hear the medical explanation," Gyulai said. "Unless the medical explanation casts new light on the matter she will lose both her medals -- as this is the sanction," he said. Whatever the outcome, he said, White is cleared to race immediately. She had intended to compete in the Golden League track meet in Brussels on Friday and the Grand Prix final in Monaco on September 13 and 14. White, the first American woman to win both sprints at a world championships, will also be able to participate in next year's Athens Olympics. If White loses the medals, she would be the biggest track name stripped of gold at a major championship since Ben Johnson at the 1988 Seoul Olympics. LOAD-DATE: September 4, 2003 LANGUAGE: ENGLISH JOURNAL-CODE: DTM Copyright 2003 Nationwide News Pty Limited 778 of 998 DOCUMENTS The Guardian (London) September 4, 2003 There's one rule for Americans and another for the rest of us BYLINE: Solomon Wariso SECTION: Guardian Sport Pages, Pg. 33 LENGTH: 784 words The news that Kelli White of the United States failed a drug test at the world championships was greeted with knowing looks from certain quarters, not just from the world's press but from the spectators, such was her margin of victory in the 100 metres final. Modafinil, the drug found in her system, was allegedly used to combat the narcolepsy she says is inherent in her family. If so she is the fastest narcoleptic I have ever seen. But the decision not to ban her but instead issue her a warning and strip her of her medals and prize money illustrates what a grey area the issue of drugs in sport has become. In 1994 I had been competing quite a lot on the grand prix circuit as a 200m runner. Feeling partic ularly run down for a couple of days, and with a big meeting in front of a home crowd in Gateshead looming, I came across a herbal supplement called Up Your Gas that purported to help alleviate tiredness. Flicking quickly through the ingredients, the only thing that looked unfamiliar alongside the likes of cayenne pepper and kola nut was "ma huang". Having never heard of it, I thought nothing of it and took a couple of tablets an hour before the race. That was at a time before the internet was widely used, when athletes were not as paranoid about herbal supplements as they are today. As we are now all too aware of, thanks to my case, ma huang is the plant from which ephedrine is derived. Nowadays every dodgy chemical or herb on the market is only a search engine away from having its entire history and chemical makeup uncovered. That is why there is perhaps more than meets the eye to Kelli White's story. By logging on and tapping modafinil into a search engine, you can see warnings that the substance is not to be used if you compete in events where drug testing is likely. The IAAF's decision to strip her of her medals and publicly warn her means it has decided modafinil is probably in the same chemical family as ephedrine and pseudo-ephedrine. One only receives a ban for ephedrine now for a second and third offence. By placing modafinil in that category, the IAAF may have sidestepped a bullet. It allows it to legitimately avoid banning White. If it couldn't do that, and decided not to ban her, athletes who have been banned in the past for other offences might have had grounds to contest those decisions. It could also be that, with White being an American, the IAAF knows that months of litigation were sure to follow if it tried to ban her. Only lawyers would have benefited then. During my hearing the head of the panel of judges, the late Sir Arthur Gold, told me that, regardless of how the substance got into my body, it was my responsibility. He may not have actually come out and said it, but I and my team got the distinct impression that, once you go into a drugs hearing, you are guilty until proven innocent. Ever since Butch Reynolds disputed the results of his positive readings back in the early 90s and won a Dollars 20m settlement in the US Supreme Court against the IAAF - a sum he never received because the IAAF doesn't fall under the Supreme Court's jurisdiction - there has been the feeling in athletics that USA Track and Field has been reluctant to ban its athletes for fear of being bankrupted. When word broke that there were several US athletes competing in the Sydney Olympics who had failed drug tests, people weren't surprised. Jerome Young, a man I competed against several times as a 400m runner in 98 and 99, was last week exposed as having won a gold medal there and the International Olympic Committee is now demanding hard answers from the USOC. But the US administration has form in turning a blind eye - it emerged recently that many American athletes in the 1988 Seoul Olympics had failed drugs tests a few months before their trials. Marion Jones herself had an irregular drug test result at the age of 15 and hired Johnny Cochrane, a family friend, to defend her against the charge. To this roll call you can add the name of Dennis Mitchell, whose massive readings of testosterone were put down to a night of heavy boozing and sex. His federation cleared him to compete until he was slapped down and banned by the IAAF. And these are just the ones we know about. Kelli White was also banned from France last year after banned corticosteroids were found in her urine sample, so failing drug tests is not new to her. It should therefore be no surprise that athletes the world over look at the Americans with distrust and suspicion, because it seems that it is one rule for them, another for the rest of us. Solomon Wariso is a former British international at 200m and 400m LOAD-DATE: September 4, 2003 LANGUAGE: ENGLISH Copyright 2003 Guardian Newspapers Limited 779 of 998 DOCUMENTS Liverpool Daily Echo September 4, 2003, Thursday ATHLETICS: WHITE CLEAR BYLINE: DAVID MARTIN SECTION: SPORT; Pg. 63 LENGTH: 412 words KELLI WHITE, accused of a doping violation after winning the 100 metres gold medal in last week's World Championships, will return to action in Friday's Golden League meeting in Brussels. The International Association of Athletic Federations (IAAF) announced her clearance after deciding the offence did not merit suspension, and manager Robert Wagner confirmed she will compete in Belgium. "Kelli will definitely be taking part," said Wagner. "She knows she needs to get back into action as quickly as possible and is looking forward to her first race since this unfortunate incident." The American athlete's urine sample tested positive for a related drugs substance called modafinil following her 100m victory on August 24. Later in the week,after completing the sprint double by winning the 200m,White's test sample proved negative. The world's governing body made their decision after expert medical advice confirmed modafinil belonged to the minor ephredine family of drugs. IAAF spokesman Nick Davies said: "The IAAF have obtained the necessary expert opinion on the stimulant modafinil and decided to class it in the category of weaker stimulants. "Under IAAF rules the eventual sanction for a doping offence for this substance would be a public warning and disqualification from the competition which means White could be stripped of her two gold medals. "Kelli White will now have the opportunity of a hearing in the United States before any decision can be taken as to whether a doping offence has been committed under our rules." If modafinil had been classed as an amphetamine, White would already have been stripped of her two gold medals and suspended for two years. The American, who claimed the substance is used under prescription by her doctor,failed to list it on her control doping form before the championships began. Wilfried Meert, promoter for the Brussels event which is the last Golden League meeting of the year, said: "Of course Kelli White will be welcome at our meeting. We must be seen to support our athletes." He added: "The IAAF should have kept to its own rules which clearly said that the substance which White has been in trouble for is not on their banned list. "They should have understood that and not be drawn into the conflict which has occurred since then. "Saying that it is a related substance when the athlete understood it was not on the list of banned ones isn't right." LOAD-DATE: September 5, 2003 LANGUAGE: ENGLISH GRAPHIC: BACK ON TRACK: Kelli White is due to make a quick return to action in Brussels tomorrow TYPE: Newspaper Copyright 2003 The Liverpool Daily Post & Echo Ltd 780 of 998 DOCUMENTS The New York Times September 4, 2003 Thursday Late Edition - Final TRACK AND FIELD; White May Lose Gold, Not Shot at Olympics BYLINE: By JERE LONGMAN SECTION: Section D; Column 1; Sports Desk; Pg. 4 LENGTH: 654 words The American sprinter Kelli White will not be barred from the 2004 Athens Olympics, but she may still lose the two gold medals she won in the 100 and 200 meters at the recent world track and field championships in Paris after testing positive for a stimulant, the sport's world governing body said yesterday. Modafinil, the drug found in White's urine sample after the 100 meters, has been classified as a lesser stimulant. If found to have committed a doping violation, she would face a public warning and disqualification from the world championships, according to the I.A.A.F., which governs track and field. She is eligible to run immediately and is expected to compete in the 100 meters tomorrow at a meet in Brussels. Had modafinil been declared a strong stimulant in the class of amphetamines, White would have faced a two-year ban from the sport, which would have precluded her participation in the 2004 Olympics. Her case remains in the early stages, and no doping violation has been declared. The I.A.A.F. said that White had until Monday evening to provide documentation that she had been taking modafinil by doctor's consent to treat the sleeping disorder narcolepsy. White said that some members of her family have had narcolepsy for years. If the world governing body decides that a doping violation has occurred, it sends the case to USA Track and Field, which then turns it over to the United States Anti-Doping Agency. (Since October 2000, the agency has handled all doping cases involving American track athletes because of international suspicion that USA Track and Field is not committed to catching drug cheaters.) The athlete is then given a hearing before the agency, which rules on the case. If the I.A.A.F. agrees on the ruling,it will stand. If the I.A.A.F. disagrees with the agency's ruling, the case is settled by the International Court of Arbitration for Sport, based in Switzerland. The I.A.A.F. made clear again yesterday that, even with a legitimate medical reason for taking modafinil, White would have difficulty convincing the world track body that she did not deserve a warning and the loss of her medals. White has admitted failing to notify the I.A.A.F., as required, that she was using modafinil and failing to get a prior exemption to use the substance. Modafinil is not named on the official list of banned substances but is considered a "related substance" and thus prohibited. Stimulants are banned because they are considered to give athletes an unfair advantage in competition. "Why on earth didn't she declare it?" Istvan Gyulai, general secretary of the I.A.A.F., said yesterday from the federation's headquarters in Monaco. "An athlete of her level must be aware of that." Athletes in Olympic-related sports are supposed to be governed by what is called strict liability, meaning they are to be held responsible if banned substances appear in their bodies, no matter the reason. "If this substance is there, regardless of why it is there, it gave her unfair advantage over her rivals," Gyulai said. "Even if she had a doctor's prescription, its presence means performance enhancement. This is what the doping fight is about, not to have an unfair advantage." White, 26, said she did not notify the I.A.A.F. that she was using modafinil because it is not named on the banned-substance list. Reached by The Associated Press yesterday in Belgium, where she is training for tomorrow's race, White said: "I'm now pretty much getting over the whole mental shock. Whatever happens, I do intend to fight to keep the medals. Whatever I have to do to keep them, I will do that." She ran the fastest times of her career in Paris: 10.85 seconds at 100 meters and 22.05 seconds at 200 meters. If she is stripped of the gold medals, Torri Edwards of the United States will be declared world champion at 100 meters and Anastasiya Kapachinskaya of Russia will be declared the winner at 200 meters. URL: http://www.nytimes.com LOAD-DATE: September 4, 2003 LANGUAGE: ENGLISH GRAPHIC: Photo: Kelli White spoke yesterday in Brussels, where she is scheduled to compete in a 100-meter race at a meet tomorrow. (Photo by Associated Press) PUBLICATION-TYPE: Newspaper Copyright 2003 The New York Times Company 781 of 998 DOCUMENTS The Times (London) September 4, 2003, Thursday White to race on after escaping ban for failed test BYLINE: David Powell, Athletics Correspondent in Brussels SECTION: Sport; 45 LENGTH: 624 words KELLI WHITE will compete in the Golden League meeting here tomorrow after being told yesterday that the worst punishment she will face for failing a drugs test at the World Championships last week is a caution and the loss of her gold medals and prize-money. The IAAF, the sport's world governing body, has ruled that the stimulant found in her sample falls into the mild rather than serious category. However, it is unclear whether modafinil, the drug for which White, the United States sprinter who won the 100 and 200 metres in Paris, tested positive, would have given her a performance advantage. The IAAF had been unable to categorise it immediately after she failed the test and only after seeking expert opinion did it rule yesterday that it was not strong enough to warrant a suspension. White responded by confirming that she would run here, in Monaco the weekend after next and in Russia and Japan to end her season, but she added that the experience had left her "very tired physically and mentally". Robert Wagner, her manager, said that she had been ready to quit for the season until she was given a sympathetic reception on a German television chat show on Tuesday, on which she appeared with Boris Henry, the javelin thrower who is her boyfriend. White had said that she was taking modafinil on prescription to counter narcolepsy and the fact that she tested negative after the 200 metres added weight to her claim. The IAAF insisted yesterday that she would have benefited from the drug, but Cephalon, the manufacturer of Provigil, under which modafinil is sold under licence, said that during pre-marketing clinical trials it had not been "systematically evaluated in athletes or patients engaged in significant physical exercise or activity". However, Nick Davies, the IAAF spokesman, said: "It is considered a stimulant, so it does have a performance- enhancing effect." The world governing body said in a statement: "Under IAAF rules, the eventual sanction for a doping offence for this substance, if proven, would be a public warning and disqualification from the competition. This means that Ms White could be stripped of her gold medals in Paris in the 100 and 200 metres events." There seems little chance of an offence not being proven because White failed to list the substance on her doping form. White's medals would pass to Torri Edwards, a fellow American, in the 100 metres and to Anastasiya Kapachinskaya, from Russia, in the 200 metres, but it could be months before the matter is resolved. The case now goes to USA Track & Field, the governing body in the US, which in turn is guided in such matters by the US Anti-Doping Agency. The IAAF statement continued: "Ms White will be afforded the opportunity of a hearing in the United States before any decision is taken on whether a doping offence has been committed under IAAF rules. The athlete is not suspended pending her hearing." In other words, she can start to make up some of the $ 120,000 (about Pounds 76,000) in World Championships prize-money that she is likely to lose. Until six years ago, White would have been suspended for three months pending a hearing, but the IAAF dropped the punishment for a mild stimulant offence, believing it to be too harsh. The feeling was that in some cases it could effectively rule an athlete out for a season, whereas a steroid offence, carrying a two-year ban and a much more serious charge, deserved a significantly greater sentence in practical terms. Another leading athlete who has tested positive is Bernard Lagat, the World Cup 1,500 metres champion from Kenya. It was announced yesterday that Lagat had tested positive for EPO after a race in Germany three weeks ago. LOAD-DATE: September 4, 2003 LANGUAGE: ENGLISH Copyright 2003 Times Newspapers Limited 782 of 998 DOCUMENTS USA TODAY September 4, 2003, Thursday, FINAL EDITION No ban for White; golds likely gone BYLINE: Dick Patrick SECTION: SPORTS; Pg. 9C LENGTH: 418 words Kelli White will have a tough time disputing a positive drug test that could strip her of two gold medals at the recent World Track & Field Championships in Paris. The 100- and 200-meter winner tested positive for modafinil, which she said was prescribed for narcolepsy, a sleep disorder that her mother and an aunt also share. Though modafinil is not on the banned list, the international track federation (IAAF) considers it "a related substance" and announced Wednesday its classification as a stimulant rather than an amphetamine, sparing White a two-year ban. "The problem is once this substance is in her body, this already constitutes a doping offense, pending a hearing and explanation," says Istvan Gyulai, the IAAF general secretary. "Even if she can explain this because of a medical prescription, that will not nullify that she was running with a performance-enhancing substance." Besides documentation from her physician, the White team plans to introduce information from Cephalon, the West Chester, Pa.-based company that produces Provigil, the U.S. form of the drug. "They say the drug is neither an amphetamine nor a stimulant," says Robert Wagner, White's agent. The IAAF plans to announce Monday whether White is guilty of a doping offense, which would mean she'd lose her medals and $ 120,000 in prize money. If the IAAF rules against her, White could continue appeals with the U.S. Anti-Drug Agency. White is in Brussels for a 100 race Friday, though she also considered ending her season. "The best thing is to go to Brussels and win," Wagner says. "We're going to ask for doping control after each race from now on." Wagner argues the Paris lab, which analyzed the sample, should be investigated since White's positive was leaked to the press against IAAF regulations. Kenyan positive: Bernard Lagat, a U.S.-based Kenyan who was third in the 1,500 at the 2000 Olympics, has been announced as positive for endurance-boosting EPO. According to his agent, James Templeton, the confirmation test has not been conducted and Lagat denies taking the drug. Lagat, featured in a series of Nike ads, did not compete at the recent worlds. "He's devastated; he cried like a baby," said Lagat's coach, James Li, the cross country coach at Arizona. "Even in a million years, it's not possible for him to do this. This guy is just so completely against this drug thing. "If I don't say this, no one will hear it. If I do say it, a lot of people won't believe it." LOAD-DATE: September 04, 2003 LANGUAGE: ENGLISH GRAPHIC: PHOTO, B/W, Benoit Doppagne, AFP/Getty Images; Making a case: Kelli White says she took modafinil to combat a sleep disorder. Her agent, Robert Wagner, says the company that produced the drug says it is neither an amphetamine nor a stimulant." Copyright 2003 Gannett Company, Inc. 783 of 998 DOCUMENTS The Associated Press September 3, 2003, Wednesday, BC cycle U.S. sprint star Kelli White not suspended but could lose golds from Worlds BYLINE: By JEROME PUGMIRE, Associated Press Writer SECTION: International News; Sports News LENGTH: 628 words DATELINE: PARIS American sprinter Kelli White will not be suspended from future track meets after testing positive for a minor stimulant, but could still be stripped of the two gold medals she won at the World Championships, IAAF general secretary Istvan Gyulai said Wednesday. Gyulai, speaking to The Associated Press by telephone from Monaco, said the IAAF will not decide whether White loses her medals until next Monday. White tested positive for the stimulant modafinil after her victory in the 100 meters at the Worlds on Aug. 24. White said she used the prescription drug for a sleep disorder. The penalty for taking a minor stimulant such as modafinil is disqualification from the tournament where the athlete tested positive - meaning White could lose the golds she won in the 100 and 200 races. Although White passed a drug test after winning the 200 on Aug. 28, the IAAF said her positive test after the 100 could be enough to cost her both medals. White had set personal best times in both races - 10.85 seconds in the 100 meters and 22.05 in the 200 meters. The IAAF extended the deadline until Monday to wait for a doctor's report explaining why White needed to take modafinil. The 26-year-old track star said she needed the drug to treat narcolepsy. "Kelli White and the U.S. federation tried to explain to us that she was ordered by her doctor to take modafinil, so the IAAF will wait to hear the medical explanation," Gyulai said. "Unless the medical explanation casts new light on the matter she will lose both her medals - as this is the sanction," he said. Whatever the outcome, he said, White is cleared to race immediately. She had planned to compete in the Golden League track meet in Brussels on Friday and the Grand Prix final in Monaco on Sept. 13-14. White, the first American woman to sweep both sprints at a world championships, will also be able to participate in next year's Athens Olympics. If White is stripped of her medals, American runner Torri Edwards will be awarded the 100 gold medal, while Zhanna Block of Ukraine would take silver and Bahamas runner Chandra Sturrup the bronze. The 200 champion would be Russia's Anastaiya Kapachinskaya. Edwards would take silver and France's Muriel Hurtis the bronze. The overall medals table would also be altered, with America's total tally of 20 medals dropping to 18, leaving Russia as the leader with 19. White would also lose $60,000 in prize money for each gold. While not specified by name on the banned list, modafinil is covered under the stimulants category of "related substances," the IAAF has said. Under IAAF rules, the penalty for use of light stimulants also includes a public warning. For harder stimulants, such as amphetamines, the sanction is disqualification and a two-year ban. If White loses the medals, she would be the biggest track name stripped of gold at a major championship since Ben Johnson at the 1988 Seoul Olympics. Last Saturday, White acknowledged taking modafinil the morning of the 100 final. But she denied ever taking a substance to enhance her performance, saying she took the medication only to treat narcolepsy and had "no idea" it contained a banned substance. White said she didn't apply for a medical waiver or include the medication on her doping control form as required because it wasn't named on the prohibited drug list. White said she and her doctor had done extensive research on modafinil before deciding to use it for narcolepsy, which causes sudden fatigue or sleepiness. The drug is sold under the brand name Provigil in the United States. However, an Internet search on modafinil turned up frequent warnings to athletes that its use could result in a positive result in an anti-doping test. LOAD-DATE: September 4, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 784 of 998 DOCUMENTS The Associated Press State & Local Wire September 3, 2003, Wednesday, BC cycle U.S. sprint star Kelli White not suspended but could lose golds from Worlds BYLINE: By JEROME PUGMIRE, Associated Press Writer SECTION: Sports News LENGTH: 634 words DATELINE: PARIS American sprinter Kelli White will not be suspended from future track meets after testing positive for a minor stimulant, but could still be stripped of the two gold medals she won at the World Championships, IAAF general secretary Istvan Gyulai said Wednesday. Gyulai, speaking to The Associated Press by telephone from Monaco, said the IAAF will not decide whether White loses her medals until next Monday. White tested positive for the stimulant modafinil after her victory in the 100 meters at the Worlds on Aug. 24. White said she used the prescription drug for a sleep disorder. The penalty for taking a minor stimulant such as modafinil is disqualification from the tournament where the athlete tested positive - meaning White could lose the golds she won in the 100 and 200 races. Although White passed a drug test after winning the 200 on Aug. 28, the IAAF said her positive test after the 100 could be enough to cost her both medals. White had set personal best times in both races - 10.85 seconds in the 100 meters and 22.05 in the 200 meters. The IAAF extended the deadline until Monday to wait for a doctor's report explaining why White needed to take modafinil. The 26-year-old track star said she needed the drug to treat narcolepsy. "Kelli White and the U.S. federation tried to explain to us that she was ordered by her doctor to take modafinil, so the IAAF will wait to hear the medical explanation," Gyulai said. "Unless the medical explanation casts new light on the matter she will lose both her medals - as this is the sanction," he said. Whatever the outcome, he said, White is cleared to race immediately. She had planned to compete in the Golden League track meet in Brussels on Friday and the Grand Prix final in Monaco on Sept. 13-14. White, who lives in the Bay Area and was the first American woman to sweep both sprints at a world championships, will also be able to participate in next year's Athens Olympics. If White is stripped of her medals, American runner Torri Edwards will be awarded the 100 gold medal, while Zhanna Block of Ukraine would take silver and Bahamas runner Chandra Sturrup the bronze. The 200 champion would be Russia's Anastaiya Kapachinskaya. Edwards would take silver and France's Muriel Hurtis the bronze. The overall medals table would also be altered, with America's total tally of 20 medals dropping to 18, leaving Russia as the leader with 19. White would also lose $60,000 in prize money for each gold. While not specified by name on the banned list, modafinil is covered under the stimulants category of "related substances," the IAAF has said. Under IAAF rules, the penalty for use of light stimulants also includes a public warning. For harder stimulants, such as amphetamines, the sanction is disqualification and a two-year ban. If White loses the medals, she would be the biggest track name stripped of gold at a major championship since Ben Johnson at the 1988 Seoul Olympics. Last Saturday, White acknowledged taking modafinil the morning of the 100 final. But she denied ever taking a substance to enhance her performance, saying she took the medication only to treat narcolepsy and had "no idea" it contained a banned substance. White said she didn't apply for a medical waiver or include the medication on her doping control form as required because it wasn't named on the prohibited drug list. White said she and her doctor had done extensive research on modafinil before deciding to use it for narcolepsy, which causes sudden fatigue or sleepiness. The drug is sold under the brand name Provigil in the United States. However, an Internet search on modafinil turned up frequent warnings to athletes that its use could result in a positive result in an anti-doping test. LOAD-DATE: September 4, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 785 of 998 DOCUMENTS The Associated Press State & Local Wire September 3, 2003, Wednesday, BC cycle Kelli White not suspended but could lose golds from worlds BYLINE: By JEROME PUGMIRE, Associated Press Writer SECTION: Sports News LENGTH: 612 words DATELINE: PARIS U.S. sprinter Kelli White will not be suspended from track meets for taking a stimulant but still could be stripped of the two gold medals she won at the World Championships. The IAAF will not decide whether White loses her medals until Monday, Istvan Gyulai, general secretary of track and field's governing body, told The Associated Press from Monaco on Wednesday. White tested positive for the stimulant modafinil after winning the 100 meters at the worlds on Aug. 24. White said she used the prescription drug for the sleep disorder narcolepsy. The penalty for taking such a minor stimulant is disqualification from the meet where the athlete tested positive - meaning White could lose the golds she won in the 100 and 200. Although White passed a drug test after winning the 200 on Aug. 28, the IAAF said her positive test after the 100 could cost her both medals. If she loses the medals, she would be the biggest track name stripped of a gold medal at a major championship since Ben Johnson at the 1988 Seoul Olympics. White set personal bests in both races - 10.85 seconds in the 100 and 22.05 in the 200. The International Association of Athletics Federations extended the deadline until Monday to wait for a doctor's report explaining why White needed to take modafinil. "Kelli White and the U.S. federation tried to explain to us that she was ordered by her doctor to take modafinil, so the IAAF will wait to hear the medical explanation," Gyulai said. "Unless the medical explanation casts new light on the matter she will lose both her medals - as this is the sanction," he said. Whatever the outcome, he said, White is cleared to race immediately. She had planned to compete in the Golden League track meet in Belgium on Friday and the Grand Prix final in Monaco on Sept. 13-14. White, of Union City in Northern California, is the first American woman to sweep both sprints at a World Championships. She also will be able to participate in next year's Athens Olympics. If White is stripped of her medals, American runner Torri Edwards will be awarded the 100 gold medal, while Zhanna Block of Ukraine would take silver and Bahamas runner Chandra Sturrup the bronze. The 200 champion would be Russia's Anastaiya Kapachinskaya. Edwards would take silver and France's Muriel Hurtis the bronze. The overall medals standings also would be altered, with America's total tally of 20 medals dropping to 18, leaving Russia as the leader with 19. White would also lose $60,000 in prize money for each gold. While not specified by name on the banned list, modafinil is covered under the stimulants category of "related substances," the IAAF has said. Under IAAF rules, the penalty for use of light stimulants also includes a public warning. For harder stimulants, such as amphetamines, the sanction is disqualification and a two-year ban. Last Saturday, White acknowledged taking modafinil the morning of the 100 final. But she denied ever taking a substance to enhance her performance, saying she took the medication only to treat narcolepsy and had "no idea" it contained a banned substance. White said she didn't apply for a medical waiver or include the medication on her doping control form as required because it wasn't named on the prohibited drug list. White said she and her doctor had done extensive research on modafinil before deciding to use it for narcolepsy, which causes sudden fatigue or sleepiness. The drug is sold under the brand name Provigil in the United States. However, an Internet search on modafinil turned up frequent warnings to athletes that its use could result in a positive doping test. LOAD-DATE: September 4, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 786 of 998 DOCUMENTS Buffalo News (New York) September 3, 2003 Wednesday, FINAL EDITION WHITE'S CHOICE TO USE DRUG WAS DOPEY SECTION: SPORTS, Pg.D1 LENGTH: 709 words The fastest woman in the world can run, but she cannot hide. Her alibi was laughable, her feigned ignorance insulting. Kelli White cheated last week while becoming the first U.S. woman to sweep the sprints at the World Track and Field Championships, and the consequences should have been more severe. White warranted the maximum penalty, a two-year suspension that would have precluded her participation in next Summer's Athens Olympics, after testing positive for the stimulant modafinil following her 100-meter victory in Paris. Instead, the International Association of Athletics Federations today ruled that White won't be suspended, although her medals remain in jeopardy. The lax decision is yet another blow to the image of a sport that long has suffered in the arena of credibility. White, a native of Oakland, said she was taking the prescription medication to combat narcolepsy, which is characterized by daytime fatigue and an urge to sleep. Makes sense. Modafinil has been used by military organizations to invigorate weary troops. However, White's insistence that this was all an innocent mistake, an oversight, is undermined by the details of her argument. She claims that she and her physician conducted extensive research on modafinil before prescribing it for her condition. She explained that she neither sought a medical waiver nor disclosed her usage because modafinil is not listed on the IAAF's list of banned substances. But White, 26, and her physician couldn't possibly have researched the effects of modafinil and determined it inconsequential to her performance. An Associated Press reporter covering the championships conducted a brief Internet search and found a Web site, www.modafinil.info, that carried this warning: "Athletes should be aware that one of the main ingredients of this pharmaceutical product would produce a positive result in anti-doping tests." A lengthy article on the Web site references an Aerospace Medical Association article that concluded: "The development of modafinil brings to light a crucial social question. What would be the impediment for its use, if a compound such as modafinil is more like caffeine than amphetamine in terms of safety, and yet, as effective as the amphetamines?" That Aerospace Medical Association article was published in 1991. How could White and her physician have thoroughly investigated the substance and concluded it fell outside the IAAF's list of banned (and related) substances? It doesn't wash. The IAAF mandates disqualification and a public warning for athletes using minor stimulants. Disqualification and a two-year ban from competition are the penalties for use of hard-core stimulants that produce effects similar to amphetamines. The remedy should have been apparent. White should have been dealt a two-year suspension and be ordered to forfeit her medals. White's rise to track prominence is a compelling story. She once was assaulted in a knife attack two weeks after running the fastest high school 200 meters in the country, suffering wounds that required more than 300 stitches and left a scar surrounding her left eye. She went on to an undistinguished career at Tennessee, emerging only within the last 18 months as a significant threat to world speed queen Marion Jones. You'd like to believe her transgression was merely an oversight, however the evidence weighs in to the contrary. The world championships should be a celebration of the sport. Instead, all that transpired in Paris pulled it deeper into the muck. International track organizations seethed when USA Track & Field overturned on appeal a failed steroids test, allowing an unnamed athlete to compete in the Sydney Olympics. The Los Angeles Times last week identified the athlete as Jerome Young, a member of the gold-medal-winning 1,600-meter relay at Sydney and a two-time gold medalist at the worlds. The International Olympic Committee now is calling for a detailed investigation. The track world bristled at U.S. defiance again during the worlds when Jon Drummond, disqualified for a false start in the 100 meters, protested by laying on the track and delaying the competition. Track has some growing up to do. e-mail: bdicesare@buffnews.com LOAD-DATE: September 5, 2003 LANGUAGE: ENGLISH Copyright 2003 The Buffalo News 787 of 998 DOCUMENTS Chicago Sun-Times September 2, 2003 Tuesday Fun to track Team Troubled's travails BYLINE: Carol Slezak SECTION: SPORTS; Pg. 103 LENGTH: 942 words HIGHLIGHT: Whether it was a crying sprinter or a positive drug test, the American drama was compelling and disgusting. The World Track and Field Championships are over, and I miss them. I especially miss opening this newspaper every morning to read about the latest U.S. mishap. Team USA? Try Team Troubled. Then again, what's new? If only someone could figure out a way to market track and field in the United States in non-Olympic years, it could become the new NASCAR. I'm telling you, the travails of Team Troubled's tracksters make for great drama. A sprinter crying in the middle of the track. Another sprinter trying to explain her way out of a positive drug test. Even when it's disgusting, it's compelling. What to make of Kelli White's drug case? White won the 100 and 200 meter sprints--yahoo!--but tested positive for the stimulant modafinil after the 100. Just like that, White went from Marion Jones territory to Ben Johnson territory. White said she takes the prescription drug to treat narcolepsy, a sleep disorder. Since modafinil is not on the banned substance list, you might think White has a good case. But it's not that simple. The subject of sprinters and doping never is. The International Association of Athletics Federation says modafinil is covered under its "related substances" stimulants category. In other words, White should have known better. At a news conference in France after her dirty test, White insisted her conscience is clean. She denied using modafinil to improve her performance. She said she didn't think it was necessary to notify the IAAF she was taking modafinil because it wasn't listed as a banned substance. She said she didn't take the drug regularly, only as needed. White also said she and her doctor researched the drug before deciding to use it to treat her narcolepsy. They must have neglected to do a Google search. Mine--"doping and modafinil"--turned up a warning that one of the main ingredients in modafinil would produce a positive result. Just once I'd like to see a sprinter hold a news conference after a positive drug test and say, "I knew what I was doing. I'm just sorry I got caught." The IAAF is investigating White's case. This could take a while. The IAAF has yet to even decide how modafinil should be classified. Is it a light stimulant or a hard stimulant? White, 26, could face a simple disqualification and warning. Or she could face a two-year ban. It's unlikely she'll get off without some form of punishment. Until White's faux pas, the best story about a woman at the World Championships had been a heartwarming one. It was the tale of Lima Azimi, the first Afghan woman to compete in a World Championships. Azimi's 100-meter time, 18.37 seconds, didn't advance the cause of Afghan athletes. But her mere appearance in France advanced the cause of all Afghan women. As Azimi told the world, "It is not important for me to win here, but it is very important for me to race here." Amen, sister. Now, back to the spoiled Americans. My goodness, the U.S. men are drama queens. Jon Drummond started things off by false-starting in his 100-meter sprint. The man-child was so incensed with the ruling he proceeded to throw a fit on the track. He laid down on the track and wouldn't get up. He went back to the starting line, although he knew he had been disqualified. He cried. Drummond subsequently withdrew from the Championships altogether. Perhaps just to make sure he didn't return anytime soon, World track officials officially suspended him from the rest of the Championships. Drummond's behavior wasn't even the strangest among the American men. Tim Montgomery's was even weirder. After coming in fifth in the 100, Montgomery disappeared. Turns out he flew home to North Carolina. But he didn't bother to tell his coaches he was leaving. Or his teammates on the 400-meter relay team, for that matter. Of course, Drummond was supposed to have been on the relay team, too. As was Maurice Greene, who withdrew with an injury. And even with three subs, Team Troubled managed to win the relay. Maybe Montgomery left France because he missed Marion Jones, who was back home with the couple's infant son. But that's no excuse for going AWOL. And isn't it just wonderful that this childish behavior was on exhibit in France of all places? No wonder the French don't like us. There were some highlights for Team Troubled at the Worlds. The gold in the men's 400-relay, for instance. A gold in the 200 meters for John Capel, who was drafted by the Bears as a wide receiver in 2001. A total of 20 medals for the United States, one more medal than runner-up Russia. Even that's subject to change when White's doping case is resolved. Craig Masback, the CEO of USA Track and Field, was pleased with Team USA's performance. 'It sets us up for next year," Masback told the Associated Press. "Ultimately, in our world, the Olympics is the big thing." Medal counts aside, if Athens provides half the drama of these World Championships, I'll be satisfied. U.S. gold medalists The U.S. led all nations with 20 medals, including 10 gold, at last week's World Track and Field Championship in Saint-Denis, France. Double-winner Kelli White could be stripped of her two golds after failing a drug test. The American gold medalists: MEN 110 hurdles--Allen Johnson. 200--John Capel. 400--Jerome Young. 4 x 100 relay--John Capel; Bernard Williams; Darvis Patton; J.J. Johnson. 4 x 400 relay--Calvin Harrison; Tyree Washington; Derrick Brew; Jerome Young. Long jump--Dwight Phillips. Decathlon--Tom Pappas. WOMEN 100--Kelli White. 200--Kelli White. 4 x 400 relay--Me'Lisa Barber; Demetria Washington; Jearl Miles Clark; Sanya Richards. LOAD-DATE: September 10, 2003 LANGUAGE: English GRAPHIC: Associated Press, American 400-relay team members celebrate their victory at the World Track and Field Championships. The team included (from left) ex-Bears draftee John Capel, Bernard Williams, Darvis Petton and J.J. Joshua. CHART; SEE BELOW. Copyright 2003 Chicago Sun-Times, Inc. 788 of 998 DOCUMENTS The International Herald Tribune September 2, 2003 Tuesday A tale of two championships for the U.S. team ; Athletics BYLINE: Jere Longman SOURCE: The New York Times SECTION: SPORT; Pg. 16 LENGTH: 1094 words DATELINE: PARIS: As the World Championships ended in a rush of U.S. gold medals, Craig Masback, the chief executive of USA Track & Field, held a news conference promising change and summing up his mixed feeling about the previous nine days with a quote from a novel about a different revolutionary era in Paris "It's a Dickensian experience: best of times, worst of times," Masback said on Sunday. He used the conference to outline a re-evaluation of the U.S. governing body for athletics in the light of controversies in Paris regarding performance-enhancing drugs and the histrionic behavior of the sprinter Jon Drummond, who sprawled on the track at the Stade de France to protest a controversial false-start rule. After a slow start in the competition, the United States won three gold medals in relay races on Sunday. Both the 10 gold medals and the 20 medals overall led the competition. But two of the golds remained in jeopardy after the sprint champion Kelli White found herself embroiled in an unresolved drug case. White's case remains under review by the International Association of Athletics Federations, the sport's world governing body. After the 100 meters final, White tested positive for modafinil, a stimulant that she said she had used to treat the sleep disorder narcolepsy. Her urine test results were negative after the later 200-meter final, USA Track and Field said on Sunday. A San Francisco Bay Area doctor told a California newspaper that he had given White samples of the drug to take on an as-needed basis. White said on Saturday that she had been experiencing constant fatigue and restlessness at night because she was falling asleep during the day. "In Kelli's case, she could get jet lag up to 12 days," Dr. Brian Goldman, a child psychiatrist, told The San Jose Mercury News. "You could be having a conversation with her, and she just falls asleep." White's mother and an aunt have severe narcolepsy, Goldman told the newspaper in an article published on Sunday. White did not report on an IAAF doping control form that she was using modafinil, as required, or ask for a special exemption to use it. The drug is not on the official list of banned substances, but it is considered a "related substance." Athletes use it at the peril of testing positive. White said she had not reported the drug because it was not on the banned list. If a doping violation is ruled, she faces a warning, which would also result in the loss of her gold medals, or a two-year ban from competition. No date for a hearing or a resolution of the case has been set, U.S. track officials said on Sunday. White intends to run in the Golden League final in Brussels on Friday. Her eligibility is uncertain. There was speculation on Sunday that her defense of the use of modafinil might also include a contention that the drug is not a stimulant and that it is not performance-enhancing. But the IAAF said it considered modafinil a stimulant. Stimulants are prohibited because they are considered to provide an unfair enhancement of performance. "They do not know the nature of the substance and cannot currently identify a possible consequence, if any," White said on Saturday. There were essentially two meets for the United States in the Stade de France. One had some brilliant performances, including the brisk anchor leg that J.J. Johnson ran in the 4x100-meter relay to edge Britain for the gold medal in 38.06 seconds. The United States was without Drummond, who was disqualified from the Championships for bringing the sport into disrepute; without Maurice Greene, the Olympic 100-meter champion, who injured a leg in Paris, and without Tim Montgomery, the world record holder, who left after a poor performance in the 100. Still, the United States succeeded with Bernard Williams and a threesome of 200-meter specialists -- the world champion John Capel, the world runner-up Darvis Patton and Johnson. The United States was the surprise winner in the women's 4x400 relay, in 3 minutes 22.63 seconds, as Sanya Richards held off Natalya Nazarova of Russia on the last leg. In the men's 400 relay, Jerome Young, the 400-meter world champion, held off Marc Raquil of France for the gold medal in 2:58.88. The 20 total medals were the most by the United States since it took 25 in the 1993 World Championships in Stuttgart. But the performances were clouded by Drummond's outburst during the 100-meter quarterfinals and by drug revelations that included a report that Young tested positive for a steroid in 1999. Masback said the distractions were a "call to action" for the track federation. In October, a summit meeting of athletes, coaches and agents will be convened in Miami to discuss a number of issues, including athlete behavior, he said. "I don't want to say we've been dead in the water on this," he said. "We've been proactive, but we've got to go to the next step." The United States also needs a rules expert at each major competition, he said. In addition, Masback called for uniform doping rules and for better education of athletes from the United States about prohibited substances. Last month, Mickey Grimes was given a warning and stripped of his gold medal in the 100 meters after testing positive for a stimulant at the Pan American Games. "Whatever we are doing is not enough," Masback said. "We've got to do more." Masback defended the federation's actions regarding Young. The Los Angeles Times reported that he had tested positive for the steroid nandrolone but been exonerated on appeal and was allowed to compete in the 2000 Olympics on the victorious 400 relay team. The case was settled by international arbitration, and Young's name was kept private by USA Track & Field until the newspaper revealed it. But Dick Pound, president of the World Anti-Doping Agency, called for the relay gold medal won in Sydney to be stripped from the U.S. team. He criticized USA Track & Field's handling of the Young case, saying the legitimacy of the Sydney relay team had been "shattered." The International Olympic Committee has also called for further investigation. "I believe we have done the appropriate thing in all circumstances," Masback said. On Sunday, he proposed an international relations department in the federation to help improve the image of the United States worldwide and to foster a better understanding of its rules. These actions seemed welcomed by IAAF officials. "The U.S. federation should sit down and figure out how not to be so unlucky in the future," Istvan Gyulai, the general secretary of the IAAF, said. LOAD-DATE: September 2, 2003 LANGUAGE: ENGLISH Copyright 2003 International Herald Tribune 789 of 998 DOCUMENTS The Associated Press September 1, 2003, Monday, BC cycle White's medals still in limbo as she heads into rest of season BYLINE: By STEPHEN WILSON, AP Sports Writer SECTION: Sports News LENGTH: 750 words DATELINE: SAINT-DENIS, France Kelli White heads into the rest of the European track season not knowing if she'll get to keep her two gold medals from the World Championships. The nine-day meet ended Sunday but the International Association of Athletics Federations is still investigating whether the U.S. sprinter committed a doping offense by testing positive for a stimulant after her victory in the 100 meters. White passed a drug test after winning her second gold, in the 200 on Thursday, IAAF general secretary Istvan Gyulai told The Associated Press. She was the first American woman to sweep both sprints at a world championships. Even though White tested clean after the 200, the IAAF said her positive test after the 100 last Sunday would be enough to cost her both medals. Depending on the severity of the offense, she could also face a two-year ban ruling her out of next year's Athens Olympics. The IAAF needs to clarify White's status soon because she is scheduled to run Friday at the Golden League meet in Brussels. She also plans to compete in the Grand Prix final in Monaco on Sept. 13-14 and an invitational meet in Moscow on Sept. 20. Gyulai said the IAAF was trying to determine the exact nature of modafinil, a prescription medication which White said she used for a sleep disorder. While not specified by name on the banned list, modafinil is covered under the stimulants category of "related substances," the IAAF said. Under IAAF rules, the penalty for use of light stimulants, such as ephedrine, is disqualification and a public warning. For harder stimulants, such as amphetamines, the sanction is disqualification and a two-year ban. Gyulai said the IAAF is contacting scientists around the world to determine how to classify modafinil. He said that could take four or five days. After that, Gyulai said, the IAAF would have three options: accept White's explanation and consider clearing her on grounds of "exceptional circumstances"; disqualify her and give her a warning; or disqualify her and recommend a two-year ban. If the IAAF decides that modafinil falls into the strong category, White would be suspended pending a hearing by USA Track & Field, Gyulai said. Her case would then be handled by the U.S. Anti-Doping Agency, and could potentially end up before the Court of Arbitration for Sport. That process could take months. If White loses the medals, she would be the biggest track name stripped of gold at a major championship since Ben Johnson at the 1988 Seoul Olympics. "She was the star of the championships, and now she's at the center of a doping case," former Olympic and world champion Michael Johnson wrote in his daily column in the French sports daily L'Equipe. "It creates trouble for our sport. It's a big cloud over these championships." At a news conference Saturday, White acknowledged taking modafinil the morning of the 100 final. But she denied ever taking a substance to enhance her performance, saying she took the medication only to treat narcolepsy and had "no idea" it contained a banned substance. White said she didn't apply for a medical waiver or include the medication on her doping control form as required because it wasn't named on the prohibited drug list. White said she and her doctor had done extensive research on modafinil before deciding to use it for narcolepsy, which causes sudden fatigue or sleepiness. The drug is sold under the brand name Provigil in the United States. An Internet search on modafinil turned up frequent warnings to athletes. "Athletes should be aware that one of the main ingredients of this pharmaceutical product would produce a positive result in anti-doping tests," said the Web site www.modafinil.info. White was not the only American athlete at the championships who came under scrutiny for drugs. The Los Angeles Times reported that 400 champion Jerome Young tested positive for steroids in 1999, but was cleared on appeal by U.S. track officials and allowed to compete in the 2000 Sydney Olympics, where he won gold as a member of the 1,600 relay team. World Anti-Doping Agency chief Dick Pound has called for the U.S. team to be stripped of the medal. Young won his second gold medal of the championships Sunday night, anchoring the U.S. 1,600 relay team to victory in the final event of the meet. "I just didn't worry about it," Young said of the doping allegations. "I just put it behind me and kept on going, and just basically used that as a motivation for me." LOAD-DATE: September 2, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 790 of 998 DOCUMENTS Associated Press Online September 1, 2003 Monday Kelli White's Medals Still in Limbo BYLINE: STEPHEN WILSON; AP Sports Writer SECTION: SPORTS LENGTH: 746 words DATELINE: SAINT-DENIS, France Kelli White heads into the rest of the European track season not knowing if she'll get to keep her two gold medals from the World Championships. The nine-day meet ended Sunday but the International Association of Athletics Federations is still investigating whether the U.S. sprinter committed a doping offense by testing positive for a stimulant after her victory in the 100 meters. White passed a drug test after winning her second gold, in the 200 on Thursday, IAAF general secretary Istvan Gyulai told The Associated Press. She was the first American woman to sweep both sprints at a world championships. Even though White tested clean after the 200, the IAAF said her positive test after the 100 last Sunday would be enough to cost her both medals. Depending on the severity of the offense, she could also face a two-year ban ruling her out of next year's Athens Olympics. The IAAF needs to clarify White's status soon because she is scheduled to run Friday at the Golden League meet in Brussels. She also plans to compete in the Grand Prix final in Monaco on Sept. 13-14 and an invitational meet in Moscow on Sept. 20. Gyulai said the IAAF was trying to determine the exact nature of modafinil, a prescription medication which White said she used for a sleep disorder. While not specified by name on the banned list, modafinil is covered under the stimulants category of "related substances," the IAAF said. Under IAAF rules, the penalty for use of light stimulants, such as ephedrine, is disqualification and a public warning. For harder stimulants, such as amphetamines, the sanction is disqualification and a two-year ban. Gyulai said the IAAF is contacting scientists around the world to determine how to classify modafinil. He said that could take four or five days. After that, Gyulai said, the IAAF would have three options: accept White's explanation and consider clearing her on grounds of "exceptional circumstances"; disqualify her and give her a warning; or disqualify her and recommend a two-year ban. If the IAAF decides that modafinil falls into the strong category, White would be suspended pending a hearing by USA Track & Field, Gyulai said. Her case would then be handled by the U.S. Anti-Doping Agency, and could potentially end up before the Court of Arbitration for Sport. That process could take months. If White loses the medals, she would be the biggest track name stripped of gold at a major championship since Ben Johnson at the 1988 Seoul Olympics. "She was the star of the championships, and now she's at the center of a doping case," former Olympic and world champion Michael Johnson wrote in his daily column in the French sports daily L'Equipe. "It creates trouble for our sport. It's a big cloud over these championships." At a news conference Saturday, White acknowledged taking modafinil the morning of the 100 final. But she denied ever taking a substance to enhance her performance, saying she took the medication only to treat narcolepsy and had "no idea" it contained a banned substance. White said she didn't apply for a medical waiver or include the medication on her doping control form as required because it wasn't named on the prohibited drug list. White said she and her doctor had done extensive research on modafinil before deciding to use it for narcolepsy, which causes sudden fatigue or sleepiness. The drug is sold under the brand name Provigil in the United States. An Internet search on modafinil turned up frequent warnings to athletes. "Athletes should be aware that one of the main ingredients of this pharmaceutical product would produce a positive result in anti-doping tests," said the Web site www.modafinil.info. White was not the only American athlete at the championships who came under scrutiny for drugs. The Los Angeles Times reported that 400 champion Jerome Young tested positive for steroids in 1999, but was cleared on appeal by U.S. track officials and allowed to compete in the 2000 Sydney Olympics, where he won gold as a member of the 1,600 relay team. World Anti-Doping Agency chief Dick Pound has called for the U.S. team to be stripped of the medal. Young won his second gold medal of the championships Sunday night, anchoring the U.S. 1,600 relay team to victory in the final event of the meet. "I just didn't worry about it," Young said of the doping allegations. "I just put it behind me and kept on going, and just basically used that as a motivation for me." LOAD-DATE: September 2, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 791 of 998 DOCUMENTS Herald Sun (Melbourne, Australia) September 1, 2003 Monday Why sprint ace Kelli took drug SOURCE: AAP BYLINE: GUY JACKSON SECTION: SPORT; Pg. 56 LENGTH: 479 words AMERICAN Kelli White, who risks being stripped of both her world championships sprint titles after testing positive for a stimulant, explained yesterday why she had taken the drug. White, the 100m and 200m champion, said she suffered from narcolepsy, a condition that causes extreme tiredness. She protested her innocence after the International Association of Athletics Federations announced it was investigating the content of the drug, Modafinil, also known by its brand name Provigil, and wanted to hear more evidence from White before deciding whether to strip her of her titles. Reading from a statement, White said: "I am under suspicion of a doping violation. The mere fact of this allegation is personally harmful and hurtful. "I have never taken any substance to enhance my performance. Close members of my family have been under doctor's care for the condition of narcolepsy for years. "I too have been diagnosed with this condition by my physician. He prescribed the drug Provigil and I have taken it in certain circumstances, including prior to the 100m. "I did not seek an IAAF medical exemption for this substance or note it on my doping control form because I had no idea that Provigil contained a banned substance." Professor Arne Ljungqvist, the head of the IAAF medical committee, earlier defined Modafinil as a drug taken "by people who easily lose concentration and awareness and actually fall asleep". He explained that although Modafinil was not on the banned list, it could be a "related substance" and part of either the drug group known as ephedrine or amphetamines, both of which are forbidden. He said White's case would not be helped by the fact she failed to declare her use of the drug. "She did not declare the substance beforehand," Ljungqvist said. "She should have done it and she should have asked for an exemption to use it. "That is a problem for her when her case is later evaluated." But White said: "As an athlete, those lists are very hard to understand. Given that it was not on the banned list, I think it is understandable why I didn't realise that I needed to declare it on my doping form. "It is kind of hard to remember everything you take in the day." After the announcement of her positive test, 26-year-old White pulled out of the US 4 x 100m relay squad that went on to finish second to France in yesterday's final. Ljungqvist said in deciding White's fate, the key factor would be Modafinil's drug category. If it is established it is related to ephedrine, the IAAF could strip White of her titles and issue a warning. But if the substance is established to be in the group of amphetamines, it would lead to White losing her titles and being suspended for two years. Ljungqvist said it was possible to suffer from narcolepsy and still be a high-level athlete. DETAILS, Page 65 LOAD-DATE: August 31, 2003 LANGUAGE: ENGLISH JOURNAL-CODE: DHS Copyright 2003 Nationwide News Pty Limited 792 of 998 DOCUMENTS The International Herald Tribune September 1, 2003 Monday Drug may cost White medals BYLINE: Jere Longman SOURCE: The New York Times SECTION: SPORT; Pg. 14 LENGTH: 815 words DATELINE: PARIS: Kelli White of the United States, the women's champion at 100 and 200 meters at the world track and field championships, has tested positive for a stimulant, and that could cost her the gold medals she won here and could prevent her from competing in the 2004 Olympics in Athens, the sport's world governing body said. The International Association of Athletics Federations, the governing body, said a urine sample provided by White showed the presence of the stimulant modafinil, which is used to treat narcolepsy, after she won the 100 meters in 10.85 seconds, her best time, on Aug. 24. No action had been taken against her by Saturday, when the IAAF revealed the failed test, and the case remained under review. [White's urine sample taken after she won the 200 meter did not test positive, athletics sources said Sunday, Reuters reported from Paris.] White was cleared to run the 4x100 relay Saturday, but she did not participate, apparently not wanting to risk disqualification of the entire team. Without White, the United States finished second to France, but the defeat was overshadowed by the potential disruption of White's career just when it seemed to reach its apex. She ran faster in the 100 and 200 here than she ever had. White's case is complicated, and no doping offense has been officially declared. But the IAAF made it clear that White would have a difficult time defending her use of the stimulant and avoiding a penalty. The possible sanctions range from a warning, which would still result in disqualification from these championships and the loss of her gold medals, to a two-year suspension, which would bar her from competing in the 2004 Olympics. She also stands to lose $120,000 in prize money for her victories. Modafinil, a prescription drug sold under the brand name Provigil in the United States, is a memory-improving and mood-brightening substance used to combat extreme sleepiness in people with narcolepsy. White, who is 26 and lives in California, said at a news conference that she had been taking the substance for several months to treat symptoms of narcolepsy, which included constant fatigue and restlessness at night because she would fall asleep during the day. Several members of her family have been under a doctor's care for narcolepsy for years, White said. "The mere fact of this allegation is personally harmful and hurtful," White said. "I have never taken any substance to enhance my performance." Modafinil has not been placed by name on the list of performance-enhancing substances banned by the International Olympic Committee and the World Anti-Doping Agency. But it is considered a related substance, meaning that athletes use it at the risk of being found guilty of doping. The European Council has asked that it be listed by name as a banned substance beginning next year. White said she had not notified the IAAF on a doping control form that she was using modafinil, believing it was unnecessary because the stimulant was not listed as a prohibited substance. She said she took the stimulant only when needed and had not tested positive at previous meets this summer, so she expected no problems at the world championships. She had contacted the IAAF and the U.S. Anti-Doping Agency while doing extensive research about the drug and found no evidence that it was prohibited. It was unclear whether the contact was person-to-person or by computer. Arne Ljungqvist of Sweden, a doctor who is a top medical official in the IAAF and the International Olympic Committee, said athletes were required to list all medications they were taking, and White listed supplements she was using. It is possible that even if White had a legitimate medical reason to use modafinil, she could lose her medals or her Olympic eligibility because she did not provide the IAAF with sufficient notice of her usage or receive a special waiver. "She should have done it," Ljungqvist said of the notification. "Even more, she should have asked for a prior exemption to use it. That is a problem for her when her case will later be evaluated." An Internet search of modafinil turned up a prescription medication Web site that warned, "Athletes should be aware that one of the main ingredients of this product would produce a positive result in anti-doping tests." Mark Gay, the general counsel of the IAAF, said the track body would investigate whether White had a doctor's prescription for the stimulant. Before any penalty can be assessed, the IAAF must also decide what class of stimulants modafinil belongs to. If modafinil is declared to be in the same performance-enhancing class as amphetamines, White faces a two-year ban, Ljungqvist said. If it is considered in a class of lesser stimulants like ephedrine, White would face a warning and disqualification from the world championships, he said. LOAD-DATE: September 1, 2003 LANGUAGE: ENGLISH Copyright 2003 International Herald Tribune 793 of 998 DOCUMENTS The Irish Times September 1, 2003 White's gold has tarnished look now BYLINE: By IAN O'RIORDAN SECTION: CITY EDITION; SPORT; Pg. 58 LENGTH: 324 words As they said in L'Equipe yesterday, 'White dans la nasse' - 'White caught in the net'. Kelli White, America's gold medal winner of the 100 and 200 metres, left Paris yesterday under the darkest cloud of controversy at a major championships since Ben Johnson cheated his way to 100 metre gold at the 1988 Seoul Olympics. It was L'Equipe who broke the story on Saturday, revealing the presence of a known stimulant in the doping test taken after White's 100 metre victory. The problem for White is her sample showed traces of modafinil, not officially on the IOC list of prohibited substances, but known to be related to substances that are. If the IAAF follow their usual procedure the least punishment White can expect is the loss of her two gold medals. If they come down hard she would receive a two-year ban. IAAF medical chief Arne Ljungqvist has talked about a "full and proper investigation" before any action will be taken. The problem, for now, is modafinil hasn't yet been classified as a minor stimulant, which would only see her lose the medal, or a major stimulant, which would also see her banned. From next year, though, it will banned outright. White appeared at a specially arranged press conference, where she admitted taking the drug, but denied using it to gain a competitive advantage. Her doctor had diagnosed the sleep disorder narcolepsy "a few months ago" and so prescribed modafinil - as he had done for several other members of her family, she said. She admitted taking Provigil, which contains modafinil, on the morning of the 100 metre final. White, 26, has more explaining to do; for instance, why she didn't, as required, declare the drug. She claims she didn't know the substance was related to anything on the banned list. It will be several weeks before the IAAF conclude their investigation but even then the doubts that surround her performances in Paris won't be easy to dispel. LOAD-DATE: September 9, 2003 LANGUAGE: ENGLISH Copyright 2003 The Irish Times 794 of 998 DOCUMENTS MX (Melbourne, Australia) September 1, 2003 Monday Race body swift to negate sprint wins SECTION: SPORT; Pg. 17 LENGTH: 241 words SLEEPLESS NIGHTS Kelli White passed a drug test after winning the 200m but still could lose her gold medals from the World Championships. Istvan Gyulai, general secretary of the International Association of Athletics Federations, said yesterday the US sprinter's latest doping test was negative. White won the 100m last Sunday and completed the double in the 200m on Thursday, becoming the first American woman to sweep both events at a world championships. The IAAF said that she tested positive for the stimulant modafinil after the 100m final and risked being stripped of all her championship results if found guilty of a doping offence. She also could face a two-year ban that would rule her out of the 2004 Athens Olympics. Even though White tested clean after the 200m, the IAAF said her positive 100m test could cost her both medals. "It doesn't change things," IAAF spokesman Nick Davies said. "It's irrelevant. We had a positive sample after the 100 metres. If we disqualify her, we disqualify her." Gyulai said the IAAF was investigating the exact nature of modafinil, a prescription medication which White said she used for a sleep disorder. While not specified by name on the banned list, modafinil is covered under "related substances", the IAAF said. The penalty for use of light stimulants is disqualification and a warning. For harder stimulants, the sanction is disqualification and a two-year ban. LOAD-DATE: September 1, 2003 LANGUAGE: ENGLISH JOURNAL-CODE: MEL Copyright 2003 Nationwide News Pty Limited 795 of 998 DOCUMENTS The New York Times September 1, 2003 Monday Late Edition - Final TRACK AND FIELD; As Championships End, Drug Imbroglio Goes On BYLINE: By JERE LONGMAN SECTION: Section D; Column 1; Sports Desk; Pg. 2 LENGTH: 1120 words DATELINE: PARIS, Aug. 31 After a slow start last week, the United States won three gold medals in relay races today as the world track and field championships concluded at the Stade de France. Both the 10 gold medals and the 20 medals over all led the competition. But two of the gold medals remained in jeopardy after the sprint champion Kelli White found herself embroiled in an unresolved drug case. As the championships ended, the chief executive of USA Track and Field outlined a re-evaluation of the national governing body in light of controversies here regarding performance-enhancing drugs and the histrionic behavior of the sprinter Jon Drummond, who lay on the track last Sunday in protest of a controversial false-start rule. "It's a Dickensian experience: best of times, worst of times," Craig Masback, the chief executive of USA Track and Field, said today at a news conference. No action was taken today in White's case, which remains under review by the International Association of Athletics Federations, track and field's world governing body. After the 100 meters last Sunday, White tested positive for modafinil, a stimulant that she said she used to treat the sleep disorder narcolepsy. Her urine test results were negative after the 200 meters, USA Track and Field said today. A San Francisco Bay Area doctor confirmed to a California newspaper that he had given White samples of the drug to take on an as-needed basis. White said on Saturday that she had been experiencing constant fatigue and restlessness at night because she was falling asleep during the day. "In Kelli's case, she could get jet lag up to 12 days," Dr. Brian Goldman, a child psychiatrist, told The San Jose Mercury News. "You could be having a conversation with her and she just falls asleep." White's mother and an aunt have severe narcolepsy, Goldman told the newspaper in an article published today. White did not report on an I.A.A.F. doping control form that she was using modafinil, as required, or ask for a special exemption to use it. The drug is not on the official list of banned substances, but it is considered a "related substance." Athletes use it at the peril of testing positive. White said she did not report the drug because it was not on the banned list. If a doping violation is ruled, she faces a warning, which would also result in the loss of her gold medals, or a two-year ban from competition. No date for a hearing or a resolution of the case has been set, United States track officials said today. White intends to run in a meet in Brussels on Friday. Her eligibility is uncertain. There was speculation today that her defense of the use of modafinil might also include a contention that the drug is not a stimulant and that it is not performance enhancing. The I.A.A.F. said it considers modafinil a stimulant, but the governing body has not classified the drug as a serious stimulant, like amphetamines, or a lesser stimulant, like ephedrine. Stimulants are prohibited because they are considered to provide an unfair enhancement of performance. "They do not know the nature of the substance and cannot currently identify a possible consequence, if any," White said on Saturday. There were essentially two meets here for the United States. One had some brilliant performances, including the brisk anchor leg that J.J. Johnson ran in the 4x100-meter relay to edge Britain for the gold medal in 38.06 seconds. The United States was without Drummond, who was disqualified from the meet for bringing the sport into disrepute; without Maurice Greene, the Olympic 100-meter champion, who injured a leg here; and without Tim Montgomery, the world record-holder, who left after a poor performance in the 100. Still, the United States succeeded with Bernard Williams and a threesome of 200-meter specialists -- the world champion John Capel, the world runner-up Darvis Patton and Johnson. "Through all the adversity, all the downfalls, we stepped up to show that the U.S. is still a strong country and always will be," Capel said. The United States was also the surprise winner in the women's 4x400 relay, in 3 minutes 22.63 seconds, as Sanya Richards held off Natalya Nazarova of Russia on the anchor leg. The United States did not dominate as usual in the men's 4x400 relay, but Jerome Young, the 400-meter world champion, held off a fast-closing Marc Raquil of France for the gold medal in 2:58.88. The 20 total medals were the most won by the United States since the 25 achieved at the 1993 world championships in Stuttgart, Germany. But the performances were clouded by Drummond's outburst during the 100-meter quarterfinals and by drug revelations that included a report that Young tested positive for a steroid in 1999. In October, a summit of athletes, coaches and agents will be convened in Miami to discuss a number of issues, including athlete comportment, Masback said. "I don't want to say we've been dead in the water on this," he said. "We've been proactive, but we've got to go to the next step." The United States also needs a rules expert at each major competition, he said. In addition, Masback called for uniform doping rules and for better education of athletes from the United States about prohibited substances. Earlier this month, Mickey Grimes was given a warning and stripped of his gold medal at 100 meters after testing positive for a stimulant at the Pan American Games. "Whatever we are doing is not enough," Masback said. "We've got to do more." Masback defended the federation's actions regarding Young. The Los Angeles Times reported that he tested positive for the steroid nandrolone, was exonerated on appeal and was allowed to compete in the 2000 Sydney Olympics on the victorious 4x400 relay team. The case was settled by international arbitration and Young's name was kept private by USA Track and Field until the newspaper revealed it. But Dick Pound, president of the World Anti-Doping Agency, called for the relay gold medal won in Sydney, Australia, to be stripped from the United States team. He criticized USA Track and Field's handling of the Young case, saying the legitimacy of the Sydney relay team had been "shattered." The International Olympic Committee has also called for further investigation. "I believe we have done the appropriate thing in all circumstances," Masback said. Today, he proposed an international relations department in the federation to help improve the image of the United States worldwide and to foster a better understanding of its rules. These actions seemed welcomed by top I.A.A.F. officials. "The U.S. federation should sit down and figure out how not to be so unlucky in the future," Istvan Gyulai, the general secretary of the I.A.A.F., said. URL: http://www.nytimes.com LOAD-DATE: September 1, 2003 LANGUAGE: ENGLISH GRAPHIC: Photo: Jerome Young of the United States crossing the finish line ahead of Marc Raquil of France to win the men's 4x400-meter relay yesterday. (Photo by Associated Press) PUBLICATION-TYPE: Newspaper Copyright 2003 The New York Times Company 796 of 998 DOCUMENTS The Northern Echo September 1, 2003 WHITE PLEADS HER CASE SECTION: Pg. 22 LENGTH: 396 words Kelli White, who has tested positive for a stimulant which is not listed by name as a banned substance, insists she should be allowed to keep the 100 metres and 200 metres gold medals which she won at the World Championships. The American tested positive for modafinil after her 100m triumph last Sunday and the IAAF have said that she may end up having to give back her medals - even though the substance is not on their list of banned drugs. The IAAF said it was covered under a clause for ''related substances'' and are looking into whether modafinil may fall under the category of ephedrine, a minor stimulant, or a strong stimulant like amphetamines. If it is classified as the latter, White could be facing a ban as well as being stripped of her medals. White defended herself vigorously at a press conference in Paris last night, revealing that she takes the drug Provigil because she has narcolepsy. The drug contains modafinil. ''I am under suspicion of a doping violation,'' said the 26-year-old White. ''The mere fact of this allegation is personally harmful and hurtful. ''Honestly, deep in my heart I know I'm innocent. "I would take full responsibility but the medication is not on the banned list. ''I have never taken any substance to enhance my performance. ''Close members of my family have been under doctors' care for the condition of narcolepsy for years. ''I, too, have been diagnosed with this condition by my physician, Dr Brian Goldman. He prescribed the drug Provigil for this condition and I have taken it in certain circumstances, including prior to the 100 metres.'' Explaining why she had not declared it before the championships in accordance with IAAF rules, White said: ''I did not seek IAAF medical exemption for this substance or note it on my doping control form, because I had no idea Provigil contained a banned substance." Meanwhile, hurdling great Colin Jackson has slammed drug testing procedures. Jackson believes the lack of a clear worldwide directive and the grey area over which drugs are legal or not is threatening to make a mockery of athletics. Jackson said: ''What we're seeing now is a whole mess - it is not structured and that is where the problem lies. ''What brings the whole credibility of the sport down is that there are no real answers to anything.' LOAD-DATE: September 27, 2003 LANGUAGE: English PUB-TYPE: Paper Copyright 2003 Newsquest (North East) Limited 797 of 998 DOCUMENTS The Vancouver Sun (British Columbia) September 1, 2003 Monday Final Edition White passes second test but could lose medals: Although testing drug free after 200 victory, U.S. sprinter faces possible two-year ban SOURCE: Associated Press SECTION: Sports; Pg. E4 LENGTH: 452 words DATELINE: SAINT-DENIS, France SAINT-DENIS, France -- Kelli White passed a drug test after winning the 200 metres for her second gold medal at the world track and field championships, but her earlier positive sample following her victory in the 100 jeopardizes both medals. Istvan Gyulai, general secretary of the International Association of Athletics Federations, confirmed Sunday the U.S. sprinter's latest doping test was negative. White won the 100 a week ago and completed the sprint double in the 200 on Thursday, becoming the first American woman to sweep both events at a world championships. The IAAF said Saturday she tested positive for the stimulant modafinil after the 100 final and risked being stripped of both gold medals if found guilty of a doping offence. She could also face a two-year suspension. Even though White tested negative after the 200, the IAAF said her positive test after the 100 would be enough to disqualify her from the entire championships and cost her both medals. "It doesn't change things," IAAF spokesman Nick Davies said. "It's irrelevant. We had a positive sample after the 100 metres. If we disqualify her, we disqualify her." Gyulai said, "It would be wrong to say, 'You are doping on Sunday, and you're out,' and then say, 'You can win the same medal Thursday at the same championships.' I believe this is an important moral message." Gyulai said the IAAF was continuing to investigate the exact nature of modafinil , a prescription medication which White said she used for a sleep disorder. While not specified by name on the banned list, modafinil is covered under the stimulants category of "related substances," the IAAF said. Under IAAF rules, the penalty for use of light stimulants, such as ephedrine, is disqualification and a public warning. For harder stimulants, such as amphetamines, the sanction is disqualification and a two-year ban. Gyulai said IAAF doping officials expect it could take four or five days to determine how to classify modafinil. After that, he said, the IAAF would have three options: Accept her explanation and consider clearing her on grounds of "exceptional circumstances"; disqualify her and give her a warning; or disqualify her and recommend a two-year ban. White denied ever taking a substance to enhance her performance. She said she took the medication only to treat narcolepsy and had "no idea" it contained a banned substance. White said she didn't apply for a medical waiver or include the medication on her doping control form because it wasn't named on the prohibited drug list. "Because I know that I did nothing wrong and sought no advantage over my competitors, I am confident that things will work out in the end," she said. LOAD-DATE: September 1, 2003 LANGUAGE: ENGLISH GRAPHIC: Color Photo: Kelli White TYPE: Sports Copyright 2003 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 798 of 998 DOCUMENTS The Washington Post September 1, 2003 Monday Final Edition White's Other Drug Test Comes Back Negative; As U.S. Racks Up a Record 20 Medals, Sprinter Hopes to Retain Her Two BYLINE: Amy Shipley, Washington Post Staff Writer SECTION: SPORTS; Pg. D01 LENGTH: 1187 words DATELINE: SAINT-DENIS, France Aug. 31 -- The United States finished the ninth World Track and Field Championships today with its biggest medal haul in 10 years and some negative news that was actually quite positive. U.S. sprinter Kelli White's drug test from Thursday's 200-meter final turned up negative, her agent disclosed today, lending credence to her claim that she took the stimulant modafinil at this meet for medical reasons, not performance enhancement, and giving her hope that she might be able to keep at least one of the two gold medals she won here. Meantime, White's physician, Brian D. Goldman, said he gave her two sample bottles of the drug -- about six to 12 pills -- to take on an "as needed basis" earlier this year after diagnosing the sleep disorder narcolepsy during a consultation in the Bay Area. "She had all the clinical indications," said Goldman, a consultant to Victor Conte at Balco Laboratories in Burlingame, Calif., which has worked with hundreds of star athletes including Marion Jones and Jones's ex-husband, C.J. Hunter, who tested positive for the steroid nandrolone just before the 2000 Summer Games in Sydney. Today's developments, however, did not extract White from what likely will be a protracted controversy surrounding her positive test after last week's 100 final, nor did it erase the ugliness that seemed to follow the American team throughout this meet, even as it won 20 medals (10 gold, 8 silver, 2 bronze), more than any other country. Russia won 19; Belarus, France and Ethiopia each claimed seven. "It's a Dickensian experience," USA Track and Field CEO Craig Masback said during an impromptu news conference. "It's a best-of-times, worst-of-times week." The championships got underway with Jon Drummond's lay-down protest of his disqualification from the 100 quarterfinals and ended tonight with U.S. gold medals in the men's and women's 4x400 relays and the men's 4x100. The victory in the short relay was something of a surprise as the U.S. team had been depleted by a thigh injury to Maurice Greene, the mid-week disappearance of Tim Montgomery, and the banishment of Drummond for his bad behavior. "These four guys were never supposed to be together," said John Capel about the team that included himself, Bernard Williams, Darvis Patton and J.J. Johnson and won in 38.06 seconds. "Through all the adversity, all of the downfalls, we stepped up to show that the United States is still a strong country and always will be." The United States was strong enough to earn more medals than it had won since the 1993 world championships, but it might not be strong enough to keep all of them. On Saturday, White learned she could be forced to relinquish her 100 and 200 golds and banned from the sport for two years as a result of the positive test for modafinil, a drug that the world track and field governing body (the IAAF) is scrambling to classify. Earlier in the week, it was revealed that American Jerome Young, the meet's 400 world champion, had tested positive for a banned steroid in 1999, but was exonerated by a U.S. arbitration panel in time to win a relay gold medal at the 2000 Summer Games. "We, like other U.S. institutions, have been naive about our place in the world, our place in the world of sports," said Masback, who said he would push for the creation of an international relations committee within USA Track and Field. "That's really come home to me this week . . . We, as a U.S. entity operating in an international framework, haven't been prepared to deal with that." Drummond's display generated an international lambasting, but White's case could have the most damning long-term implications. Though modafinil is not specifically banned by the IAAF, the organization could levy punishment if it determines that the drug is similar to amphetamines or ephedrine. That would be a severe blow both to White and the United States, as she emerged this year as a potential rival to Jones, the five-time Olympic medalist. Goldman said he attended a conference recently in San Francisco given by Cephalon, which markets modafinil under the brand-name Provigil, and said a number of experts stated that modafinal gives no competitive advantage to athletes. "Various doctors and scientists spoke," Goldman said. "It doesn't seem to have any value as a performance-enhancing drug." Added Goldman, who spoke by phone from the Bay Area: "In my experience, it doesn't help people who are normal, unlike the asthma drugs." Goldman said White informed him that she had a family history of narcolepsy -- her mother and maternal aunt have severe cases -- and a slate of other symptoms: trouble overcoming jetlag; the tendency to fall into deep sleeps during the day; and problems sleeping at night. She also suffered from mild depression while in college at Tennessee, he said. Goldman said his colleagues at Balco researched the drug in detail and knew it wasn't banned either by the IAAF or International Olympic Committee, so they weren't concerned about giving her the samples. He said he was aware that the IAAF requires medical declarations for all prescription drugs, but he did not think a declaration necessary in this case since she was instructed to take the drug only as needed. Her agent, Robert Wagner, said she told him she had taken the drug before the U.S. championships in June, a meet in Oslo and an unannounced drug test in London. Goldman said White was referred to him through Balco, which has worked with Montgomery, Matt Biondi, Jim Courier, John Elway, Renaldo Nehemiah and dozens of other star athletes, according to Goldman and company literature. Conte defended Hunter after his positive tests for nandrolone, saying the supplements he took were contaminated. "I'm just a doctor," Goldman said. "My job is to make people well when the appropriate medical indications suggest something could help. We sometimes give people samples. If it works for them, they come back to us and say they would like a written prescription." Wagner said he was prepared for the case to drag on for some time but said White -- who remains eligible to compete -- intended to run this Friday at a meet in Brussels. He said she stayed away from Stade de France today, choosing to watch her boyfriend, Boris Henry, on television compete in the javelin final. Henry, who competes for Germany, won the bronze. "It is very hard to focus on my competition today because of what is happening with my girlfriend Kelli White right now," Henry said afterward. "I just want to go and see her now. I need to be with her now." Notes: Morocco's Hicham El Guerrouj and Ethiopia's Kenenisa Bekele both failed -- barely -- in their attempts to become double gold medalists. In the men's 5,000, Kenya's Eliud Kipchoge (12 minutes 52.79 seconds) barely edged El Guerrouj (12:52.83), the 1,500 champion, in a sprint to the finish. Bekele, the 10,000 meter champion, claimed the bronze in 12:53.12. . . . Catherine Ndereba won Kenya's only other gold medal, winning the marathon in a championship record of 2:23.55 seconds, holding off Japan's Mizuki Noguchi, who finished in 2:24.14. LOAD-DATE: September 1, 2003 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2003 The Washington Post 799 of 998 DOCUMENTS The Associated Press August 31, 2003, Sunday, BC cycle IAAF: White tested negative after second gold medal BYLINE: By STEPHEN WILSON, AP Sports Writer SECTION: Sports News LENGTH: 624 words DATELINE: SAINT-DENIS, France Kelli White passed a drug test after winning the 200 meters but still could lose her two gold medals from the World Championships, track officials said Sunday. The results from the second test were revealed one day after officials from the International Association of Athletics Federations said White had tested positive following her victory in the 100. White won gold in the 100 a week ago and completed the sprint double in the 200 on Thursday, becoming the first American woman to sweep both events at a world championships. Even though White tested clean after the 200, the IAAF said her positive test after the 100 would be enough to cost her both medals. "It would be wrong to say, 'You are doping on Sunday, and you're out,' and then say, 'You can win the same medal Thursday at the same championships,"' Istvan Gyulai, general secretary of the IAAF, said Sunday. "I believe this is an important moral message." The IAAF said Saturday that White risked being stripped of all her championship results if found guilty of a doping offense. She also could face a two-year suspension that would rule her out of the 2004 Athens Olympics. Gyulai said the IAAF was continuing to investigate the exact nature of modafinil , a prescription medication which White said she used for a sleep disorder. While not specified by name on the banned list, modafinil is covered under the stimulants category of "related substances," the IAAF said. Under IAAF rules, the penalty for use of light stimulants, such as ephedrine, is disqualification and a warning. For harder stimulants, such as amphetamines, the sanction is disqualification and a two-year ban. Gyulai said the IAAF is trying to determine how to classify modafinil. He said that could take four or five days. After that, Gyulai said, the IAAF could: accept White's explanation and consider clearing her on grounds; disqualify her and give her a warning; or, disqualify her and recommend a two-year ban. If the IAAF decides modafinil falls into the strong category, White would be suspended pending a hearing by USA Track & Field, Gyulai said. Her case would then be handled by the U.S. Anti-Doping Agency, and could potentially end up before the Court of Arbitration for Sport - a process that could take months. The IAAF needs to clarify White's status soon because she is scheduled to run Friday at the Golden League meet in Brussels. She also plans to compete in the Grand Prix final in Monaco on Sept. 13-14 and an invitational meet in Moscow on Sept. 20. USA Track & Field chief executive Craig Masback said he had only been notified of White's test result from the 100, and can't take action until getting more details from the IAAF. At a news conference Saturday, White acknowledged taking modafinil the morning of the 100 final. But she denied ever taking a substance to enhance her performance, saying she took the medication to treat narcolepsy and had no idea it contained a banned substance. White said she didn't apply for a medical waiver or include the medication on her doping control form as required because it wasn't named on the prohibited drug list. She said she and her doctor did extensive research on modafinil before deciding to use it for narcolepsy, which causes sudden fatigue or sleepiness. If White loses the medals, she would be the biggest track name stripped of gold at a major championship since Ben Johnson at the 1988 Seoul Olympics. "She was the star of the championships, and now she's at the center of a doping case," former Olympic and world champion Michael Johnson wrote in his daily column in the French sports daily L'Equipe. "It creates trouble for our sport. It's a big cloud over these championships." LOAD-DATE: September 1, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 800 of 998 DOCUMENTS Associated Press Worldstream August 31, 2003 Sunday White's medals still in limbo as she heads into rest of season BYLINE: STEPHEN WILSON; AP Sports Writer SECTION: SPORTS LENGTH: 749 words DATELINE: SAINT-DENIS, France Kelli White heads into the rest of the European track season not knowing if she'll get to keep her two gold medals from the World Championships. The nine-day meet ended Sunday, but the International Association of Athletics Federations is still investigating whether the U.S. sprinter committed a doping offense by testing positive for a stimulant after her victory in the 100 meters. White passed a drug test after winning her second gold, in the 200 meters on Thursday, IAAF general secretary Istvan Gyulai told The Associated Press. She was the first American woman to sweep both sprints at a world championships. Even though White tested clean after the 200, the IAAF said her positive test after the 100 last Sunday would be enough to cost her both medals. Depending on the severity of the offense, she could also face a two-year ban ruling her out of next year's Athens Olympics. The IAAF needs to clarify White's status soon because she is scheduled to run Friday at the Golden League meet in Brussels. She also plans to compete in the Grand Prix final in Monaco on Sept. 13-14 and an invitational meet in Moscow on Sept. 20. Gyulai said the IAAF was trying to determine the exact nature of modafinil, a prescription medication which White said she used for a sleep disorder. While not specified by name on the banned list, modafinil is covered under the stimulants category of "related substances," the IAAF said. Under IAAF rules, the penalty for use of light stimulants, such as ephedrine, is disqualification and a public warning. For harder stimulants, such as amphetamines, the sanction is disqualification and a two-year ban. Gyulai said the IAAF is contacting scientists around the world to determine how to classify modafinil. He said that could take four or five days. After that, Gyulai said, the IAAF would have three options: accept White's explanation and consider clearing her on grounds of "exceptional circumstances"; disqualify her and give her a warning, or disqualify her and recommend a two-year ban. If the IAAF decides that modafinil falls into the strong category, White would be suspended pending a hearing by USA Track & Field, Gyulai said. Her case would then be handled by the U.S. Anti-Doping Agency, and could potentially end up before the Court of Arbitration for Sport. That process could take months. If White loses the medals, she would be the biggest track name stripped of gold at a major championship since Ben Johnson at the 1988 Seoul Olympics. "She was the star of the championships, and now she's at the center of a doping case," former Olympic and world champion Michael Johnson wrote in his daily column in the French sports daily L'Equipe. "It creates trouble for our sport. It's a big cloud over these championships." At a news conference Saturday, White acknowledged taking modafinil the morning of the 100 final. But she denied ever taking a substance to enhance her performance, saying she took the medication only to treat narcolepsy and had "no idea" it contained a banned substance. White said she didn't apply for a medical waiver or include the medication on her doping control form as required because it wasn't named on the prohibited drug list. White said she and her doctor had done extensive research on modafinil before deciding to use it for narcolepsy, which causes sudden fatigue or sleepiness. The drug is sold under the brand name Provigil in the United States. An Internet search on modafinil turned up frequent warnings to athletes. "Athletes should be aware that one of the main ingredients of this pharmaceutical product would produce a positive result in anti-doping tests," said the Web site www.modafinil.info. White was not the only American athlete at the championships who came under scrutiny for drugs. The Los Angeles Times reported that 400-meter champion Jerome Young tested positive for steroids in 1999, but was cleared on appeal by U.S. officials and allowed to compete in the 2000 Sydney Olympics, where he won gold as a member of the 4x400-meter relay team. World Anti-Doping Agency chief Dick Pound has called for the U.S. team to be stripped of the medal. Young won his second gold medal of the championships Sunday night, anchoring the 4x400-meter relay team to victory in the final event of the meet. "I just didn't worry about it," Young said of the doping allegations. "I just put it behind me and kept on going, and just basically used that as a motivation for me." LOAD-DATE: September 1, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 801 of 998 DOCUMENTS Associated Press Online August 31, 2003 Sunday IAAF: White Tested Negative After Medal BYLINE: STEPHEN WILSON; AP Sports Writer SECTION: SPORTS LENGTH: 621 words DATELINE: SAINT-DENIS, France Kelli White passed a drug test after winning the 200 meters but still could lose her two gold medals from the World Championships, track officials said Sunday. The results from the second test were revealed one day after officials from the International Association of Athletics Federations said White had tested positive following her victory in the 100. White won gold in the 100 a week ago and completed the sprint double in the 200 on Thursday, becoming the first American woman to sweep both events at a world championships. Even though White tested clean after the 200, the IAAF said her positive test after the 100 would be enough to cost her both medals. "It would be wrong to say, 'You are doping on Sunday, and you're out,' and then say, 'You can win the same medal Thursday at the same championships,"' Istvan Gyulai, general secretary of the IAAF, said Sunday. "I believe this is an important moral message." The IAAF said Saturday that White risked being stripped of all her championship results if found guilty of a doping offense. She also could face a two-year suspension that would rule her out of the 2004 Athens Olympics. Gyulai said the IAAF was continuing to investigate the exact nature of modafinil , a prescription medication which White said she used for a sleep disorder. While not specified by name on the banned list, modafinil is covered under the stimulants category of "related substances," the IAAF said. Under IAAF rules, the penalty for use of light stimulants, such as ephedrine, is disqualification and a warning. For harder stimulants, such as amphetamines, the sanction is disqualification and a two-year ban. Gyulai said the IAAF is trying to determine how to classify modafinil. He said that could take four or five days. After that, Gyulai said, the IAAF could: accept White's explanation and consider clearing her on grounds; disqualify her and give her a warning; or, disqualify her and recommend a two-year ban. If the IAAF decides modafinil falls into the strong category, White would be suspended pending a hearing by USA Track & Field, Gyulai said. Her case would then be handled by the U.S. Anti-Doping Agency, and could potentially end up before the Court of Arbitration for Sport - a process that could take months. The IAAF needs to clarify White's status soon because she is scheduled to run Friday at the Golden League meet in Brussels. She also plans to compete in the Grand Prix final in Monaco on Sept. 13-14 and an invitational meet in Moscow on Sept. 20. USA Track & Field chief executive Craig Masback said he had only been notified of White's test result from the 100, and can't take action until getting more details from the IAAF. At a news conference Saturday, White acknowledged taking modafinil the morning of the 100 final. But she denied ever taking a substance to enhance her performance, saying she took the medication to treat narcolepsy and had no idea it contained a banned substance. White said she didn't apply for a medical waiver or include the medication on her doping control form as required because it wasn't named on the prohibited drug list. She said she and her doctor did extensive research on modafinil before deciding to use it for narcolepsy, which causes sudden fatigue or sleepiness. If White loses the medals, she would be the biggest track name stripped of gold at a major championship since Ben Johnson at the 1988 Seoul Olympics. "She was the star of the championships, and now she's at the center of a doping case," former Olympic and world champion Michael Johnson wrote in his daily column in the French sports daily L'Equipe. "It creates trouble for our sport. It's a big cloud over these championships." LOAD-DATE: September 1, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 802 of 998 DOCUMENTS Contra Costa Times August 31, 2003 Sunday FINAL EDITION WHITE FAILS DRUG TEST; A DOPING VIOLATION COULD ERASE THE SPRINTER'S GOLDS AND HER PLACE IN ATHENS BYLINE: ANN TATKO, TIMES STAFF WRITER SECTION: SPORTS; Pg. B01 LENGTH: 721 words Sprinter Kelli White denied knowingly taking a drug that may cost her both of her world championship gold medals and a chance to compete at next summer's Olympics. The International Association of Athletics Federation revealed Saturday that White, a former resident of El Sobrante, had tested positive for the stimulant modafinil after winning the 100-meter world title last Sunday. Results of her drug test from Thursday's win in the 200 are not yet known. Modafinil is a drug that stimulates the nervous system and helps relieve fatigue and excessive daytime sleepiness. Although not listed on the IAAF's banned substance list, modafinil is classified as a "related compound," which means athletes may be at risk of a doping violation if they take it. "I know that I did nothing wrong and sought no advantage over my competitors," White said, reading a statement at a press conference in Saint-Denis, France, site of the World Track and Field Championships. "I am confident that things will work out in the end." White said her doctor, Brian Goldman, prescribed Provigil, which contains modafinil, because of a sleeping disorder that runs in her family. An IAAF spokesman said the federation has handed the possible doping violation over to USA Track and Field, which now must hold a hearing and determine what, if any, disciplinary action should be taken. Although the investigation continues, IAAF officials said that early findings indicate White likely will lose the gold medals she won in the 100 and 200. The bigger question is whether the investigation ends with a suspension, as well. The IAAF must decide if modafinil is a "strong" or "light" stimulant. While both result in disqualification, a light stimulant carries only a public warning, whereas a strong stimulant results in a two-year suspension from competition. White said she has taken the drug throughout the season, passing drug tests at the U.S. championships at Stanford and international meets in Europe. For that reason, she said, she didn't seek a medical waiver or list the drug on doping control forms. "Given that it was not on the banned list, I think it is understandable why I didn't realize that I needed to declare it," she said. That assumption may hurt White's chances of avoiding disciplinary action, said IAAF vice president Arne Ljungqvist, the federation's anti-doping chief. "She did declare other supplements she was taking, but not this particular one," Ljungqvist told The Associated Press. "She should have done it. Even more, she should have asked for a prior exemption to use it. That is, of course, a problem for her when her case will later be evaluated." White's agent, Robert Wagner, said by phone that White may provide her medical records to investigators to prove the medicine was prescribed. "This is an unfortunate situation of unwittingly taking something that perhaps she shouldn't have," he said. "Even more unfortunate, it happens for a lot of athletes because of the complexities of what is or is not a (banned substance)." White encountered another possible doping violation last July when meet doctors at a competition in Saint-Denis gave her medication for a foot injury. The medicine contained corticoid, an anti-inflammatory steroid. She received a six-month ban from competition in France but was cleared by the IAAF. The latest allegation of doping, however, appears more serious. Ljungqvist said he knows of at least three past cases in which athletes used modafinil for performance-enhancing reasons. White said she was upset by the suggestion that she is another one of those athletes. "The mere fact of this allegation is personally harmful and hurtful," she said. "I have never taken any substance to enhance my performance." The allegation prompted White to withdraw Saturday from the U.S. women's 400 relay team, which went on to place second behind France. IAAF officials didn't prohibit her from competing but did note that disciplinary action resulting in disqualification could extend to the relay, too. In addition to disqualification and suspension, White also could lose $120,000 in prize money. IAAF officials said they expect a ruling from the USA Track and Field hearing later this week. The Associated Press contributed to this story. LOAD-DATE: November 10, 2005 LANGUAGE: ENGLISH GRAPHIC: Photo 1, KELLI WHITE'S Olympic future may hinge on the strength of a stimulant in her sleep medication. (MICHEL EULER, AP); Photo 2, Kelli White. (Rusty Kennedy, AP) Copyright 2003 Contra Costa Times All Rights Reserved 803 of 998 DOCUMENTS The New York Times August 31, 2003 Sunday Late Edition - Final TRACK AND FIELD; U.S. Sprinter Tests Positive For Stimulant BYLINE: By JERE LONGMAN SECTION: Section 8; Column 5; Sports Desk; Pg. 1 LENGTH: 1000 words DATELINE: PARIS, Aug. 30 Kelli White of the United States, the women's champion at 100 and 200 meters at the world track and field championships, has tested positive for a stimulant, and that could cost her the gold medals she won here and could prevent her from competing in the 2004 Olympics in Athens, the sport's world governing body said today. According to the International Association of Athletics Federations, the governing body, a urine sample provided by White showed the presence of the stimulant modafinil, which is used to treat narcolepsy, after she won the 100 meters in 10.85 seconds, her best time, last Sunday. No action has been taken against her while the case remains under review. White was cleared to run the 4x100 relay today, but she did not participate, apparently not wanting to risk disqualification of the entire team. Without White, the United States finished second to France. Allen Johnson of the United States won his fourth world championship in the 110 hurdles, taking the gold medal in 13.12 seconds, but his victory was overshadowed by the potential disruption of White's career just when it seemed to reach its apex. She ran faster in the 100 and 200 here than she ever had. Her case is complicated, and no doping offense has been officially declared. But the I.A.A.F. made it clear that White would have a difficult time successfully defending her use of the stimulant and avoiding a penalty. Possible sanctions range from a warning, which would still result in disqualification from these championships and the loss of her gold medals, to a two-year suspension, which would bar her from competing in the 2004 Olympics. She also stands to lose $120,000 in prize money for her victories here. Modafinil, a prescription drug sold under the brand name Provigil in the United States, is a memory-improving and mood-brightening substance used to combat extreme sleepiness in people with narcolepsy. White, who is 26 and lives in Union City, Calif., said at a news conference that she had been taking the substance for several months to treat the symptoms of narcolepsy, which included constant fatigue and restlessness at night because she fell asleep during the daytime. "I wanted to feel normal," White said. Several members of her family have been under a doctor's care for narcolepsy for years, White said. She said she had been prescribed Provigil by a San Francisco-area doctor named Brian Goldman. A doctor by that name who advises professional and Olympic athletes in the Bay Area was located on a Web site, but he could not be reached for comment. "The mere fact of this allegation is personally harmful and hurtful," White said. "I have never taken any substance to enhance my performance." Modafinil has not been placed by name on the list of banned performance-enhancing substances considered by the International Olympic Committee and the World Anti-Doping Agency. But modafinil is considered a related substance, meaning that athletes use it at the risk of being found guilty of doping. The European Council has asked that modafinil be listed by name as a banned substance beginning next year. White said she did not notify the I.A.A.F. on a doping control form that she was using modafinil, believing it was unnecessary because the stimulant is not listed as a prohibited substance. She said she took the stimulant only on an as-needed basis and had not tested positive at previous meets this summer, so she expected no problems at the world championships. She said she contacted both the I.A.A.F. and the United States Anti-Doping Agency while doing extensive research about the drug and found no evidence that it was prohibited. It was unclear whether the contact was person-to-person or by computer. Arne Ljungqvist of Sweden, a doctor who is a top medical official in both the I.A.A.F. and the International Olympic Committee, noted that athletes were required to list all medications they were taking. White did list supplements that she was using, he said. It is possible that even if White had a legitimate medical reason to use modafinil, she could lose her medals or her Olympic eligibility because she did not provide the I.A.A.F. with sufficient notice of her usage or receive a special waiver. "She should have done it," Ljungqvist said of the notification. "Even more, she should have asked for a prior exemption to use it. That is a problem for her when her case will later be evaluated." An Internet search of modafinil today turned up a prescription medication Web site that warned: "Athletes should be aware that one of the main ingredients of this product would produce a positive result in anti-doping tests." Mark Gay, the general counsel of the I.A.A.F., said the track body would investigate whether White indeed did have a doctor's prescription to use the stimulant. Before any penalty can be assessed, the I.A.A.F. must also decide what class of stimulants modafinil belongs to. If modafinil is declared to be in the same performance-enhancing class as amphetamines, White faces a two-year ban, Ljungqvist said. If modafinil is considered in a class of lesser stimulants like ephedrine, White would face a warning and disqualification from the world championships, he said. The International Tennis Federation classifies modafinil as a Class 2, or lesser, prohibited substance. A first-time offense carries a three-month ban from competition. "We need to have this exactly clarified because we cannot jump to a wrong judgment in such a situation," Ljungqvist said of the I.A.A.F. Today was not White's first brush with a doping controversy. Last summer, she tested positive for a corticosteroid at a meet in Paris and was later prohibited from competing in France, which has strict drug laws, for six months, Reuters reported. The ban ended in June. A track official from the United States said that the corticosteroid was contained in a topical cream White used to treat a foot problem. She was not prevented from competing elsewhere, including the United States. URL: http://www.nytimes.com LOAD-DATE: August 31, 2003 LANGUAGE: ENGLISH GRAPHIC: Photos: Kelli White, 26, of Union City, Calif. (Photo by Reuters)(pg. 1); Kelli White, the world champion in the 100 and 200, said she took modafinil to treat the symptoms of narcolepsy. (Photo by Associated Press)(pg. 8) PUBLICATION-TYPE: Newspaper Copyright 2003 The New York Times Company 804 of 998 DOCUMENTS The Observer August 31, 2003 ATHLETICS: WORLD CHAMPIONSHIPS: White tests positive for stimulant BYLINE: PETER NICHOLS IN PARIS SECTION: Observer Sport Pages, Pg. 12 LENGTH: 495 words KELLI WHITE, THE American sprinter who has been one of the revelations of these championships, winning the double of 100 metres and 200 metres, has tested positive for a stimulant, Modafinil. In a statement issued by the sport's governing body, the IAAF, it stated that White had claimed that she was taking the drug 'on prescription for a medical condition', but her failure to ask for a prior exemption makes it likely that she will lose both titles. The test was taken after White's victory in the 100m final last Sunday and the positive result was known on Wednesday. The news was not released by the IAAF, but was revealed in yesterday's L'Equipe newspaper, the French sports daily. The sample after Thursday's 200m final has not yet been analysed, but Arne Ljungqvist, chairman of the IAAF medical commission, felt that it could also yield a positive for the drug. 'It has a fairly short half-life of 10 to 12 hours, but it breaks down quite slowly,' said Ljungqvist. But even if that sample were clean, White would still stand to lose both titles. 'An athlete is banned not from the event, but from the competition,' said Ljungqvist. Modafinil is a drug used in the treatment of narcolepsy (or sleeping sickness), but has also been noted as a performance enhancer, including in rally-driving, where its ability to stimulate the brain keeps the drivers alert. The drug is not yet named in either the IAAF banned list nor that of the World Anti-Doping Agency (Wada), but Ljungqvist was in no doubt that it would fall into the 'related compounds' category. 'We have also made a request for Modafinil to be named in the list for Wada,' said Ljungqvist. As Modafinil is not pharmacologically related to amphetamines, White could escape a two-year suspension, but she could still lose her titles, to her team-mate Torri Edwards in the 100m and the Russian Anastasiya Kapachinskaya in the 200m. L'Equipe also revealed that White had previously tested positive for a corticosteroid called triamcinolone acetonide at the Golden League meeting in the same stadium a year ago. On that occasion, the IAAF did not consider it to be a doping offence, but the CPLD (Le Conseil de Prevention et de Lutte contre le Dopage in France, which polices drug use in sport), imposed a six-month ban on White from competing in the country, as the American did not have a valid prescription for the drug. Once the IAAF investigation is concluded for this positive, it is down to the US governing body (USTAF) to determine what action should be taken against the sprinter. 'If we don't agree with what they do, we have the option to take the case to CAS (the court of arbitration for sport),' said Ljungqvist. The USTAF have a reputation for failing to censor their own athletes. Only four days ago, it was revealed that 400m winner Jerome Young had tested positive in 1999, but was cleared by USTAF and allowed to compete in the Sydney Olympics. LOAD-DATE: September 3, 2003 LANGUAGE: ENGLISH PUB-TYPE: PAPER Copyright 2003 Guardian Newspapers Limited 805 of 998 DOCUMENTS St. Louis Post-Dispatch (Missouri) August 31, 2003 Sunday Five Star Edition SPORTS DIGEST SECTION: SPORTS; Sports Digest Column; Pg. C7 LENGTH: 499 words TRACK AND FIELD American sprinter flunks drug test Kelli White provided some of the rare highlights for an underachieving U.S. team at the World Championships - until she flunked a drug test, putting her two sprint gold medals at risk and depriving a favored American relay team of its anchor. Track's world governing body is investigating a sample from White, the only American woman to win an event at the World Championships in Saint-Denis, France and the only U.S. woman to win both the 100 and 200 meters at a world meet. Now, her sprint crowns are in jeopardy. And, after White's withdrawal, the U.S. 400-meter relay team lost to France on Saturday night. L'Equipe, a Paris sports daily, reported Saturday morning that White - the first U.S. woman to sweep the sprints at the worlds - had tested positive for a stimulant she later said she uses for a sleeping disorder. The IAAF later confirmed it. White denied ever taking drugs to enhance her performance. "Because I know that I did nothing wrong and sought no advantage over my competitors, I am confident that things will work out in the end," she said. White's positive test for the stimulant modafinil came after her win Monday in the 100. Arne Ljungqvist, vice president of the International Association of Athletics Federations and head of that organization's anti-doping commission, said White's 200 medal is in jeopardy, too. Modafinil stimulates the central nervous system and is used to fight fatigue and sleepiness. White said that she was prescribed modafinil for narcolepsy earlier this year, and that she and close members of her family have been diagnosed with the disorder. Also Saturday, Allen Johnson won his fourth world title in the 110-meter hurdles, edging U.S. teammate Terrence Trammell by eight-hundredths of a second. BOXING Klitschko wins Wladimir Klitschko (41-2) stopped Fabio Moli (29-3) just 97 seconds into the first round of a heavyweight fight in Munich, Germany. NFL Boller tabbed to start for Ravens Kyle Boller will start at quarterback when the Baltimore Ravens open the NFL regular season in Pittsburgh next Sunday, winning the job from incumbent Chris Redman. "The physical skills are obvious; anyone that's seen the kid - even in a practice - can recognize that," Ravens coach Brian Billick said "But his ability to absorb the offense has been shocking to me, and I've been doing this for a while." * In a move that was a bit surprising, the Redskins cut former Florida quarterback Danny Wuerffel and Gibran Hamdan, which means coach Steve Spurrier will start the season with just Patrick Ramsey and Rob Johnson available at quarterback. HORSE RACING Trotting Derby is rained out The World Trotting Derby in Du Quoin, Ill. was rained out. Mutineer had been the favorite to take the $550,000 event. The race was not rescheduled. The entry fees and stakes payments totaling about $35,000 per horse were to be split by Mutineer and the six other entrants. LOAD-DATE: August 31, 2003 LANGUAGE: English Copyright 2003 St. Louis Post-Dispatch, Inc. 806 of 998 DOCUMENTS Sunday Life August 31, 2003 Athletics: White under drugs cloud LENGTH: 199 words KELLI White is under threat of losing her World Championship gold medals in the 100 metres and 200m after testing positive for modafinil. Only mitigating circumstances that the American took the medication for health reasons, it seems, will prevent her from being punished. White has claimed she was prescribed the substance as treatment for a medical condition which runs in her family. IAAF senior vice-president Dr Arne Ljungqvist says that track and field's world governing body is not certain which family of drugs modafinil falls into. If modafinil is categorised as ephedrine, it would be classed as a minor offence and the American would lose her gold medals. Should it fall into the more serious category of being an amphetamine, White would most likely pay the ultimate penalty and receive a two-year suspension. "It needs to be clarified where it belongs," said Ljungqvist, chairman of the IAAF's medical commission. The Swede added: "Modafinil is used as a medication for disorders related to sudden loss of consciousness, and awareness and (when) you fall asleep. "It's a known disorder which requires some sort of stimulant to keep you awake." LOAD-DATE: August 31, 2003 LANGUAGE: ENGLISH Copyright 2003 Belfast Telegraph Newspapers 807 of 998 DOCUMENTS The Sunday Herald August 31, 2003 American sprint champion White fails drug test in Paris BYLINE: By Natasha Woods In Paris SECTION: Pg. 1 LENGTH: 576 words KELLI White, the biggest track star to emerge from the IAAF World Championships, was at the centre of a doping scandal last night after it emerged she tested positive for a stimulant after winning the 100m in Paris. The American, who set personal bests when taking both the 100m and 200m titles, now faces the possibility of being stripped of two gold medals. She could also be given a two-year ban from the sport if investigations by the IAAF classify the prescription drug she took as a 'heavy stimulant'. White, who has inherited Marion Jones' mantle as the Queen of world sprinting, claims the traces of modafinil found relate to a drug she takes to treat narcolepsy, a medical condition which runs in her family. "I have never taken any substance to enhance my performance," she said last night. "This allegation is personally harmful and hurtful. I know I am innocent. I worked hard for the medals I earned this week and I'm going to work very hard to keep them." White, who says she had been taking modafinil for three months to combat tiredness and memory problems, failed to declare she was taking the medicine on official forms or ask for a prior exemption to use it; both breaches of the governing body's rules. "That will be a problem for her when her case is later evaluated," said Professor Arne Ljungqvist, the IAAF's senior vice-president. Modafinil, as White rightly pointed out, is not specifically named as a banned substance under IOC rules. But it is classed as a "related substance" which carries the same penalties. "The IAAF classify substances into two groups - heavy stimulants and light. It remains to be clarified exactly where this belongs because classification results in different sorts of punishments," explained Ljungqvist. A light stimulant brings a public warning and disqualification from the event in which the doping offence happened; a strong stimulant and a two-year ban is added to the punitive measures. Therefore it's likely she will lose her medals at least, although last summer Commonwealth Games and now world 100m champion Kim Collins was only given a warning when he failed to declare his asthma medication. White was cleared to run in the final of the 4x100m relay last night as the IAAF continue their investigations, but she withdrew. "I don't understand, I've been on this medication for months and I've had a few drugs tests and they have been fine, so I didn't think it would be a problem here," she added. It remains crass naivety that she wouldn't record it on her doping control forms here in Paris. And there are further suspicions. Modafinil may be used to treat disorders where concentration, awareness and consciousness are affected, but the IAAF are investigating whether it has performance-enhancing properties. "Modafinil has been observed as a possible substance for the purpose of performance enhancement as a stimulant. There is an awareness around that it may be used as a doping substance by those wanting to take that chance," said Ljungqvist. Once the IAAF reach their decision as to whether a doping offence has occurred it will then be up the US track and field authorities to take action. Given the USATF's record on doping - they failed to report 13 positive tests before the Sydney Olympics - the IAAF reserve the right to take the case to the Court of Arbitration in Sport if they are not satisfied with the American's action. LOAD-DATE: September 02, 2003 LANGUAGE: English PUB-TYPE: Paper Copyright 2003 Scottish Media Newspapers Limited 808 of 998 DOCUMENTS Sunday Express August 31, 2003 DRUGS SHAME THREATENS KELLI BYLINE: By John Wragg SECTION: SPORT; Pg. 94 LENGTH: 193 words WORLD champion Kelli White faces being stripped of her two sprint gold medals after the American team were caught in another drugs sensation. White, 25, tested positive for Modafinil after winning the 100m and the findings of the sample she provided after her 200m win on Thursday have yet to be announced. She told the IAAF, athletics' world governing body, that she had taken the drug on prescription for a medical condition that runs in the family. But she did not disclose what she was taking before the competition, which is against IAAF rules. Dr Arne Ljungqvist, head of drug testing, confirmed that Modafinil is not on the banned list but is related to substances regarded as illegal. There is also a move to put Modafinil, which is used to avoid sleepiness and boost concentrtaion, on the banned list for the Athens Olympics next year. The trouble for White, who escaped another ban in France at a Golden League meeting when she claimed she was only taking painkillers, follows the disclosure that another American, Jerome Young, who won the 400m, was the USA athlete believed to have taken drugs at the Sydney Olympics. LOAD-DATE: September 1, 2003 LANGUAGE: English PUB-TYPE: Newspaper Copyright 2003 EXPRESS NEWSPAPERS 809 of 998 DOCUMENTS Sunday Tribune August 31, 2003 White may lose medals after failing drugs test; ATHLETICS NEWS SECTION: Pg. 1 LENGTH: 143 words KELLI WHITE is under threat of losing her World Championship gold medals in the 100 and 200 metres after testing positive for modafinil. Only mitigating circumstances that the American sprinter took the medication for health reasons, it seems, will prevent her from being punished. White has claimed she was prescribed the substance as treatment for a medical condition which runs in her family. IAAF senior vice-president Dr Arne Ljungqvist says that track and field's world governing body is not certain which family of drugs modafinil falls into. If modafinil is categorised as ephedrine, it would be classed as a minor offence and the American would lose her gold medals. Should it fall into the more serious category of being an amphetamine, White would most likely pay the ultimate penalty and receive a two-year suspension. LOAD-DATE: March 1, 2004 LANGUAGE: ENGLISH Copyright 2003 The Sunday Tribune plc 810 of 998 DOCUMENTS The Times Union (Albany, NY) August 31, 2003 Sunday THREE STAR EDITION White's medals at risk BYLINE: Combined Wire Services SECTION: SPORTS, Pg. C2 LENGTH: 506 words DATELINE: SAINT-DENIS, France Kelli White provided some rare highlights for an underachieving U.S. team at the World Championships -- until she flunked a drug test, putting her two gold medals at risk and depriving a favored American relay team of its anchor. Track's world governing body is investigating a sample from White, the only American woman to win an event at these World Championships and the only U.S. woman to win both the 100 and 200 meters at a world meet. After White's withdrawal, the U.S. 400-meter relay team lost to France on Saturday night. White said her positive drug test stemmed from prescription medicine for a sleep disorder. "Because I know that I did nothing wrong and sought no advantage over my competitors, I am confident that things will work out in the end," she said. "I have never taken any substance to enhance my performance." White's positive test for the stimulant modafinil came after her win Monday in the 100. Modafinil is used to fight fatigue and sleepiness. White said she was prescribed modafinil for narcolepsy earlier this year and that she and close members of her family have been diagnosed with the disorder. Also Saturday, Allen Johnson won his fourth world title in the 110-meter hurdles, edging U.S. teammate Terrence Trammell by eight-hundredths of a second. Liu Xiang of China won the bronze. Other winners were Mirela Manjani of Greece in the women's javelin, Jaouad Gharib of Morocco in the men's marathon, Eunice Barber of France in the women's long jump and 18-year-old Tirunesh Dibaba of Ethiopia in the women's 5,000 meters.    HOCKEY  Defenseman Oleg Tverdovsky is returning to Russia after playing last season for the New Jersey Devils. He signed a two-year contract with Avangard of the Super League. Tverdovsky, 27, was traded to the Devils last season. He had an erratic season that was limited by a head injury. He played 50 games and had five goals and eight assists.    UNIVERSITY GAMES  Olympic and world champion swimmer Yana Klochkova of Ukraine won her fourth gold medal and China captured 13 finals to ensure its top spot in the standings at the World University Games in Daegu, South Korea. The United States, without any representatives in men's basketball or track and field, will finish with its fewest medals at a University Games since 1989, when it had 26 from four sports. The United States has five golds, 13 silvers and 16 bronzes from nine sports and the prospect of only one more medal from today's bronze-medal volleyball game with France on the competition's final day.    ROWING  The United States won gold medals Saturday in the women's coxless four and men's coxed pairs, both non-Olympic events, at the World Rowing Championships in Milan, Italy. The one-week competition ends today, highlighted by the men's and women's eights.     BOXING  Wladimir Klitschko stopped Fabio Moli just 97 seconds into the first round of a heavyweight fight in Munich, Germany. Klitschko (41-2) threw a left that Moli (29-3) ducked into. LOAD-DATE: September 3, 2003 LANGUAGE: ENGLISH Copyright 2003 The Hearst Corporation 811 of 998 DOCUMENTS The Washington Post August 31, 2003 Sunday Final Edition What Is Modafinil? SECTION: SPORTS; Pg. E04 LENGTH: 80 words Modafinil is a memory-improving and mood-brightening psychostimulant. It enhances wakefulness but is less likely than other stimulants to cause jitteriness and anxiety. Modafinil has been proved clinically useful in treating narcolepsy, a neurological disorder marked by uncontrollable attacks of daytime sleepiness. Modafinil is banned by the International Tennis Federation and carries a three-month suspension for first-time offenders. -- From News Services, Staff Reports LOAD-DATE: August 31, 2003 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2003 The Washington Post 812 of 998 DOCUMENTS The Washington Post August 31, 2003 Sunday Final Edition Double Gold Medalist Tests Positive; U.S. Sprinter White Says She Used Stimulant to Deal With Narcolepsy BYLINE: Amy Shipley, Washington Post Staff Writer SECTION: SPORTS; Pg. E01 LENGTH: 840 words DATELINE: SAINT-DENIS, France Aug. 30 -- U.S. sprinter Kelli White might have to give up the two gold medals she won here at the ninth World Track and Field Championships because a drug test taken a week ago, after her victory in the 100 meters, showed the presence of a stimulant known as modafinil. Although modafinil is not on the Olympic movement's banned list, it could trigger punitive action under an often-used clause in the rules that prohibits substances related to banned drugs. Citing that clause, the IAAF -- track and field's world governing body -- could disqualify White and rescind her gold medals in the 100 and 200. White's status for the 2004 Athens Olympics could be in jeopardy as well. Depending on the nature of the stimulant, which IAAF officials say will be determined in the coming weeks, White could face a two-year competition ban. White today acknowledged taking the drug but denied using it for a competitive advantage. She said her physician diagnosed narcolepsy "a few months ago" and prescribed modafinil on an "as needed basis." She said she had taken the drug "a few times" throughout the track season, including the morning of the 100 final. She said other family members have been treated for narcolepsy but declined to elaborate. "I have never taken any substance to enhance my performance," White said, reading from a statement. ". . . Because I know that I did nothing wrong and sought no advantage over my competitors, I am confident that things will work out in the end." Though her case could take weeks to resolve, today's news was a severe blow to White, who had emerged this season as a fierce and legitimate rival to five-time Olympic medalist Marion Jones. White voluntarily withdrew from tonight's 4x100 relay final, a move that likely cost the United States the gold medal. In a major upset, Americans Angela Williams, Chryste Gaines, Inger Miller and Torri Edwards finished second to France. However, if White had competed and later was disqualified from the meet, the relay team's results would have been nullified. White said her physician, Brian Goldman of San Francisco, recently prescribed for her the brand-name drug Provigil, which contains modafinil, at her request. She said she asked about the substance because she was having trouble sleeping at night, was tired all of the time and was suffering from memory loss. "This year, I did contact my doctor about it," she said. "The reason I started taking the medication is I wanted to feel normal. I wanted to have a regular season this year, so I wanted to take the medication." White said she did not declare the drug on her testing disclosure form because she knew it was not on the banned list. She said she researched it extensively, contacting both the U.S. Anti-Doping Agency and IAAF. White had a drug-testing problem in France last year. At a grand prix meet in Paris, she tested positive for corticosteroids -- commonly used painkillers that are banned in France, but not banned by any bodies in the Olympic movement. Though she received no penalty from any sports body, she was banned from competition in France for six months. Despite her troubles then, she said it did not occur to her to declare the substance on the disclosure form, though she said she listed a number of other substances she was taking. She also said that she occasionally forgets to mention a substance that she takes very early in the day. "I've been on the medication for months now," she said. "I have had a few drug tests. They were fine. I never thought it would be a problem now." IAAF medical chief Arne Ljungqvist said athletes are required to declare any substances, medications or supplements they use on their drug disclosure forms. White's case will go to USA Track and Field, which will hold a hearing and recommend action. The IAAF, however, has ultimate jurisdiction and can impose the penalty it chooses. "We haven't yet found whether her explanation holds water," IAAF attorney Mark Gay said. "It may or may not. We have to establish the facts." Ljungqvist said White's test results from Thursday's 200 final were not yet available. In recent years, the IAAF and other Olympic bodies have become reluctant to accept any excuses from athletes for drug violations of any kind. At the 2002 Winter Games in Salt Lake City, several cross-country skiers were banned for using a substance that was not mentioned on the International Olympic Committee's prohibited list, but that was determined to be similar to the banned endurance-enhancing drug erythropoietin (EPO). Ljungqvist said that if modafinil is found to be related to amphetamines, a strong class of stimulants, White would face a possible two-year ban. If the substance is found to be related to ephedrine, a less potent stimulant, she would face a possible public warning, but she still would be disqualified from this meet and forced to give up her medals. "We need more information in this case," Ljungqvist said. "We need to know exactly how to classify the substance. We need to evaluate her own statement." LOAD-DATE: August 31, 2003 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2003 The Washington Post 813 of 998 DOCUMENTS XINHUA GENERAL NEWS SERVICE August 31, 2003, Sunday Kelli White in trouble for taking upcoming-banned stimulant SECTION: WORLD NEWS; SPORTS LENGTH: 230 words PARIS, Aug. 30 (Xinhua) -- Modafinil, a medical substance which can prevent a person from sleepiness but will be banned for athletes from Athens Olympics, put American female star sprinter Kelli White in trouble on Saturday. A sample provided by White, who had been crowned in women's 100m and 200m races at the ninth athletic worlds, tested positive for Modafinil, an IAAF statement said here. Modafinil can be easily got from pharmacy on prescription in the United States. A substance similar to Modafinil had been banned for athletes years ago but was ticked off from the list later. The statement said, "Today we have received an explanation from the athlete to the following effect; Ms White has been taking the substance on prescription to treat a medical condition that runs in her family." As both the nature of the substance and the content of her explanation require further inquiry and investigation, the IAAF has taken the view that bearing in mind the very serious consequences for the athlete of being suspended and being removed form competition at this late stage, the most appropriate course of action is to allow her to compete pending the completion of the necessary scientific and factual investigations. So far, the IAAF has not yet received the results of the analysis on her sample provided after the 200m final. LOAD-DATE: August 31, 2003 LANGUAGE: ENGLISH COPYRIGHT 2003 XINHUA NEWS AGENCY 814 of 998 DOCUMENTS XINHUA GENERAL NEWS SERVICE August 31, 2003, Sunday Modafinil not on ban list, I am innocent: White SECTION: WORLD NEWS; SPORTS LENGTH: 338 words PARIS, Aug. 30 (Xinhua) -- Kelli White, the new American sprint queen who had been crowned in 100m and 200m at the ninth athletics worlds but failing a doping test later, said here Saturday that she was innocent as the medical substance she took is not on the ban list. Modafinil, a medical substance which can prevent a person from sleepiness but will be banned for athletes at Athens Olympics, put White in trouble as it was in a sample provided by White for doping test. White, who was in black and without any smile on her face, told a press conference that it was a big surprise for her when she got to know the news from newspaper this morning. She said she took the medicine on her personal doctor's prescription because she wanted to be fine form and have a regular season. Answering a question, White said," I do not take the medicine everyday." She said she only took it for months and even before the 100m final in Paris but nothing happened before. Modafinil can be easily got from pharmacy on prescription in the United States. A substance similar to Modafinil had been banned for athletes years ago but was ticked off from the list later. An IAAF statement issued today said, "We have received an explanation from the athlete to the following effect; Ms White has been taking the substance on prescription to treat a medical condition that runs in her family." As both the nature of the substance and the content of her explanation require further inquiry and investigation, the IAAF has taken the view that bearing in mind the very serious consequences for the athlete of being suspended and being removed form competition at this late stage, the most appropriate course of action is to allow her to compete pending the completion of the necessary scientific and factual investigations. However, White did not appear on the track to compete for the 4x100m relay for the American team, who had to settle in the second place in the final. The French team took the gold. LOAD-DATE: August 31, 2003 LANGUAGE: ENGLISH COPYRIGHT 2003 XINHUA NEWS AGENCY 815 of 998 DOCUMENTS Yorkshire Post August 31, 2003 Drugs test cloud over White's victories SOURCE: Yorkshire Post LENGTH: 415 words Kelli White, who tested positive for a stimulant which is not listed by name as a banned substance, insists she should be allowed to keep the gold medals which she won in the 100m and 200m at the World Championships. The American tested positive for modafinil after her 100m triumph last Sunday and the IAAF have said that she may end up having to give back her medals - even though the substance is not on their list of banned drugs. The IAAF said it was covered under a clause for "related substances" and are looking into whether modafinil may fall under the category of ephedrine, a minor stimulant, or a strong stimulant like amphetamines. If it is classified as the latter, White could be facing a ban as well as being stripped of her medals. White defended herself vigorously at a press conference in Paris on Saturday, revealing that she takes the drug Provigil because she has narcolepsy. The drug contains modafinil. "I am under suspicion of a doping violation," said the 26-year-old White. "The mere fact of this allegation is personally harmful and hurtful. "Honestly, deep in my heart I know I'm innocent. "I would take full responsibility but the medication is not on the banned list. "I have never taken any substance to enhance my performance. Close members of my family have been under doctors' care for the condition of narcolepsy for years. "I, too, have been diagnosed with this condition by my physician, Dr Brian Goldman. He prescribed the drug Provigil for this condition and I have taken it in certain circumstances, including prior to the 100 metres". Explaining why she had not declared it before the championships in accordance with IAAF rules, White said: "I did not seek IAAF medical exemption for this substance or note it on my doping control form, because I had no idea Provigil contained a banned substance. "Neither Provigil nor the substance in Provigil identified (modafinil acide) by the IAAF, are on any lists of banned substances. "I treat these matters very carefully. I have carefully and consistently noted other substances used to treat injuries on my doping control form". Hurdling great Colin Jackson has slammed drug testing procedures and believes the lack of a clear worldwide directive and the grey area over which drugs are legal or not is threatening to make a mockery of athletics. He said: "What we're seeing now is a whole mess - it is not structured and that is where the problem lies. LOAD-DATE: June 25, 2004 Copyright 2003 Johnston Press Plc 816 of 998 DOCUMENTS The Associated Press August 30, 2003, Saturday, BC cycle SECTION: Sports News LENGTH: 137 words A brief explanation of the drug modafinil, for which double gold medalist Kelli White tested positive at the track and field World Championships: Modafinil is a memory-improving and mood-brightening psychostimulant. It enhances wakefulness but is less likely than other stimulants to cause jitteriness and anxiety. Modafinil has been proved clinically useful in treating narcolepsy, a neurological disorder marked by uncontrollable attacks of daytime sleepiness. Narcolepsy affects more than 1 in 2,000 Americans. In some cases, patients experience dreamlike hallucinations or become physically weak or paralyzed for a few seconds. Modafinil is marketed in the United States by Cephalon, Inc. as Provigil. --- On the Net: www.modafinil.com www.provigil.com www.cephalon.com www.narcolepsy.com LOAD-DATE: August 31, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 817 of 998 DOCUMENTS The Associated Press August 30, 2003, Saturday, BC cycle White scratched from 400-meter relay final BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Sports News LENGTH: 447 words DATELINE: SAINT-DENIS, France American sprinter Kelli White was scratched from the 400-meter relay final Saturday as an investigation into a positive drug sample by the double world champion jeopardized both her sprint gold medals. Track's world governing body confirmed it is probing a sample from White, the only American woman to win an event at these World Championships. She won the 100 on Sunday and became the first U.S. woman to complete a world sprint sweep by capturing the 200 on Thursday. White's positive drug test for the stimulant modafinil came after her win in the 100. Arne Ljungqvist, vice president of the International Association of Athletics Federations and head of that organization's anti-doping commission, said White's 200 medal is in jeopardy as well. Modafinil stimulates the central nervous system and is used to fight fatigue and sleepiness. Ljungqvist said at a news conference that the IAAF is aware of other cases is which modafinil has been used by athletes "for the purpose of performance enhancement." White could not immediately be reached for comment. USA Track and Field officials had no comment. "It is very clear that it is a stimulant, but whether it is a soft stimulant or a strong stimulant is not clear," IAAF general secretary Istvan Gyulai told The Associated Press. "If it ends as a doping case - at the moment all indications are toward that direction - then she will be deprived of the gold medal." Gyulai and Ljungqvist said if it is a "soft" stimulant, White would be disqualified from the 100 and stripped of her medal. If it is a "strong" stimulant, she also would face a two-year international ban. Ljungqvist said he did not think the case would be resolved during the World Championships, because it still must go through a USATF hearing. Gyulai and Ljungvist said White told IAAF officials she has a doctor's prescription for modafinil as a treatment for narcolepsy, a sleep disorder. She told IAAF officials she has a history of narcolepsy in her family. Athletes are required to declare the use of any drug for medical purposes, and both Gyulai and Ljungqvist said White did not do that. Gyulai said she told officials she did not see modafinil on the IAAF list of banned substances, so she did not make a declaration. Gyulai said it is not specifically listed as a banned drug, but is "covered by a clause on related compounds." "Of course it is an embarrassing factor for her that she would neither declare nor get prior exemption," Ljungqvist said. "She should have done it. Even more, she should have asked for a prior exemption to use it, that is of course a problem for her when her case will later be evaluated." LOAD-DATE: August 31, 2003 LANGUAGE: ENGLISH GRAPHIC: AP Photos Copyright 2003 Associated Press All Rights Reserved 818 of 998 DOCUMENTS The Associated Press August 30, 2003, Saturday, BC cycle White withdraws from relay final amid drug probe BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Sports News LENGTH: 522 words DATELINE: SAINT-DENIS, France Kelli White withdrew from the U.S. 400-meter relay team Saturday night as an investigation into a positive drug test by the double world champion jeopardized both her sprint gold medals. Track's world governing body confirmed it is investigating a sample from White, the only American woman to win an event at these World Championships. She won the 100 on Sunday and became the first U.S. woman to complete a world sprint sweep by capturing the 200 on Thursday. On the track, Allen Johnson won his fourth world title in the 110-meter hurdles, edging U.S. teammate Terrence Trammell by eight-hundredths of a second. Liu Xiang of China took the bronze. White's positive drug test for the stimulant modafinil came after her win in the 100. Arne Ljungqvist, vice president of the International Association of Athletics Federations and head of that organization's anti-doping commission, said White's 200 medal is in jeopardy as well. Modafinil stimulates the central nervous system and is used to fight fatigue and sleepiness. Ljungqvist said at a news conference the IAAF is aware of other cases is which modafinil has been used by athletes "for the purpose of performance enhancement." White could not immediately be reached for comment but set a news conference for later in the evening. USA Track and Field officials had no comment. "It is very clear that it is a stimulant, but whether it is a soft stimulant or a strong stimulant is not clear," IAAF general secretary Istvan Gyulai told The Associated Press. "If it ends as a doping case - at the moment all indications are toward that direction - then she will be deprived of the gold medal." Gyulai and Ljungqvist said if it is a "soft" stimulant, White would be disqualified from the 100 and stripped of her medal. If it is a "strong" stimulant similar to an amphetamine, she also would face a two-year international ban. Ljungqvist said he did not think the case would be resolved during the World Championships because it still must go through a USATF hearing. Gyulai and Ljungqvist said White told IAAF officials she has a doctor's prescription for modafinil as a treatment for narcolepsy, a sleep disorder. She told IAAF officials she has a history of narcolepsy in her family. Athletes are required to declare the use of any drug for medical purposes, and Gyulai and Ljungqvist said White did not do that. Gyulai said she told officials she did not see modafinil on the IAAF list of banned substances, so she did not make a declaration. Gyulai said it is not specifically listed as a banned drug but is "covered by a clause on related compounds." "Of course, it is an embarrassing factor for her that she would neither declare nor get prior exemption," Ljungqvist said. "She should have done it. Even more, she should have asked for a prior exemption to use it, that is of course a problem for her when her case will later be evaluated." Other winners Saturday were Mirela Manjani of Greece in the women's javelin, Jaouad Gharib of Morocco in the men's marathon and 18-year-old Tirunesh Dibaba of Ethiopia in the women's 5,000 meters. LOAD-DATE: August 31, 2003 LANGUAGE: ENGLISH GRAPHIC: AP Photos Copyright 2003 Associated Press All Rights Reserved 819 of 998 DOCUMENTS The Associated Press August 30, 2003, Saturday, BC cycle U.S. relay loses after Kelli White withdraws amid drug probe BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Sports News LENGTH: 613 words DATELINE: SAINT-DENIS, France The heavily favored U.S. 400-meter relay team lost to France on Saturday after anchor and double world champion Kelli White withdrew because of a positive drug test that jeopardizes both her sprint gold medals. Track's world governing body said it is investigating a sample from White, the only American woman to win an event at these World Championships. She won the 100 on Sunday and became the first U.S. woman to complete a world sprint sweep by capturing the 200 on Thursday. White's positive drug test for the stimulant modafinil came after her win in the 100. Arne Ljungqvist, vice president of the International Association of Athletics Federations and head of that organization's anti-doping commission, said White's 200 medal is in jeopardy as well. Modafinil stimulates the central nervous system and is used to fight fatigue and sleepiness. Ljungqvist said at a news conference the IAAF is aware of other cases is which modafinil has been used by athletes "for the purpose of performance enhancement." White could not immediately be reached for comment, but set a news conference for later Saturday. USA Track and Field officials had no comment. White would have anchored the relay. Instead it was Torri Edwards, who got the baton with a lead but was passed in the final few meters by France's Christine Arron. As the French sprinters danced to the cheers of a joyous crowd, the dispirited Americans shook their heads. "I felt a little bit fatigued, but I did the best I could," said Edwards, who won silver in the 100 and bronze in the 200 and now could move up to gold and silver if White is disqualified. Ljungqvist said he did not think the doping case involving White would be resolved during the World Championships because it still must go through a USATF hearing. "It is very clear that it is a stimulant, but whether it is a soft stimulant or a strong stimulant is not clear," IAAF general secretary Istvan Gyulai told The Associated Press. "If it ends as a doping case - at the moment all indications are toward that direction - then she will be deprived of the gold medal." Gyulai and Ljungqvist said if it is a "soft" stimulant, White would be disqualified from the 100 and stripped of her medal. If it is a "strong" stimulant similar to an amphetamine, she also would face a two-year international ban. Gyulai and Ljungqvist said White told IAAF officials she has a doctor's prescription for modafinil as a treatment for narcolepsy, a sleep disorder. She told IAAF officials she has a history of narcolepsy in her family. Athletes are required to declare the use of any drug for medical purposes, and Gyulai and Ljungqvist said White did not do that. Gyulai said she told officials she did not see modafinil on the IAAF list of banned substances, so she did not make a declaration. Gyulai said it is not specifically listed as a banned drug but is "covered by a clause on related compounds." "Of course, it is an embarrassing factor for her that she would neither declare nor get prior exemption," Ljungqvist said. "She should have done it. Even more, she should have asked for a prior exemption to use it, that is of course a problem for her when her case will later be evaluated." Also Saturday, Allen Johnson won his fourth world title in the 110-meter hurdles, edging U.S. teammate Terrence Trammell by eight-hundredths of a second. Liu Xiang of China took the bronze. Other winners were Mirela Manjani of Greece in the women's javelin, Jaouad Gharib of Morocco in the men's marathon, Eunice Barber won France in the women's long jump and 18-year-old Tirunesh Dibaba of Ethiopia in the women's 5,000 meters. LOAD-DATE: August 31, 2003 LANGUAGE: ENGLISH GRAPHIC: AP Photos Copyright 2003 Associated Press All Rights Reserved 820 of 998 DOCUMENTS The Associated Press August 30, 2003, Saturday, BC cycle White denies taking drugs to enhance performance BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Sports News LENGTH: 724 words DATELINE: SAINT-DENIS, France U.S. sprinter Kelli White said her positive drug test at the World Championships stemmed from prescription medicine for a sleep disorder, and the double gold medalist denied ever taking drugs to enhance her performance. Track's world governing body is investigating a sample from White, whose gold medals in the 100 and 200 meters are in jeopardy. She is the only American woman to win an event at these World Championships. "Because I know that I did nothing wrong and sought no advantage over my competitors, I am confident that things will work out in the end," said White, who withdrew from the U.S. 400-meter relay team. "The mere fact of this allegation is personally harmful and hurtful. I have never taken any substance to enhance my performance." Without White, the heavily favored Americans lost to France in the relay final on Saturday night. White's positive drug test for the stimulant modafinil came after her win in the 100. Arne Ljungqvist, vice president of the International Association of Athletics Federations and head of that organization's anti-doping commission, said White's 200 medal is in jeopardy, too. Modafinil stimulates the central nervous system and is used to fight fatigue and sleepiness. Ljungqvist said at a news conference the IAAF is aware of other cases is which modafinil has been used by athletes "for the purpose of performance enhancement." White said at a news conference Saturday night that she was prescribed modafinil for narcolepsy, and that she and close members of her family have been diagnosed with the condition. White, who was somber but composed during the news conference, said she found out about the positive test by reading the French sports daily L'Equipe. White said she is confident she'll be able to keep her medals. "Honestly, deep in my heart, I do believe so," she said. "I believe I'm innocent, I know I'm innocent. I've worked very hard for the medals I earned this week, and I'm going to work very hard to keep them." Ljungqvist said he did not think the doping case involving White would be resolved during the World Championships because it still must go through a USATF hearing. "It is very clear that it is a stimulant, but whether it is a soft stimulant or a strong stimulant is not clear," IAAF general secretary Istvan Gyulai told The Associated Press. "If it ends as a doping case - at the moment all indications are toward that direction - then she will be deprived of the gold medal." Gyulai and Ljungqvist said if it is a "soft" stimulant, White would be disqualified from the 100 and stripped of her medal. If it is a "strong" stimulant similar to an amphetamine, she also would face a two-year international ban. Athletes are required to declare the use of any drug for medical purposes and seek an exemption for its use, but White neither declared her use of modafinil nor sought such an exemption. Since the drug is not on the IAAF's list of banned substances, White said she saw no need to make sure a declaration. Gyulai said modafinil is not specifically listed as a banned drug, but is "covered by a clause on related compounds." "Of course, it is an embarrassing factor for her that she would neither declare nor get prior exemption," Ljungqvist said. "She should have done it. Even more, she should have asked for a prior exemption to use it, that is of course a problem for her when her case will later be evaluated." White would have anchored the relay. Instead it was Torri Edwards, who got the baton with a lead but was passed in the final few meters by France's Christine Arron. As the French sprinters danced to the cheers of a joyous crowd, the dispirited Americans shook their heads. "I felt a little bit fatigued, but I did the best I could," said Edwards, who won silver in the 100 and bronze in the 200 and now could move up to gold and silver if White is disqualified. Also Saturday, Allen Johnson won his fourth world title in the 110-meter hurdles, edging U.S. teammate Terrence Trammell by eight-hundredths of a second. Liu Xiang of China took the bronze. Other winners were Mirela Manjani of Greece in the women's javelin, Jaouad Gharib of Morocco in the men's marathon, Eunice Barber won France in the women's long jump and 18-year-old Tirunesh Dibaba of Ethiopia in the women's 5,000 meters. LOAD-DATE: August 31, 2003 LANGUAGE: ENGLISH GRAPHIC: AP Photos Copyright 2003 Associated Press All Rights Reserved 821 of 998 DOCUMENTS The Associated Press August 30, 2003, Saturday, BC cycle American double gold medalist denies taking drugs to enhance performance BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: International News LENGTH: 965 words DATELINE: SAINT-DENIS, France U.S. sprinter Kelli White said her positive drug test at the World Championships stemmed from prescription medicine for a sleep disorder, and the double gold medalist denied ever taking drugs to enhance her performance. Track's world governing body is investigating a sample from White, whose gold medals in the 100 and 200 meters are in jeopardy. She is the only American woman to win an event at these World Championships, and the only U.S. woman to win both sprints at a world meet. "Because I know that I did nothing wrong and sought no advantage over my competitors, I am confident that things will work out in the end," said White, who withdrew from the U.S. 400-meter relay team. "The mere fact of this allegation is personally harmful and hurtful. I have never taken any substance to enhance my performance." Without White, the heavily favored Americans lost to France in the relay final on Saturday night. White's positive test for the stimulant modafinil came after her win Monday in the 100. Arne Ljungqvist, vice president of the International Association of Athletics Federations and head of that organization's anti-doping commission, said White's 200 medal is in jeopardy, too. Modafinil stimulates the central nervous system and is used to fight fatigue and sleepiness. Ljungqvist said at a news conference that the IAAF is aware of other cases in which modafinil has been used by athletes "for the purpose of performance enhancement." White responded at her own news conference Saturday night, saying that she was prescribed modafinil for narcolepsy earlier this year, and that she and close members of her family have been diagnosed with the disorder. She said she went to her doctor after feeling tired all the time and having trouble with her memory. White, who was somber but composed during the news conference, is confident she'll be able to keep her medals. "Honestly, deep in my heart, I do believe so," she said. "I believe I'm innocent; I know I'm innocent. I've worked very hard for the medals I earned this week, and I'm going to work very hard to keep them." It's not the first time White has been involved in a disputed drug test in France. In July 2002, after running in a meet at Saint-Denis, White's sample turned up traces of a corticoid - an anti-inflammatory steroid. She was suspended for six months by France's anti-doping agency because she lacked a medical certificate, but the IAAF cleared her. And it was just the latest controversy for the U.S. team at the World Championships. The head of the World Anti-Doping Agency called for the U.S. 1,600-meter relay team from the Sydney Olympics to return its medals after a report that Jerome Young, a surprise winner here in the 400 meters, failed a drug test in 1999 but was quietly cleared by U.S. officials and allowed to run in the 2000 Games. Also, American sprinter Jon Drummond withdrew from the meet after a tantrum in the men's 100 quarterfinals. Drummond threw a fit after being disqualified for a false start. Ljungqvist said he did not think White's doping case would be resolved during the World Championships. "It is very clear that it is a stimulant, but whether it is a soft stimulant or a strong stimulant is not clear," IAAF general secretary Istvan Gyulai told The Associated Press. "If it ends as a doping case - at the moment all indications are toward that direction - then she will be deprived of the gold medal." Gyulai and Ljungqvist said if it is a "soft" stimulant, White would be disqualified from the 100 and stripped of her medal. If it is a stronger stimulant similar to an amphetamine, she also would face a two-year international ban. Athletes are required to declare the use of any drug for medical purposes and seek an exemption for its use, but White neither declared her use of modafinil nor sought such an exemption. Since the drug is not on the IAAF's list of banned substances, White said she saw no need to make sure a declaration. "The reason that I did not declare this on my doping control list is because I do not take it every day. It is on an as-needed basis," she said. "Because I took it so early in the day, I never thought to list it. After a competition, it's kind of hard to remember everything you take during the day." Gyulai said modafinil is not specifically listed as a banned drug, but is "covered by a clause on related compounds." "Of course, it is an embarrassing factor for her that she would neither declare nor get prior exemption," Ljungqvist said. "She should have done it. Even more, she should have asked for a prior exemption to use it, that is of course a problem for her when her case will later be evaluated." White would have anchored the relay. Instead it was Torri Edwards, who got the baton with a lead but was passed in the final few meters by France's Christine Arron. As the French sprinters danced to the cheers of a joyous crowd, the dispirited Americans shook their heads. "I felt a little bit fatigued, but I did the best I could," said Edwards, who won silver in the 100 and bronze in the 200 and now could move up to gold and silver if White is disqualified. Arron said she was glad White withdrew from the race. "It's good that White wasn't there," Arron said. "It would have shown a lack of respect for us if she had run." Also Saturday, Allen Johnson won his fourth world title in the 110-meter hurdles, edging U.S. teammate Terrence Trammell by eight-hundredths of a second. Liu Xiang of China took the bronze. Other winners were Mirela Manjani of Greece in the women's javelin, Jaouad Gharib of Morocco in the men's marathon, Eunice Barber won France in the women's long jump and 18-year-old Tirunesh Dibaba of Ethiopia in the women's 5,000 meters. LOAD-DATE: August 31, 2003 LANGUAGE: ENGLISH GRAPHIC: AP Photos Copyright 2003 Associated Press All Rights Reserved 822 of 998 DOCUMENTS The Associated Press August 30, 2003, Saturday, BC cycle Double gold medalist White denies taking drugs to enhance performance BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Sports News LENGTH: 1011 words DATELINE: SAINT-DENIS, France Kelli White provided some of the rare highlights for an underachieving U.S. team at the World Championships - until she flunked a drug test, putting her two sprint gold medals at risk and depriving a favored American relay team of its anchor. Track's world governing body is investigating a sample from White, the only American woman to win an event at these World Championships and the only U.S. woman to win both the 100 and 200 meters at a world meet. Now, her sprint crowns are in jeopardy. And, after White's withdrawal, the U.S. 400-meter relay team lost to France on Saturday night. It's just the latest controversy for the U.S. team at the World Championships. American sprinter Jon Drummond withdrew from the meet after a tantrum in the men's 100 quarterfinals. Drummond threw a fit after being disqualified for a false start. Then the head of the World Anti-Doping Agency called for the U.S. 1,600-meter relay team from the Sydney Olympics to return its medals after a report that Jerome Young, a surprise winner here in the 400 meters, failed a drug test in 1999 but was quietly cleared by U.S. officials and allowed to run in the 2000 Games. There also have been plenty of disappointments on the track - including medal shutouts in events Americans usually rule, such as the men's 100 and the women's pole vault. White said her positive drug test stemmed from prescription medicine for a sleep disorder, and she denied ever taking drugs to enhance her performance. "Because I know that I did nothing wrong and sought no advantage over my competitors, I am confident that things will work out in the end," she said. "The mere fact of this allegation is personally harmful and hurtful. I have never taken any substance to enhance my performance." White's positive test for the stimulant modafinil came after her win Monday in the 100. Arne Ljungqvist, vice president of the International Association of Athletics Federations and head of that organization's anti-doping commission, said White's 200 medal is in jeopardy, too. Modafinil stimulates the central nervous system and is used to fight fatigue and sleepiness. Ljungqvist said at a news conference that the IAAF is aware of other cases in which modafinil has been used by athletes "for the purpose of performance enhancement." White responded at her own news conference Saturday night, saying that she was prescribed modafinil for narcolepsy earlier this year, and that she and close members of her family have been diagnosed with the disorder. She said she went to her doctor after feeling tired all the time and having trouble with her memory. White, who was somber but composed during the news conference, is confident she'll be able to keep her medals. "Honestly, deep in my heart, I do believe so," she said. "I believe I'm innocent; I know I'm innocent. I've worked very hard for the medals I earned this week, and I'm going to work very hard to keep them." It's not the first time White has been involved in a disputed drug test in France. In July 2002, after running in a meet at Saint-Denis, White's sample turned up traces of a corticoid - an anti-inflammatory steroid. She was suspended for six months by France's anti-doping agency because she lacked a medical certificate, but the IAAF cleared her. Ljungqvist said he did not think White's doping case would be resolved during the World Championships. "It is very clear that it is a stimulant, but whether it is a soft stimulant or a strong stimulant is not clear," IAAF general secretary Istvan Gyulai told The Associated Press. "If it ends as a doping case - at the moment all indications are toward that direction - then she will be deprived of the gold medal." Gyulai and Ljungqvist said if it is a "soft" stimulant, White would be disqualified from the 100 and stripped of her medal. If it is a stronger stimulant similar to an amphetamine, she also would face a two-year international ban. Athletes are required to declare the use of any drug for medical purposes and seek an exemption for its use, but White neither declared her use of modafinil nor sought such an exemption. Since the drug is not on the IAAF's list of banned substances, White said she saw no need to make sure a declaration. "The reason that I did not declare this on my doping control list is because I do not take it every day. It is on an as-needed basis," she said. "Because I took it so early in the day, I never thought to list it. After a competition, it's kind of hard to remember everything you take during the day." Gyulai said modafinil is not specifically listed as a banned drug, but is "covered by a clause on related compounds." "Of course, it is an embarrassing factor for her that she would neither declare nor get prior exemption," Ljungqvist said. "She should have done it. Even more, she should have asked for a prior exemption to use it, that is of course a problem for her when her case will later be evaluated." White would have anchored the relay. Instead it was Torri Edwards, who got the baton with a lead but was passed in the final few meters by France's Christine Arron. As the French sprinters danced to the cheers of a joyous crowd, the dispirited Americans shook their heads. "I felt a little bit fatigued, but I did the best I could," said Edwards, who won silver in the 100 and bronze in the 200 and now could move up to gold and silver if White is disqualified. Arron said she was glad White withdrew from the race. "It's good that White wasn't there," Arron said. "It would have shown a lack of respect for us if she had run." Also Saturday, Allen Johnson won his fourth world title in the 110-meter hurdles, edging U.S. teammate Terrence Trammell by eight-hundredths of a second. Liu Xiang of China took the bronze. Other winners were Mirela Manjani of Greece in the women's javelin, Jaouad Gharib of Morocco in the men's marathon, Eunice Barber won France in the women's long jump and 18-year-old Tirunesh Dibaba of Ethiopia in the women's 5,000 meters. LOAD-DATE: August 31, 2003 LANGUAGE: ENGLISH GRAPHIC: AP Photos Copyright 2003 Associated Press All Rights Reserved 823 of 998 DOCUMENTS The Associated Press August 30, 2003, Saturday, BC cycle White had 'no idea' medication included banned substance BYLINE: By STEPHEN WILSON, AP Sports Writer SECTION: Sports News LENGTH: 719 words DATELINE: SAINT-DENIS, France Kelli White insists she did nothing wrong. The American sprinter says she took medication only to treat a sleep disorder, not to enhance her performance, and had no idea it contained a banned substance. She says she didn't bother to apply for a medical waiver or include the medication on her doping control form because it wasn't on the prohibited drug list. That was White's defense Saturday as she came under investigation for a positive test that could cost her two gold medals from the World Championships. "I have never taken any substance to enhance my performance," said White, who pulled out of Saturday's 400-meter relay final. "Because I know that I did nothing wrong and sought no advantage over my competitors, I am confident that things will work out in the end." Convincing world track officials of her innocence won't be easy - the rule book and precedent aren't on her side. The International Association of Athletics Federations said White risks being stripped of her gold medals in the 100 and 200 meters after testing positive for the stimulant modafinil. She also could face a two-year suspension. Under the sport's strict policy, athletes are disqualified from an event if a banned substance is found in their system - regardless of the circumstances. In one of the most celebrated cases of its kind, Romanian teenage gymnast Andreaa Raducan was stripped of the all-around gold medal at the 2000 Sydney Olympics after testing positive for a stimulant contained in a cold pill. Olympic officials acknowledged the measure was harsh but said they had to apply the rules. IAAF officials indicated the central issue in White's case was not so much whether she should be disqualified and lose the medals but whether she also should receive a warning or a two-year suspension. Under IAAF rules, the penalty for use of light stimulants, such as ephedrine, is disqualification and a public warning. For harder stimulants, such as amphetamines, the sanction is disqualification and a two-year ban. The IAAF said it was trying to determine the status of modafinil, which stimulates the central nervous system. While not specified by name on the banned list, modafinil is covered under the stimulants category of "related substances," the IAAF said. In recent years, athletes have been warned repeatedly to refrain from using supplements or other substances that could trigger a positive test. They are told to clear all medications with team doctors. Under IAAF rules, athletes must notify the federation in advance of any products they take for medical reasons. To apply for a medical waiver, athletes must provide records proving they need to take a substance for therapeutic reasons. But White insisted she didn't need to do that. "Given that it (modafinil) was not on the banned list, I think it is understandable why I didn't realize that I needed to declare it," White said. "We thoroughly researched this," she added. "It wasn't on the banned list." White said she was diagnosed with narcolepsy this year and began taking the drug Provigil, which contains modafinil, a few months ago on the prescription of her personal doctor, Brian Goldman. "It has improved the condition in my day-to-day life and helped me function normally," White said. "I was extremely tired all the time, not sleeping well in the evening due to sleeping in the daytime," White said. "My memory isn't very good. I needed just to be right." White said she had been taking the medication at the time of competitions in the United States, London and Oslo, Norway, and passed all drug tests at the time. "I never thought that this would be a problem now," she said. White said she used the substance the morning of Sunday's 100-meter final. She didn't say whether she also used the medication before Thursday's 200-meter race. Pressed on why she didn't list the substance on her forms, White said: "Because it isn't a medication that I take every single day. It's on an as-needed basis, and because I took it so early in the day I never thought to list it. After a competition, it's kind of hard to remember everything you take during the day." White tried to be philosophical. "Things happen in life," she said, "and I will just have to deal with the consequences." LOAD-DATE: August 31, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 824 of 998 DOCUMENTS Associated Press Worldstream August 30, 2003 Saturday Fact box on drug at center of Kelli White case BYLINE: The Associated Press SECTION: SPORTS LENGTH: 111 words A brief explanation of the drug modafinil, for which double gold medalist Kelli White tested positive at the World Championships: Modafinil is a memory-improving and mood-brightening psychostimulant. It enhances wakefulness but is less likely than other stimulants to cause jitteriness and anxiety. Modafinil has been proved clinically useful in treating narcolepsy, a neurological disorder marked by uncontrollable attacks of daytime sleepiness. In some cases, patients experience dreamlike hallucinations or become physically weak or paralyzed for a few seconds. On the Net: www.modafinil.com www.provigil.com www.cephalon.com www.narcolepsy.com LOAD-DATE: August 31, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 825 of 998 DOCUMENTS Associated Press Worldstream August 30, 2003 Saturday White says she had 'no idea' medication included banned substance BYLINE: STEPHEN WILSON; AP Sports Writer SECTION: SPORTS LENGTH: 717 words DATELINE: SAINT-DENIS, France Kelli White insists she did nothing wrong. The American sprinter says she only took medication to treat a sleep disorder, not to enhance her performance, and had no idea it contained a banned substance. She says she didn't bother to apply for a medical waiver or include the medication on her doping control form because it wasn't on the prohibited drug list. That was White's defense Saturday as she came under investigation for a positive test that could cost her two gold medals from the World Championships. "I have never taken any substance to enhance my performance," she said. "Because I know that I did nothing wrong and sought no advantage over my competitors, I am confident that things will work out in the end." Convincing world track officials of her innocence won't be easy - the rule book and precedent aren't on her side. The International Association of Athletics Federations said White risks being stripped of her gold medals in the 100 and 200 meters after testing positive for the stimulant modafinil. She also could face a two-year suspension. Under the sport's strict liability policy, athletes are disqualified from an event if a banned substance is found in their system - regardless of the circumstances. In one of the most celebrated cases of its kind, Romanian teenage gymnast Andreaa Raducan was stripped of the all-around gold medal at the 2000 Sydney Olympics after testing positive for a stimulant contained in a cold pill. Olympic officials acknowledged the measure was harsh, but said they had to apply the rules. IAAF officials indicated the central issue in White's case was not so much whether she should be disqualified and lose the medals, but whether she also should receive a warning or a two-year suspension. Under IAAF rules, the penalty for use of light stimulants, such as ephedrine, is disqualification and a public warning. For harder stimulants, such as amphetamines, the sanction is disqualification and a two-year ban. The IAAF said it was trying to determine the status of modafinil, which stimulates the central nervous system. While not specified by name on the banned list, modafinil is covered under the stimulants category of "related substances," the IAAF said. In recent years, athletes have been warned repeatedly to refrain from using supplements or other substances which could trigger a positive test. They are told to clear all medications with team doctors. Under IAAF rules, athletes must notify the federation in advance of any products they take for medical reasons. To apply for a medical waiver, athletes must provide records proving they need to take a substance for therapeutic reasons. But White insisted she didn't need to do that. "Given that it (modafinil) was not on the banned list, I think it is understandable why I didn't realize that I needed to declare it," White said. "We thoroughly researched this," she added. "It wasn't on the banned list." White said she was diagnosed with narcolepsy this year and began taking the drug Provigil, which contains modafinil, a few months ago on the prescription of her personal doctor, Brian Goldman. "It has improved the condition in my day-to-day life and helped me function normally," White said. "I was extremely tired all the time, not sleeping well in the evening due to sleeping in the daytime," White said. "My memory isn't very good. I needed just to be right." White said she had been taking the medication at the time of competitions in the United States, London and Oslo, Norway, and passed all drug tests at the time. "I never thought that this would be a problem now," she said. White said she used the substance the morning of Sunday's 100-meter final. She didn't say whether she also used the medication ahead of Thursday's 200-meter race. Pressed on why she didn't list the substance on her forms, White said, "Because it isn't a medication that I take every single day. It's on an as-needed basis, and because I took it so early in the day I never thought to list it. After a competition, it's kind of hard to remember everything you take during the day." White, who pulled out of Saturday's 400-meter relay final, tried to be philosophical. "Things happen in life," she said, "and I will just have to deal with the consequences." LOAD-DATE: August 31, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 826 of 998 DOCUMENTS The Associated Press State & Local Wire August 30, 2003, Saturday, BC cycle White denies taking drugs to enhance performance BYLINE: By ROB GLOSTER, AP Sports Writer SECTION: Sports News LENGTH: 724 words DATELINE: SAINT-DENIS, France U.S. sprinter Kelli White said her positive drug test at the World Championships stemmed from prescription medicine for a sleep disorder, and the double gold medalist denied ever taking drugs to enhance her performance. Track's world governing body is investigating a sample from White, whose gold medals in the 100 and 200 meters are in jeopardy. She is the only American woman to win an event at these World Championships. "Because I know that I did nothing wrong and sought no advantage over my competitors, I am confident that things will work out in the end," said White, who withdrew from the U.S. 400-meter relay team. "The mere fact of this allegation is personally harmful and hurtful. I have never taken any substance to enhance my performance." Without White, the heavily favored Americans lost to France in the relay final on Saturday night. White's positive drug test for the stimulant modafinil came after her win in the 100. Arne Ljungqvist, vice president of the International Association of Athletics Federations and head of that organization's anti-doping commission, said White's 200 medal is in jeopardy, too. Modafinil stimulates the central nervous system and is used to fight fatigue and sleepiness. Ljungqvist said at a news conference the IAAF is aware of other cases is which modafinil has been used by athletes "for the purpose of performance enhancement." White said at a news conference Saturday night that she was prescribed modafinil for narcolepsy, and that she and close members of her family have been diagnosed with the condition. White, who was somber but composed during the news conference, said she found out about the positive test by reading the French sports daily L'Equipe. White said she is confident she'll be able to keep her medals. "Honestly, deep in my heart, I do believe so," she said. "I believe I'm innocent, I know I'm innocent. I've worked very hard for the medals I earned this week, and I'm going to work very hard to keep them." Ljungqvist said he did not think the doping case involving White would be resolved during the World Championships because it still must go through a USATF hearing. "It is very clear that it is a stimulant, but whether it is a soft stimulant or a strong stimulant is not clear," IAAF general secretary Istvan Gyulai told The Associated Press. "If it ends as a doping case - at the moment all indications are toward that direction - then she will be deprived of the gold medal." Gyulai and Ljungqvist said if it is a "soft" stimulant, White would be disqualified from the 100 and stripped of her medal. If it is a "strong" stimulant similar to an amphetamine, she also would face a two-year international ban. Athletes are required to declare the use of any drug for medical purposes and seek an exemption for its use, but White neither declared her use of modafinil nor sought such an exemption. Since the drug is not on the IAAF's list of banned substances, White said she saw no need to make sure a declaration. Gyulai said modafinil is not specifically listed as a banned drug, but is "covered by a clause on related compounds." "Of course, it is an embarrassing factor for her that she would neither declare nor get prior exemption," Ljungqvist said. "She should have done it. Even more, she should have asked for a prior exemption to use it, that is of course a problem for her when her case will later be evaluated." White would have anchored the relay. Instead it was Torri Edwards, who got the baton with a lead but was passed in the final few meters by France's Christine Arron. As the French sprinters danced to the cheers of a joyous crowd, the dispirited Americans shook their heads. "I felt a little bit fatigued, but I did the best I could," said Edwards, who won silver in the 100 and bronze in the 200 and now could move up to gold and silver if White is disqualified. Also Saturday, Allen Johnson won his fourth world title in the 110-meter hurdles, edging U.S. teammate Terrence Trammell by eight-hundredths of a second. Liu Xiang of China took the bronze. Other winners were Mirela Manjani of Greece in the women's javelin, Jaouad Gharib of Morocco in the men's marathon, Eunice Barber won France in the women's long jump and 18-year-old Tirunesh Dibaba of Ethiopia in the women's 5,000 meters. LOAD-DATE: August 31, 2003 LANGUAGE: ENGLISH GRAPHIC: AP Photos Copyright 2003 Associated Press All Rights Reserved 827 of 998 DOCUMENTS Associated Press Online August 30, 2003 Saturday Sprinter Denies Taking Drugs for Event BYLINE: ROB GLOSTER; AP Sports Writer SECTION: SPORTS LENGTH: 960 words DATELINE: SAINT-DENIS, France U.S. sprinter Kelli White said her positive drug test at the World Championships stemmed from prescription medicine for a sleep disorder, and the double gold medalist denied ever taking drugs to enhance her performance. Track's world governing body is investigating a sample from White, whose gold medals in the 100 and 200 meters are in jeopardy. She is the only American woman to win an event at these World Championships, and the only U.S. woman to win both sprints at a world meet. "Because I know that I did nothing wrong and sought no advantage over my competitors, I am confident that things will work out in the end," said White, who withdrew from the U.S. 400-meter relay team. "The mere fact of this allegation is personally harmful and hurtful. I have never taken any substance to enhance my performance." Without White, the heavily favored Americans lost to France in the relay final on Saturday night. White's positive test for the stimulant modafinil came after her win Monday in the 100. Arne Ljungqvist, vice president of the International Association of Athletics Federations and head of that organization's anti-doping commission, said White's 200 medal is in jeopardy, too. Modafinil stimulates the central nervous system and is used to fight fatigue and sleepiness. Ljungqvist said at a news conference that the IAAF is aware of other cases in which modafinil has been used by athletes "for the purpose of performance enhancement." White responded at her own news conference Saturday night, saying that she was prescribed modafinil for narcolepsy earlier this year, and that she and close members of her family have been diagnosed with the disorder. She said she went to her doctor after feeling tired all the time and having trouble with her memory. White, who was somber but composed during the news conference, is confident she'll be able to keep her medals. "Honestly, deep in my heart, I do believe so," she said. "I believe I'm innocent; I know I'm innocent. I've worked very hard for the medals I earned this week, and I'm going to work very hard to keep them." It's not the first time White has been involved in a disputed drug test in France. In July 2002, after running in a meet at Saint-Denis, White's sample turned up traces of a corticoid - an anti-inflammatory steroid. She was suspended for six months by France's anti-doping agency because she lacked a medical certificate, but the IAAF cleared her. And it was just the latest controversy for the U.S. team at the World Championships. The head of the World Anti-Doping Agency called for the U.S. 1,600-meter relay team from the Sydney Olympics to return its medals after a report that Jerome Young, a surprise winner here in the 400 meters, failed a drug test in 1999 but was quietly cleared by U.S. officials and allowed to run in the 2000 Games. Also, American sprinter Jon Drummond withdrew from the meet after a tantrum in the men's 100 quarterfinals. Drummond threw a fit after being disqualified for a false start. Ljungqvist said he did not think White's doping case would be resolved during the World Championships. "It is very clear that it is a stimulant, but whether it is a soft stimulant or a strong stimulant is not clear," IAAF general secretary Istvan Gyulai told The Associated Press. "If it ends as a doping case - at the moment all indications are toward that direction - then she will be deprived of the gold medal." Gyulai and Ljungqvist said if it is a "soft" stimulant, White would be disqualified from the 100 and stripped of her medal. If it is a stronger stimulant similar to an amphetamine, she also would face a two-year international ban. Athletes are required to declare the use of any drug for medical purposes and seek an exemption for its use, but White neither declared her use of modafinil nor sought such an exemption. Since the drug is not on the IAAF's list of banned substances, White said she saw no need to make sure a declaration. "The reason that I did not declare this on my doping control list is because I do not take it every day. It is on an as-needed basis," she said. "Because I took it so early in the day, I never thought to list it. After a competition, it's kind of hard to remember everything you take during the day." Gyulai said modafinil is not specifically listed as a banned drug, but is "covered by a clause on related compounds." "Of course, it is an embarrassing factor for her that she would neither declare nor get prior exemption," Ljungqvist said. "She should have done it. Even more, she should have asked for a prior exemption to use it, that is of course a problem for her when her case will later be evaluated." White would have anchored the relay. Instead it was Torri Edwards, who got the baton with a lead but was passed in the final few meters by France's Christine Arron. As the French sprinters danced to the cheers of a joyous crowd, the dispirited Americans shook their heads. "I felt a little bit fatigued, but I did the best I could," said Edwards, who won silver in the 100 and bronze in the 200 and now could move up to gold and silver if White is disqualified. Arron said she was glad White withdrew from the race. "It's good that White wasn't there," Arron said. "It would have shown a lack of respect for us if she had run." Also Saturday, Allen Johnson won his fourth world title in the 110-meter hurdles, edging U.S. teammate Terrence Trammell by eight-hundredths of a second. Liu Xiang of China took the bronze. Other winners were Mirela Manjani of Greece in the women's javelin, Jaouad Gharib of Morocco in the men's marathon, Eunice Barber won France in the women's long jump and 18-year-old Tirunesh Dibaba of Ethiopia in the women's 5,000 meters. LOAD-DATE: August 31, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 828 of 998 DOCUMENTS Associated Press Online August 30, 2003 Saturday White Had 'no Idea' on Banned Substance BYLINE: STEPHEN WILSON; AP Sports Writer SECTION: SPORTS LENGTH: 714 words DATELINE: SAINT-DENIS, France Kelli White insists she did nothing wrong. The American sprinter says she took medication only to treat a sleep disorder, not to enhance her performance, and had no idea it contained a banned substance. She says she didn't bother to apply for a medical waiver or include the medication on her doping control form because it wasn't on the prohibited drug list. That was White's defense Saturday as she came under investigation for a positive test that could cost her two gold medals from the World Championships. "I have never taken any substance to enhance my performance," said White, who pulled out of Saturday's 400-meter relay final. "Because I know that I did nothing wrong and sought no advantage over my competitors, I am confident that things will work out in the end." Convincing world track officials of her innocence won't be easy - the rule book and precedent aren't on her side. The International Association of Athletics Federations said White risks being stripped of her gold medals in the 100 and 200 meters after testing positive for the stimulant modafinil. She also could face a two-year suspension. Under the sport's strict policy, athletes are disqualified from an event if a banned substance is found in their system - regardless of the circumstances. In one of the most celebrated cases of its kind, Romanian teenage gymnast Andreaa Raducan was stripped of the all-around gold medal at the 2000 Sydney Olympics after testing positive for a stimulant contained in a cold pill. Olympic officials acknowledged the measure was harsh but said they had to apply the rules. IAAF officials indicated the central issue in White's case was not so much whether she should be disqualified and lose the medals but whether she also should receive a warning or a two-year suspension. Under IAAF rules, the penalty for use of light stimulants, such as ephedrine, is disqualification and a public warning. For harder stimulants, such as amphetamines, the sanction is disqualification and a two-year ban. The IAAF said it was trying to determine the status of modafinil, which stimulates the central nervous system. While not specified by name on the banned list, modafinil is covered under the stimulants category of "related substances," the IAAF said. In recent years, athletes have been warned repeatedly to refrain from using supplements or other substances that could trigger a positive test. They are told to clear all medications with team doctors. Under IAAF rules, athletes must notify the federation in advance of any products they take for medical reasons. To apply for a medical waiver, athletes must provide records proving they need to take a substance for therapeutic reasons. But White insisted she didn't need to do that. "Given that it (modafinil) was not on the banned list, I think it is understandable why I didn't realize that I needed to declare it," White said. "We thoroughly researched this," she added. "It wasn't on the banned list." White said she was diagnosed with narcolepsy this year and began taking the drug Provigil, which contains modafinil, a few months ago on the prescription of her personal doctor, Brian Goldman. "It has improved the condition in my day-to-day life and helped me function normally," White said. "I was extremely tired all the time, not sleeping well in the evening due to sleeping in the daytime," White said. "My memory isn't very good. I needed just to be right." White said she had been taking the medication at the time of competitions in the United States, London and Oslo, Norway, and passed all drug tests at the time. "I never thought that this would be a problem now," she said. White said she used the substance the morning of Sunday's 100-meter final. She didn't say whether she also used the medication before Thursday's 200-meter race. Pressed on why she didn't list the substance on her forms, White said: "Because it isn't a medication that I take every single day. It's on an as-needed basis, and because I took it so early in the day I never thought to list it. After a competition, it's kind of hard to remember everything you take during the day." White tried to be philosophical. "Things happen in life," she said, "and I will just have to deal with the consequences." LOAD-DATE: August 31, 2003 LANGUAGE: ENGLISH Copyright 2003 Associated Press All Rights Reserved 829 of 998 DOCUMENTS Facts on File World News Digest August 23, 2003 Sports:World Track Championships Held SECTION: Pg. 699A1 LENGTH: 995 words The biennial World Track and Field Championships were held August 23-31 in Paris, France. The U.S. topped the medals table, winning 20, and also garnered the most gold medals, with 10. Russia was second in medals, with 19, and Ethiopia, Belarus and France tied for a distant third, with seven each. However, a doping scandal called into question whether a U.S. sprinter who had won two events would be allowed to keep her medals. U.S. Sprinter Tests Positive for Drug The International Association of Athletics Federations (IAAF), track and field's world governing body, August 30 announced that U.S. sprinter Kelli White had tested positive for the banned stimulant modafinil. White, 26, August 24 had won the women's 100 meters, posting a time of 10.85 seconds. She won her second gold medal of the championships August 28, posting a time of 22.05 seconds in the 200 meters. Both times were career bests. The IAAF said that a urine sample provided by White after her victory in the 100 meters was found to contain modafinil. White at a news conference August 30 said she had been taking modafinil for several months to treat narcolepsy, a sleep disorder. She said she did not notify the IAAF that she was taking the drug and get a prior exemption to use it because it was not on the official list of banned substances. Athletes were required to inform the IAAF of any medications or supplements they were taking. White's physician, Brian Goldman, August 31 confirmed that he had given White the drug for the sleep disorder. Also August 31, USA Track & Field, the sport's governing body in the U.S., said the results of a urine test taken after White's win in the 200 meters were negative. The IAAF September 3 announced that since modafinil had been classified as a lesser stimulant, White would not be suspended for testing positive. Had modafinil been classified as a strong stimulant, such as amphetamines, White would have faced a two-year ban. However, White could still be stripped of the two gold medals she won at the world championships. The IAAF September 3 said that White had until September 8 to provide evidence that she had been taking modafinil at the direction of a doctor for the treatment of narcolepsy. The IAAF would then determine if a doping violation had occurred. Athletes in Olympic-related sports were held accountable for any banned substance found in their bodies, and the IAAF said that White could have a difficult time avoiding the loss of her medals, even if she proved she was taking modafinil for a legitimate reason. U.S. Sprinter Disrupts Men's 100 Heat U.S. sprinter Jon Drummond August 24 disrupted a quarterfinal heat for the men's 100 meters when he refused to leave the track after being disqualified for a false start. Drummond was disqualified under a new false-start rule instituted earlier in 2003. Under the previous rule, each individual sprinter was allowed one false start (a false start was defined as a runner leaving the blocks less than a tenth of a second after the starter's pistol was fired), and was disqualified from the race for a second violation. Under the new rule, the entire field of a race was judged to have committed a false start if one sprinter left early. Any sprinter who committed a subsequent false start was disqualified. In Drummond's August 24 heat, Jamaican sprinter Dwight Thomas was called for a false start. On the restart, both Drummond and Jamaica's Asafa Powell were disqualified for false starts: Drummond for leaving 0.052 of a second early and Powell for leaving 0.086 of a second early. Drummond claimed that he had flinched, setting off the computerized false-start detection equipment at the starting blocks. Drummond complained to officials, then lay down on the track and refused to get up for several minutes in protest of his disqualification. He eventually left the track, only to return minutes later and stand in front of the starting blocks, waving his arms to the crowd. Officials postponed the heat and ran the two remaining men's 100-meter quarterfinal heats. When officials tried to rerun the postponed heat, the crowd jeered and whistled loudly, further delaying the race. It was eventually completed about 45 minutes after its scheduled start. Kim Collins of the Caribbean island nation of St. Christopher (St. Kitts) and Nevis August 25 won the men's 100-meter final in 10.07 seconds. It was the slowest winning time at the world championships since 1983. In every Olympics and world championships since then, the winner of the men's 100 meters had posted a time under 10 seconds. Drummond August 26 withdrew from the U.S. team for the rest of the world championships. He had been scheduled to compete with the men's 4x100-meter relay team later in the competition. The IAAF that day disqualified him from the championships for "bringing the sport into disrepute." Other Highlights In other highlights of the World Track and Field Championships: Allen Johnson of the U.S. August 30 won the gold medal in the men's 110-meter hurdles. It was Johnson's fourth world championship gold medal in the event. Hicham el-Guerrouj of Morocco August 27 won his fourth consecutive world championships gold medal in the men's 1,500 meters. Lima Azimi August 23 became the first Afghan woman to participate in a major international event in any sport when she ran in a first-round heat for the 100 meters. Azimi also became the first Afghan athlete, male or female, to compete in the world track and field championships since 1983. British triple jumper Jonathan Edwards August 22 announced that he would retire after the world championships. Edwards, 37, had won gold in the event at the 1995 and 2001 world championships and in the 2000 Summer Olympics, and had set two world records in 1995. Edwards, who had injured his ankle earlier in August, competed for the final time August 25, but withdrew after finishing only two jumps. LOAD-DATE: September 15, 2003 LANGUAGE: ENGLISH Copyright 2003 Facts on File, Inc. 830 of 998 DOCUMENTS Espicom Business Intelligence May 22, 2003 Provigil improves symptoms of ADHD in children LENGTH: 445 words Data from two double-blind, placebo-controlled Phase II studies presented at the 156th Annual Meeting of the American Psychiatric Association, held from 17th to 22nd May, in San Francisco, CA, show that Cephalon's Provigil (modafinil) C-IV improves attention deficit hyperactivity disorder (ADHD) symptoms in children in both school and home settings. These studies also showed that modafinil was well tolerated with different dose regimens. Preclinical studies suggest that modafinil works selectively through the sleep/wake centres to activate the cortex of the brain. During one four-week study, 248 children with ADHD aged six to 13 years were randomised to receive either once- or twice-daily doses of modafinil in different combinations of 300mg doses or placebo. Children weighing >30kg (66lbs) could be assigned to any of the 300mg treatment groups or to a group receiving a 400mg a day dose. In the study, 69 per cent of patients were treatment naive, with 31 per cent having had prior stimulant treatment for their symptoms. The primary outcome was a change from baseline in the School Version of the ADHD Rating Scale IV, a tool for the assessment of ADHD symptoms as completed by the patient's teacher. The 300mg regimen of modafinil administered once daily and a split dose regimen (200/100mg) significantly improved symptoms as measured by the teacher-rated ADHD Rating scale (p<0.05). In addition, the 300mg once-daily dose improved symptoms of ADHD across all other rating scales used in the study including the parent rated home version of the ADHD rating scale and the Conner's Parent ADHD Rating Scale. Side effects reported in the study were mild-to-moderate with insomnia, abdominal pain, loss of appetite, cough, fever and rhinitis reported more frequently in the modafinil-treated groups, compared to placebo. In a second four-week, double-blind, placebo-controlled, cross-over study, 48 children (aged six to 13 years) were randomised to receive placebo or modafinil 100, 200, or 300mg and children weighing >=30kg could be assigned to any of the 100 to 300mg treatment groups or to a group receiving 400mg once daily. The ADHD Rating Scale-IV (home version) was the primary efficacy measurement tool. The most significant improvements were seen in patients receiving the 300 or 400mg dose of modafinil (p<0.05) as assessed in the home environment by the parent-rated ADHD Rating Scale. The most common side effects observed in the modafinil treated group as compared to placebo were abdominal pain and headache. Based on results from these studies, Cephalon will be initiating Phase III studies in children with ADHD later in 2003. LOAD-DATE: May 22, 2003 LANGUAGE: ENGLISH Copyright 2003 ESPICOM Business Intelligence Ltd. 831 of 998 DOCUMENTS FD (Fair Disclosure) Wire May 7, 2003 Wednesday Event Brief of Q1 2003 Cephalon, Inc. Earnings Conference Call - Final LENGTH: 3955 words CORPORATE PARTICIPANTS . Robert Grupp, Cephalon, VP, Corporate Communications . Frank Baldino, Jr. Ph.D, Cephalon, Chairman, CEO . Kevin Buchi, Cephalon, SVP, CFO . Robert Roche, Cephalon, SVP, Sales and Marketing . Paul Blake, Cephalon, SVP, Clinical Research and Regulatory Affairs . John Osborne, Cephalon, SVP , Secretary, and General Counsel OVERVIEW Management announced 1Q03 diluted EPS of $0.21 on total product sales of $137.6m. 2003 guidance was reiterated for sales of $650-660m and EPS of $1.50. Q&A Focus: patent litigation, FDA discussions and marketing programs. FINANCIAL DATA A. Key Data From Call 1. 1Q03 Diluted EPS = $0.21. 2. 1Q03 Total Product Sales = $137.6m. 3. Total revenue = $144.7m. 4. Cash, cash equivalents and investments = $546.8m. 5. Reiterating 2003 product sales guidance of $650-660m. 6. 2003 EPS guidance = $1.50. 7. 2Q03 product sales guidance = $155m. 8. 2Q03 diluted EPS guidance is $0.30. PRESENTATION SUMMARY S1. 1Q03 Performance (F.B.) 1. Reported 1Q03 Diluted EPS of $0.21. 1. Exceeded guidance. 2. Topics on Investors' Minds. 1. Prescription trends for key products. 1. Co. has enjoyed consistent strong sequential prescription growth Q after Q. 2. Based on unique benefits and ability to execute strategic plan. 3. 1Q03 saw moderation of prescription growth due to disruption caused by expansion and reorganization of sales force. 4. Added over 100 new employees to US commercial organization. 5. Realigned every territory. 6. Inevitable disruption was underestimated. 7. Impact was temporary. 8. Positive effects, coupled with important marketing initiatives, will allow co. to meet guidance. 2. 8-10% of Provigil sales come from outside US. 1. Rate of sequential prescription growth required in US is less than 10% per quarter for rest of year. 3. Actiq Recall In Europe. 1. Initiated precautionary recall of certain lots of Actiq in Europe. 2. Manufactured in Salt Lake City facility, where Actiq has been manufactured for Europe for several years. 3. Drug recalls not uncommon. 4. Have contacted relevant regulatory authorities. 5. Salt Lake City continues to manufacture Actiq for Europe and for US as planned later in 2Q03. 6. Not a material event. 7. All costs were included in 1Q03 results. 4. Update on Generic Modafinil Filings. 1. Four generic companies have filed ANDAs to market generic form of modafinil. 2. No unexpected disclosures or innovative chemistry apparent. 3. Co. initiated patent infringement lawsuit against each company. 4. Legal process will run its course over next several years. 5. Remain confident in strength of patent provision and expect to prevail. 6. Co. has sound strategy to develop follow on compounds to Provigil. 7. Provigil is first entrant into new category of weight-promoting products. 8. Anticipate that R-Isomer of modafinil will be next, with clinical trials beginning next month. 1. Targeting launch of this product in late 2005. 9. Regardless of outcome of patent infringement, r- modafinil will build upon and extend the Provigil brand. S2. Product Detail (B.F.) 1. 2003 Is Transitional Year for Provigil. 1. Preparing for expected approval of SNDA. 1. Filed last December seeking broader label to treat sleep disorders. 2. Expect FDA action in 4Q. 3. Positive decision will allow expansion of marketing message and expansion of physician universe. 4. Increase in central nervous system US sales force is complete. 5. Begun rolling out new marketing programs to increase reach of key product messages. 6. Clinical development programs have produced important data that will be presented and published in 2003. 7. Will have significant presence at major psychiatry, neurology and sleep meetings during the year. 8. Two platform presentations at American Psychiatric Association meeting this month, discussing positive results from clinical trial for Provigil to treat ADHD in children. 9. Pleased with response to expanded label in UK granted in 2002. 10. Have broadened message and increased physician call universe. 11. Result is increase in UK sales vs. 1Q02. 12. Filed application for obstructive sleep apnea label in France in 1Q03, and plan similar filings in Germany and Italy next month. 13. Continue to believe there is enormous untapped potential in Provigil. 2. Actiq Is Only Drug Approved to Treat Breakthrough Cancer Pain. 1. In 2003, sales and marketing efforts focused on raising awareness of breakthrough cancer pain and product's benefits. 2. Data have been presented that explore the use of Actiq to treat breakthrough pain unrelated to cancer. 1. In March, positive data was presented at American Academy of Pain Medicine demonstrating utility of Actiq in treating migraine pain. 2. Similar studies were presented at the American Pain Society meeting. 3. Migraine patients often require rescue treatment in hospital emergency departments. 4. Data suggests Actiq may play role in outpatient treatment of severe migraine pain. 5. Will conduct additional studies in utility of Actiq in patients with breakthrough or episodic pain. 3. Gabitiril is Only SGRI Available Today. 1. With understanding of mechanism, proven safety profile and low potential for interactions, physicians prescribe for a range of clinical disorders. 2. In 1Q03, completed two dose-ranging studies in general anxiety disorder and naturopathic pain. 3. Data demonstrated beneficial impact on widely accepted anxiety and pain scales. 4. Showed benefit on standard quality of sleep measures. 5. Both studies provide important dosing information. 6. Expect to initiate larger studies on generalized anxiety disorder and post-traumatic stress disorder. 7. Patient feedback and clinical data point to benefit of Gabitiril in treating overlapping symptoms of insomnia, anxiety and pain. 4. Expect 2003 to be Best Year Ever. 1. With three substantial products in US, expanded sales force, continuing positive clinical data and expanding European business, positioned for excellent year. 2. Will continue to balance risk, while driving sales and earnings growth. S3. 1Q03 Financial Detail (K.B.) 1. Total Product Sales Were $137.6m in 1Q03. 1. 44% increase over 1Q02. 2. Total revenue was $144.7m, up 30% over prior year. 1. Sales of Provigil were $55.8m. 2. Actiq sales were $46.2m. 3. Gabitiril sales were $12.7m. 4. Other European product sales were $22.9m. 3. Sales growth was modest, but EBITDA of $35.9m and EPS of $0.21 per share exceeded guidance. 1. 1Q03 results included increase in R&D and SG&A, although expenses did not rise to level indicated in guidance. 4. Ended quarter with cash, cash equivalents and investments of $546.8m. 1. Provide flexibility to pursue attractive strategic opportunities. 5. Reiterating 2003 product sales guidance of $650-660m. 1. Represents sales growth of 40% YoverY. 6. 2003 EPS guidance remains at $1.50, including tax provision of 38%. 7. Pre-tax earnings will grow by almost 100% in 2003. 8. SEC discourages use of non-GAAP measures such as EBITDA. 1. As a result, EBITDA guidance will no longer be provided. 9. 2Q03 product sales guidance is $155m. 10. 2Q03 diluted EPS guidance is $0.30. 11. Expect sales to ramp, resulting in greater EPS in 2H03. 12. 2Q03 guidance includes Provigil sales of $65-68m, Actiq sales of $50-55m, Gabitiril sales of $15-18m and other product sales of $21-23m. QUESTION AND ANSWER SUMMARY Q1. (Matt Geller, CIBC World Markets) How do you see sales picking up throughout the year? What do you see catalyzing the increase? Can you talk about Gabitril for insomnia and how it differs from other drugs? A. (Robert Roche) We anticipate the ramp up we've seen in past years. We're beginning to see it in the early stages of 2Q for all three products, and we expect that to continue and we'll be able to reach our targets. A. (Paul Blake) In insomnia, we start off with the expectation that an SGRI will have an effect. We have some pre-clinical data and pilot work that encourages us. We have a pilot study that should report in 3Q. At a meeting last week I presented some data that showed secondary endpoints in studies of general anxiety disorders and neuropathic pain where Gabitril worked also showed benefits in insomnia. We're expecting a positive signal from our phase II work looking at total sleep time, latency to persistent sleep and wake after sleep onset. Q2. (Eric Schmidt, SG Cowan) Can you touch on usage of cash, which went down QoverQ, as well as inventory effects in 1Q? A. (Kevin Buchi) The largest use of cash was a $30m investment we made into NDS Proteomics. Other changes were in working capital areas. We saw an increase in accounts receivable, associated with higher sales, increases in inventory. Nothing else noteworthy. Provigil showed another slight decrease in inventories and we ended the quarter with Provigil inventories below a month and a half. That's wholesale and retail. Q3. (Eric Schmidt, SG Cowan) You mentioned no innovative chemistry disclosures in the ANDA filings. Can you educate us on that? What should we expect going forward? A. (Frank Baldino) For obvious reasons, we're not going to talk about our strategy or what the findings are. Simply stated, there was a lot of concern on the street about innovative approaches to getting around the particle size patent. Frankly, we haven't seen that. A. (John Osborne) As you know, different courts have different timetables. This kind of litigation is reasonably complex, involves a fair amount of discovery and usually takes several years. We can't be any more specific than that. A. (Frank Baldino) I think it's fair to say that disclosure from us in this matter will be almost non-existent. A. (John Osborne) We're prepared to litigate this in the courts, but not by speaking to the investment community. Q4. (Corey Davis, JP Morgan) Do you still expect an FDA panel meeting for Provigil's new claim? Any idea when that may be? A. (Frank Baldino) We have not been officially informed of a panel meeting by the FDA. We assume we'll have one, probably in the later half of the year. We're preparing as if we'll have one later in the year. We're confident it will be later than the June, July time frame. When we get notice, we'll inform the street. Q5. (Corey Davis, JP Morgan) Gabitril's revenue growth was below volume growth, so I assume inventory dropped on that as well. The 1.5 months you gave is different from IMS wholesale data. Where's the difference there, and what's the chance that inventory will come down further in 2Q? A. (Kevin Buchi) We track wholesaler and retailer data. The data you buy from IMS is just wholesaler. The difference is material held on retail pharmacy shelves. Gabitril is a smaller product, so we tend to see more fluctuation in inventory levels. Sales were below underlying prescription demand, so I expect it will be more variable given its size. Q6. (Corey Davis, JP Morgan) Will Provigil inventories come down in 2Q? A. (Kevin Buchi) It's really hard to tell. We've said we think inventories have reached the bottom, but it continues to slide. I'm reluctant to say it's at the bottom. It's hard to conceive of wholesale getting below two weeks, and it's not a whole lot above that at this point. Q7. (Corey Davis, JP Morgan) In the past, you've given a breakdown of Provigil use. I'm particularly interested in ADHD and whether you're getting hurt by Stratera, and whether that might come back. A. (Frank Baldino) I think where our business is coming from really hasn't changed. The largest market area has been psychiatry for the last couple of years. As far as ADHD is concerned, the first big presentation will be this year at the American Psychiatric Association meeting. After that, we should see some more interest in the physician community. Right now, it's about 12-15% of our business. Stratera has had zero impact on the small part of the market that Provigil is dominating. Q8. (Geraldine O'Keeffe, Fordis Bank) You mentioned a new marketing program for Provigil. Can you expand on that? A. (Robert Roche) The marketing programs conceived and implemented for Provigil in 2003 are far greater in magnitude and scope than in the past. Our increase in marketing expenditure in 2003 is about $55m higher than at any point in the past. We've tripled our investment in Provigil marketing and marketing in general. The programs we're pursuing are the standard promotional activities used worldwide, but because of the nature of our products, and because the information needs to be shared under unrestricted educational grants, that's a huge proportion of what we're doing. We've invested heavily in continuing medical education programs, consultancy meetings, speakers training meetings, etc. There will be a lot of expenditure around the symposia data being rolled out toward the middle or 3Q of this year, and the exciting new information we'll be sharing Q9. (Geraldine O'Keeffe, Fordis Bank) So will you be marketing in the areas you already have approval for, or for areas you expect to get approval for? A. (Robert Roche) We market only in the area for which we have approval. We sell the benefits of Provigil to a wide variety of physician groups, we focus on the features of the products, and those physicians have made the determination that the drug can be helpful in a wide variety of patient populations. A. (Frank Baldino) Basically, we're going to continue to invest more aggressively in those techniques that have worked well for us in the past. We're expecting the broader label for Provigil this year, and internally, we're preparing for the launch into a broader market in early '04. That's when you'll see the largest impact of Provigil growth, larger than anything we've seen to date. Q10. (Jim Birchenough, Lehman Brothers) Are you moving toward sleep specialists or are you still focusing on high-prescribing psychiatrists? How many reps do you have and how are they divided? A. (Robert Roche) We continue to focus on the three primary physician groups we've been working with for the past few years: sleep specialists, neurologists, psychiatrists. That's what we're doing today. The sales expansion allows us to interact with a greater number of physicians especially in psychiatry. That's where the sales and marketing muscle is being allocated. Q11. (Jim Birchenough, Lehman Brothers) There's been a seasonal use to Provigil with a slowdown over the summer. Are you getting into markets that are less seasonal? A. (Robert Roche) The guidance we provided indicates strong growth in 2Q, and we anticipate 8-10% prescription growth in 3Q and 4Q, so we're anticipating a strong 2H. Q12. (Jim Birchenough, Lehman Brothers) When do you expect the Surtax (phonetic) acquisition to close? Where is your focus in terms of in-licensing other products? How are discussions going on a Provigil partnership? A. (Frank Baldino) Surtax is a difficult deal. We made a fair bid, the shareholders have not tendered their shares yet. It's targeted to close or expire at the end of May, so by then we'll know if we'll be able to capture 90% of the company. In terms of in-licensing, we're going to continue to focus on areas where we've established some strength. We see opportunities there and we intend to pursue those. If the opportunity is very good, we'll go beyond that. Regarding partnerships, we believe there are only a couple of ways to go. By June, we need to make a strategic decision in anticipation of a broad label approval for Provigil. We're talking to a number of companies with a lot of potential, and we're also looking internally to see if we can do it ourselves. That decision will be made in June, and we'll let you know when it's made. The first priority in a partner is to find someone with the expertise and focus to make these products much larger than they are. That's driving our discussions. I'd rather get strong economics on the products we have today. Q13. (Chris Juner (phonetic), T. Rowe Price) Could you repeat your comments about the timing of the follow on isomer strategy? Could you review the individual half-lives of both isomers as it relates to the parent compound and whether there's a theoretical concern that it would disturb sleep? A. (Paul Blake) The r isomer has a half life of 12-15 hours and the s isomer has a half life of 2-3 hours. When you give Provigil you end up with the net result of 50% of each. When we give the r isomer alone, we expect the half life to be 12-15 hours, which we think will give a nice response and should not disturb sleep. We've done a number of studies, one of which has just been accepted for publication, using Provigil twice daily in people who need a greater effect. Split doses we think we'll be able to mirror without any disturbance of sleep. We expect to confirm this in the clinical program beginning next week Q14. (Chris Juner, T. Rowe Price) Can you go over again the timeline for the execution of the r IND filing in this country? A. (Paul Blake) We'll be executing the program next week and we expect to file by the end of next year. Q15. (Marc Goodman, Morgan Stanley) Where was Provigil inventory at the end of the year? A. (Kevin Buchi) A little north of 1.5. Q16. (Marc Goodman, Morgan Stanley) How much did that hurt revenues in the quarter? A. (Kevin Buchi) If we dollarized the published prescription numbers, we'd come up with a number around $52m. Q17. (Marc Goodman, Morgan Stanley) How low do you think these guys are going to go? A. (Kevin Buchi) It's really hard to say. We've been consistently surprised that inventories continue to get drawn down to these levels. Our assumption has been that normal inventory levels would be somewhere north of where we are today. Everyone has an incentive to manage inventories as tightly as possible. It's just getting tighter and tighter. I don't think it can go a whole lot lower that they are right now. A. (Frank Baldino) The inventory information we get is the same as you get. It happens, we track it. You can't manage that. Looking at where demand is, if you have to have an inventory situation, I'd rather it be low than high. I think we're in a really strong position here. Q18. (Marc Goodman, Morgan Stanley) What about the other two products? Any comments on April for the three products? A. (Kevin Buchi) I don't have any comments on April for the three products. We gave our sales guidance and you should assume we take all the data available into account. We don't spend as much time or effort worrying about the other two products because they tend not to be as material and the inventories have not fluctuated as much. Our initial focus occurred in 3Q01 when we had some wholesalers speculating on price increases. It's a schedule two substance so it's more expensive to hold inventories so we'd expect less speculation Q19. (Marc Goodman, Morgan Stanley) SG&A, R&D, is guidance the same as it was before? A. (Kevin Buchi) Yes, we believe the numbers being below guidance in 1Q was simply timing, and we'll catch up in April. Q20. (Felicia Reed, Adams, Harkness & Hill) For Provigil, Actiq and Gabitril, what was the contribution for ex-US sales? A. (Kevin Buchi) For Provigil, $6.2m, for Actiq, about $600,000, for Gabitril about $1.3m. Q21. (Felicia Reed, Adams, Harkness & Hill) And that was included in the other sales line? A. (Kevin Buchi) No, that was included in the sales line for each product. Q22. (Michael King, Banc of America Securities) Regarding the generic filers, one recently said they expected others to file. Do you expect others? A. (Frank Baldino) It's hard to predict the future. We know when people file. We've had four. In the next decade or so, people can file whenever they wish. We don't see that happening. There's an advantage to being the first guy in, who gets a six-month advantage over the others. Then they all pile in for whatever's left after that. A. (John Osborne) Perhaps more important than whether or not there is another, the point in filing a single suit is to obtain a single ruling on our patent in validity and scope. If someone else decides to take a shot, we would join them in the same action. I don't know that the number will affect our position. A. (Frank Baldino) No matter how many filings you have, they'll be wrapped in the same suit that will go on for several years. We're operating with confidence in our patents, but we're building the r isomer and moving on to the new Provigil and expect to build that franchise. Our job is to ensure to the shareholders that the follow on products continue to grow and for the new markets we're creating, to preserve EPS growth independent of whatever decision comes down. Q23. (Michael King, Banc of America Securities) Are you willing to say which court you'd like to see the patent case litigated in? A. (John Osborne) It's public record. We've filed our action in US District Court in New Jersey. Q24. (Michael King, Banc of America Securities) Does your '03 guidance assume any price increases? A. (Kevin Buchi) I'd rather not comment on that. Q25. (Jim Dawson, Buckingham Research) How much of the product sales guidance is based on positive data for Provigil and Gabitril coming out this year? A. (Kevin Buchi) None of the guidance is based on generating new data you're not already aware of, either for the quarter or the year. A. (Frank Baldino) Guidance is based on the performance we think we can achieve with the marketing programs we have, with the sales messages we're delivering, coupled with the data delivery that's already been made public at upcoming meetings. We don't have any additional data we haven't shared with the street. Q26. (Jim Dawson, Buckingham Research) What has your conversation been like with the FDA on the SNDA for Provigil? A. (Frank Baldino) We don't comment on FDA discussions. That's been our policy for some time and we're going to stay with that. [CCBN reserves the right to make changes to documents, content, or other information on this web site without obligation to notify any person of such changes. In the conference calls upon which Event Briefs are based, companies may make projections or other forward-looking statements regarding a variety of items. Such forward-looking statements are based upon current expectations and involve risks and uncertainties. Actual results may differ materially from those stated in any forward-looking statement based on a number of important factors and risks, which are more specifically identified in the companies' most recent SEC filings. Although the companies may indicate and believe that the assumptions underlying the forward-looking statements are reasonable, any of the assumptions could prove inaccurate or incorrect and, therefore, there can be no assurance that the results contemplated in the forward-looking statements will be realized. 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All Rights Reserved 832 of 998 DOCUMENTS Generic Line April 9, 2003 CEPHALON SUES GENERIC FIRMS TO DEFEND MODAFINIL PATENT SECTION: Vol. 20, No. 7 LENGTH: 271 words Cephalon has filed a patent infringement lawsuit against four generic drugmakers that seek to market an equivalent of the company's narcolepsy drug Provigil ( modafinil), the biopharmaceutical firm announced March 31. The suit, filed in the U.S. District Court for the District of New Jersey, alleges generic firms Teva, Mylan, Ranbaxy and Barr want to infringe the '516 patent covering the composition of Provigil, which does not expire until 2014. According to Cephalon, the firms Teva and Mylan claimed the '516 patent is invalid, while Ranbaxy and Barr principally claimed the patent would not be infringed by their respective products. "We have reviewed each of these filings in detail. We have not found anything in them that is surprising or unanticipated," said Cephalon Senior Vice President and General Counsel John Osborn. Barr confirmed it had filed an abbreviated new drug application (ANDA) for 100-mg and 200-mg tablets for generic modafinil on Dec. 24, 2002, the first day it was legally entitled to file. Provigil had sales of about $217 million for the 12 months ending in January, Barr said. But Cephalon said it would be years before a generic modafinil could be sold in the U.S. The FDA has granted Provigil orphan drug exclusivity, which prevents the approval of any ANDA for a modafinil product until at least December 2005. This period could be extended until June 2006 if the agency grants the company a six-month extension for a pediatric study. Cephalon announced in February that at least one generic firm was seeking to market generic modafinil (Generic Line, Feb. 12, Page 2). LOAD-DATE: April 25, 2003 LANGUAGE: ENGLISH Copyright 2003 Washington Business Information, Inc., All Rights Reserved 833 of 998 DOCUMENTS Espicom Business Intelligence April 1, 2003 Cephalon files patent infringement lawsuit against generic companies LENGTH: 323 words Cephalon has filed a lawsuit in US District Court in New Jersey against four generic drug companies for infringement of its US Patent No. RE37516. The '516 patent covers the pharmaceutical compositions of the form of modafinil contained in Provigil tablets (C-IV) and does not expire until 2014. The lawsuit against Teva Pharmaceutical Industries, Mylan Pharmaceuticals, Ranbaxy Pharmaceuticals and Barr Laboratories is based upon ANDAs filed by each of the companies seeking FDA approval for a generic equivalent of modafinil to be sold in the US. A company may file an ANDA requesting permission to market a generic drug prior to expiration of a pioneer company's patent only if it alleges that the patent either is invalid, unenforceable or would not be infringed by the proposed generic product. In their filings, Teva and Mylan principally claimed that Cephalon's '516 patent is invalid, and Ranbaxy and Barr principally claimed the '516 patent would not be infringed by their respective generic products. Even if the lawsuit is unsuccessful and an ANDA application eventually is approved by the FDA, it will be years before a generic equivalent modafinil product can be sold in the US. In addition to the pharmaceutical composition patent that protects Provigil until 2014, the drug has orphan drug exclusivity that prevents the approval of any ANDA for a modafinil product prior to June 2006, provided the FDA grants the company a six-month extension to the December 2005 orphan drug exclusivity upon completion of a paediatric study. Provigil was approved by the FDA for the treatment of excessive daytime sleepiness associated with narcolepsy in December 1998 and was launched in the US by Cephalon in February 1999. In December 2002, the company filed an sNDA with the FDA seeking to expand its US labelling to cover the treatment of excessive sleepiness associated with disorders of sleep and wakefulness in adults. LOAD-DATE: April 2, 2003 LANGUAGE: ENGLISH Copyright 2003 ESPICOM Business Intelligence Ltd. 834 of 998 DOCUMENTS Pharma Marketletter March 31, 2003 Cephalon files patent suits over generic Provigil LENGTH: 143 words Cephalon of the USA has filed a lawsuit in the US District Court in New Jersey against four generic drug companies for infringement of its US patent no RE37516. The '516, which patent covers the pharmaceutical compositions of the form of modafinil contained in Provigil (modafinil), does not expire until 2014, according to the company. The lawsuit against Teva Pharmaceuticals USA, Mylan Pharmaceutical, Ranbaxy Pharmaceuticals and Barr Laboratories is based upon Abbreviated New Drug Applications filed by each of the companies seeking US Food and Drug Administration approval for a generic equivalent of modafinil to be sold in the USA. In their filings, Teva and Mylan principally claimed that Cephalon's '516 patent is invalid, while Ranbaxy and Barr maintained that the patent would not be infringed by their respective generic products. LOAD-DATE: March 31, 2003 LANGUAGE: ENGLISH Copyright 2003 Marketletter Publications Ltd. 835 of 998 DOCUMENTS PR Newswire March 31, 2003 Monday Cephalon, Inc. Files Patent Infringement Lawsuit Against Generic Companies SECTION: FINANCIAL NEWS LENGTH: 952 words DATELINE: WEST CHESTER, Pa. March 31 Cephalon, Inc. (Nasdaq: CEPH) announced today that it has filed a lawsuit in U.S. District Court in New Jersey against four generic drug companies for infringement of Cephalon's U.S. Patent No. RE37516. The '516 patent covers the pharmaceutical compositions of the form of modafinil contained in PROVIGIL(R) Tablets $(C-IV$) and does not expire until 2014. The lawsuit against Teva Pharmaceuticals USA, Inc., Mylan Pharmaceutical Inc., Ranbaxy Pharmaceuticals Inc., and Barr Laboratories, Inc. is based upon Abbreviated New Drug Applications (ANDAs) filed by each of the companies seeking U.S. Food and Drug Administration (FDA) approval for a generic equivalent of modafinil to be sold in the United States. A company may file an ANDA requesting permission to market a generic drug prior to expiration of a pioneer company's patent only if it alleges that the patent either is invalid, unenforceable, or would not be infringed by the proposed generic product. In their filings, Teva and Mylan principally claimed that Cephalon's '516 patent is invalid, and Ranbaxy and Barr principally claimed the '516 patent would not be infringed by their respective generic products. "We have reviewed each of these filings in detail. We have not found anything in them that is surprising or unanticipated. Our patent was approved by the United States Patent and Trademark Office based on the results of extensive research by Cephalon, and we continue to believe that our patent position for this product is strong," said John E. Osborn, Senior Vice President and General Counsel of Cephalon. Even if the lawsuit is unsuccessful and an ANDA application eventually is approved by the FDA, it will be years before a generic equivalent modafinil product can be sold in the United States. In addition to the pharmaceutical composition patent that protects PROVIGIL until 2014, the drug has orphan drug exclusivity that prevents the approval of any ANDA for a modafinil product prior to June 2006, provided the FDA grants the company a six-month extension to the December 2005 orphan drug exclusivity upon completion of a pediatric study. Also, the lawsuit triggers a stay that precludes the FDA from approving any ANDA for up to 30 months to allow the court adequate time to resolve the infringement lawsuit. Because this lawsuit commenced prior to the end of the New Chemical Entity exclusivity period for PROVIGIL and within 45 days of the date of notice by a generic company, the 30-month stay effectively begins at the expiration of the NCE exclusivity period on December 24, 2003. PROVIGIL was approved by the FDA for the treatment of excessive daytime sleepiness associated with narcolepsy in December 1998 and was launched in the United States by Cephalon in February 1999. In December 2002, the company filed a Supplemental New Drug Application with the FDA seeking to expand its U.S. labeling to cover the treatment of excessive sleepiness associated with disorders of sleep and wakefulness in adults. Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products to treat sleep and neurological disorders, cancer and pain. Cephalon currently employs approximately 1,300 people in the United States and Europe. U.S. sites include the company's headquarters in West Chester, Pennsylvania, and offices and manufacturing facilities in Salt Lake City, Utah. Cephalon also has European operations in the United Kingdom, France and Germany. The company currently markets three proprietary products in the United States: PROVIGIL, GABITRIL(R) (tiagabine hydrochloride) and ACTIQ(R) (oral transmucosal fentanyl citrate) $(C-II$) and more than 20 products internationally. Further information about Cephalon and full prescribing information on its U.S. products is available at www.cephalon.com or by calling 1-800-896-5855. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding the patent litigation, potential generic competition, the strength of the PROVIGIL patent position, anticipated scientific progress on its research programs, development of potential pharmaceutical products, interpretation of clinical results, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, sales and earnings guidance, and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. SOURCE Cephalon, Inc. CONTACT: Robert S. (Chip) Merritt of Cephalon, +1-610-738-6376 or cmerritt@cephalon.com URL: http://www.prnewswire.com LOAD-DATE: April 1, 2003 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS, MEDICAL AND LEGAL AFFAIRS EDITORS PUBLICATION-TYPE: Newswire Copyright 2003 PR Newswire Association, Inc. 836 of 998 DOCUMENTS United Press International March 26, 2003 Wednesday Drugs, nutrition may aid soldier function BYLINE: By STEVE MITCHELL LENGTH: 619 words DATELINE: WASHINGTON, March 26 (UPI) Fatigue and sleep deprivation can take a toll quickly on soldiers in combat conditions, such as those being experienced in Iraq, but the U.S. military is well aware of this problem and has implemented programs to improve soldier performance using both nutrition and drugs, experts said Wednesday. "There is a lot of focus on performance enhancing," Janice Rosado, a civilian physical scientist at the Natick Soldier Center's Combat Feeding Directorate in Natick, Mass., told United Press International. "Whatever we can do to give the war fighter an edge, we will do," said Rosado, who is involved with research focused on developing nutritional supplements, such as energy bars and drinks, that might improve soldier performance. The Army "wants to give (soldiers) every edge they possibly can and if they can find a safe, effective way of doing that through a performance-enhancing bar or drink they would want to do that," she said. Two products close to being in a soldier's standard gear are an energy bar known as HooAH! (named after the famous military call) and a sports drink known as ERGO, for Energy Rich Glucose Optimized Drink. These products consist mainly of carbohydrates and would be included in something called a first strike ration, Rosado said. The ration is intended to be used "for the first few days of conflict where soldiers are on the move and do not have time to stop and eat," she said. "It would be carb-loaded because it would be just for a few days when you really just need to be able to have a lot of carbs for energy," she said. Rosado's department has done studies in conjunction with the U.S. Army Research Institute of Environmental Medicine and found both HooAH! and ERGO increased physical performance, such as how far soldiers could go on a march, by 17 percent compared to soldiers who did not take the supplements. The agencies plan to do further studies to determine if the products enhance cognitive performance, she said. One factor that can impair cognitive performance significantly is lack of sleep, said David Dinges, chief of the University of Pennsylvania's Division of Sleep and Chronobiology and director of a research center for the Air Force Office of Scientific Research focused on developing drugs that can lessen the deleterious effects of sleep deprivation. "Sleep deprivation impairs the brain, it impairs the ability to perform," Dinges told UPI. "It can alter your ability to pay attention, you don't respond as quickly ... your ability to think quickly and accurately at the same time is slower." This can impact soldier performance and perhaps contribute to mistakes that lead to friendly fire incidents or other fatalities, he said. One promising remedy may be a drug called modafinil that is approved for the treatment of excessive sleepiness in people with narcolepsy, Dinges said. His lab is "trying to understand whether that drug used in healthy people can promote cognitive capability but not have negative consequences." Dinges has conducted experiments with soldiers, in which they stayed awake for 88 hours or about 3.5 days, while taking modafinil. He could not divulge the details of the results because the study has not yet been published. However, he said, modafinil "looks promising." Although modafinil might not be the final solution for improving soldier performance under sleep deprivation conditions, Dinges said, "The potential for finding additional medicines that are very specifically targeting areas of brain that are involved in keeping you awake ... is very, very good." "Over the next 10 years I think we're going to see one or two things come along" that safely promote wakefulness, he said. LOAD-DATE: March 27, 2003 LANGUAGE: ENGLISH Copyright 2003 U.P.I. 837 of 998 DOCUMENTS Times Colonist (Victoria, British Columbia) March 24, 2003 Monday Final Edition Doctors worry over stimulant that has no 'crash' consequence SOURCE: CanWest News Service BYLINE: Tom Spears SECTION: Canada; Pg. B6 LENGTH: 1004 words DATELINE: OTTAWA OTTAWA - U.S. soldiers are staying awake for days and nights on end in Iraq, and many are almost certainly benefiting from military research into pills that let them work for 40 hours straight -- without feeling "wired" and without crashing afterwards. Soldiers in past wars have taken stimulants when they can't afford to fall asleep, but these have all had side effects -- poor judgment, jumpiness and the need for extra sleep as soon as the soldier stops popping them. But the new stay-awake pills appear to have no side effects, at least in the short term. They don't make people feel powerful or dizzy or happy or sexually charged. There's no jumpiness, no wired feeling, no crashing later. Modafinil just helps them stay awake and feel normal, though one sleep expert says it delivers a kick like 20 cups of coffee. U.S. military studies found that soldiers can stay awake and function alertly for 40 hours, grab eight hours of sleep, and then stay awake for 40 more, all without the impaired judgment of old-fashioned uppers. That's beginning to scare some doctors, who say that modafinil, sold in Canada as Alertec and in the U.S. as Provigil, may threaten the health of people who abuse it. Just as steroids help a body-builder pump iron longer, modafinil may help a computer geek work all day and night at his screen without getting tired, but also without a caffeine-style buzz or the side-effects of amphetamines. Modafinil was designed to help people with narcolepsy stay awake. These people, 150,000 of them in the United States, sometimes fall asleep suddenly in the middle of the day. Some doctors also prescribe modafinil to patients with multiple sclerosis to help them feel less tired. Modafinil is not addictive. But what happens when a student or an office worker starts popping modafinil to stay awake for the next 30 or 40 hours, for the deadline that just has to be met? And what happens when there's another must-do job after that, and then another, and another? Increasingly, Americans who feel the need to stay awake, and who don't have a serious sleep disorder, are getting "off-label" prescriptions for modafinil. In other words, doctors are prescribing the drug for people for whom it was never intended. That's why there are 150,000 Americans with narcolepsy, but as many as 250,000 are getting regular prescriptions for modafinil. The drug was first approved for use in Canada in 1999. "I'm sure it's being used that way. I've heard about it anecdotally. You can understand how hard it would be to study such a situation, particularly when it's intermittent," says Dr. Tom Scammell, a sleep expert at Beth Israel Deaconess Medical Center in Boston. "Most clinicians I talk to are really down on that." Less than a year ago, the U.S. supplier of the drug posted a summary of who was taking it on their Web site, Scammell recalls. A quarter had narcolepsy, others had multiple sclerosis, some had depression, "and then there was a large category of 'other.'" These include people taking the drug just because they want to stay awake, not because they need it. While the drug itself may not be hurting them directly, he feels that lack of sleep may be dangerous. "In a nutshell, we do not know all of the consequences of sleep deprivation. However, there are some consequences that are very clear. When somebody is sleep deprived they become sluggish. Their reaction times are slower than usual. They become clumsy. Somebody who's been sleep-deprived for just one night drives as badly as somebody who is legally intoxicated. "If you look at the number of cars accidents (as a rate), it's highest between 2 and 5 a.m. because people are sleepy." People who are tired sometimes show blood-sugar levels similar to people with diabetes. "And there are some labs that have felt that they see differences in immune function as well. And that certainly supports what everybody's grandmother would tell them" i.e. that losing sleep may make you sick. A Washington Post reporter who sat up for 30 hours on the drug happily wrote he felt fine, adding: "Modafinil may have the power to change Washington, D.C., and other high-powered cities." That's where doctors fear the misuse may come from. It's not a "feel-good" drug, but one that people may take if they're under heavy pressure to perform at work or school. "It's just one of these misuses, in my view, of a medical application. You could probably get the same thing with 20 cups of coffee, but you wouldn't like it," says Dr. Judith Leech, a respirologist who sees patients with sleep disorders at the Ottawa Hospital. "Get some sleep! Don't use a pill to stay awake! Does that make good medical sense? On the other hand, people will use it that way. "I think sleep is a good thing. The healthy thing to do is to sleep more if you're tired, right? "Compared with other stimulants that have been prescribed, such as dexedrine and ritalin, it (modafinil) doesn't work the same way so it doesn't have the same side effects," she adds. It doesn't cause high blood pressure or feeling wired -- all the effects that are part of the nervous system's "fight or flight" reflex. "On the other hand we don't really know which brain chemical it does work on. Personally I'm not really big on stimulating people's brains with things I'm not sure of, unless there's a medical indication." Leech notes that soldiers have been offered drugs before to keep them awake: if it isn't modafinil, it's something else that may in fact be worse, such as amphetamines. "On the other hand, what I use in somebody whose life is totally impaired by a brain chemistry disorder is different from what I think you should use in an army person" or other healthy people. "It's bad to use drugs for bad reasons. "There's a reason why we get sleepy." Sleep helps the brain store memories and recuperate from work, and helps the body build its immune system. "And you deprive yourself of those things if you use a stimulant to overcome it." LOAD-DATE: March 24, 2003 LANGUAGE: ENGLISH TYPE: News Copyright 2003 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 838 of 998 DOCUMENTS The Denver Post March 23, 2003 Sunday 1ST EDITION KEEPING TROOPS AWAKE, ALERT Anti-sleep drug getting unplanned use BYLINE: Diedtra Henderson Denver Post Science Writer SECTION: A SECTION; Pg. A-18 LENGTH: 987 words Mere mortals might feel sleepy with just a few hours of lost  shuteye, but the armed forces expect no such weakness in fighters  strapped into aircraft or battling on the field. The federal 'Continuous Assisted Performance' project is pursuing  genetic tinkering that would permit military pilots to fly 24-hour  missions without any sleep and without popping the amphetamine  'go' pills now the norm on lengthy flights. And the Air Force is  testing a new wonder drug that has the promise of letting pilots  remain awake and alert for up to four days without amphetamine's   side effects. The research is happening against the backdrop of nighttime bombing  missions in Iraq and as a military court found insufficient  evidence for criminal charges against two F-16 pilots accused of  killing four Canadians in a friendly fire mishap an hour after the  pilots popped 'go' pills. The military researchers' ultimate goal: seven sleepless days for  combat troops, during which they don't lose the power to reason,  react or realize the impact of their actions. Right now, popping a modafinil - a pill designed for people who  fall deeply and unexpectedly asleep - has the most promise. Already an Army researcher at Alabama's Fort Rucker gave pilots  modafinil. Another group got nothing. The pilots were kept awake  for 40 hours during which they sat at flight simulators. 'When the pilots were not receiving the modafinil, they were  having significant problems staying awake - particularly when you  got around that point of 3 in the morning to noon the next day,'  said researcher John Caldwell. Instructions had to be repeated for unmedicated pilots, who also  nodded off during the simulated flight. Those pilots also flubbed  basic flight requirements: They couldn't maintain precise altitude,  heading or air speed. Modafinil 'wiped out' most of those  effects, Caldwell said. Canadian and French military forces have conducted similar  research. Caldwell's next research project using the drug, this time for the  Air Force, will do head-to-head tests comparing the effects of  single doses of modafinil, Dexedrine and caffeine tablets for  military volunteers kept awake for 38 hours. 'Do you get the same amount of boost from these three doses and,  if you do, does the effect last the same?' Caldwell asked. Popular media accounts - some using reporters who popped pills to  see if they could banish sleep - make Sheryl Williams, spokeswoman  for the pharmaceutical company Cephalon, hopping mad. Cephalon has a pending application to expand the use of its  modafinil drug, Provigil, to medical conditions beyond narcolepsy.  Williams fears that recreational use by hard-charging civilians who  want to make sleep optional might put the FDA in a denying mood. 'We have not applied to have this drug used as a substitute for  sleep, nor would we ever do that,' Williams said. 'The biggest  worry that we have is the average American - that person who is out  there reading these things, thinking there is something out there  they could take they could substitute for sleep.' Sleep remains an uncharted frontier for science. Researchers  haven't worked out all of the whys and hows, but sleep is essential  for humans and most other animals. Deprive most living creatures of  those restful, recharging hours, and a cascade of problems begins,  including memory loss, hobbled reason, impaired judgment, reduced  sexual capacity, weakened immunity - even early death. Recent research suggests that the crux may not be the benefit of  sleep but the high cost of remaining awake. 'There seems to be a wear and tear of staying awake too long,'  said Hans P.A. Van Dongen, an assistant research professor at the  University of Pennsylvania school of medicine. Tallying a high number of wide- awake hours predicts almost precisely how poorly people will  perform on reaction tests. Recent work indicates that the brain  builds up a certain chemical as the body remains awake. Caffeine,  as it turns out, binds to the same receptor as that brain chemical,  temporarily zapping its ability to turn on sleep. Still, clinical trials on how to keep troops fighting-sharp while sleep-deprived continue at military bases. Bomber missions, with aerial refueling, may extend 24 to 25 hours. 'In the case of a bomber, you usually have a two-person crew. You  catch a couple of hours here or there, but that's not a full,  restful sleep,' said Betty Anne Mauger, a spokeswoman for the Air  Force surgeon general. 'The overall thing we're dealing with is  fatigue.' Depending on the weight of the pilot and the individual's ground- tested tolerance for amphetamines, a flight that long might mean  popping 10 milligrams of Dexedrine every four hours. Affidavits from experts presented in the friendly fire case  suggested even such low doses of amphetamines could contribute to  muddled thinking and extreme tunnel vision. 'Those negative effects would be enhanced by adding stress,' said  Charles W. Gittins, the attorney who represented Maj. Harry  Schmidt, who dropped a 500-pound bomb on what he thought were  Taliban forces. Gittins said after the first Gulf War, an F-15C aircraft with the  58th Tactical Fighter Squadron ran off the runway, a mishap tied by  accident investigators to the pilot's use of Dexedrine. Air Force public affairs representatives from national  headquarters, Eglin Air Force Base - where the squadron is  headquartered - and Langley Air Force Base, which convened the  investigation panel, couldn't immediately track down the accident  investigation summary. Denver Post science writer Diedtra Henderson can be reached at dhenderson@denverpost.com or at 303-820-1910. LOAD-DATE: March 25, 2003 LANGUAGE: ENGLISH GRAPHIC: PHOTO: Reuters/Russell Boyce A British pilot rests as he waits in his Harrier GR-7 in Kuwait. The U.S. military is seeking ways to keep sleep-deprived troops fighting-sharp. Copyright 2003 The Denver Post All Rights Reserved 839 of 998 DOCUMENTS Ottawa Citizen March 23, 2003 Sunday Final Edition New drug may help soldiers stay awake: Doctors unsure of long-term effect SOURCE: The Ottawa Citizen BYLINE: Tom Spears SECTION: News; Pg. A5 LENGTH: 831 words U.S. soldiers are staying awake for days and nights on end in Iraq, and many are almost certainly benefiting from military research into pills that let them work for 40 hours straight, without feeling "wired" and without crashing afterward. Soldiers in past wars have taken stimulants when they can't afford to fall asleep, but these have all had side effects: poor judgment, jumpiness and the need for extra sleep as soon as the soldier stops popping them. But the new stay-awake pills appear to have no side effects, at least in the short term. U.S. military studies found that soldiers can stay awake and function alertly for 40 hours, get eight hours of sleep, and then stay awake for 40 more, all without the impaired judgment of old-fashioned uppers. That's beginning to scare some doctors, who say that modafinil, sold in Canada as Alertec and in the U.S. as Provigil, might threaten the health of people who abuse it. Modafinil is designed to help people with narcolepsy stay awake. These people, 150,000 of them in the United States, sometimes fall asleep suddenly in the middle of the day. Some doctors also prescribe modafinil to patients with multiple sclerosis to help them feel less tired. Modafinil is not addictive. But what happens when a student or an office worker starts popping modafinil to stay awake for the next 30 or 40 hours for a deadline project? And what happens if the cycle continues? Increasingly, Americans who feel the need to stay awake, and who don't have a serious sleep disorder, are getting "off-label" prescriptions for modafinil. That's why there are 150,000 Americans with narcolepsy, but as many as 250,000 are using modafinil. The drug was first approved for use in Canada in 1999. "I'm sure it's being used that way. You can understand how hard it would be to study such a situation, particularly when it's intermittent," says Dr. Tom Scammell, a sleep expert at Beth Israel Deaconess Medical Center in Boston. "Most clinicians I talk to are really down on that." Less than a year ago, the U.S. supplier of the drug posted a patient summary on its Web site, Dr. Scammell recalls, showing one-quarter had narcolepsy, while others had multiple sclerosis and some had depression. "And then there was a large category of 'Other.'" These include people taking the drug just because they want to stay awake, not because they need it. And while the drug itself might not be hurting them directly, he believes that lack of sleep might be dangerous. "In a nutshell, we do not know all of the consequences of sleep deprivation. However, there are some consequences that are very clear. When somebody is sleep deprived they become sluggish. Their reaction times are slower than usual. They become clumsy. Somebody who's been sleep-deprived for just one night drives as badly as somebody who is legally intoxicated. "If you look at the number of cars accidents (as a rate) it's highest between 2 and 5 a.m. because people are sleepy." People who are tired sometimes show blood-sugar levels similar to people with diabetes. A Washington Post reporter who sat up for 30 hours on the drug happily wrote he felt fine, adding: "Modafinil may have the power to change Washington, D.C., and other high-powered cities." Doctors fear the that modafinil, while not a "feel-good" drug, is one that people may take if they're under heavy pressure. "It's just one of these misuses, in my view, of a medical application. You could probably get the same thing with 20 cups of coffee, but you wouldn't like it," says Dr. Judith Leech, a respirologist who sees patients with sleep disorders at the Ottawa Hospital. "Get some sleep! Don't use a pill to stay awake! Does that make good medical sense? "I think sleep is a good thing. The healthy thing to do is to sleep more if you're tired, right?" "Compared with other stimulants that have been prescribed, such as dexedrine and ritalin, it (modafinil) doesn't work the same way so it doesn't have the same side effects," she adds. It doesn't cause high blood pressure or feeling wired, all the effects that are part of the nervous system's "fight or flight" reflex. "On the other hand we don't really know which brain chemical it does work on. Personally I'm not really big on stimulating people's brains with things I'm not sure of, unless there's a medical indication." Dr. Leech notes that soldiers have been offered drugs before to keep them awake: if it isn't modafinil, it may be something worse, such as amphetamines. "On the other hand, what I use in somebody whose life is totally impaired by a brain chemistry disorder is different from what I think you should use in an army person" or other healthy people. "It's bad to use drugs for bad reasons. There's a reason why we get sleepy." Sleep helps the brain store memories and recuperate from work, and helps the body build its immune system. "And you deprive yourself of those things if you use a stimulant to overcome it." LOAD-DATE: March 23, 2003 LANGUAGE: ENGLISH GRAPHIC: Photo: Oleg Popov, Reuters; U.S. soldiers, shown here removing an injured prisoner near Basra, can't always sleep when they should. Modafinil would allow them function well for up to 40 hours without 'crashing' afterwards. TYPE: News Copyright 2003 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 840 of 998 DOCUMENTS Slate Magazine March 7, 2003, Friday Wake Up, Little Susie BYLINE: David Plotz SECTION: superman LENGTH: 1592 words On most days, my accumulated sleep deficit and post-lunch stupor gang up on me around 2 p.m., and I begin my slow fade. My eyes droop. Saliva dribbles onto my sweater. If I were trying to write this sentence at 2 p.m. on a normal day, it would read something like: If I were tryyyyyyyyyyyyyyy But today, I am bright-eyed and bushy-tailed, a chatty Kathy with my officemates, eager to spend all afternoon banging on the keyboard. (I normally prefer chewing my fingers off to writing.) I am not exactly wired, but I'm more alert, more focused, more Plotz-like. Today I am my own Superman, dosed on 100 milligrams of modafinil. Every year, we need the same amount of sleep, and every year we get less. Since the invention of artificial illumination, sleep has been a bear market. There are many reasons we catch fewer Z's: Round-the-clock workplaces, longer commutes, brighter lights, 24-hour Krispy Kreme stores, the Home Shopping Network "the list goes on. According to University of Pennsylvania professor of psychology David Dinges, Americans probably sleep about six and a half to seven hours per night, compared to the more than eight hours our bodies want. We have learned to cope with a regular sleep deficit, but we pay a price (and not just $4.05 for the venti latte). Studies by Dinges and military scientists have proved that performance deteriorates when you sleep less than eight hours. People who rest seven or six or five hours a night may not feel tired, but their thinking and dexterity are suffering. We medicate ourselves with caffeine, a drug that raises alertness but at a cost of jitteriness, irregular heartbeat, and addiction. Folks who really need to stay awake dope themselves with amphetamines "stimulants that can ward off sleep for days but cause terrible crashes when they wear off. (And we don't know what long-term damage they cause.) The military is enthralledwith the possibility of doing away with shut-eye. The supersecret Defense Advanced Research Projects Agency is investigating drugs that would keep soldiers awake for a week. The Air Force prescribes go pills "small doses of the amphetamine Dexedrine "to pep up long-haul pilots. (But hopped-up pilots may be dangerous: The American pilots who accidentally bombed and killed Canadian soldiers last spring were taking go pills.) Avoiding sleep for a week might be necessary in an extreme situation like war, but the run-of-the-mill, office-working, wannabe Superman requires something different. We don't want a pill that will keep us Exceling and Power Pointing for three days straight. We just want something that makes us feel alert through an entire normal day "a drug that makes us feel as lively for the 18-hour-day we have to live as for the 16-hour-day we ought to live. Hence my rendezvous with modafinil. The drug, made by Cephalon, is marketed under the creepy, pharma-Orwellian name Provigil. The FDA approved it in 1998 to treat narcolepsy, but it is starting to have a underground life as a pick-me-up for the routinely sleep-deprived. The military has tested it heavily, particularly on pilots. The way modafinil works is not understood. It seems to slow the release of GABA, a sleep promoter in the brain. It also may act on the histamine system, which is connected to sleep regulation. What is clear is that modafinil differs from most other pick-me-ups, which tend to be indiscriminate in their function. Amphetamines like Dexedrine, for example, promote wakefulness by interfering with uptake of the neurotransmitter dopamine, causing dopamine to flood the brain. Dopamine, says Joyce Walsleben, director of the NYU Sleep Disorders Center, is a broad hitter that sets the heart racing, causes twitchiness, and makes you feel high. When the effect of such stimulants wears off, the crash is nasty. Caffeine affects a different pathway, involving adenosine, but that, too, spills over the brain's flood wall, making coffee drinkers jittery. But modafinil tiptoes around dopamine, confining its activity to the particular neurological processes connected to wakefulness. It doesn't seem to act as a broad stimulant. (This is one reason, Walsleben says, that modafinil has not become a street drug. Unlike cocaine or amphetamines, modafinil doesn't make you feel high, and it acts very slowly, taking a couple of hours or more to kick in.) Narcoleptics seem to love modafinil. (By boosting alertness throughout the day, modafinil reduces the narcoleptic's compulsion to nod off.) Now doctors are getting barraged by requests from regular folks who want to use it to cut down on sleep. The seduction of modafinil is that you can feel as peppy after six hours sleep as you would after nine. (It may also have a more.) Doctors see modafinil as an occasional pick-me-up. They doubt you could take the drug everyday without consequences: Most sleep researchers agree that the longer sleep is necessary for hormonal regulation, among other essential bodily functions. (Drugs aren't the only way we may steal less sleep. Click to read about how we may enlist gene therapy to help us stay awake.) Tired of merely writing about enhancement (and tired, period), I decided to conduct my own unscientific trial of modafinil. As the father of a 2-year-old, I live in a constant haze of sleep deprivation. I vowed to take modafinil for a week and see what happened. Could it transform a lazy, exhausted hack into a brilliant Jeffrey Goldberg? Or recast a grouchy father into Superdad? I persuaded my doctor "and no, you can't have his number "to prescribe me a week's supply of Provigil, seven 200-milligram pills. Here is the diary I kept. Day 1, Monday 6:45 a.m.: Woken up by my daughter after the usual six and a half hours. 7 a.m.: I open the bottle. The pills are monstrous. I start to chicken out. I've never smoked pot, much less taken cocaine or amphetamines. I decide to halve the dosage. When I cut the first pill with my pocketknife, half of it shoots off my bureau, slides across the floor, and disappears under a dresser, no doubt to be discovered and eaten by my daughter someday in the near future. I pop the other 100-milligram half. 10 a.m.: At the office. I've felt no rush, but alertness has snuck up on me. I am incredibly attentive, but not on edge. I really, really feel like working, a rare sensation. 12 p.m.: I reach for my usual lunchtime Coca-Cola, then think better of it. Caffeine plus this sprightliness and I will be ping-ponging off the walls. 2 p.m.: This is when I usually fold. Today I am the picture of vivacity. I am working about twice as fast as usual. I have a desperate urge to write, to make reporting calls, to finish my expense account "activities I religiously avoid. I find myself talking very loudly and quickly. A colleague says I am grinning like a feral chipmunk. 6 p.m.: Annoyed to have to leave the office when there is all this lovely work to do. 9 p.m.: Home. After dinner, I race upstairs to start working again. This is totally out of character, especially on a Monday Night Football evening. 12 a.m.: I want the day to keep going but force myself to go to bed. I fall asleep easily enough, but it's a weird night. I have lots of dreams, which is unusual. All are about Getting Things Done. Day 2, Tuesday6:30 a.m.: I wake up feeling good, cut another pill in two, and pop a half. 9 a.m.-7 p.m.: I work like a fiend again. These have been the two most productive days I've had in years. Idea for new Provigil ad slogan: Bosses' Little Helper. 1 a.m.: Again I'm alert through the late evening "so alert that I infuriate my wife by chattering at her long past her bedtime. This time, when I do conk out, I sleep deeply. Day 3, Wednesday7 a.m.: My one-man clinical trial starts to fall apart. Everyone says modafinil is not addictive, but I wake up worried about how long my supply will last. I count the pills and realize I have only five and a half left. That's just an 11-day supply. I remember that I offered a sample to a friend yesterday. I am annoyed "one day less for me. I start to cut up the remaining pills, wondering if I can divide them into thirds instead of halves. I realize that maybe I can find a different supplier. I log onto the Internet to see if I can get modafinil on the sly. I find it cheap at the Discount Mexican Pharmacy. I feel delighted and relieved. Then I feel terrified that I am delighted and relieved. Discount Mexican Pharmacy?! 7:30 a.m.: I end my experiment after two days. I am acting like a lunatic. I stash the remaining pills in a distant corner of the medicine cabinet. I calm myself with the reminder that I have 11 more great days to look forward to. So is modafinil a drug for future superpeople? Maybe. There are good reasons for doubt, though. The drug is approved only for treating narcolepsy, and doctors are not going to prescribe it like aspirin anytime soon. Though patients don't seem to get addicted to modafinil or to build a tolerance, according to Walsleben, the drug has been in use for only 10 years, and no one knows for certain that it's safe over the long term. (Cephalon and other drug companies, incidentally, are working on even more powerful wakefulness drugs, but none is on the market yet.) I loved taking modafinil for two days. I worked supernaturally hard and well. But I'd be afraid to make it a habit. I'll use it again for a special occasion "when I am late for a deadline, perhaps. In the meantime, I'll just yawn my way through the midafternoon. LOAD-DATE: March 13, 2003 LANGUAGE: ENGLISH Copyright 2003 Washingtonpost.Newsweek Interactive Company, LLC. All rights reserved 841 of 998 DOCUMENTS Washington Drug Letter February 17, 2003 CEPHALON PLANS VIGOROUS DEFENSE OF MODAFINIL PATENT SECTION: Vol. 35, No. 7 LENGTH: 163 words The first abbreviated new drug application (ANDA) for a generic version of Cephalon's narcolepsy drug Provigil (modafinil) has been accepted by the FDA, the biopharmaceutical firm announced. The identity of the generic applicant was not immediately available. Cephalon said that even if the FDA approves the ANDA, it would be years before a generic equivalent could be sold in the U.S. The composition patent for modafinil in Provigil does not expire until 2014, the company said. The FDA has also granted Provigil orphan drug exclusivity, which prevents the approval of any ANDAs for a modafinil product until at least December 2005. "We have anticipated the possibility of a filing for some time, and we believe that our patent position for this product is strong," said John Osborn, senior vice president and general counsel of Cephalon. The company launched Provigil in 1999. The drug had U.S. sales of more than $200 million last year, according to the firm. LOAD-DATE: February 28, 2003 LANGUAGE: ENGLISH Copyright 2003 Washington Business Information, Inc., All Rights Reserved 842 of 998 DOCUMENTS Generic Line February 12, 2003 CEPHALON VOWS TO DEFEND MODAFINIL ON GENERIC CHALLENGE SECTION: Vol. 20, No. 3 LENGTH: 157 words The FDA has accepted the first ANDA for a generic version of Cephalon's narcolepsy drug Provigil (modafinil), the biopharmaceutical firm announced last week. The identity of the generic applicant was not disclosed. Cephalon said that even if the FDA approves the ANDA, it would be years before a generic equivalent could be sold in the U.S. The composition patent for the modafinil ingredient does not expire until 2014, the company said. The FDA has also granted Provigil orphan drug exclusivity, which prevents the approval of any ANDAs for a modafinil product until at least December 2005. "We have anticipated the possibility of a filing for some time, and we believe that our patent position for this product is strong," said John Osborn, senior vice president and general counsel of Cephalon. The company launched Provigil in 1999. The drug had U.S. sales of more than $200 million last year, according to the firm. LOAD-DATE: February 28, 2003 LANGUAGE: ENGLISH Copyright 2003 Washington Business Information, Inc., All Rights Reserved 843 of 998 DOCUMENTS Espicom Business Intelligence February 10, 2003 Cephalon learns of generic modafinil filing LENGTH: 162 words The FDA has accepted an ANDA for a generic form of modafinil, the active ingredient found in Cephalon's Provigil Tablets (C-IV). Provigil is protected in the US by a patent that does not expire until 2014 and that covers the pharmaceutical composition of the form of modafinil contained in Provigil. The product was also granted orphan drug exclusivity that prevents the approval of any ANDA for a modafinil product prior to June 2006, provided the FDA grants the company a 6-month extension to the December 2005 orphan drug exclusivity upon completion of a paediatric study. Provigil was approved by the FDA for the treatment of excessive daytime sleepiness associated with narcolepsy in December 1998 and was launched in the US by Cephalon in February 1999. In December 2002, the company filed an sNDA with the FDA seeking to expand its US labelling to cover the treatment of excessive sleepiness associated with disorders of sleep and wakefulness in adults. LOAD-DATE: February 11, 2003 LANGUAGE: ENGLISH Copyright 2003 ESPICOM Business Intelligence Ltd. 844 of 998 DOCUMENTS Calgary Herald (Alberta, Canada) February 6, 2003 Thursday Final Edition Latest 'go' pill has few side-effects SOURCE: Ottawa Citizen BYLINE: Joanne Laucius SECTION: Vitality; Pg. E4 LENGTH: 422 words DATELINE: OTTAWA A prescription drug being touted as the next lifestyle drug can keep you up all day and all night. And all day and all night again. Modafinil has been proven to keep military helicopter pilots awake for almost two days straight while still performing complex tasks. It is being tested on soldiers, medical staff and truck drivers. There have been predictions it may soon be used to perk up drowsy shift workers and students cramming for exams. Modafinil -- marketed as Provigil in the U.S. and Alertec in Canada -- has the same effect as six cups of coffee, but it doesn't leave the user feeling jittery. So far, it has only been approved to treat a few sleep-related disorders, including narcolepsy, which causes people to fall asleep suddenly. Studies, including one conducted in Ottawa about five years ago, showed modafinil was not addictive. Unlike amphetamines, it didn't affect blood pressure or cause irritability, cognitive problems or psychotic episodes. There were some side-effects, including dizziness and headaches. And, although it has been called a stimulant, it isn't, said neurologist Dr. Roger Broughton, the founding president of the Canadian Sleep Society. It's a "wake-maintaining substance." Broughton sees potential uses for modafinil -- and truck drivers and sleepy students aren't among them. On the other hand, modafinil may be valuable for soldiers in combat and for police and firefighters in civilian disaster situations. "If it's proven that in the military vein it helps soldiers and airmen stay awake in combat without harm or side-effects, that's a rational use," said Broughton, who is the medical director of the Sleep Medicine Centre in Ottawa. But, for casual use, a lot more work has to be done. "We don't know the long-term effects of the drug. The fact that a lot of sleepy people want this drug doesn't mean they need access." In the U.S., there has been speculation that modafinil is being used for unapproved purposes. About 150,000 people have narcolepsy, but the drug's manufacturer, Cephalon, reports 250,000 new modafinil users every three months. Even Cephalon senior vice-president Paul Blake has said he is concerned about the casting of the drug as an alternative to a good night's rest. Meanwhile, Broughton says the drug has proved effective for several other uses that have not yet received approval, including treatment for fatigue and sleepiness in patients with attention deficit hyperactivity disorder, multiple sclerosis and Parkinson's disease. LOAD-DATE: February 6, 2003 LANGUAGE: ENGLISH TYPE: News Copyright 2003 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 845 of 998 DOCUMENTS PR Newswire February 5, 2003 Wednesday Cephalon, Inc. Learns of Generic Modafinil Filing; Company Intends to Vigorously Defend the Product's 2014 Patent SECTION: FINANCIAL NEWS LENGTH: 729 words DATELINE: WEST CHESTER, Pa. Feb. 5 Cephalon, Inc. (Nasdaq: CEPH) reported today that the U.S. Food and Drug Administration (FDA) has accepted an abbreviated new drug application (ANDA) for a generic form of modafinil, the active ingredient found in the company's PROVIGIL(R) Tablets $(C-IV$). Even if an ANDA application eventually is approved by the FDA, it will be years before a generic equivalent modafinil product can be sold in the United States. PROVIGIL is protected in the United States by a patent that does not expire until 2014 and that covers the pharmaceutical composition of the form of modafinil contained in PROVIGIL. PROVIGIL also was granted orphan drug exclusivity that prevents the approval of any ANDA for a modafinil product prior to June 2006, provided the FDA grants the company a six-month extension to the December 2005 orphan drug exclusivity upon completion of a pediatric study. "Wehave anticipated the possibility of a filing for some time, and we believe that our patent position for this product is strong," said John E. Osborn, Senior Vice President and General Counsel of Cephalon. "We will thoroughly evaluate any filing when it becomes available to us, and we are prepared to vigorously protect our intellectual property rights." PROVIGIL was approved by the FDA for the treatment of excessive daytime sleepiness associated with narcolepsy in December 1998 and was launched in the United States by Cephalon in February 1999. In December 2002, the company filed a Supplemental New Drug Application with the FDA seeking to expand its U.S. labeling to cover the treatment of excessive sleepiness associated with disorders of sleep and wakefulness in adults. Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products to treat sleep and neurological disorders, cancer and pain. Cephalon currently employs approximately 1,500 people in the United States and Europe. U.S. sites include the company's headquarters in West Chester, Pennsylvania, and offices and manufacturing facilities in Salt Lake City, Utah. Cephalon also has European operations in the United Kingdom, France and Germany. The company currently markets three proprietary products in the United States: PROVIGIL, GABITRIL(R) (tiagabine hydrochloride) and ACTIQ(R) (oral transmucosal fentanyl citrate) $(C-II$) and more than 20 products internationally. Further information about Cephalon and full prescribing information on its U.S. products is available at www.cephalon.com or by calling 1-800-896-5855. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding potential generic competition and our responses thereto, the strength of the PROVIGIL patent position, anticipated scientific progress on its research programs, development of potential pharmaceutical products, interpretation of clinical results, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, sales and earnings guidance, and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion. SOURCE Cephalon, Inc. CONTACT: Media: Robert Grupp, +1-610-738-6402 or rgrupp@cephalon.com; or Investors: Robert S. (Chip) Merritt, +1-610-738-6376 or cmerritt@cephalon.com, both of Cephalon URL: http://www.prnewswire.com LOAD-DATE: February 6, 2003 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS AND MEDICAL EDITORS PUBLICATION-TYPE: Newswire Copyright 2003 PR Newswire Association, Inc. 846 of 998 DOCUMENTS St. John's Telegram (Newfoundland) January 31, 2003 Friday Final Edition Awake, but not wired: Studies show the drug modafinil perks up the drowsy with few side-effects SOURCE: Southam Newspapers BYLINE: Joanne Laucius SECTION: Lifestyles; Pg. B6 LENGTH: 498 words DATELINE: OTTAWA OTTAWA - A prescription drug being touted as the next lifestyle drug can keep you up all day and all night. And all day and all night again. Modafinil has already been proven to keep military helicopter pilots awake for almost two days straight while still performing complex tasks. It is being tested on soldiers, medical staff and truck drivers. There have been predictions it may soon be used to perk up drowsy shift workers and even students cramming for exams. Modafinil -- marketed as Provigil in the U.S. and Alertec in Canada -- has the same effect as six cups of coffee, but it doesn't leave the user feeling jittery. So far, however, it has only been approved to treat a few sleep-related disorders including narcolepsy, which causes people to fall asleep suddenly. It has been used in France for about 15 years. Studies, including one conducted in Ottawa about five years ago, showed modafinil was not addictive. Unlike amphetamines, it didn't affect blood pressure or cause irritability, cognitive problems or psychotic episodes. There were some side-effects, including dizziness and headaches. And although it has been called a stimulant, it isn't, said neurologist Dr. Roger Broughton, the founding president of the Canadian Sleep Society. It's a "wake-maintaining substance." Broughton sees potential uses for modafinil -- and truck drivers and sleepy students aren't among them. On the other hand, modafinil may be valuable for soldiers in combat and for police and firefighters in civilian disaster situations. "If it's proven that in the military vein it helps soldiers and airmen stay awake in combat without harm or side-effects, that's a rational use," said Broughton, who is the medical director of the Sleep Medicine Centre at the Ottawa Hospital's General campus. "You don't want pilots to be sleepy when they're at war." But for casual use, a lot more work has to be done. "People just want to pop a pill," said Broughton. "We don't know the long-term effects of the drug. The fact that a lot of sleepy people want this drug doesn't mean they need access." In the U.S., there has already been speculation that modafinil is being used for unapproved purposes. About 150,000 people have narcolepsy, but the drug's manufacturer, Cephalon, reports 250,000 new modafinil users every three months. Even Cephalon senior vice-president Paul Blake has said he is concerned about the casting of the drug as an alternative to a good night's rest. "Provigil is not a substitute for sleep," he said earlier this month. Meanwhile, Broughton says the drug has proved effective for several other uses that have not yet received approval, including treatment for fatigue and sleepiness in patients with attention deficit hyperactivity disorder, multiple sclerosis and Parkinson's disease. As for demand outside of its approved uses, he hasn't seen it. "It's a controlled drug -- which is controlled as much as narcotics. That's the law for the moment." LOAD-DATE: January 31, 2003 LANGUAGE: ENGLISH GRAPHIC: Photo: Southam News; Modafinil can keep you up for days, with no jitters and few side-effects, but sleep specialists still say nothing beats a good night's sleep. TYPE: News Copyright 2003 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 847 of 998 DOCUMENTS Ottawa Citizen January 29, 2003 Wednesday Final Edition Awake, but not wired: Studies show drug perks up the drowsy with few side effects SOURCE: The Ottawa Citizen BYLINE: Joanne Laucius SECTION: News; Pg. A12 LENGTH: 500 words A prescription drug being touted as the next lifestyle drug can keep you up all day and all night. And all day and all night again. Modafinil has already been proven to keep military helicopter pilots awake for almost two days straight while still performing complex tasks. It is being tested on soldiers, medical staff and truck drivers. There have been been predictions it may soon be used to perk up drowsy shift workers and even students cramming for exams. Modafinil -- marketed as Provigil in the U.S. and Alertec in Canada -- has the same effect as six cups of coffee, but it doesn't leave the user feeling jittery. But so far, it has only been approved to treat a few sleep-related disorders including narcolepsy, which causes people to fall asleep suddenly. It has been used in France for about 15 years. Studies, including one conducted in Ottawa about five years ago, showed modafinil was not addictive. Unlike amphetamines, it didn't affect blood pressure or cause irritability, cognitive problems or psychotic episodes. There were some side effects, including dizziness and headaches. And although it has been called a stimulant, it isn't, said neurologist Dr. Roger Broughton, the founding president of the Canadian Sleep Society. It's a "wake-maintaining substance." Dr. Broughton sees potential uses for modafinil -- and truck drivers and sleepy students aren't among them. On the other hand, modafinil may be valuable for soldiers in combat and for police and firefighters in civilian disaster situations. "If it's proven that in the military vein it helps soldiers and airmen stay awake in combat without harm or side effects, that's a rational use," said Dr. Broughton, who is the medical director of the Sleep Medicine Centre at the Ottawa Hospital's General campus. "You don't want pilots to be sleepy when they're at war." But for casual use, a lot more work has to be done. "People just want to pop a pill," said Dr. Broughton. "We don't know the long-term effects of the drug. The fact that a lot of sleepy people want this drug doesn't mean they need access. " In the U.S., there has already been speculation that modafinil is being used for unapproved purposes. About 150,000 people have narcolepsy, but the drug's manufacturer, Cephalon, reports 250,000 new modafinil users every three months. Even Cephalon senior vice-president Paul Blake has said he is concerned about the casting of the drug as an alternative to a good night's rest. "Provigil is not a substitute for sleep," he said earlier this month. Meanwhile, Dr. Broughton says the drug has proved effective for several other uses that have not yet received approval, including treatment for fatigue and sleepiness in patients with attention deficit hyperactivity disorder, multiple sclerosis and Parkinson's disease. As for demand outside of its approved uses, he hasn't seen it. "It's a controlled drug -- which is controlled as much as narcotics. That's the law for the moment." LOAD-DATE: January 29, 2003 LANGUAGE: ENGLISH GRAPHIC: Photo: The Ottawa Citizen; Modafinil can keep you up for days, with no jitters and few side effects, but sleep specialists still say nothing beats a good night's sleep. TYPE: News Copyright 2003 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 848 of 998 DOCUMENTS San Mateo County Times (San Mateo, CA) January 25, 2003 Saturday Military researching pilot fatigue BYLINE: By John Jurgensen SECTION: MORE HEADLINE NEWS LENGTH: 703 words HARTFORD COURANT Along with the beef stew and peanut butter bundled into their rations, Persian Gulf War soldiers had instant coffee to keep them going. Lacking hot water, many ripped open the packets of Taster's Choice and swallowed the dry coffee crystals. Thousands of feet above the ground forces, where the stakes were higher, Air Force pilots were gulping amphetamine pills issued by military physicians. The "go pills" helped fliers stay alert during the long, grueling combat sorties. More than a decade later, despite steady advancements in weaponry, the strategy behind keeping soldiers awake has barely changed. Nor has it since World War II, when amphetamines were first doled out to U.S. troops. But the ongoing trial of two Air Force pilots involved in a friendly-fire incident in Afghanistan a formidable adversary, but the military is challenging it with new research. Majs. Harry Schmidt and William Umbach face court-martial for dropping a 500-pound bomb on Canadian troops last April, killing four and wounding eight. Their defense has contended that the amphetamines they took during a 20-hour workday impaired their judgment. The Air Force dismisses the claim, describing the drug as a "medical tool," prescribed in small[5-milligram], controlled doses. A majority of fighter pilots surveyed after Desert Storm said they used stimulants, and 61 percent of those who did said stimulants were essential to the missions. John Caldwell, a research psychologist at Brooks Air Force Base in San Antonio, puts exhausted pilots through round-the-clock missions in flight simulators while evaluating their mood, cognition and performance. Although he defends the military's use of go pills, he acknowledges new solutions are needed for the age-old problem of staying awake. "Every year we extend the duration of these missions," Caldwell said, citing the experience of B-2 bomber pilots who may spend more than 30 hours in the cockpit. Foremost, Caldwell prescribes careful scheduling, strategic napping and sound sleep. For that, he's helped develop a computerized tool that will help commanders predict the alertness of personnel in various scenarios. But when shut-eye is nonexistent, the remedies are pharmacological. Because the Army can't drop controlled substances into ration packs, caffeine will likely remain the drowsy GI's drug of choice. But for Air Force pilots, Dexedrine remains the "gold standard stimulant," according to Caldwell. "Any new alertness-enhancing compound must be compared to dextro-amphetamine to ensure that the new product is better and not just different." Modafinil, a drug designed to help narcoleptics stay awake, has offered the most promise. Though its workings remain mysterious, modafinil causes wakefulness with little disruption of sleep architecture, unlike amphetamines. But Col. Gregory Belenky, a director of neuropsychiatry at Walter Reed Army Institute of Research in Silver Spring, Md., doesn't think modafinil is much better than a more historical stimulant. We compared caffeine to modafinil. In our study, we did not see any difference. Modafinil has less potential for abuse than amphetamines, but because physicians must administer it, its widespread use on the battlefield presents a logistical challenge, Belenky said. Looking for other creative ways to overcome the limits of biology, the U.S. Defense Advanced Research Projects Agency has sponsored studies investigating the brain chemistry of sleepless migrating birds and the effects of magnetic fields on neurons. But at the Soldier Center of Excellence in Natick, Mass., researchers are working with well-known substances to power up everyday rations. The trick, said senior food technologist Jack Briggs, is making them taste good while achieving the required shelf life. We need to ensure that after three years, what we want to deliver is still there. The results, including ERGO [a powdered drink] and HooAH [an energy bar], are battle-ready improvements on products already on the market. They provide a potent fuel of carbohydrates, lipids, protein and, of course, caffeine.> Distributed by the Los Angeles Times-Washington Post News Service LOAD-DATE: June 17, 2003 LANGUAGE: ENGLISH Copyright 2003 MediaNews Group, Inc. and ANG Newspapers 849 of 998 DOCUMENTS Espicom Business Intelligence December 20, 2002 Cephalon reacquires rights to modafinil in European markets LENGTH: 155 words Cephalon has reacquired all rights to modafinil in Germany and Spain. Cephalon markets modafinil in the US under the brandname Provigil. The company reacquired rights to modafinil in Germany, Austria, Switzerland and certain countries in Central and Eastern Europe from Merckle and in Spain from Cepa Schwarz Pharma. Financial terms were not disclosed. Merckle and Cepa acquired marketing rights to the drug from Laboratoire L Lafon in 1993. Cephalon acquired Lafon in 2001. Modafinil is marketed in Europe for the treatment of excessive daytime sleepiness associated with narcolepsy, under the brandnames Provigil in the UK, Modiodal in France and Spain, Vigil in Germany, and Modasomil in Austria and Switzerland. Earlier this month, Cephalon also received marketing approval in the UK to expand the label of the product to treat excessive daytime sleepiness in patients with obstructive sleep apnea/hypopnea syndrome. LOAD-DATE: December 20, 2002 LANGUAGE: ENGLISH Copyright 2002 ESPICOM Business Intelligence Ltd. 850 of 998 DOCUMENTS PR Newswire December 18, 2002 Wednesday Cephalon Reacquires Rights to Modafinil in Major European Markets; Product Rights in Additional Countries Further Strengthens Cephalon's International Marketing Presence SECTION: FINANCIAL NEWS LENGTH: 876 words DATELINE: WEST CHESTER, Pa. Dec. 18 Cephalon, Inc. (Nasdaq: CEPH), an international biopharmaceutical company, announced that it has reacquired all rights to modafinil in Germany and Spain, two of Europe's largest pharmaceutical markets. Cephalon markets modafinil in the United States under the brand name PROVIGIL(R) (modafinil) tablets $(C-IV$). The company reacquired rights to modafinil in Germany, Austria, Switzerland and certain countries in Central and Eastern Europe from Merckle GmbH, and in Spain from Cepa Schwarz Pharma. Financial terms of the agreements were not disclosed. Merckle and Cepa Schwarz Pharma acquired marketing rights to the drug from Laboratoire L. Lafon in 1993. Cephalon acquired Lafon in 2001. "We have made tremendous progress this year in our strategy to consolidate worldwide rights for all of our marketed products," said Frank Baldino, Jr., Chairman and CEO of Cephalon. "Modafinil already is an important contributor to our European business in the United Kingdom and France. This marketing experience, together with the product's excellent performance in the United States, should enable us to effectively position modafinil in these additional European markets." Modafinil is marketed in Europe for the treatment of excessive daytime sleepiness associated with narcolepsy, under the brand names PROVIGIL in the United Kingdom, MODIODAL(R) in France and Spain, VIGIL(R) in Germany, and MODASOMIL(R) in Austria and Switzerland. Earlier this month, Cephalon also received marketing approval in the United Kingdom to expand the label of PROVIGIL to treat excessive daytime sleepiness in patients with obstructive sleep apnea/hypopnea syndrome. In the past year, Cephalon has significantly expanded its international business and now holds extensive European and Asian rights to the three products that it markets in the United States: PROVIGIL, ACTIQ, and GABITRIL. In October, Cephalon reacquired all rights to ACTIQ in 12 countries, principally in Europe. In January, Cephalon acquired worldwide rights to GABITRIL (excluding Canada, Latin America, and Japan). In December 2001, Cephalon purchased Laboratoire L. Lafon and acquired control of worldwide rights to PROVIGIL. PROVIGIL PROVIGIL is the first in a new class of wake-promoting agents. While its exact mechanism of action is not known, the drug acts selectively in areas of the brain believed to regulate normal wakefulness. Launched in the United States in February 1999, the drug is currently approved in more than 20 countries for the treatment of excessive daytime sleepiness associated with narcolepsy. For full prescribing information about PROVIGIL, please visit http://www.PROVIGIL.com. Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products to treat sleep and neurological disorders, cancer and pain. Cephalon currently employs more than 1,200 people in the United States and Europe. U.S. sites include the company's headquarters in West Chester, Pennsylvania, and offices and manufacturing facilities in Salt Lake City, Utah. Cephalon's major European offices are located in Guildford, England, Martinsried, Germany, and at Laboratoire L. Lafon in Maisons-Alfort, France. Further information about Cephalon and full prescribing information on its U.S. products is available at www.cephalon.com or by calling +1-800-896-5855. In addition to historical facts or statements of current condition, this press release contains forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs, development of potential pharmaceutical products, interpretation of clinical results, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, including its ability to favorably position modafinil in Europe, sales and earnings projections including the impact of the German operations on Cephalon's business, the importance of PROVIGIL, ACTIQ and GABITRIL and other marketed products to Cephalon's European territories and other statements regarding matters that are not historical facts. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries, as well as more specific risks and uncertainties such as those set forth below and in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements ultimately may prove to be incorrect. Therefore, you should not rely on any such factors or forward- looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The U.S. Private Securities Litigation Reform Act of 1995 permits this discussion.                       MAKE YOUR OPINION COUNT - Click Here                http://tbutton.prnewswire.com/prn/11690X45175747 SOURCE Cephalon, Inc. CONTACT: Robert W. Grupp, +1-610-738-6402 or rgrupp@cephalon.com, or Investor Contact, Chip Merritt, +1-610-738-6376 or cmerritt@cephalon.com, both of Cephalon URL: http://www.prnewswire.com LOAD-DATE: December 19, 2002 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS AND MEDICAL EDITORS PUBLICATION-TYPE: Newswire Copyright 2002 PR Newswire Association, Inc. 851 of 998 DOCUMENTS Health Media Group Media Watch Services December 13, 2002 Modafinil approved for sleep apnoea SOURCE: Doctor 12/12/02; p.6 SECTION: Health Media Group Media Watch Services LENGTH: 66 words Modafinil (Provigil), used to treat narcolepsy, can now be prescribed for sleep apnoea. It is estimated that 30 per cent of sleep apnoea patients do not respond to continuous positive airways pressure, and the use of modafinil will be of benefit to them. Initially the drug will be prescribed by specialists as a second-line treatment for daytime sleepiness associated with sleep apnoea. LOAD-DATE: December 16, 2002 Copyright Health Media Ltd 2002 852 of 998 DOCUMENTS Health Media Group Media Watch Services December 13, 2002 Modafinil approved for sleep apnoea SOURCE: Doctor 12/12/02; p.6 BYLINE: Health Newswire reporters SECTION: Health Media Group Media Watch Services LENGTH: 66 words Modafinil (Provigil), used to treat narcolepsy, can now be prescribed for sleep apnoea. It is estimated that 30 per cent of sleep apnoea patients do not respond to continuous positive airways pressure, and the use of modafinil will be of benefit to them. Initially the drug will be prescribed by specialists as a second-line treatment for daytime sleepiness associated with sleep apnoea. LOAD-DATE: March 31, 2003 Copyright Health Media Ltd 2002 853 of 998 DOCUMENTS PR Newswire December 3, 2002 Tuesday Cephalon Receives Approval to Expand Marketing of Provigil in the United Kingdom; -Drug to be marketed for Obstructive Sleep Apnea Hypopnea Syndrome and Narcolepsy - SECTION: FINANCIAL NEWS LENGTH: 958 words DATELINE: WEST CHESTER, Pa. Dec. 3 Cephalon, Inc. (Nasdaq: CEPH) today announced that it has received marketing approval from the Medicines Control Agency (MCA) in the United Kingdom to expand the label of PROVIGIL(R) (modafinil) to treat excessive daytime sleepiness in patients with obstructive sleep apnea/hypopnea syndrome. The 200 mg tablet of PROVIGIL was also approved, in addition to the 100 mg dosage currently available in this territory. Cephalon UK Limited will officially launch the new indication at a symposium during the British Thoracic Society meeting being held December 4-6 in London. "We are pleased that the data used to support this label expansion was accepted by the UK regulatory authority," said Paul Blake, MB, FRCP, Senior Vice President of Clinical Research and Regulatory Affairs at Cephalon. "Achievement of this milestone will enable us to grow the market for modafinil in the United Kingdom and sets the stage for regulatory submissions in other European countries over the next year." The UK approval is the first of two regulatory milestones that Cephalon expects to achieve this year for PROVIGIL. Cephalon intends to file an application with the U.S. Food and Drug Administration at year-end seeking to expand the label of PROVIGIL to include treatment of excessive sleepiness associated with sleep disorders beyond narcolepsy. PROVIGIL Modafinil is the first in a new class of wake-promoting agents and is currently approved in more than 20 countries for the treatment of excessive daytime sleepiness associated with narcolepsy. PROVIGIL was initially launched in the UK in 1998 for the treatment of narcolepsy. In controlled clinical trials, PROVIGIL has been found to be generally well tolerated with a low incidence of adverse events relative to placebo. The most commonly observed adverse events associated with the use of PROVIGIL were headache, infection, nausea, nervousness, anxiety and insomnia. Obstructive Sleep Apnea Hypopnea Syndrome Obstructive sleep apnea/hypopnea syndrome is a serious and potentially life-threatening sleep disorder affecting four percent of middle-aged men and two percent of middle-aged women. Individuals with obstructive sleep apnea hypopnea syndrome experience frequent awakenings throughout the night as a result of blockage of the airway during sleep. This disruption of sleep leads to excessive daytime sleepiness causing many people to doze off repeatedly throughout the day -- at their jobs and at home. The most commonly used standard treatment is continuous positive airway pressure (CPAP). A nasal CPAP device can prevent airway closure while in use, but despite this treatment many patients continue to experience residual excessive sleepiness. Cephalon, Inc. Founded in 1987, Cephalon, Inc., is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products to treat sleep and neurological disorders, cancer and pain. Cephalon employs 1,200 people in the United States and Europe. The company markets three proprietary products in the United States and 22 products internationally. Full prescribing information on Cephalon's US products is available by calling 1-800-896-5855. Cephalon's biotechnology pipeline is focused on the identification of novel molecules that affect cell survival and death. Additional information about Cephalon and its subsidiaries can be obtained by visiting the company's Website at http://www.cephalon.com . Cephalon UK Limited has headquarters in Guildford and markets drugs to treat a number of central nervous system disorders. In collaboration with Novartis, Cephalon UK markets Tegretol(R) (carbamazepine), Ritalin(R) (methylphenidate), Anafranil(R) (clomipramine) and Lioresal(R) (baclofen). Also included in this collaboration is PROVIGIL (modafinil) for the UK. In addition, Cephalon UK also markets Gabitril(R) (tiagabine monohydrate) and Actiq (R) (fentanyl -- as citrate) in the UK and Ireland. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs, development of potential pharmaceutical products, interpretation of clinical results, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, sales and earnings projections, and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties such as those set forth below and in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion.                       MAKE YOUR OPINION COUNT - Click Here                http://tbutton.prnewswire.com/prn/11690X10888858 SOURCE Cephalon, Inc. CONTACT: Media: Sheryl Williams +1-610-738-6493, swilliam@cephalon.com, or Investors: Robert Chip Merritt, +1-610-738-6376, cmerritt@cephalon.com, both of Cephalon, Inc. URL: http://www.prnewswire.com LOAD-DATE: December 4, 2002 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS, MEDICAL AND HEALTH EDITORS PUBLICATION-TYPE: Newswire Copyright 2002 PR Newswire Association, Inc. 854 of 998 DOCUMENTS Pharma Marketletter November 11, 2002 Modafinil may have cognitive-enhancing effect LENGTH: 157 words Modafinil, the active ingredient in Cephalon's narcolapsy drug Provigil, may have a cognition-enhancing effect, according to a study from the Department of Psychiatry at the University of Cambridge, UK. Data showed that modafinil appears to improve certain mental abilities, without the common side effects noted by the use of other mental stimulants, such as amphetamine. Danielle Turner of the UoC took 60 healthy young men and tested them, using touch-sensitive computer screens and easy-to-understand computer games, after they had received either modafinil or placebo. "In the study, the volunteers given modafinil performed significantly better in neuropsychological tests involving short-term memory and showed less impulsive responding and an increased tendency to reflect on the tasks they were given," she added. Modafinil has also shown no evidence of addiction, one common side effect of mental stimulants. LOAD-DATE: November 12, 2002 LANGUAGE: ENGLISH Copyright 2002 Marketletter Publications Ltd. 855 of 998 DOCUMENTS Health Newswire Consumer November 5, 2002 Sleep drug "boosts brain" BYLINE: Deirdre Lee SECTION: Health Newswire Consumer LENGTH: 294 words HIGHLIGHT: A drug normally prescribed to treat sleep disorders also boosts certain mental abilities, a UK study suggests. Researchers at Cambridge University found that volunteers who took a medication called modafinil - normally prescribed for narcolepsy - showed improved ability in planning complex problems, recalling long strings of numbers and remembering abstract patterns. The discovery could lead to new treatments for people with conditions such as Attention Deficit Hyperactivity Disorder (ADHD), who suffer from selective impairments in memory, problem solving and planning, say researchers. The study involved 60 healthy young males who were tested using touch-sensitive computer screens and easy-to-understand "computer games" after they had taken either a dummy tablet (placebo) or modafinil. Researcher Danielle Turner from the Department of Psychiatry says, "In the study, the volunteers given modafinil performed significantly better at neuropsychological tests involving short-term memory, and showed less impulsive responding and an increased tendency to reflect on the tasks they were given." Of particular importance was the discovery that modafinil seemed to make people stop and think, say researchers. After taking it, the volunteers were significantly better at inhibiting impulsive responding and reflecting on problems. This could prove valuable for people with ADHD who have increased impulsiveness, say researchers. Encouragingly, modafinil also appeared to boost brainpower, with no evidence of addiction and fewer side effects than mental stimulants previously prescribed, like amphetamine. "The next important step is to confirm these positive effects on mental functioning (cognition) in patients," says Ms Turner. Future research will test whether young adults with ADHD show similar improvements to the healthy volunteers. LOAD-DATE: January 15, 2003 Copyright Health Media Ltd 2002 856 of 998 DOCUMENTS Health Newswire Consumer November 5, 2002 Sleep drug "boosts brain" BYLINE: Deirdre Lee SECTION: Health Newswire Consumer LENGTH: 294 words HIGHLIGHT: A drug normally prescribed to treat sleep disorders also boosts certain mental abilities, a UK study suggests. Researchers at Cambridge University found that volunteers who took a medication called modafinil - normally prescribed for narcolepsy - showed improved ability in planning complex problems, recalling long strings of numbers and remembering abstract patterns. The discovery could lead to new treatments for people with conditions such as Attention Deficit Hyperactivity Disorder (ADHD), who suffer from selective impairments in memory, problem solving and planning, say researchers. The study involved 60 healthy young males who were tested using touch-sensitive computer screens and easy-to-understand "computer games" after they had taken either a dummy tablet (placebo) or modafinil. Researcher Danielle Turner from the Department of Psychiatry says, "In the study, the volunteers given modafinil performed significantly better at neuropsychological tests involving short-term memory, and showed less impulsive responding and an increased tendency to reflect on the tasks they were given." Of particular importance was the discovery that modafinil seemed to make people stop and think, say researchers. After taking it, the volunteers were significantly better at inhibiting impulsive responding and reflecting on problems. This could prove valuable for people with ADHD who have increased impulsiveness, say researchers. Encouragingly, modafinil also appeared to boost brainpower, with no evidence of addiction and fewer side effects than mental stimulants previously prescribed, like amphetamine. "The next important step is to confirm these positive effects on mental functioning (cognition) in patients," says Ms Turner. Future research will test whether young adults with ADHD show similar improvements to the healthy volunteers. LOAD-DATE: March 31, 2003 Copyright Health Media Ltd 2002 857 of 998 DOCUMENTS Espicom Business Intelligence October 24, 2002 Cephalon achieves positive results in Provigil SWSD trial LENGTH: 195 words Results of Cephalon's clinical study evaluating Provigil (modafinil) C-IV in patients with shift-work sleep disorder (SWSD) showed statistical significance on both primary endpoints of the study. The 12-week, randomised, double-blind, placebo-controlled study included 209 patients with an international classification of sleep disorders (ICSD)-confirmed diagnosis of SWSD randomised to either modafinil 200mg or placebo. Patients in the study received modafinil or placebo as a single dose given prior to the start of their night shift. The study showed that modafinil significantly improved wakefulness compared to placebo, as measured by the Multiple Sleep Latency Test (MSLT), an objective measure of sleepiness (p<0.01). In addition, patients treated with modafinil showed significant improvement in their clinical condition as measured by the CGI-C when compared to patients treated with placebo (p<0.0001). Modafinil was well tolerated. The most commonly reported adverse events in this study were consistent with those described in the current product label. The complete study data are expected to be presented at a major medical meeting in 2003. LOAD-DATE: October 28, 2002 LANGUAGE: ENGLISH Copyright 2002 ESPICOM Business Intelligence Ltd. 858 of 998 DOCUMENTS The Sunday Times (Perth, Australia) October 6, 2002, Sunday US drug sales a wake-up call BYLINE: Liam Bartlett LENGTH: 800 words So much to do, there's plenty on the farm I'll sleep when I'm dead Saturday night I like to raise a little harm I'll sleep when I'm dead. -- Warren Zevon THE excitable boy had it just right. Hard workers or party animals with too much to do and not enough time to do it in have only one choice -- delay the shut-eye until you drop. Unfortunately, Zevon now has terminal lung cancer so his options are almost up but for the rest of the population, another possibility is coming soon to a pharmacy near you. From November, the Australian company CSL will sell a drug called Modafinil. In local chemist shops it will be marketed under the trade name Modavigil and if the American experience is any indication it is set to change the life of a lot more people than it was designed for. Modafinil has been dubbed the two-days-awake pill because it artificially shuts off your urge to sleep for at least 40 hours. The tablet that challenges Mother Nature was originally tested on US army helicopter pilots, allowing them to stay up safely for almost two days while remaining alert, focused and as capable of solving complex problems as the well rested. Then, after a good eight hours sleep, they can get up and do it again -- for another 40 hours, before finally catching up on their sleep. Researchers claim Modafinil has the potential to replace caffeine because it works without the jitter, buzz or addictive characteristics of caffeine and causes none of the euphoria, crash or potential for paranoid delusion of stimulants like amphetamines or cocaine. However, it does have the power to change the way we work and live and judging by its usage patterns, the social impact might already have begun. In the US, the sales of Modafinil have doubled over the past 12 months to $150 million. While that might not sound huge given the size of the US pharmaceuticals market it is certainly out of kilter with the drug's official reason for being. The US Food and Drug Administration has approved Modafinil marketing only to narcoleptics, who fall asleep frequently and uncontrollably. But at best estimate there are only 125,000 to 250,000 narcoleptics in America and yet the drug's owners are claiming that more than a million prescriptions have been written with sales now soaring. Similarly here in Australia the numbers people put narcoleptics around 16,000 -- hardly a huge market for CSL to bother buying the exclusive licence and shunting them into pharmacies at a wholesale price of $87.50 for 30 tablets. No doubt they are punting on a range of other possibilities that this drug, designed to help the sick, might have to augment the lives of the healthy. We've already seen this happen with Viagra, where the social ends up outweighing the medical. In a world of increasing competition where there never seems to be enough hours in the day, the potential for lifestyle usage is enormous. Think of the long distance truckies or the taxi drivers who would be tempted to see out a 40-hour shift in one hit. What about students cramming for exams or hospital and emergency service personnel who are already burning the candle at both ends? I can imagine the odd Canberra lobbyist who would love to sit on the end of a phone for two days without blinking. And the expression "shop-till-you-drop" could take on an alarming new dimension come Christmas. More seriously, perhaps the whole concept of what is a "normal" human capability is at stake as people are tempted to control their sleep in order to be more competitive. One could speculate that this medicine and other modified forms that will undoubtedly follow, could create even more demand for people to be available around the clock. Nobody is saying exactly how Modafinil works and its long-term effects are largely unknown, but researchers marvel at the way it seems to target specific regions of the brain believed to regulate normal wakefulness. The US FDA has already had to warn Modafinil's owners, Cephalon that their promotional material was overreaching their approved target of narcoleptics. But in this country there are no such conditions placed on marketing under its inclusion on the Australian Register of Therapeutic Goods. Other than requiring a prescription from your local doctor, the great awakening is easy at $3 a pop, plus whatever retail margin the pharmacists decide to add. And this could be just the start. More drugs in the pipeline include those that attack shyness, forgetfulness and the mental decline of ageing. Others add muscle mass and boost the ability to learn -- at least in mice. But even mice need their sleep. Or do they? *  Liam Bartlett hosts the Statewide Morning Program on ABC Radio. Email: liam@your.abc.net.au LOAD-DATE: October 5, 2002 LANGUAGE: ENGLISH JOURNAL-CODE: SDT Copyright 2002 Nationwide News Pty Limited 859 of 998 DOCUMENTS Deseret News (Salt Lake City) September 22, 2002, Sunday Narcolepsy pill may emerge as 'lifestyle' drug of the busy BYLINE: By Carey Goldbert The Boston Globe SECTION: WIRE; Pg. A08 LENGTH: 1327 words Just to see what it was like, the Cambridge computer programmer stayed awake four straight days. He felt fine, he reported later, not jittery, nicely focused. "Imagine," he wrote in an e-mail, "having all the time you could want to goof off, knowing that you still have just as much time as usual to spend on things you have to do." On the other hand, he added, "if you lack imagination and run out of things to do, you could end up bored real fast." The programmer, who asked that he not be identified, has not repeated his "little experiment," partly because of its questionable legality. To stay awake, he borrowed a prescription drug, modafinil, that is meant for narcoleptics, whose affliction causes excessive sleepiness. But he appears to have plenty of company in his desire to cheat time by cheating sleep. In the three years since the drug was introduced under the brand name Provigil for narcolepsy, sales have skyrocketed to more than 250,000 prescriptions every three months, outstripping the needs of the nation's estimated 150,000 narcoleptics. Cephalon, the company that makes Provigil, says the seemingly excess prescriptions mainly go to patients with other diseases that cause fatigue. But the buzz about modafinil as a potential elixir for millions of "sleep when I die" Americans has been building for months. Some predict it may become the next Viagra or Prozac, the next "lifestyle drug." Sleep specialists hate that idea. Though modafinil causes few side effects, they say, and though it shows little potential for addiction, using it lightly to deprive the body of sleep, especially long-term, is asking for trouble. Nonetheless, talk about modafinil has been spreading, including debates online and in print about whether such a pill could be a dream come true for the underslept or a nightmare for a society that is already running too fast. A Washington Post reporter who tried staying up for two days on Provigil gave it warm reviews in the paper, writing that "Modafinil may have the power to change Washington, D.C., and other high-powered cities." But then, he wrote that story during a 40-hour period of modafinil-enhanced wakefulness, so his judgment may have been affected. Modafinil is believed to target areas of the brain responsible for maintaining wakefulness more precisely than caffeine or other stimulants, so it does not bring on a wired feeling or later crash, but experts say it does not completely do away with all the mental impairment that comes with sleep deprivation. The military, too, has added to the attention paid modafinil by reporting publicly that it has been testing the drug as "performance enhancement" for combatants who must stay awake for days. It turned out that they could function well for 40 hours, sleep eight hours, and then get up and go another 40 hours before needing rest. For all the talk, however, it remains unclear how much Provigil is already being used by otherwise healthy sleep-cheaters. Since the biotech firm Cephalon introduced Provigil in early 1999, the drug's sales have jumped to a rate of $200 million per year if current sales keep up. Quarterly sales are up about 70 percent over last year, and prescriptions are now running at the rate of 250,000 in a three-month period, according to IMS Health, a health information company. Those numbers seem particularly high given that there are only an estimated 150,000 narcoleptics in the country. And company officials have acknowledged that perhaps only a quarter of the prescriptions are going to narcoleptics. But they also say that they are not encouraging the use of Provigil by people who do not need it, and they have no indication that it is being widely abused. Rather, they believe it is being prescribed "off-label" by doctors to help patients with a variety of sleep disorders. And they are seeking approval from the Food and Drug Administration to broaden Provigil's label to include a wider variety of diseases that cause fatigue. However, there is anecdotal evidence of a nonmedical demand for Provigil. For example, Dr. Richard J. Castriotta, a sleep expert at the University of Texas, said that a handful of people have asked him for a Provigil prescription just to perk them up, but he has refused them. Meanwhile, Web sites offer to sell Provigil without a prescription. Modafinil may be OK for pilots or emergency workers, Castriotta said, but it would be wrong "to make that leap and say, 'Well, gosh, why can't I just sleep three hours a night as a way of life?' We don't know enough about sleep deprivation to be able to determine what the long-range effects might be, and that's very, very dangerous." He and other researchers predicted that in any case, because Provigil is a controlled substance, and because it brings users no euphoria, it is unlikely to be very widely abused. But in a country where more than half the population is averaging more than three cups of coffee per day, it does seem to have broad potential appeal -- particularly for the truckers and students and new parents and others whose lives sometimes require all-nighters. International Antiaging Systems, a company that has one of the offshore pharmacy Web sites that sell modafinil, says that its modafinil sales have at least doubled in the last year, but it would not specify the numbers involved. A swath of studies, many sponsored by Cephalon, are underway to see if Provigil might help patients with the fatigue caused by diseases ranging from multiple sclerosis to attention deficit to sleep apnea to depression. Much of the initial research shows tentative promise. Another set of extensive studies is looking at whether modafinil will help shift workers who have to stay awake at times when their bodies beg to sleep. Their numbers are estimated at about 15 million. Provigil's side effects tend to be mild, Cephalon says, with headache and nausea the most common. It can also interact poorly with some other drugs; in particular, it can reduce the effects of birth control pills. The prospect of Provigil or even better "wake-enhancing" drugs gaining broad usage deeply concerns sleep specialists like Dr. Thomas Scammell of Beth Israel Deaconess Medical Center, a leading authority on modafinil. "For society, it does bring up a really key question," he said. "The simplest way to answer it is to say, 'If I could give you a pill that would take away your hunger, does that mean you shouldn't eat?' Well, duh, you've got to eat and you know why, because you'll waste away." "The problem," he added, "is that the science of sleep research hasn't reached the point that we can say, 'If you don't get enough sleep, X, Y, and Z will happen to you." However, a growing body of research does indicate that lack of sleep may be even more harmful than previously thought. It may be contributing to obesity by changing the metabolisms of the underslept and to heart disease by causing low-grade inflammation. But Americans are nonetheless sleeping less and working more, according to the National Sleep Foundation. Its polls have found that Americans sleep an average of about seven hours a night during the work week, an hour and a half less than in 1900, and that one third of adults are so sleepy in the daytime they could be dangerous. Federal highway officials say lack of sleep causes 100,000 crashes a year. To Dr. Daniel F. Kripke, a sleep expert at the University of California at San Diego, excitement over a new drug like modafinil is neither new nor very exciting -- not to a veteran doctor who remembers when cocaine and amphetamines spurred similar reactions. "I think it is a promising drug but it has only been tested a little," said Dr. Kripke, whose own research suggests that people who sleep somewhat less than average may live longer. "I'm very much in favor of broader scientific testing," he said, "but I'm not in favor of people jumping off the deep end." LOAD-DATE: September 22, 2002 LANGUAGE: ENGLISH Copyright 2002 The Deseret News Publishing Co. 860 of 998 DOCUMENTS Espicom Business Intelligence September 17, 2002 Positive results for Provigil ADHD study LENGTH: 181 words Cephalon has released results from an investigational, multi-centre study in 248 children aged between 6 and 13 years. The results show that Provigil (modafinil) tablets significantly improves symptoms of attention deficit hyperactivity disorder (ADHD) in children. In the 4-week, randomised, double-blind, placebo-controlled, parallel design study, children and adolescents with ADHD were assigned to 1 of 4 dose regimens of modafinil daily or placebo. The primary efficacy endpoint measure was the teacher-completed school version of the ADHD Rating Scale IV. All of the modafinil-treated groups showed a reduction in symptoms of ADHD, with certain groups reaching statistical significance compared to placebo (p<0.05). The greatest significance was achieved in the group assigned to modafinil 300mg once daily (p<0.01). The drug was generally well tolerated and the side effects seen were consistent with those described in the product label, with insomnia being the most frequent. The complete study data are expected to be presented at a major medical meeting in 2003. LOAD-DATE: October 3, 2002 LANGUAGE: ENGLISH Copyright 2002 ESPICOM Business Intelligence Ltd. 861 of 998 DOCUMENTS Espicom Business Intelligence September 17, 2002 Positive results for Provigil ADHD study LENGTH: 181 words Cephalon has released results from an investigational, multi-centre study in 248 children aged between 6 and 13 years. The results show thatProvigil (modafinil) tablets significantly improves symptoms of attention deficit hyperactivity disorder (ADHD) in children. In the 4-week, randomised, double-blind, placebo-controlled, parallel design study, children and adolescents with ADHD were assigned to 1 of 4 dose regimens of modafinil daily or placebo. The primary efficacy endpoint measure was the teacher-completed school version of the ADHD Rating Scale IV. All of the modafinil-treated groups showed a reduction in symptoms of ADHD, with certain groups reaching statistical significance compared to placebo (p<0.05). The greatest significance was achieved in the group assigned to modafinil 300mg once daily (p<0.01). The drug was generally well tolerated and the side effects seen were consistent with those described in the product label, with insomnia being the most frequent. The complete study data are expected to be presented at a major medical meeting in 2003. LOAD-DATE: October 3, 2002 LANGUAGE: ENGLISH Copyright 2002 ESPICOM Business Intelligence Ltd. 862 of 998 DOCUMENTS Espicom Business Intelligence September 2, 2002 Modafinil cleared for marketing in Australia, New Zealand and South Korea LENGTH: 142 words Cephalon has been granted marketing approval formodafinil in Australia, New Zealand and South Korea. Cephalon licensees,CSL in Australia and New Zealand andChoongwae in Korea, will market modafinil under the brandnames,Modavigil andProvigil, respectively. Approved for the treatment of excessive daytime sleepiness associated with narcolepsy, the launch of the products in these markets is expected to occur within 6 months. Cephalon markets modafinil as Provigil tablets in the US and other countries. Modafinil is approved worldwide in >20 countries. It is the first drug in a new class of wake-promoting agents, which improve daytime wakefulness yet preserve the ability to sleep at night. The most common side effects associated with Provigil in clinical trials include headache, nausea, infection, nervousness, anxiety and insomnia. LOAD-DATE: October 3, 2002 LANGUAGE: ENGLISH Copyright 2002 ESPICOM Business Intelligence Ltd. 863 of 998 DOCUMENTS PR Newswire August 30, 2002 Friday Cephalon Announces Modafinil Receives Marketing Clearance In Australia, New Zealand and South Korea SECTION: FINANCIAL NEWS LENGTH: 834 words DATELINE: WEST CHESTER, Pa. Aug. 30 Cephalon, Inc. (Nasdaq: CEPH), an international biopharmaceutical company, announced today that regulatory authorities have granted marketing approval for modafinil in Australia, New Zealand and the Republic of Korea. Cephalon licensees, CSL Limited in Australia and New Zealand and Choongwae Pharma Corporation in the Republic of Korea will market modafinil under the brand names of MODAVIGIL(R) and PROVIGIL(R) respectively. Approved for the treatment of excessive daytime sleepiness (EDS) associated with narcolepsy, launch of the products in these markets is expected to occur within six months. Worldwide, modafinil is approved in more than 20 countries. "PROVIGIL continues to experience significant growth in the United States and European markets, and our partnerships with CSL and Choongwae provide the opportunity to extend this growth into the Asia/Pacific region," said Robert Roche, Senior Vice President, Pharmaceutical Operations at Cephalon. Cephalon markets modafinil as PROVIGIL(R) (modafinil) tablets $(C-IV$) in the United States and other countries. PROVIGIL is the first drug in a new class of wake-promoting agents, which improve daytime wakefulness yet preserve the ability to sleep at night. The most common side effects associated with PROVIGIL in clinical trials include headache, nausea, infection, nervousness, anxiety and insomnia. CSL Limited CSL Limited (ASX: CSL) is Australia's largest domestic pharmaceutical company. CSL develops, manufactures and markets biological products for human use and markets vaccines and other prescription pharmaceuticals in Australia and New Zealand. The prescription pharmaceuticals include antibiotics, dermatologicals emergency products, neurological products, analgesic products, and urological products supplied by other manufacturers. Choongwae Pharma Choongwae Pharma is a leading pharmaceutical company whose products include cardiovascular and anti-cancer agents, biological products, intravenous solutions and other healthcare products. Recognized as one of the most preferred pharmaceutical companies in Korea by its customers, Choongwae Pharma is committed to providing premium-quality pharmaceutical products and services. Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products to treat sleep and neurological disorders, cancer and pain. Cephalon currently employs approximately 1,200 people in the United States and Europe. U.S. sites include the company's headquarters in West Chester, Pennsylvania, and offices and manufacturing facilities in Salt Lake City, Utah. Cephalon's major European offices are located in Guildford, England, and at Laboratoire L. Lafon in Maisons-Alfort, France. The company currently markets three proprietary products in the United States: PROVIGIL(R) (modafinil) Tablets $(C-IV$), GABITRIL(R) (tiagabine hydrochloride) and ACTIQ(R) (oral transmucosal fentanyl citrate) $(C-II$) and more than 20 products internationally. Further information about Cephalon and full prescribing information on its U.S. products is available at www.cephalon.com or by calling 1-800-896-5855. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs, development of potential pharmaceutical products, interpretation of clinical results, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, sales and earnings guidance, and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion.                      MAKE YOUR OPINION COUNT - Click Here                http://tbutton.prnewswire.com/prn/11690X71363274 SOURCE Cephalon, Inc. CONTACT: Sheryl Williams of Cephalon, +1-610-738-6493, or cell, +1-484-432-0046, swilliam@cephalon.com URL: http://www.prnewswire.com LOAD-DATE: August 31, 2002 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS AND MEDICAL EDITORS PUBLICATION-TYPE: Newswire Copyright 2002 PR Newswire Association, Inc. 864 of 998 DOCUMENTS The Jerusalem Post August 25, 2002 Sunday Still sick, but not as tired BYLINE: JUDY SIEGEL-ITZKOVICH SECTION: HEALTH; Pg. 9 LENGTH: 611 words HIGHLIGHT: Rx FOR READERS I am a 47-year-old woman and have suffered from relapsing-remitting multiple sclerosis for over 10 years. I take Copaxone by injection. Fortunately, I am in good condition and have only negligible neurological deficits My only symptom is tiredness. I have to sleep several hours in the afternoon, and it reduces my time for activity. It's as if the disease takes over my body and makes my brain tired. Is there any treatment for this type of MS-induced narcolepsy that does not have annoying side effects? S.P., Beersheba Prof. Avinoam Reches, chairman of the Israel Neurology Society and a senior neurologist at Hadassah-University Hospital in Jerusalem's Ein Kerem, says: Narcolepsy in multiple sclerosis patients occurs quite often, but we don't understand the mechanisms. The amount of rest that patients need varies. We prescribe the drug Provigil, which is generically known as modafinil and manufactured by the Cephalon company. It has no negative interaction with the injectible Teva drug for MS, Copaxone, but if you take other drugs, you should consult with your doctor. Modafinil is given not only for sleepiness during the day in MS patients, but also to those who sleep due to other conditions. It promotes daytime wakefulness without affecting nighttime sleep, and has been found to be well- tolerated, with only mild to moderate side effects in a minority of users. The pill should be taken in the morning to help you stay awake during the day , but it is a prescription drug, and your daily dose and schedule should be determined by your doctor. As a complication of flu, my husband suffered hearing loss and developed tinnitus. A composer, singer, and lover of music, he was understandably distraught. A few months later, loud noises like shouting or car horns began to cause him acute pain. Three Tel Aviv-area ear specialists found no organic reason for the pain. They could not even give a name to what he had, but we later got a diagnosis, "hyperacusis," from an Israeli doctor on the Internet. My husband started wearing ear plugs to block out noise (though I warned him that this would make him only more sensitive and intolerant toward even "normal" noise) and two years later he cannot go out of the house, or even sit in a quiet room with a couple of people, without ear plugs. As far as he is concerned, he has this problem under control. I worry, though, especially as we're planning to have children, and I don't want our baby to see ear plugs as the norm or, worse, to always have to "be quiet around Daddy." Moreover, I find there are inconsistencies and emotional elements in his response to noise that suggest his problem is psychological/neurological. What can be done, and what kind of specialist deals with this condition? R.E. Tel Aviv Prof. Rafi Feinmesser, head of the ear, nose and throat department at the Rabin Medical Center-Beilinson Campus in Petah Tikva, replies: When hyperacusis occurs, it is usually due to damage to the auditory nerve. The nervous system reacts in a compensatory way by creating increased auditory signals, so the patient hears more noise. It is not a psychiatric problem. Your husband subjectively hears more noise. Earplugs could help him. It's also possible that biofeedback or auto-suggestion could improve his situation. His is certainly an extreme case, but every ear,nose and throat specialist knows of hyperacusis. Go to another expert for help. Rx For Readers welcomes queries from readers. Write Rx For Readers, The Jerusalem Post, POB 81, Jerusalem 91000, fax your question to Judy Siegel-Itzkovich at (02) 538- 9527, or e-mail it to jusie@jpost.co.il, giving initials, age and place of residence. LOAD-DATE: October 4, 2011 LANGUAGE: ENGLISH GRAPHIC: Photo: Taking a nap is great, but narcolepsy requires a pill. PUBLICATION-TYPE: Newspaper Copyright 2002 The Jerusalem Post All Rights Reserved 865 of 998 DOCUMENTS National Post (Canada) August 14, 2002 Wednesday National Edition Could this be the new lifestyle drug?: Narcolepsy medicine tested for use on the healthy but sleep-deprived SOURCE: National Post BYLINE: Sharon Kirkey SECTION: Arts & Life; Pg. AL1 LENGTH: 1625 words Patients who come to see Dr. Roger Broughton are the sort who might fall asleep in their car waiting for the light to change. They might doze off in the middle of a conversation or while taking a shower or walking in the mall. A strong emotion, even laughter, can make their bodies go as slack as a rag doll. They suffer from narcolepsy, a rare condition characterized by the overwhelming and irresistible urge to sleep, no matter what people do to try to stay awake. Several years ago, Dr. Broughton, a professor of neurology at the University of Ottawa, was the lead investigator in a multi-centre Canadian trial that found a new drug called modafinil could keep people with narcolepsy awake and alert with less of the jitteriness, agitation and other side effects of amphetamines and other central nervous-system stimulants. For many people with narcolepsy, modafinil has now become "the best stimulant they've ever been on," reports Dr. Broughton, who is also director of the Sleep Medicine Centre at The Ottawa Hospital's General Campus. But it's what the pill might do for everyone else that has people really buzzing. Researchers have begun testing the medicine's effects on shift workers, soldiers, long-haul truck drivers and rescue workers. In one trial involving U.S. Army helicopter pilots, modafinil kept the aviators alert and able to perform complicated manoeuvres on flight simulators during two days and one night without sleep. The study was conducted to measure modafinil's effect on sleep-deprived "normals" -- otherwise healthy volunteers required to perform demanding tasks despite sleep loss. If the drug can keep pilots clear-headed during two 40-hour periods of continuous wakefulness, what might it mean for a country where at least half of the population is suffering from sleep deprivation? Could modafinil soon become the ultimate lifestyle drug: a pill we can pop to dodge our body's need for sleep, a way of cramming more into our increasingly and dangerously over-extended lives? The Canadian distributors of modafinil (sold as Alertec in Canada, and Provigil in the United States) insist the drug "clearly is not intended" for such purposes. (However, the U.S. Food and Drug Administration criticized modafinil's U.S. manufacturer, Cephalon, earlier this year, for using sales aids and journal ads that suggested the drug is safe and effective "for anyone with daytime sleepiness.") "While [Alertec] has an effect on alertness and there may be applications beyond narcolepsy, I don't see it becoming a drug you go [to your doctor] and ask for" for non-therapeutic indications, says Dan Brazier, president of DRAXIS Pharmaceutica Inc., which holds the exclusive Canadian licence to market and sell Alertec. So far, the drug is only approved in Canada for the treatment of narcolepsy. But once a drug is approved for a specific use, physicians can prescribe it for other purposes, a common and legal practice called "off-label" prescribing. According to The Washington Post, three-quarters of the US$150-million worth of modafinil tablets sold in the United States last year "were swallowed by people who didn't have narcolepsy." In Canada, Brazier will say only that Alertec's sales are growing, though not to the extent that they are in the U.S., where more than 700,000 prescriptions for the drug have been written since it was approved in 1999. And, says Brazier, based on the evidence from France, Germany and other countries where modafinil has been available for years, there is no evidence "to suggest that non-therapeutic use is being sought out." But as researchers begin testing the drug on an ever-broadening array of problems, where will doctors draw the line? "Pharmacological developments like modafinil will pose great temptations to society," warned David Dinges, a University of Pennsylvania sleep-deprivation researcher, recently in the Houston Chronicle. "They'll have the potential to satisfy our relentless desire to control time." Some doctors in Canada have already prescribed modafinil for off-label purposes. Dr. Jon Fleming, the co-director of the Sleep Program at University Hospital in Vancouver, says he has, on occasion, written prescriptions for Alertec to treat jet lag, and for shift workers who are at risk of dozing off during the drive to or from work. But those are "one-off" situations, Dr. Fleming says. "Like all clinical situations, you have to assess impairment, and then assess risks and benefits," he says. "The important thing for anybody who has sleepiness is to identify the cause. If the cause relates to lifestyle issues and insufficient nocturnal sleep, the treatment should always be to try and improve nocturnal sleep." Yet studies show people just aren't spending enough time in bed, says Dr. Fleming. The amount of sleep an individual needs is highly variable; some can get by on six hours a night, others may need closer to 10 hours. But in general, doctors typically recommend adults get eight hours of sleep nightly. A recent U.S. study, however, found one-third of those surveyed were getting less than six hours of sleep a night. Ironically, almost half of those polled said they are sleeping less in order "to be more productive." But sleep debts eventually catch up. "A lot of us don't use the top 10% of our brain most of the day --we're not called upon to do original artwork or think up a computer game -- so, if you're doing the laundry or walking to the mailbox, you can get by fine," says Dr. Judy Leech, a sleep physician at The Ottawa Hospital. "But the memory, the concentration, the originality part of the brain is the first to go when you don't have sleep. Those guys in Silicon Valley, when they were putting bunks in their offices? It was like this big new discovery suddenly that sleep is something people need to perform better." No one knows sleep's exact function. "We know obviously that if you don't have any, if you have absolutely none, probably within two or three weeks you would become psychotic," Dr. Leech says. But researchers believe sleep has a restorative effect on all body functions. For example, growth hormones peak at night during sleep. So do parts of the immune system. "You even make more bone at night," says Dr. Leech. Osteocalcin, which increases bone turnover, is higher at night. "So lots of things are going on and, if you sort of screw those up, I'm not saying you won't grow, but you know how you feel lousy if you don't sleep? It might not just be the lack of sleep, it might be because you disturbed all the other hormones," says Dr. Leech. Studies involving shift workers have found the sleep-deprived workers tend to get sick more frequently and are at a greater risk for high blood pressure, weight gain and gastrointestinal problems than workers who get more sleep. In addition, it's during sleep that we put down memory, filing it from the short-term to the long-term "hard drive," Dr. Leech says. "That's how come when you practice the piano today, you play better tomorrow." Modafinil caused a stir in the sleep research field when it was approved in the United States and Canada several years ago. The drug was heralded as the first new drug since 1959 to be approved for the treatment of narcolepsy. According to the journal American Family Physician, the drug's exact mechanism is unknown, but studies done on animals found it acts on the area of the brain that controls wakefulness and helps regulate the body's internal biological clock. It also appears to cause less agitation, anxiety and insomnia than Ritalin and amphetamines, the traditional treatments for narcolepsy, "and may have less potential for abuse": Patients report that they don't get the same high as they do with other stimulants. Finally, it doesn't interfere with nighttime sleep, or leave people with the hangover effects of other stay-awake pills. "Side effect-wise," says Dr. Leech, modafinil "is pretty minimal." For example, the drug doesn't increase blood pressure. The most common complaints are headache. "But there still could be long-term side effects that are untoward that we don't know of," she says. For that reason, Dr. Leech and others maintain that the drug should be reserved for those with a bona fide sleep disorder, or other medical problems that can cause excessive sleepiness either due to the illness itself or the drugs used to treat it. For example, modafinil is being tested to treat chronic daytime fatigue in patients with multiple sclerosis, sleep apnea and Parkinson's. Dr. Leech concedes that "In some things like shift work, where, obviously, people don't sleep the correct number of hours, maybe [modafinil] would fit in." As for people who have deliberately deprived themselves of sleep, Dr. Leech would advise they need to take better control of their lives. "I think it's pretty superficial to say, 'Oh well, I'll take Alertec to stay awake," she says. Some basic sleep hygiene can help people get the most out of the time they do spend in bed: Always have the same wake-up time. "People focus on the bedtime but the main thing is the get-up time," Dr. Leech says, "because that's what really sets your internal clock." Keep the bedroom for sex and sleep (no television, no Internet). Avoid caffeine later in the day. Cigarettes and alcohol are equally stimulating -- alcohol may help people fall asleep, "but as you withdraw from it in the night, it gives you worse sleep, so you're tossing and turning at 3 a.m.," says Dr. Leech. Keep the bedroom cool and dark. "We all don't get enough sleep at times. It's a function of society," says Dr. Leech. "But I'd prefer my pilot was well rested rather than had a chemical stimulant to stay awake." LOAD-DATE: August 14, 2002 LANGUAGE: ENGLISH GRAPHIC: Black & White Photo: Adrian Dennis, Agence France-Presse; Researchers have begun testing the effects of modafinil on such sleep-deprived workers as long-haul truck drivers, soldiers and U.S. Army helicopter pilots. TYPE: News Copyright 2002 National Post, All Rights Reserved 866 of 998 DOCUMENTS CBS News Transcripts July 9, 2002 Tuesday SHOW: The Early Show (7:00 AM ET) - CBS Checking the efficacy of Modafinil, the drug that is supposed to help people stay awake and alert for extended periods ANCHORS: JANE CLAYSON BYLINE: TRACY SMITH LENGTH: 1020 words JANE CLAYSON, co-host: If you've ever wished for more hours in the day, a new drug could help turn back the clock. Our Tracy Smith decided to see how it works so well. Tracy, hi. TRACY SMITH reporting: Be careful what you wish for. CLAYSON: I'm not sure I want to do this. I'm not sure I want to stay awake for 40 hours. SMITH: I'm not sure whether I could. Modafinil is a drug that's used for sleeping disorders, and it's now being tested as a way to keep people awake safely for up to 40 hours. So does it work? Well, as I said, it's still being tested, but with my doctor's consent, I conducted a little test of my own. Think of it as time in a bottle. One little pill and up to 40 straight hours without sleep. Coffee can give you the jitters; Modafinil can keep you alert, jitter-free, all day and all night, maybe. 'Dizziness, mental mood changes, loss of appetite, dry mouth.' Like any drug, it may not agree with you. 'Nausea, diarrhea or headache may occur.' Those are the most common. And the label can be confusing. 'Report promptly trouble sleeping.' Trouble sleeping? I thought that was the whole point! But the best way for me to see if it worked was to take one and see what happened. On the last Monday morning in June, I got up with Julie. Morning, Julie. All right, it is 4:30 AM. Here's to the next 40 hours. The idea was to work a normal day and see just how long I could stay alert. I'm excited because I'm thinking about all the things that I can do with this extra time. Well, for me it's an extra eight or nine hours every night that I could be doing something else. Part of this assignment was a flight to Houston, Texas, to talk to someone who's testing the drug on people who work the night shift. Mr. MAX HIRSCHKOWITZ (Sleep Researcher): I don't care how good your exercise program is or how good your nutritional program is, if you don't get enough sleep, you feel like crap. SMITH: And there's nothing--no drug that--at the present... Mr. HIRSCHKOWITZ: Not at the present time. SMITH: ...that's going to fix that. Mr. HIRSCHKOWITZ: Not at the present time. SMITH: Somehow, just hearing him say that made me feel like turning in. But oh, the night was still young. Unidentified Man: America stays up late, and I'm one of those people who serve the people that stay up late, and I'm proud of it. SMITH: Houston after dark is like any other big city. An army of night workers drive the trucks, wait the tables and staff the hospitals. They have their own ideas about staying awake without taking a pill. Mr. LEROY BECK (Houston VA Medical Center): Trying to find something to do to keep myself busy. That's probably the main thing, staying busy. If you can do that, I think you can make it. Unidentified Man: Anything that allows you to stay up for two or three days, isn't that--that seems unnatural to me. Mr. BECK: Don't look at the clock. You know, just keep working and working. Unidentified Man: Now maybe if I was doing a job that required me to be really, really alert, I might consider it, where other lives were at stake, but I serve sandwiches. Mr. BECK: I myself, I like coffee when I'm really sleepy. SMITH: How much coffee? Mr. BECK: Oh, like a ton of coffee. You know, we go through pots of coffee. SMITH: By half past midnight, a pot of coffee sounded pretty good to me. I still felt alert, but I was beat. All right. So it is 1:15 AM Houston time. I was up at 3:30 AM New York time, which would be 2:30 AM here, so carry the one--that's just about 23 hours that I've been up now. How do I look? Don't answer that. The truth is, I looked like I felt: exhausted. A key feature of Modafinil is that it allows you to sleep if you want to, and by 2 AM, I wanted to. By 3, I did. Seriously, people shouldn't look at this as a replacement for their five cups of coffee, for those who do drink that? Mr. HIRSCHKOWITZ: Not at this point. Not at this point. SMITH: Someday? Mr. HIRSCHKOWITZ: Perhaps. SMITH: Now it didn't work for me right away, but your experience could be different. When the Army tested Modafinil on helicopter pilots, they were able to stay up for days and perform in simulators almost as well as they did with a full night's sleep. For more about Modafinil Go to WWW.CBSNEWS.COM CLAYSON: So I'm with the guy who says it seems unnatural. There have to be side effects here, as well. SMITH: The short-term side effects are nausea, headache, dizziness. I didn't get any of those. I felt terrific. Long-term effects, they don't know yet. This drug came out in 1998... CLAYSON: Right. SMITH: ...so nobody knows. CLAYSON: So did they find out or did they tell you why it didn't work so well on you? SMITH: Well, the problem is when I interviewed the doctor, I still thought it was working, and then he started talking about the placebo effect, and then I started thinking, 'Oh, maybe--maybe I'm not really awake' and I think I crashed after that. CLAYSON: Right. Right. How addictive is it, is the question? SMITH: It's not. It doesn't make you high. You feel perfectly normal, so there's no addictive qualities, physically. Now psychologically could be different. CLAYSON: Right. So this is now only being prescribed to narcoleptics. SMITH: That's right. CLAYSON: And if you want to get a prescription... SMITH: You can ask your doctor. CLAYSON: ...it's not FDA-approved yet. SMITH: No, but you can ask your doctor and they could approve it just like Botox was prescribed before it was approved, for wrinkles. CLAYSON: Would you do it again? SMITH: I might if I had a crucial interview or something and I was up the night before, might take it. CLAYSON: And you felt OK. SMITH: I have two extra ones here, so... CLAYSON: Oh! Stay away. I don't want it. Tracy, it's an interesting story though, thank you. SMITH: No problem. CLAYSON: And good to see you. 7:37 now. Up next, two best-selling authors who also happen to be mother and daughter. We're back with that on THE EARLY SHOW after this. (Announcements) LOAD-DATE: July 9, 2002 LANGUAGE: ENGLISH TYPE: Analysis Copyright 2002 CBS Worldwide Inc. All Rights Reserved 867 of 998 DOCUMENTS CNBC News Transcripts July 8, 2002 Monday SHOW: Early Today (4:30 AM ET) - CNBC Researchers debating use of drug to keep people awake longer ANCHORS: NANETTE HANSEN BYLINE: Dr. IAN SMITH LENGTH: 392 words NANETTE HANSEN, anchor: Welcome back. I am told sleep is a basic need for everybody. We seem to do without it on this shift, though. Seventy million Americans have trouble sleeping. But if given the option, would you stay awake longer to get more done if there were few side effects? NBC's Dr. Ian Smith takes a look at a controversial drug that might help the sleep deprived stay awake. Dr. IAN SMITH reporting: Now a provocative question has been raised among sleep researchers about whether a medicine being tested to treat excessive daytime sleepiness might be misused by otherwise healthy people who just want to stay awake. The drug is modafinil, marketed as Provigil, already approved to treat narcoleptics like Juliet Block. Ms. JULIET BLOCK: It helps a lot, and it--it gets me through the day, like anyone else could get through the day. SMITH: Modafinil is different from older stimulants, which affect the central nervous system and can leave users nauseous or jittery. Instead, it acts only on the hypothalamus, the area of the brain which houses the sleep center. It can keep people awake and alert for extended periods of time. That quality has even led the military to give it to pilots on some combat missions. The company which makes modafinil is funding studies in the hopes of getting FDA approval to use it for other sleep disorders. Neurologist Dr. Thomas Scammel says the very attributes that make modafinil so effective in treating sleep disorders may invite trouble. Dr. THOMAS SCAMMEL (Harvard Medical School): If you have a drug with minimal side effects that can help keep people awake, there's a real temptation for people to work longer hours, to perhaps stay up all night if this drug can easily make that possible. Unidentified Man: It's essential to life. It's as essential as breathing. It's essential as the beat of your heart and there's nothing that will replace it. No drug, no substance--not caffeine, no vitamins, no herbs. It's gotta be sleep. SMITH: Especially since recent studies show that sleep deprivation doesn't just make us drowsy, but increases our risk for diabetes and hormonal imbalances. So while these powerful medications may keep us going longer, there's no masking the long-term effects sleeplessness can have on our bodies. Dr. Ian Smith, NBC News, New York. LOAD-DATE: July 8, 2002 LANGUAGE: ENGLISH TYPE: Newscast Copyright 2002 CNBC, Inc. 868 of 998 DOCUMENTS NBC News Transcripts July 7, 2002 Sunday SHOW: NBC Nightly News (6:30 PM ET) - NBC New medicine to help sleeplessness might be misused by people who want to stay awake ANCHORS: JOHN SEIGENTHALER BYLINE: Dr. IAN SMITH LENGTH: 509 words JOHN SEIGENTHALER, anchor: Now to LIFELINE and something we all need and never get enough of--sleep. TEXT: NIGHTLY QUESTION PROBLEM SLEEPING? A 50 MILLION B 70 MILLION C 100 MILLION SEIGENTHALER: This week's Newsweek magazine devotes its cover to the subject and gives us the answer to our NIGHTLY QUESTION, which is B. Seventy million Americans have trouble sleeping. And now there is a drug that might be used to help the sleep deprived to stay alert. Here's NBC's Dr. Ian Smith. Dr. IAN SMITH reporting: Twenty-first century America now working around the clock, squeezing out every precious minute to stay awake, but at a cost. Dr. GARY ZAMMIT (Sleep Disorders Institute, St. Lukes Roosevelt Hospital Center): We know that people who are sleep deprived are not functioning at peak. SMITH: Now, a provocative question has been raised among sleep researchers about whether a medicine being tested to treat excessive daytime sleepiness might be misused by otherwise healthy people who just want to stay awake. The drug is modafinil, marketed as Provigil, already approved to treat narcoleptics like Juliet Block. Ms. JULIET BLOCK: It helps a lot, and it--it gets me through the day like anyone else could get through the day. SMITH: Modafinil is different from older stimulants which affect the central nervous system and can leave users nauseous or jittery. Instead, it acts only on the hypothalamus, the area of the brain which houses the sleep center. It can keep people awake and alert for extended periods of time. That quality has even led the military to give it to pilots on some combat missions. The company which makes modafinil is funding studies in the hopes of getting FDA approval to use it for other sleep disorders. Neurologist Dr. Thomas Gamil says the very attributes that make modafinil so effective in treating sleep disorders may invite trouble. Dr. THOMAS GAMIL: If you have a drug with minimal side effects that can help people awake, there's a real temptation for people to work longer hours, to perhaps stay up all night if this drug can easily make that possible. SMITH: A real concern, especially where there's an economic incentive to delay sleep. But Cephalon, the company which makes modafinil, says there is no evidence of misuse. While some envision a day where new medications will double and even triple the time we stay awake, experts insist that sound sleep remains fundamental to human biology. Dr. ZAMMIT: It's essential to life. It's as essential as breathing. It's as essential as the beat of your heart, and there's nothing that will replace it--no drug, no substance, not caffeine, no vitamin, no herb. It's got to be sleep. SMITH: Especially since recent studies show that sleep deprivation doesn't just make us drowsy but increases our risk for diabetes and hormonal imbalances. So while these powerful medications may keep us going longer, there's no masking the long-term effects sleeplessness can have on our bodies. Dr. Ian Smith, NBC News, New York. LOAD-DATE: July 8, 2002 LANGUAGE: ENGLISH TYPE: Profile Copyright 2002 National Broadcasting Co. Inc. 869 of 998 DOCUMENTS The Washington Post June 29, 2002 Saturday Final Edition A Pill to Keep You Going SECTION: EDITORIAL; Pg. A22 LENGTH: 296 words While Joel Garreau ["The Great Awakening," Style, June 17] adequately characterized the appropriate and inappropriate uses of Cephalon's product, modafinil (Provigil), we are concerned that he consumed the product while writing his story without identifying the medical condition for which he was prescribed the drug. Cephalon has worked for more than nine years to develop modafinil for patients with serious sleep disorders. It is our expectation that clinical studies completed and currently underway will help Cephalon and those with sleep disorders understand the implications of potential broader use of the product for other disorders where excessive sleepiness is a major symptom. PAUL BLAKE Senior Vice President Clinical Research and Regulatory Affairs Cephalon Inc. West Chester, Pa. * I am one of the sleep researchers quoted in Joel Garreau's story, which dealt with issues related to sleep and the medication, modafinil. As such, I wish to clarify a few points. My statement about unexpected toxic effects of new medications was a general comment about the need for caution in drug development and use. It was not intended to include modafinil. Modafinil has been tested for efficiency and safety and has been in use long enough that it can be regarded as safe. Specifically, modafinil was in clinical trials in France in the 1980s and in the United States in the early 1990s. Pharmacological induction of many days of wakefulness with little or no intervening sleep will need careful study. I am unaware of long-term studies even in animals. The results of such research would be of great interest to many components of society and, of course, to Post readers. WILLIAM C. DEMENT Director Stanford Sleep Disorders And Research Center Palo Alto, Calif. LOAD-DATE: June 29, 2002 LANGUAGE: ENGLISH DOCUMENT-TYPE: LETTER PUBLICATION-TYPE: Newspaper Copyright 2002 The Washington Post 870 of 998 DOCUMENTS The Washington Post June 21, 2002 Friday Final Edition Staying Awake To Modafinil's Possibilities BYLINE: Donna Britt SECTION: METRO; DONNA BRITT; Pg. B01 LENGTH: 821 words What would you do if you could stay awake and alert for 40-hour stretches? Label your videos and organize your closets while the world slept? Drive straight through from the District to Santa Fe, N.M.? (That's 31 hours' road time, plus eight hours for bathroom and food breaks.) Start your novel? Party till you didn't drop from exhaustion? Prepare to find out. You've probably heard a lot less about the drug modafinil than you have about Viagra, but I'm convinced that will change. Why? Because Viagra addresses male sexual dysfunction, which only affects millions of men and their partners. Modafinil shuts off human beings' urge to sleep. Who doesn't that affect? As someone who's been sleepy for two decades -- my eldest child is 20 -- I read Post reporter Joel Garreau's article about the drug with excitement and dismay. In trials on healthy people, modafinil allowed users to stay up for almost two days while remaining nearly as focused, alert and capable of problem-solving as the well-rested. After eight hours of sleep, Garreau writes, users can rise and go another 40 hours. Reportedly, modafinil users don't experience the jitters or addiction -- with its euphoric ups and spiraling downs -- suffered by users of amphetamines, cocaine and even coffee. Considering its downside, why is caffeine the world's most widely used drug? Why is there a Starbucks on every other corner? Because most Americans don't get enough sleep -- two-thirds of us, according to the National Sleep Foundation. So why aren't people more excited about modafinil? The military may salivate at the prospect of an ever-ready "24-hour soldier"; my friends with young children sigh at the notion of being awake enough for occasional lovemaking. But when I described the drug to my manicurist, she responded, "No way. Why would anyone want to stay up 40 hours?" "Forty hours? That's scary," echoed bakery manager Melbin Perdigon, 25. "Maybe if you were doing a really long drive . . . " Silver Spring artist Ellen Jacobson was leaving a video store, clutching "The Princess Bride." Exhausted by her son's graduation, Jacobson hoped her daughter, 5, would watch "Princess" while she napped. But pop a pill to eradicate her sleepiness? Please. "We have life cycles for a reason," said Jacobson, a potter and painter. "If people have that much to do, they should cut some things out and prioritize." So she'd never consider modafinil? Pause. "Maybe when I'm getting ready for my holiday sale. . . . But it would seem like you'd be going against nature. "This is not going to solve the problem of time." Time, we long ago decided, is the Enemy. Despite our desperate battles with it, our endless manipulations, it ticks on -- taking a toll on our bodies, minds, careers and every relationship we find too little time to nurture. So we worry, plan and strategize. We introduce our skin to industrial-strength moisturizers, our bodies to energy boosters and memory enhancers, our kids to after-after-school care and marathon TV sessions. We spend more time working than we would like. Forty more hours a week? We'd probably do more of what we regret doing now. Even sleep researchers who tout modafinil wonder about its long-term effects. Accumulated sleep deprivation is suspected of causing obesity and illness. Still, modafinil, currently marketed to people with sleep disorders, is bound to be sought by truck drivers, hospital interns, pilots, exam takers -- and everybody else who pulls all-nighters. In a world of 24-hour laundromats, diners, shopping services, TV channels and copier stores, that means millions. Who won't go for it? Those who, realizing that the body repairs itself during sleep, believe that not sleeping for extended periods must be physically harmful. But what of the soul? Is tampering with something as fundamental as sleep . . . wrong? Even God rested after His labors. District pastor Allen White, who says he hates sleep because he would rather stay awake to play the piano and pray, says modafinil reminds him of Psalm 127: "It is vain for you to rise up early, to retire late, to eat the bread of painful labors; for He gives to His beloved even in his sleep." Even without our constant labor, the passage suggests, God provides. "It means we can go to sleep and everything will be all right," says White. "People think if they're not doing something every second, nothing will get done. That's vanity." That's life as many of us know it. If modafinil scares you, don't even consider the next generation of "wake-performing" drugs. Scientists say they'll keep us awake indefinitely -- without adding sleep debt. Decades from now, people wary of modafinil may seem as quaint as those who once said, "If God wanted man to fly, He'd have given him wings." But we'll be too miserable from never getting a break from our ever-wakeful families and co-workers to take any pleasure in it. LOAD-DATE: June 21, 2002 LANGUAGE: ENGLISH DOCUMENT-TYPE: COLUMN PUBLICATION-TYPE: Newspaper Copyright 2002 The Washington Post 871 of 998 DOCUMENTS The Washington Post June 21, 2002 Friday Final Edition Staying Awake To Modafinil's Possibilities BYLINE: Donna Britt SECTION: METRO; DONNA BRITT; Pg. B01 LENGTH: 821 words What would you do if you could stay awake and alert for 40-hour stretches? Label your videos and organize your closets while the world slept? Drive straight through from the District to Santa Fe, N.M.? (That's 31 hours' road time, plus eight hours for bathroom and food breaks.) Start your novel? Party till you didn't drop from exhaustion? Prepare to find out. You've probably heard a lot less about the drug modafinil than you have about Viagra, but I'm convinced that will change. Why? Because Viagra addresses male sexual dysfunction, which only affects millions of men and their partners. Modafinil shuts off human beings' urge to sleep. Who doesn't that affect? As someone who's been sleepy for two decades -- my eldest child is 20 -- I read Post reporter Joel Garreau's article about the drug with excitement and dismay. In trials on healthy people, modafinil allowed users to stay up for almost two days while remaining nearly as focused, alert and capable of problem-solving as the well-rested. After eight hours of sleep, Garreau writes, users can rise and go another 40 hours. Reportedly, modafinil users don't experience the jitters or addiction -- with its euphoric ups and spiraling downs -- suffered by users of amphetamines, cocaine and even coffee. Considering its downside, why is caffeine the world's most widely used drug? Why is there a Starbucks on every other corner? Because most Americans don't get enough sleep -- two-thirds of us, according to the National Sleep Foundation. So why aren't people more excited about modafinil? The military may salivate at the prospect of an ever-ready "24-hour soldier"; my friends with young children sigh at the notion of being awake enough for occasional lovemaking. But when I described the drug to my manicurist, she responded, "No way. Why would anyone want to stay up 40 hours?" "Forty hours? That's scary," echoed bakery manager Melbin Perdigon, 25. "Maybe if you were doing a really long drive . . . " Silver Spring artist Ellen Jacobson was leaving a video store, clutching "The Princess Bride." Exhausted by her son's graduation, Jacobson hoped her daughter, 5, would watch "Princess" while she napped. But pop a pill to eradicate her sleepiness? Please. "We have life cycles for a reason," said Jacobson, a potter and painter. "If people have that much to do, they should cut some things out and prioritize." So she'd never consider modafinil? Pause. "Maybe when I'm getting ready for my holiday sale. . . . But it would seem like you'd be going against nature. "This is not going to solve the problem of time." Time, we long ago decided, is the Enemy. Despite our desperate battles with it, our endless manipulations, it ticks on -- taking a toll on our bodies, minds, careers and every relationship we find too little time to nurture. So we worry, plan and strategize. We introduce our skin to industrial-strength moisturizers, our bodies to energy boosters and memory enhancers, our kids to after-after-school care and marathon TV sessions. We spend more time working than we would like. Forty more hours a week? We'd probably do more of what we regret doing now. Even sleep researchers who tout modafinil wonder about its long-term effects. Accumulated sleep deprivation is suspected of causing obesity and illness. Still, modafinil, currently marketed to people with sleep disorders, is bound to be sought by truck drivers, hospital interns, pilots, exam takers -- and everybody else who pulls all-nighters. In a world of 24-hour laundromats, diners, shopping services, TV channels and copier stores, that means millions. Who won't go for it? Those who, realizing that the body repairs itself during sleep, believe that not sleeping for extended periods must be physically harmful. But what of the soul? Is tampering with something as fundamental as sleep . . . wrong? Even God rested after His labors. District pastor Allen White, who says he hates sleep because he would rather stay awake to play the piano and pray, says modafinil reminds him of Psalm 127: "It is vain for you to rise up early, to retire late, to eat the bread of painful labors; for He gives to His beloved even in his sleep." Even without our constant labor, the passage suggests, God provides. "It means we can go to sleep and everything will be all right," says White. "People think if they're not doing something every second, nothing will get done. That's vanity." That's life as many of us know it. If modafinil scares you, don't even consider the next generation of "wake-performing" drugs. Scientists say they'll keep us awake indefinitely -- without adding sleep debt. Decades from now, people wary of modafinil may seem as quaint as those who once said, "If God wanted man to fly, He'd have given him wings." But we'll be too miserable from never getting a break from our ever-wakeful families and co-workers to take any pleasure in it. LOAD-DATE: June 21, 2002 LANGUAGE: ENGLISH DOCUMENT-TYPE: COLUMN PUBLICATION-TYPE: Newspaper Copyright 2002 The Washington Post 872 of 998 DOCUMENTS Newsbytes June 17, 2002, Monday The Great Awakening BYLINE: Joel Garreau; Washington Post Staff Writer LENGTH: 4025 words DATELINE: United States Grubb's Pharmacy is an unassuming if not seedy two-story clapboard landmark amid the grand brick townhouses of East Capitol Street. Not only is it one of the busiest pharmacies in the District. But being only four blocks from the Capitol, it is also the neighborhood provider of potions and portents to congressmen, lobbyists, super-lawyers, Supreme Court justices, ambitious aides and all those other classic Type A Washingtonians who think that whatever they're working on is The Most Important Thing in the World. And of course sometimes they may be right. Yet Grubb's is filling only about five prescriptions a month for a drug named modafinil. "It's nothing like Viagra. That was a national explosion," says Edward F. Dillon, the pharmacist. "Or a drug like Propecia, for hair loss. Or Prozac. Let me tell you. When Time magazine put that on the cover, you could definitely see the spike." This may be the calm before the storm, however. For modafinil may have the power to change Washington. What it does is shut off your urge to sleep. "It's a standing joke among sleep doctors that nobody sleeps in New York or Washington," says Helene Emsellem, director of the Center for Sleep and Wake Disorders in Chevy Chase. "Except in New York they do it for pleasure, while in Washington they do it to work." In trials on healthy people like Army helicopter pilots, modafinil has allowed humans to stay up safely for almost two days while remaining practically as focused, alert, and capable of dealing with complex problems as the well-rested. Then, after a good eight hours' sleep, they can get up and do it again -- for another 40 hours, before finally catching up on their sleep. Originally aimed at narcoleptics, who fall asleep frequently and uncontrollably, modafinil works without the jitter, buzz, euphoria, crash, addictive characteristics or potential for paranoid delusion of stimulants like amphetamines or cocaine or even caffeine, researchers say. As with an increasing number of the so-called superhuman, posthuman or trans-human drugs or genetic manipulations rapidly entering our lives, modafinil thus calls into question some fundamental underpinnings of hundreds of thousands of years of thought regarding what are normal human capabilities. The implications for Washington are profound. The Defense Advanced Research Projects Agency is searching for ways to create the "metabolically dominant soldier." Among the projects it is pursuing is the creation of a warrior who can fight 24 hours a day, seven days straight. "Eliminating the need for sleep while maintaining the high level of both cognitive and physical performance of the individual will create a fundamental change in war-fighting," says the Defense Sciences Office on its Web site. As usual, DARPA did not comment directly for this report. William C. Dement, director of the Stanford University Sleep Center, who is known as "the father of sleep medicine" for his pioneering work in the '50s, embraces the idea of modafinil use for official Washington. "If Donald Rumsfeld had to stay awake for a long period of time, I would want him fully alert," he says. Francis Fukuyama of Johns Hopkins University recently published "Our Posthuman Future: Consequences of the Biotechnology Revolution," a book that is scathingly critical of what he sees as runaway biotech that could rob us of our very human nature. When asked about modafinil and its effects on Washington, he responded with a 2:50 a.m. e-mail from Europe, where he was finishing a grueling three-week trip. "I haven't heard of this but I'm not surprised," he wrote. "I better get some," he half-joked. Modafinil and its follow-on technologies hold the potential for changing society. "This could replace caffeine," says Joyce Walsleben, director of the NYU Sleep Disorders Center. Caffeine -- the globe's most widely used drug -- today is a bigger food additive in dollar terms than salt. The U.S. soft drink industry alone sold 10 billion 192-ounce cases of bubbly last year, most of it caffeinated. Modafinil's sales are still small. But it did double sales to $150 million in only the last year, according to Cephalon, the pharmaceutical company that markets it under the trade name Provigil. Its potential for changing how people work and live is intriguing. In an increasingly 24-7 world, will such medicine create even more demand for people to be available round-the-clock? Were Robert Frost's lines from 1923 prophetic? The woods are lovely, dark and deep. But I have promises to keep, And miles to go before I sleep, And miles to go before I sleep. Will people feel that they need to routinely control their sleep in order to be competitive? Will unenhanced people suffer fewer promotions and raises than their modified colleagues? Will this start an arms race over human consciousness? To get some hint of what such a Washington life might be like, the bulk of the writing of this article, a task not unlike others with many moving parts -- software development or the juggling of a diplomatic flap -- was accomplished in one 40-hour period enabled by the prescribed use of modafinil. 10 a.m. Thursday. Third hour awake. Back from working out at the gym. Gazing at the white 200 mg. tab of modafinil. Hey, how scary can this be. It's not like this is life's first all-nighter. This one is even legal. Ironic. Four decades after the '60s, some of the most startling drugs are those available by prescription. But safety first. Take the advice of the sleep docs. Cut the tab in half. If, as sometimes happens, there is going to be a headache or nausea, start with a low dose. Humans have been manipulating their sleep chemistry for a long time. Caffeine is as old as coffee in Arabia, tea in China and chocolate in the New World. For at least as long, sleep has been seen as a universal solvent. "Now blessing light on him that first invented this same sleep!" says Sancho Panza in "Don Quixote." "It covers a man all over, thoughts and all, like a cloak; 'tis meat for the hungry, drink for the thirsty, heat for the cold, and cold for the hot. 'Tis the current coin that purchases all the pleasures of the world cheap; and the balance that sets the king and the shepherd, the fool and the wise man even." The effects of medicated sleeplessness on a vast healthy population is still unknown. "Before you start taking it for the rest of your life, find out what it does to your heart valves or some damn thing," Dement says. "A lot of people know the story of fen-phen or thalidomide. If you take it all the time, and try to stay awake all the time, there's a big chance that there may be some hitherto unknown toxic effect." Nonetheless, modafinil (pronounced mo-DAF-i-nil) is distinguished by its apparently precise neurological focus. Nobody knows exactly how modafinil works, but researchers marvel at the way it seems to target very specific regions of the brain believed to regulate normal wakefulness. It's that narrow effect that is lacking in other stimulants, resulting in their notorious side effects. In fact, on the wall of his office at a company named Hyperion, off Boston's Interstate 495 near Worcester, Mass., sleep researcher Dale M. Edgar has a sign. "It's about the sleepiness, stupid," it reads. As with the rest of the cascade of new drugs that promise to augment human performance, here are three groups of people who will ultimately be attracted to new wakefulness drugs, researchers say. In this order, they are: The sick. The otherwise healthy with a critical need. The rest of us. It's the future of the third group -- the millions who, in the immortal words of Kiss, "wanna rock and roll all nite and party every day" -- that deeply concerns the sleep business. The Food and Drug Administration so far has approved modafinil marketing only to narcoleptics, as the FDA reminded Cephalon in January, when it charged that the company's promotional materials were overreaching. Cephalon will soon submit an application to the FDA to expand its marketing to people with other sleep disorders, including the ones associated with sleep apnea and Parkinson's disease. There are only 125,000 to 250,000 narcoleptics in the United States. Cephalon brags that hundreds of thousands of patients have taken Provigil, with over a million prescriptions written as of 2001, and sales soaring. Nonetheless, Cephalon spokesman Sheryl Williams says that "we are not aware of any significant prescribing of the drug for nonmedical conditions." What exactly is a "nonmedical condition"? This enters the murky world of the second group -- healthy people engaged in "mission-critical tasks for which sleepiness is not an option," as Edgar puts it. "Like flying a big C-17 transport plane from Charleston Air Force Base to Afghanistan virtually nonstop," says Edgar. "That happened. There are lots of examples in the Air Force. It's what they call susops -- sustained operations. You really, really need something on those long flights, and not just for the pilots. The payload specialists in back have no place to sleep, and they have to be on the ready to deploy the load. It's hard, but it's also critical to the success of the mission, and reducing accidents." The crucial issue is not staying awake. It's doing so without making lethal mistakes. The fatal decision to launch the Challenger space shuttle was made by people handling very complex data after days of irregular work hours and insufficient sleep, as all sleep researchers remind themselves. Fort Rucker, Ala., is 58,000 hot and steamy acres of Southern pine and the occasional wild magnolia. All the Army's helicopter pilots are trained there. John Caldwell has a low, impressively equipped, sprawling brick sleep laboratory with the Air Crew Health and Performance Division of the U.S. Army Aeromedical Research Laboratory. His modafinil study is the one that kept awake the helicopter pilots -- "normals without any pathological conditions," as he so clinically puts it. The pilots flew a simulator in which they had to respond quickly to commands -- to fly for two minutes straight and level at 3,000 feet maintaining 120 knots at a heading of 180, for example, then perform a turn of 360 degrees over exactly two minutes, maintaining speed and altitude. Then the pilots had to perform four different tasks simultaneously -- watching warning lights come on and dials deviate from normal, while monitoring the fuel levels and clearing blockages, while holding a target constant, while responding on the radio to someone commanding, "NGT 504, NGT 504, set communications radio to 121.5" Caldwell expresses a sentiment volunteered by almost every sleep researcher. "One thing I want to make clear -- when we look at compounds like modafinil or amphetamines or caffeine, those are emergency kinds of measures, not a replacement for sleep. It's not nice to fool with Mother Nature." Says Stanford's Dement: "The real problem is the accumulated sleep debt, not daily need. It's established fact that lost sleep accumulates. You quickly become too tired to be functional." Even with a substance like modafinil that can keep you wakeful, if you don't ultimately catch up on the sleep you missed, bad things will happen, sleep researchers have always believed. "Your grandmother was right. If you don't get enough sleep, you're going to get sick," says Chevy Chase researcher Emsellem. When you're facing a critical situation, however, it's better to have help being alert, Caldwell firmly believes. "Combat operations are very unpredictable." Even with a 14-hour-a-day rest schedule, "if the enemy attacks during the 14 hours off, we're going to have to respond." "There are a lot of other medically justified scenarios," says Edgar. "Think of emergency medical services. What happens when a building collapses? As we unfortunately learned recently, teams work around the clock. Can you justify it to save lives? Absolutely. Particularly if it's a hazardous situation. Somebody needs to do the job, and if there is something that is safe, effective, and non-habit-forming, I think the answer is yes." Sleep research is a very young science, and the number of things it doesn't know about substances like modafinil is daunting. "How long can somebody stay awake and not suffer? Hard to say. The jury is still out," says Edgar, who is on leave from Stanford. He is now ensconced in a serene research facility sporting green glass that matches the stripes of the mallard ducks on the pond. Inside are a sophisticated array of computers and hundreds of mice and rats. In his small office, wraparound screens stream brain wave activity being transmitted live from around the world over the Internet. Edgar has taken up a new role as senior vice president for preclinical research at Hypnion, which he describes as the world's first biotech company specifically dedicated to solving problems of sleep-wake disorders. "Do you function as if you were rested? The answer is you're probably better off than if you haven't taken it, but you're not at 100 percent. Where are you? Fifty percent on cognitive performance? Is that good enough?" But then Edgar drops the bomb. "The next generation of wake-performing therapeutics will be more effective. You'll be able to stay awake for X amount of time and not add sleep debt. Ideally, it means being able to be up all day, all night, and all the next day and not have incremental increase in sleepiness or in sleep debt. It would be medication that gives you an interest-free loan. "It could change the world. A complete paradigm shift. I'm not trying to plug my company. But we are in the forefront. We could see this being a reality, starting to become available, in about five years." Friday, 2 a.m., Hour 19. The effortless mental focus brought on by modafinil is remarkable. No attention deficit here. The feeling is that you have been given a gift of time, and it is too precious to waste. The focus is almost more interesting than the sleep-avoidance. In fact, it makes you wonder what it will be like to grow up in a world in which this stuff is common. Suppose you are just getting started in a career and you're a basket of insecurities. Suppose you could regularly produce at levels unheard of even by today's workaholic standards simply by popping a pill. Could you resist it? Worse yet, suppose you were competing for raises and promotions against someone who was happy to grab whatever enhancements were available. Will it become routine to hear "There'll be plenty of time to sleep when you're 40"? You can't get high on modafinil. There's no euphoria to it. When they first take it, a lot of test subjects figure they must have gotten the placebo. On this do sleep researchers base their hope that wakefulness agents won't be the next glam drug phenom, hyped on magazine covers and distributed with abandon to people for whom they were never intended, under circumstances that have never been studied. But they know the facts. Two-thirds of all Americans don't get enough sleep, according to the National Sleep Foundation. Sleep deprivation may be a factor in the national epidemic of obesity. America is full of people burning the candle at both ends, wanting to know only where they can get more wax. "Most of them are impaired. A lot of jobs you can do almost in your sleep -- lifting boxes onto shelves in a department store," says Dement. "But I'm frequently an expert witness in cases that involve falling asleep at the wheel. A recent case involved a man who was working two jobs, and on the night job he was frequently observed to fall asleep. His supervisor escorted him out the door. He drove into an oncoming lane and killed three people." The graveyard shift is hardly just for factory workers anymore. The world is open 24-7 -- restaurants, health clubs, Wal-Marts, Home Depots, help desks, stock and commodities traders, catalogue sales and overnight shippers, to mention a few. Why do people getting off the red-eye from Los Angeles or to London seem so ruefully proud even when they look like dog meat? The classic hero figure of capitalism is the CEO who says he never needs more than a few hours of sleep -- he's proud of being on the go all the time. Washington has its own special breeds of sleep-defiers. Think of the rat calculus of campaign strategists running the maze of late October before Election Day. Hunched and harried, they work the phones to the Coast until 2 or 3 in the morning, while writing the candidate's talking points for the next day, and then hitting the Eastern time zone phones at dawn. The badge of special honor is simultaneously to be advising campaigns from Washington in the time zones of Britain and Israel. Friday, 4 a.m., Hour 21. When this stuff takes over, it takes over. Gently, not violently. No apparent loss of acuity. But you have definitely kicked into a gear you didn't know you had. Playing computer games like FreeCell as an informal way of testing cognitive ability. Do you dare send e-mails? Will you regret them when you return to normal? Speaking of rhythms, remember to eat. Got to keep up strength. Discomfort still far less than it would have been had coffee been used to accomplish this task. Getting awful sick of herb tea, though. So what about the dreaded third group -- the rest of us, those who are in a fundamentally different situation from the first two groups? We have a choice whether to live a saner life or try to solve our problems with a pill. "The young professional who wants to work and play and do everything, and doesn't want to spend time sleeping?" asks University of Pennsylvania sleep researcher David Dinges. "That's another matter." Yes, sleep researchers grudgingly admit, there are going to be some way-off-label users. The college students crashing on term papers. Truck drivers. Barge operators. Airline pilots. The physician in long hours of training. The new parent. Ever watch the White House-based television show "The West Wing?" They never seem to go home. That is not fantasy. "Sleepiness is everywhere," says Neil Feldman, medical director of the St. Petersburg, Fla., Sleep Disorder Center, who is conducting a shift work study for Cephalon. "We're a 24-hour society. We no longer live by the night/day cycle. We live by whatever our occupation demands. Physicians on call at night. Nuclear power plant operators. Police, firemen. Plus the world is becoming a smaller place. Trans-meridian travel, commonly known as jet lag. There are economic demands -- more than one job -- plus raising children. "How many have fallen asleep at the wheel of a car? Something like 25 percent at least momentarily once during the year. Sleep deprivation is everywhere. Our society looks at people who sleep as less strong people. People who nap are slugs." Suppose a lawyer came to you and said, "I have a client on death row and the governor has just given me three days to draft his appeal before he is executed." "I'd probably prescribe the drug," Feldman said. "But three pills. Not a hundred. I can rationalize that." "People ask me about it almost daily," says Dement. "Everybody would like to be able to have more time to do whatever they want to do. I could stand in front of a roomful of Stanford undergrads right now and say, 'If you feel tired, raise your hand,' and every hand would go up." Such a fundamental change in human nature is hardly without risks. "Emphasize the idea that we may be playing with fire here," says Emsellem. "Who knows why we get cancer? Chronic sleep deprivation may be a risk factor for long-term disease. I would love to get by on five hours of sleep because I don't like to lie in bed, leashed by a sleep requirement. I would love to be unleashed. But at the same time, prove that it is safe. I don't need another round of winter flu, thank you very much. Getting sick, being constitutionally exhausted." "When you have debate on this topic," says Edgar, "on one side, people say: 'Just sleep more. Do what you have to do and the economy be damned. Get the sleep that you need and that's that.' On the other side, people are saying: 'But wait a minute. This is a 24-hour world. Those services have to be performed at the highest level they can. People make mistakes.' " How do you compete? Edgar sighs. "This gets into this fair and legitimate debate. Type A people in Washington go until they drop. You don't know the ultimate consequences. The extra load on the kidneys, liver, pancreas, endocrine functions. This could be really important." "The final twist is that caffeine is a food additive," says Edgar. Replacing caffeine with modafinil -- "that would be the revolutionary next step. Just as one replaces sugar with NutraSweet. Everybody drinks soda pop with caffeine from the age of 5 up. Yeah. You're changing the world. Yeah. I'm telling you as a sleep scientist the kinds of things we see on the horizon. It's exciting. Changing lives. Saving lives. That's for certain. "Is it appropriate for college students pulling an all-nighter? No. Sleep physiologists will all tell you the same thing. There is no true substitute for sleep itself. We say that with conviction," Edgar says. Suppose that will no longer be the case? "The more far-out question is: What if we eventually had something that was absolutely safe that could substitute for sleep?" asks Dinges. "Is that the direction we want to go? Many would say yes. I don't know what the implications are for our species. Probably not bad. This is pure speculation. Should humans try to live without sleep? I don't know. We're already trying to do that." Friday afternoon, 4 p.m., Hour 33. Tired from all this writing. But not sleepy. Interesting to imagine a future in which those are two distinctly separate things. The problem isn't wakefulness. The problem is cranking through three or four days' worth of work in one burst. Started to yawn at 8 a.m., at the bottom of circadian rhythms. Lay down for a two-hour nap. As researchers say, this stuff doesn't prevent you from sleeping, it just controls the desire to. Arose alert. Went back to productive work. Naps are good, as the sleep researchers ceaselessly point out. Glad this experiment occurred in a home office, and not downtown. Wouldn't relish driving at this point. Don't feel impaired, but wouldn't want to test the proposition. Have no interest in taking any more pills to further the experiment. Looking forward to returning to the planet of the mortals with a glass of wine and a good supper. Wonder what this will read like after a good night's sleep? The concern is this: One is always taught never to hand in a complicated project at the end of the day. Read it over one last time with fresh eyes in the morning. But fresh eyes are optional, when you don't have to sleep. Fatigue still hasn't set in. It wouldn't be hard to hand this in and begin preparations for the next project with a whole afternoon in front of you. What happens when fresh eyes are a choice, not an inevitable part of the rhythms of life? We will be asking ourselves these questions about human nature with increased frequency as biotechnology advances and drugs originally designed for the sick begin to augment the healthy. We have already seen this happen with Viagra. It now sponsors network evening news shows, a development that would have boggled scenario planners just five years ago. More drugs are in the works that attack shyness, forgetfulness and the mental decline of aging. Others add muscle mass and boost the ability to learn, at least in mice. Saturday morning, 10 a.m., Hour 51, after eight hours of sleep. Would need to have an awfully compelling reason to want to do this again. But can imagine how others might differ. Sure was a lot of living packed into the last two days. Got so much done that there is a whole unencumbered weekend in sight. What a concept. Reported By TechNews.com, http://www.TechNews.com (20020617/WIRES /) LOAD-DATE: June 18, 2002 LANGUAGE: ENGLISH TYPE: news Copyright 2002 Post-Newsweek Business Information, Inc. 873 of 998 DOCUMENTS The Washington Post June 17, 2002 Monday Final Edition The Great Awakening; With a Pill Called Modafinil, You Can Go 40 Hours Without Sleep -- and See Into the Future BYLINE: Joel Garreau, Washington Post Staff Writer SECTION: STYLE; Pg. C01 LENGTH: 3996 words Grubb's Pharmacy is an unassuming if not seedy two-story clapboard landmark amid the grand brick townhouses of East Capitol Street. Not only is it one of the busiest pharmacies in the District. But being only four blocks from the Capitol, it is also the neighborhood provider of potions and portents to congressmen, lobbyists, super-lawyers, Supreme Court justices, ambitious aides and all those other classic Type A Washingtonians who think that whatever they're working on is The Most Important Thing in the World. And of course sometimes they may be right. Yet Grubb's is filling only about five prescriptions a month for a drug named modafinil. "It's nothing like Viagra. That was a national explosion," says Edward F. Dillon, the pharmacist. "Or a drug like Propecia, for hair loss. Or Prozac. Let me tell you. When Time magazine put that on the cover, you could definitely see the spike." This may be the calm before the storm, however. For modafinil may have the power to change Washington. What it does is shut off your urge to sleep. "It's a standing joke among sleep doctors that nobody sleeps in New York or Washington," says Helene Emsellem, director of the Center for Sleep and Wake Disorders in Chevy Chase. "Except in New York they do it for pleasure, while in Washington they do it to work." In trials on healthy people like Army helicopter pilots, modafinil has allowed humans to stay up safely for almost two days while remaining practically as focused, alert, and capable of dealing with complex problems as the well-rested. Then, after a good eight hours' sleep, they can get up and do it again -- for another 40 hours, before finally catching up on their sleep. Originally aimed at narcoleptics, who fall asleep frequently and uncontrollably, modafinil works without the jitter, buzz, euphoria, crash, addictive characteristics or potential for paranoid delusion of stimulants like amphetamines or cocaine or even caffeine, researchers say. As with an increasing number of the so-called superhuman, posthuman or trans-human drugs or genetic manipulations rapidly entering our lives, modafinil thus calls into question some fundamental underpinnings of hundreds of thousands of years of thought regarding what are normal human capabilities. The implications for Washington are profound. The Defense Advanced Research Projects Agency is searching for ways to create the "metabolically dominant soldier." Among the projects it is pursuing is the creation of a warrior who can fight 24 hours a day, seven days straight. "Eliminating the need for sleep while maintaining the high level of both cognitive and physical performance of the individual will create a fundamental change in war-fighting," says the Defense Sciences Office on its Web site. As usual, DARPA did not comment directly for this report. William C. Dement, director of the Stanford University Sleep Center, who is known as "the father of sleep medicine" for his pioneering work in the '50s, embraces the idea of modafinil use for official Washington. "If Donald Rumsfeld had to stay awake for a long period of time, I would want him fully alert," he says. Francis Fukuyama of Johns Hopkins University recently published "Our Posthuman Future: Consequences of the Biotechnology Revolution," a book that is scathingly critical of what he sees as runaway biotech that could rob us of our very human nature. When asked about modafinil and its effects on Washington, he responded with a 2:50 a.m. e-mail from Europe, where he was finishing a grueling three-week trip. "I haven't heard of this but I'm not surprised," he wrote. "I better get some," he half-joked. Modafinil and its follow-on technologies hold the potential for changing society. "This could replace caffeine," says Joyce Walsleben, director of the NYU Sleep Disorders Center. Caffeine -- the globe's most widely used drug -- today is a bigger food additive in dollar terms than salt. The U.S. soft drink industry alone sold 10 billion 192-ounce cases of bubbly last year, most of it caffeinated. Modafinil's sales are still small. But it did double sales to $ 150 million in only the last year, according to Cephalon, the pharmaceutical company that markets it under the trade name Provigil. Its potential for changing how people work and live is intriguing. In an increasingly 24-7 world, will such medicine create even more demand for people to be available round-the-clock? Were Robert Frost's lines from 1923 prophetic? The woods are lovely, dark and deep. But I have promises to keep, And miles to go before I sleep, And miles to go before I sleep. Will people feel that they need to routinely control their sleep in order to be competitive? Will unenhanced people suffer fewer promotions and raises than their modified colleagues? Will this start an arms race over human consciousness? To get some hint of what such a Washington life might be like, the bulk of the writing of this article, a task not unlike others with many moving parts -- software development or the juggling of a diplomatic flap -- was accomplished in one 40-hour period enabled by the prescribed use of modafinil. 10 a.m. Thursday. Third hour awake. Back from working out at the gym. Gazing at the white 200 mg. tab of modafinil. Hey, how scary can this be. It's not like this is life's first all-nighter. This one is even legal. Ironic. Four decades after the '60s, some of the most startling drugs are those available by prescription. But safety first. Take the advice of the sleep docs. Cut the tab in half. If, as sometimes happens, there is going to be a headache or nausea, start with a low dose. Humans have been manipulating their sleep chemistry for a long time. Caffeine is as old as coffee in Arabia, tea in China and chocolate in the New World. For at least as long, sleep has been seen as a universal solvent. "Now blessing light on him that first invented this same sleep!" says Sancho Panza in "Don Quixote." "It covers a man all over, thoughts and all, like a cloak; 'tis meat for the hungry, drink for the thirsty, heat for the cold, and cold for the hot. 'Tis the current coin that purchases all the pleasures of the world cheap; and the balance that sets the king and the shepherd, the fool and the wise man even." The effects of medicated sleeplessness on a vast healthy population is still unknown. "Before you start taking it for the rest of your life, find out what it does to your heart valves or some damn thing," Dement says. "A lot of people know the story of fen-phen or thalidomide. If you take it all the time, and try to stay awake all the time, there's a big chance that there may be some hitherto unknown toxic effect." Nonetheless, modafinil (pronounced mo-DAF-i-nil) is distinguished by its apparently precise neurological focus. Nobody knows exactly how modafinil works, but researchers marvel at the way it seems to target very specific regions of the brain believed to regulate normal wakefulness. It's that narrow effect that is lacking in other stimulants, resulting in their notorious side effects. In fact, on the wall of his office at a company named Hyperion, off Boston's Interstate 495 near Worcester, Mass., sleep researcher Dale M. Edgar has a sign. "It's about the sleepiness, stupid," it reads. As with the rest of the cascade of new drugs that promise to augment human performance, here are three groups of people who will ultimately be attracted to new wakefulness drugs, researchers say. In this order, they are: * The sick. * The otherwise healthy with a critical need. * The rest of us. It's the future of the third group -- the millions who, in the immortal words of Kiss, "wanna rock and roll all nite and party every day" -- that deeply concerns the sleep business. The Food and Drug Administration so far has approved modafinil marketing only to narcoleptics, as the FDA reminded Cephalon in January, when it charged that the company's promotional materials were overreaching. Cephalon will soon submit an application to the FDA to expand its marketing to people with other sleep disorders, including the ones associated with sleep apnea and Parkinson's disease. There are only 125,000 to 250,000 narcoleptics in the United States. Cephalon brags that hundreds of thousands of patients have taken Provigil, with over a million prescriptions written as of 2001, and sales soaring. Nonetheless, Cephalon spokesman Sheryl Williams says that "we are not aware of any significant prescribing of the drug for nonmedical conditions." What exactly is a "nonmedical condition"? This enters the murky world of the second group -- healthy people engaged in "mission-critical tasks for which sleepiness is not an option," as Edgar puts it. "Like flying a big C-17 transport plane from Charleston Air Force Base to Afghanistan virtually nonstop," says Edgar. "That happened. There are lots of examples in the Air Force. It's what they call susops -- sustained operations. You really, really need something on those long flights, and not just for the pilots. The payload specialists in back have no place to sleep, and they have to be on the ready to deploy the load. It's hard, but it's also critical to the success of the mission, and reducing accidents." The crucial issue is not staying awake. It's doing so without making lethal mistakes. The fatal decision to launch the Challenger space shuttle was made by people handling very complex data after days of irregular work hours and insufficient sleep, as all sleep researchers remind themselves. Fort Rucker, Ala., is 58,000 hot and steamy acres of Southern pine and the occasional wild magnolia. All the Army's helicopter pilots are trained there. John Caldwell has a low, impressively equipped, sprawling brick sleep laboratory with the Air Crew Health and Performance Division of the U.S. Army Aeromedical Research Laboratory. His modafinil study is the one that kept awake the helicopter pilots -- "normals without any pathological conditions," as he so clinically puts it. The pilots flew a simulator in which they had to respond quickly to commands -- to fly for two minutes straight and level at 3,000 feet maintaining 120 knots at a heading of 180, for example, then perform a turn of 360 degrees over exactly two minutes, maintaining speed and altitude. Then the pilots had to perform four different tasks simultaneously -- watching warning lights come on and dials deviate from normal, while monitoring the fuel levels and clearing blockages, while holding a target constant, while responding on the radio to someone commanding, "NGT 504, NGT 504, set communications radio to 121.5" Caldwell expresses a sentiment volunteered by almost every sleep researcher. "One thing I want to make clear -- when we look at compounds like modafinil or amphetamines or caffeine, those are emergency kinds of measures, not a replacement for sleep. It's not nice to fool with Mother Nature." Says Stanford's Dement: "The real problem is the accumulated sleep debt, not daily need. It's established fact that lost sleep accumulates. You quickly become too tired to be functional." Even with a substance like modafinil that can keep you wakeful, if you don't ultimately catch up on the sleep you missed, bad things will happen, sleep researchers have always believed. "Your grandmother was right. If you don't get enough sleep, you're going to get sick," says Chevy Chase researcher Emsellem. When you're facing a critical situation, however, it's better to have help being alert, Caldwell firmly believes. "Combat operations are very unpredictable." Even with a 14-hour-a-day rest schedule, "if the enemy attacks during the 14 hours off, we're going to have to respond." "There are a lot of other medically justified scenarios," says Edgar. "Think of emergency medical services. What happens when a building collapses? As we unfortunately learned recently, teams work around the clock. Can you justify it to save lives? Absolutely. Particularly if it's a hazardous situation. Somebody needs to do the job, and if there is something that is safe, effective, and non-habit-forming, I think the answer is yes." Sleep research is a very young science, and the number of things it doesn't know about substances like modafinil is daunting. "How long can somebody stay awake and not suffer? Hard to say. The jury is still out," says Edgar, who is on leave from Stanford. He is now ensconced in a serene research facility sporting green glass that matches the stripes of the mallard ducks on the pond. Inside are a sophisticated array of computers and hundreds of mice and rats. In his small office, wraparound screens stream brain wave activity being transmitted live from around the world over the Internet. Edgar has taken up a new role as senior vice president for preclinical research at Hypnion, which he describes as the world's first biotech company specifically dedicated to solving problems of sleep-wake disorders. "Do you function as if you were rested? The answer is you're probably better off than if you haven't taken it, but you're not at 100 percent. Where are you? Fifty percent on cognitive performance? Is that good enough?" But then Edgar drops the bomb. "The next generation of wake-performing therapeutics will be more effective. You'll be able to stay awake for X amount of time and not add sleep debt. Ideally, it means being able to be up all day, all night, and all the next day and not have incremental increase in sleepiness or in sleep debt. It would be medication that gives you an interest-free loan. "It could change the world. A complete paradigm shift. I'm not trying to plug my company. But we are in the forefront. We could see this being a reality, starting to become available, in about five years." Friday, 2 a.m., Hour 19. The effortless mental focus brought on by modafinil is remarkable. No attention deficit here. The feeling is that you have been given a gift of time, and it is too precious to waste. The focus is almost more interesting than the sleep-avoidance. In fact, it makes you wonder what it will be like to grow up in a world in which this stuff is common. Suppose you are just getting started in a career and you're a basket of insecurities. Suppose you could regularly produce at levels unheard of even by today's workaholic standards simply by popping a pill. Could you resist it? Worse yet, suppose you were competing for raises and promotions against someone who was happy to grab whatever enhancements were available. Will it become routine to hear "There'll be plenty of time to sleep when you're 40"? You can't get high on modafinil. There's no euphoria to it. When they first take it, a lot of test subjects figure they must have gotten the placebo. On this do sleep researchers base their hope that wakefulness agents won't be the next glam drug phenom, hyped on magazine covers and distributed with abandon to people for whom they were never intended, under circumstances that have never been studied. But they know the facts. Two-thirds of all Americans don't get enough sleep, according to the National Sleep Foundation. Sleep deprivation may be a factor in the national epidemic of obesity. America is full of people burning the candle at both ends, wanting to know only where they can get more wax. "Most of them are impaired. A lot of jobs you can do almost in your sleep -- lifting boxes onto shelves in a department store," says Dement. "But I'm frequently an expert witness in cases that involve falling asleep at the wheel. A recent case involved a man who was working two jobs, and on the night job he was frequently observed to fall asleep. His supervisor escorted him out the door. He drove into an oncoming lane and killed three people." The graveyard shift is hardly just for factory workers anymore. The world is open 24-7 -- restaurants, health clubs, Wal-Marts, Home Depots, help desks, stock and commodities traders, catalogue sales and overnight shippers, to mention a few. Why do people getting off the red-eye from Los Angeles or to London seem so ruefully proud even when they look like dog meat? The classic hero figure of capitalism is the CEO who says he never needs more than a few hours of sleep -- he's proud of being on the go all the time. Washington has its own special breeds of sleep-defiers. Think of the rat calculus of campaign strategists running the maze of late October before Election Day. Hunched and harried, they work the phones to the Coast until 2 or 3 in the morning, while writing the candidate's talking points for the next day, and then hitting the Eastern time zone phones at dawn. The badge of special honor is simultaneously to be advising campaigns from Washington in the time zones of Britain and Israel. Friday, 4 a.m., Hour 21. When this stuff takes over, it takes over. Gently, not violently. No apparent loss of acuity. But you have definitely kicked into a gear you didn't know you had. Playing computer games like FreeCell as an informal way of testing cognitive ability. Do you dare send e-mails? Will you regret them when you return to normal? Speaking of rhythms, remember to eat. Got to keep up strength. Discomfort still far less than it would have been had coffee been used to accomplish this task. Getting awful sick of herb tea, though. So what about the dreaded third group -- the rest of us, those who are in a fundamentally different situation from the first two groups? We have a choice whether to live a saner life or try to solve our problems with a pill. "The young professional who wants to work and play and do everything, and doesn't want to spend time sleeping?" asks University of Pennsylvania sleep researcher David Dinges. "That's another matter." Yes, sleep researchers grudgingly admit, there are going to be some way-off-label users. The college students crashing on term papers. Truck drivers. Barge operators. Airline pilots. The physician in long hours of training. The new parent. Ever watch the White House-based television show "The West Wing?" They never seem to go home. That is not fantasy. "Sleepiness is everywhere," says Neil Feldman, medical director of the St. Petersburg, Fla., Sleep Disorder Center, who is conducting a shift work study for Cephalon. "We're a 24-hour society. We no longer live by the night/day cycle. We live by whatever our occupation demands. Physicians on call at night. Nuclear power plant operators. Police, firemen. Plus the world is becoming a smaller place. Trans-meridian travel, commonly known as jet lag. There are economic demands -- more than one job -- plus raising children. "How many have fallen asleep at the wheel of a car? Something like 25 percent at least momentarily once during the year. Sleep deprivation is everywhere. Our society looks at people who sleep as less strong people. People who nap are slugs." Suppose a lawyer came to you and said, "I have a client on death row and the governor has just given me three days to draft his appeal before he is executed." "I'd probably prescribe the drug," Feldman said. "But three pills. Not a hundred. I can rationalize that." "People ask me about it almost daily," says Dement. "Everybody would like to be able to have more time to do whatever they want to do. I could stand in front of a roomful of Stanford undergrads right now and say, 'If you feel tired, raise your hand,' and every hand would go up." Such a fundamental change in human nature is hardly without risks. "Emphasize the idea that we may be playing with fire here," says Emsellem. "Who knows why we get cancer? Chronic sleep deprivation may be a risk factor for long-term disease. I would love to get by on five hours of sleep because I don't like to lie in bed, leashed by a sleep requirement. I would love to be unleashed. But at the same time, prove that it is safe. I don't need another round of winter flu, thank you very much. Getting sick, being constitutionally exhausted." "When you have debate on this topic," says Edgar, "on one side, people say: 'Just sleep more. Do what you have to do and the economy be damned. Get the sleep that you need and that's that.' On the other side, people are saying: 'But wait a minute. This is a 24-hour world. Those services have to be performed at the highest level they can. People make mistakes.' " How do you compete? Edgar sighs. "This gets into this fair and legitimate debate. Type A people in Washington go until they drop. You don't know the ultimate consequences. The extra load on the kidneys, liver, pancreas, endocrine functions. This could be really important." "The final twist is that caffeine is a food additive," says Edgar. Replacing caffeine with modafinil -- "that would be the revolutionary next step. Just as one replaces sugar with NutraSweet. Everybody drinks soda pop with caffeine from the age of 5 up. Yeah. You're changing the world. Yeah. I'm telling you as a sleep scientist the kinds of things we see on the horizon. It's exciting. Changing lives. Saving lives. That's for certain. "Is it appropriate for college students pulling an all-nighter? No. Sleep physiologists will all tell you the same thing. There is no true substitute for sleep itself. We say that with conviction," Edgar says. Suppose that will no longer be the case? "The more far-out question is: What if we eventually had something that was absolutely safe that could substitute for sleep?" asks Dinges. "Is that the direction we want to go? Many would say yes. I don't know what the implications are for our species. Probably not bad. This is pure speculation. Should humans try to live without sleep? I don't know. We're already trying to do that." Friday afternoon, 4 p.m., Hour 33. Tired from all this writing. But not sleepy. Interesting to imagine a future in which those are two distinctly separate things. The problem isn't wakefulness. The problem is cranking through three or four days' worth of work in one burst. Started to yawn at 8 a.m., at the bottom of circadian rhythms. Lay down for a two-hour nap. As researchers say, this stuff doesn't prevent you from sleeping, it just controls the desire to. Arose alert. Went back to productive work. Naps are good, as the sleep researchers ceaselessly point out. Glad this experiment occurred in a home office, and not downtown. Wouldn't relish driving at this point. Don't feel impaired, but wouldn't want to test the proposition. Have no interest in taking any more pills to further the experiment. Looking forward to returning to the planet of the mortals with a glass of wine and a good supper. Wonder what this will read like after a good night's sleep? The concern is this: One is always taught never to hand in a complicated project at the end of the day. Read it over one last time with fresh eyes in the morning. But fresh eyes are optional, when you don't have to sleep. Fatigue still hasn't set in. It wouldn't be hard to hand this in and begin preparations for the next project with a whole afternoon in front of you. What happens when fresh eyes are a choice, not an inevitable part of the rhythms of life? We will be asking ourselves these questions about human nature with increased frequency as biotechnology advances and drugs originally designed for the sick begin to augment the healthy. We have already seen this happen with Viagra. It now sponsors network evening news shows, a development that would have boggled scenario planners just five years ago. More drugs are in the works that attack shyness, forgetfulness and the mental decline of aging. Others add muscle mass and boost the ability to learn, at least in mice. Saturday morning, 10 a.m., Hour 51, after eight hours of sleep. Would need to have an awfully compelling reason to want to do this again. But can imagine how others might differ. Sure was a lot of living packed into the last two days. Got so much done that there is a whole unencumbered weekend in sight. What a concept. LOAD-DATE: June 17, 2002 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2002 The Washington Post 874 of 998 DOCUMENTS Edmonton Journal (Alberta) May 20, 2002 Monday Final Edition An assault on sleep: Canadian military researchers look for a way to keep the troops awake: OVERCOMING THE INSTINCT TO SLEEP SOURCE: Southam Newspapers; Ottawa Citizen BYLINE: Tim Lougheed SECTION: Living Well; Pg. C2 LENGTH: 840 words DATELINE: Ottawa Perhaps from the time the first human being had to pull an all-nighter, the enemies of sleep have been hard at work on ways of helping us overcome this very powerful natural instinct. But while stimulants such as amphetamines or caffeine have become well-established for their effectiveness, along with their various side effects, researchers are now focusing on a new and very different drug that was developed less than 20 years ago. Modafinil is a synthetic compound discovered in the early 1980s by a small family-owned French pharmaceutical firm, Lafon Laboratories. Although its biochemical mechanism is still not fully understood, the drug was quickly hailed as a revolutionary new treatment for narcolepsy. This chronic condition causes people to suffer from a constant, irresistible urge to fall asleep, yet the quality of their sleep is poor. Conventional stimulants can help narcoleptics resolve their symptoms temporarily, but these treatments do not address the underlying problem. Modafinil apparently does, at least for some patients. By managing their dosage, these individuals are able to stay awake through the day and get a restful night's sleep, with few significant side effects. Above all, the drug continues to remain effective, even after it has been taken for as long as 15 years. The unique properties of modafinil have inspired active exploration of possible applications. "There's a whole world of researchers that are working on this drug right now," says Joseph Baranski, a member of the human factors division of Defence R&D Canada. The Toronto-based facility is one of five federal military research installations across Canada, and has taken a leading role in examining the elements that enable people to perform at their best under ordinary and extraordinary circumstances. Not surprisingly, sleep is among the foremost of those elements. And it takes on special significance when it comes to planning intense missions that might require troops to remain awake and alert for several days at a time. The U.S. military has published studies about the use of amphetamines by its pilots flying night missions. Over the last decade Defence R&D Canada has compared the value of amphetamines and modafinil under simulated mission-critical conditions. Ross Pigeau, head of the agency's human factors division, led a major study conducted in 1994. Subjects were kept awake continuously for 64 hours, and kept busy with a series of computer tasks lasting almost two hours at a time. At key points, some participants were given amphetamines, some were given modafinil, and some were given placebos, although no one knew who was getting what. As measured by the quality of computer work, modafinil managed to stave off a serious drop in mental competence after almost three days. For people taking nothing, that drop could amount to two-thirds of performance. Modafinil kept the decrease to about half of that amount, with the added virtue of not disturbing the quality of sleep afterward, which amphetamines can do. "It seems that the mechanism of it is much different than amphetamines," says Pigeau. "Amphetamine is a general nervous system stimulant. It just gooses up the whole nervous system. Whereas modafinil apparently stops you from feeling sleepy. It essentially inhibits the natural sleep-inducing processes of the brain." In fact, modafinil does not attack sleep so much as it promotes wakefulness. Over the past few decades, scientists studying sleep have learned even more about what it means to be awake. According to Roger Broughton, who has been in the field for 40 years, there are in upwards of seven distinct brain centres controlling this aspect of our consciousness. Modafinil acts on at least one of them. "There are multiple brain systems with different transmitters that sustain wakefulness," says Broughton, who conducts sleep research at the Ottawa Hospital's General campus. "We don't really know yet their hierarchical interactions. But almost all of them do other things as well." He was one of the principal researchers in a definitive Canadian study, published in 1997, which led to Health Canada's approval of modafinil in 1999. The drug is still listed as a controlled substance, although it can be found for sale on the Internet through mail-order drug warehouses operating out of offshore legal havens such as Britain's Channel Islands. Because the neurological mechanism of modafinil is still being fathomed, researchers are highly cautious about its widespread use. For now the prospect worries Timothy Monk, director of the human chronobiology research program at the University of Pittsburgh Medical Centre. "What I worry about is the issue of somebody who wants to succeed in business and work 100-hour weeks, and the way to do that is to pop a modafinil. "That is a cause for concern, given that we don't know the effects of only having four hours of sleep and then avoiding the negative sleepiness with a pill." LOAD-DATE: May 20, 2002 LANGUAGE: ENGLISH GRAPHIC: Photo: Southam Newspapers, Ottawa Citizen; Canadian research looks at ways to enable people to perform at their best without sleep. TYPE: News Copyright 2002 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 875 of 998 DOCUMENTS Internet Wire May 20, 2002 Monday Attention Science Writers: New Clinical Data In Treating Symptoms Of Depression LENGTH: 1063 words DATELINE: May 20, 2002; INTERNET WIRE Depression affects more than 18 million American adults annually. Patients experience persistent sadness, anxiousness, or emptiness along with feelings of hopelessness, pessimism and guilt, and a loss of interest or pleasure in hobbies and activities that they once enjoyed. In addition, patients also suffer from equally debilitating physical symptoms, such as fatigue and excessive daytime sleepiness (EDS). These patients also report feeling a "lack of energy" and constant weariness, drowsiness and exhaustion, despite the amount of sleep they receive. Further, antidepressant medications often exacerbate fatigue and EDS, leaving the patient feeling sleepy, sluggish, lethargic and, ultimately, hopeless about ever being "cured" of depression. Mental health professionals have just begun to understand the importance of managing these less noticeable, yet equally harmful, symptoms of depression that have a tremendous impact on the patient's recovery. WHAT:Study results on modafinil, the latest therapeutic agent being investigated for the management of EDS and fatigue in patients with depression. Abstract attached:  -- Adjunct Modafinil Rapidly Improves Fatigue and Wakefulness in Patients with Major Depressive Disorder- Doghramji, K., et al.  -- Effect of Adjunct Modafinil on Energy and Concentration in Depressed Patients- Menza, M.A., et al. WHO:Study Investigators: Karl Doghramji, M.D. Associate Professor of Psychiatry and Human Behavior Jefferson Medical College Philadelphia, PA Matthew A. Menza, M.D. Chief of Clinical Psychopharmacology Robert Wood Johnson Medical School Piscataway, NJ WHEN:      Monday, May 20, 2002 11 a.m.- 12: 30 p.m. EST Thursday, May 23, 2002 11 a.m.- 12: 30 p.m. EST WHERE:155th Annual Meeting of the American Psychiatric Association Philadelphia Convention Center Level 200, Room 204 A Please visit www.provigil.com for complete prescribing information. -------------------------------------------------------------------------------- ------------------------------------------------------------ Modafinil Rapidly Improves Fatigue and Wakefulness in Patients With Major Depressive Disorder Karl Doghramji, M.D., Sleep Disorders Center, Thomas Jefferson University, 1015 Walnut St, Ste 319, Philadelphia, PA 19107; Matthew Menza, M.D., Murray Rosental, D.O., Ronald Fieve, M.D. OBJECTIVE: and sleepiness are primary symptoms of major depressive disorder (MDD) that often do not resolve with antidepressant therapy and may require additional therapeutic measures. Modafinil, a novel wake-promoting agent, improves wakefulness in patients with excessive sleepiness, and reduces fatigue in patients with multiple sclerosis. This study evaluated the effects of Modafinil on fatigue and sleepiness in patients with MDD. METHOD: with partial response to antidepressants given for at least 6 weeks for a current major depressive episode were enrolled in this -week, randomized, double-blind, placebo-controlled, multicenter study. Patients received Modafinil (100-400 mg/day) or placebo as adjunct treatment to ongoing antidepressant therapy. Changes in fatigue and daytime sleepiness were evaluated using the Fatigue Severity Scale (FSS) and Epworth Sleepiness Scale (ESS), respectively. Adverse events were recorded. RESULTS: 136 patients randomized, 118 (87%) completed the study. Most patients were fatigued (82%), and half (51%) were sleepy. Modafinil rapidly improved fatigue and daytime wakefulness, with significantly greater mean changes from baseline than placebo in FSS scores at week 2 (p < 0.05) and ESS scores at week 1 (p < 0.01). Modafinil was well tolerated in combination with a variety of antidepressants. CONCLUSION: may be a useful adjunct for the management of fatigue and sleepiness in patients who are partial responders to antidepressant therapy. FUNDING: by Cephalon, Inc. Literature References: 1. Menza MA, Kaufman KR, Castellanos A. Modafinil augmentation of antidepressant treatment in depression. J Clin Psychiatry 2000;61:378-381. 2. DeBattista C, Solvason HB, Kendrick E, Schatzberg AF. Modafinil as an adjunctive agent in the treatment of fatigue and hypersomnia associated with major depression. In: New Research Program and Abstracts of the 154th Annual Meeting of the American Psychiatric Association; May 9, 2001; New Orleans, LA. Abstract NR532:144 -------------------------------------------------------------------------------- ------------------------------------------------------------ Use of Modafinil in Depression To recognize the potential benefit of Modafinil, a wake promoting medicine in the treatment of some depressed patients Menza MA, et al: Modafinil Augmentation of Antidepressant Treatment in Depression. J Clin Psychiatry 2000; 61:378-381 Mitchell PB: Novel Antidepressants Not Available in the United States. Psychopharmacology Bull 1995; 31(3): 509-519 OBJECTIVE: study is a retrospective review of the use of Modafinil, a wake promoting agent, as an adjunct in the treatment of depression in a general psychiatric practice. METHODS: records of seventy-eight (N=78) depressed Caucasian outpatients who were deemed in need of adjunctive treatment with a stimulant over a 9 months period were reviewed. There were 49 females and 29 males. Their mean age was 44 years (+/- 14). 55 patients (71%) had previously failed or did not tolerate other stimulants. 60 patients (77%) were diagnosed with Unipolar Depression, 13 (71%) with Bipolar Depression, and 5 with other depression diagnoses. Outcome measures included the Visual Analog Scale (VAS), the Carroll Depression (self) Rating Scale, the CGI-C pre and post treatment. RESULTS: were significant improvement in the CGI-S score (p < 0.001), CDRS (p < 0.02) and VAS (p < 0.03). The mean CGI-C was 1.91 (+/- 0.94) Modafinil was well tolerated at an average dose of 249mg/day (+/- 122mg) and a range of 100 to 800 mg/day. CONCLUSIONS: Modafinil is a useful adjunct in the treatment of depression, especially when stimulants are needed for help with sleepiness and fatigue, or incomplete remission with antidepressants.  CONTACT: Sheryl Williams Cephalon 610-738-6493 swilliam@cephalon.com Andrea Pelliciarri Hill and Knowlton 212-885-0623 apellicc@hillandknowlton.com LOAD-DATE: May 21, 2002 LANGUAGE: ENGLISH Copyright 2002 Internet Wire, Incorporated. All rights reserved. 876 of 998 DOCUMENTS Ottawa Citizen May 13, 2002 Monday Final Edition An assault on sleep: A drug used to keep narcoleptics awake is being tested by Canadian military researchers as a way to keep troops awake and alert for days, reports Tim Lougheed. SOURCE: The Ottawa Citizen BYLINE: Tim Lougheed SECTION: News; Pg. A12 LENGTH: 936 words Perhaps from the time the first human being had to pull an all-nighter, the enemies of sleep have been hard at work on ways of helping us overcome this very powerful natural instinct. But while stimulants such as amphetamines or caffeine have become well-established for their effectiveness, along with their various side effects, researchers are now focusing on a new and very different drug that was developed less than 20 years ago. Modafinil is a synthetic compound discovered in the early 1980s by a small family-owned French pharmaceutical firm, Lafon Laboratories. Although its biochemical mechanism is still not fully understood, the drug was quickly hailed as a revolutionary new treatment for narcolepsy. This chronic condition causes people to suffer from a constant, irresistible urge to fall asleep, yet the quality of their sleep is poor. Conventional stimulants can help narcoleptics resolve their symptoms temporarily, but these treatments do not address the underlying problem. Modafinil apparently does, at least for some patients. By managing their dosage, these individuals are able to stay awake through the day and get a restful night's sleep, with few significant side effects. Above all, the drug continues to remain effective, even after it has been taken for as long as 15 years. If modafinil works such wonders in people who need to sleep all the time, could it help the rest of us cut down the amount of sleep we must have each night? The short answer is no, but the unique properties of modafinil have inspired active exploration of other possible applications. "There's a whole world of researchers that are working on this drug right now," says Joseph Baranski, a member of the human factors division of Defence R&D Canada. The Toronto-based facility is one five federal military research installations across Canada, and has taken a leading role in examining the elements that enable people to perform at their best under ordinary and extraordinary circumstances. Not surprisingly, sleep is among the foremost of those elements. And it takes on special significance when it comes to planning intense missions that might require troops to remain awake and alert for several days at a time. The U.S. military has published studies about the use of amphetamines by its pilots flying night missions, who have access to the drug but are not under orders to take it. Canada has no policy of similar sleep-fighting drug use in military settings, but over the last decade Defence R&D Canada has compared the value of amphetamines and modafinil under simulated mission-critical conditions. Ross Pigeau, head of the agency's human factors division, led a major study conducted in 1994. Subjects were kept awake continuously for 64 hours, and kept busy with a series of computer tasks lasting almost two hours at a time. At key points, some participants were given amphetamines, some were given modafinil, and some were given placebos, although no one knew who was getting what. As measured by the quality of computer work, modafinil managed to stave off a serious drop in mental competence after almost three days. For people taking nothing, that drop could amount to two-thirds of performance. Modafinil kept the decrease to about half of that amount, with the added virtue of not disturbing the quality of sleep afterward, which amphetamines can do. "It seems that the mechanism of it is much different than amphetamines," says Mr. Pigeau. "Amphetamine is a general nervous system stimulant. It just gooses up the whole nervous system. Whereas modafinil apparently stops you from feeling sleepy. It essentially inhibits the natural sleep-inducing processes of the brain." In fact, modafinil does not attack sleep so much as it promotes wakefulness. Over the past few decades, scientists studying sleep have learned even more about what it means to be awake. According to Roger Broughton, who has been in the field for 40 years, there are in upwards of seven distinct brain centres controlling this aspect of our consciousness. Modafinil acts on at least one of them. "There are multiple brain systems with different transmitters that sustain wakefulness," says Dr. Broughton, who conducts sleep research at the Ottawa Hospital's General campus. "We don't really know yet their hierarchical interactions. But almost all of them do other things as well." He was one of the principal researchers in a definitive Canadian study, published in 1997, which led to Health Canada's approval of modafinil in 1999. The drug is still listed as a controlled substance, although it can be found for sale on the Internet through mail-order drug warehouses operating out of offshore legal havens such as Britain's Channel Islands. Because the neurological mechanism of modafinil is still being fathomed, researchers are highly cautious about speculating as to whether it will find a place alongside such popular and widely available stimulants as caffeine. For now the prospect worries Timothy Monk, director of the human chronobiology research program at the University of Pittsburgh Medical Centre. "The potential use for modafinil is clear and to some extent proven," says Dr. Monk, who is currently examining its use by groups like firefighters and astronauts. "What I worry about more is the issue of somebody who wants to succeed in business and work 100-hour weeks, and the way to do that is to pop a modafinil. That is a cause for concern, given that we don't know the effects of only having four hours of sleep and then avoiding the negative sleepiness with a pill." LOAD-DATE: May 13, 2002 LANGUAGE: ENGLISH GRAPHIC: Colour Photo: Stephen Thorne, the canadian press; Defence R&D Canada is examining whether modafinil, a narcolepsy drug, can be given to troops who must perform at their best under extraordinary circumstances, even if they are severely sleep-deprived. TYPE: News Copyright 2002 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 877 of 998 DOCUMENTS Neurology Alert May 1, 2002 CME Questions LENGTH: 279 words CME Questions Regarding functional recovery after perinatal brachial plexus injury (PRPP): a. spontaneous recovery rates are high in Grade 1 and Grade 2 injuries. b. sensory function may recover in infants with high-grade avulsions only if surgery is performed by age 3 months. c. following surgery, there is substantial loss of topographic localization of stimuli. d. a substantial number of children report pain several years following severe perinatal brachial plexus injury. e. only nonoperated patients describe severe pain years after perinatal brachial plexus injury. In the treatment of fatigue in MS, Rammohan et al found that: a. modafinil was well tolerated in patients. b. 200 mg/d of modafinil significantly improves fatigue. c. 400 mg/d did not significantly improve fatigue. d. None of the above e. All of the above Electrical stimulation following nerve injury: a. depresses BDNF levels in regenerating nerve. b. enhances nerve growth factor (NGF) levels. c. increases trkB mRNA expression in the injured nerve. d. All of the above e. None of the above In patients with a spontaneous CSF leak, all of the following suggest an underlying connective tissue disorder except: a. hyperflexible joints. b. laxity of joints c. history of a carotid artery dissection. d. retinal detachment at a young age. e. mental retardation. Microendoscopic decompressive laminotomy: a. is the procedure of choice for lumbar spinal stenosis. b. is associated with an increased incidence of dural tears. c. may be as effective for spinal stenosis as unilateral open laminotomy. d. is associated with a decreased incidence of injury to the exiting nerve roots. e. None of the above LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2002 AHC Media LLC All Rights Reserved 878 of 998 DOCUMENTS The Washington Post April 28, 2002 Sunday Final Edition For Sleep-Deprived, a Dream Drug?; Doctors Question Use of Narcolepsy Medicine to Support Lifestyle Choice BYLINE: Shankar Vedantam, Washington Post Staff Writer SECTION: A SECTION; Pg. A03 LENGTH: 1377 words Merrill Mitler travels frequently, often sleeping consecutive days in different time zones. When his body clock feels out of sync with his schedule, he swallows a medicine that was approved to treat sleepiness associated with a rare disorder he doesn't have. Americans last year bought $ 150 million worth of the drug modafinil, which was approved to treat narcolepsy, an unusual disorder that causes people to fall asleep suddenly. Three-quarters of the pills were swallowed by people who didn't have narcolepsy. Doctors are prescribing the drug to patients with other disorders and, increasingly, to people with no disorder at all. Three years after it was approved, the medicine is raising questions about how many healthy Americans might soon want it simply to sleep less -- yet another example of a medicine being used not to treat illness, but to support a lifestyle choice. Unlike amphetamines and conventional stimulants, modafinil does not give people a jolt. Doctors believe it is not addictive and say it is generally safe, with only occasional side effects such as headache or nausea. But no one knows what might happen if people use the drug to do away with sleep for prolonged periods. "The biggest questions are societal," said Thomas Scammell, a neurologist at Harvard Medical School. "What's to keep us from working 24-7? . . . To take a drug and try to counter this natural necessity of sleep is to defy nature. It's like if I can give you a pill to take away your appetite -- does it mean it's okay not to eat?" The drug's manufacturer, Cephalon Inc. of West Chester, Pa., had promoted it as effective for more than just narcolepsy. But after the Food and Drug Administration charged in January that Cephalon's promotional materials were "false, lacking in fair balance or otherwise misleading," the company promised to limit its promotional pitches to narcolepsy. The company plans eventually to present studies to the FDA that would expand the drug's approval for sleepiness associated with a variety of psychiatric and neurological disorders. Studies are also underway to test whether modafinil can help healthy truck drivers navigate night journeys and get to their destinations safely by dawn. The military is investigating whether modafinil can help healthy soldiers stay awake for lengthy periods in combat. A large trial is studying the medicine's effectiveness among shift workers. At one site of this study, the Scripps Research Institute in San Diego, psychologist Mitler is evaluating whether modafinil can help people fight their normal circadian rhythms. His use of the medicine suggests he knows the result. "Do you need a pill to treat a normal condition?" Mitler said. "There is all sorts of precedent for that -- we take aspirin for sore muscles associated with exercise. Muscles are supposed to hurt when they are not trained. Yet we medicalize it in order to treat the discomfort." "The side effects of caffeine are much more severe than the side effects of modafinil," said Mitler, who believes that decisions about modafinil are best left to individuals and their doctors. Americans have long been fascinated by sleep -- or rather, with not sleeping: Students glorify in tales of all-nighters; sleeping on the job has often been grounds for getting fired; and the ultimate capitalist utopia is the 24-hour workday. A spokeswoman for Cephalon acknowledged that the company sought to expand the market for modafinil beyond narcoleptics. Studies are showing that the medicine, which is sold as Provigil, could help people with sleepiness associated with depression, Parkinson's disease and other disorders, she said. "There are so many conditions where people have pathological sleepiness where we can help them," said the spokeswoman, Sheryl Williams. "Can we stop people from using the product for other things? Absolutely not, but the right place to be is in treating serious medical problems." Once a drug is approved for one use, doctors are free to prescribe it for others. Williams said most of the medicine's "off-label" use was in treating psychiatric and neurological conditions. "We have not seen in our tracking data a significant proportion of patients with nonmedical conditions," she said. But treating sleepiness can blur the line between medical disorders and lifestyle problems, since sleepiness is not a disorder. The shift workers in Mitler's study, for example, are known to be at heightened risk for accidents and to have increased medical problems associated with their irregular sleep. But there may not be anything intrinsically wrong with them since their problems often go away when they resume normal schedules. Yet, doctors have classified sleep disturbances caused by the workers' lifestyle as a disorder. The American Psychiatric Association, for instance, says, "Circadian Rhythm Sleep Disorder" can occur when people's "circadian sleep-wake cycle is normal" but there is a "conflict between the pattern of sleep and wakefulness generated by the circadian system and the desired pattern of sleep and wakefulness required by shift work." "These individuals are impaired," Mitler said. "Whether you call it a disorder or not is less important than the fact that they are impaired. Physicians have found themselves in the mix simply by declaring this a treatable disorder." Cephalon eventually would like modafinil to be recognized as a treatment for all sleepiness associated with any disorder. But in warning the company about its promotional materials in January, the FDA noted that "Provigil is not approved to treat such symptoms as sleepiness, tiredness, decreased activity, lack of energy and fatigue." "Provigil is indicated to improve wakefulness in patients with excessive daytime sleepiness associated with narcolepsy," the FDA wrote to a senior official at the company Jan. 3. "Provigil is not approved for use as a daytime stimulant." After Cephalon agreed to alter its marketing materials, the FDA considered the matter resolved. Notwithstanding the FDA's protests, there is every indication that modafinil is effective in keeping healthy people awake. It may soon be common for shift workers, soldiers and truck drivers to pop the pills before embarking on long journeys or difficult projects. Nancy Wesensten, a researcher at the Walter Reed Army Institute of Research in Silver Spring, has shown that healthy people who have been kept awake for 54 hours -- more than two nights -- still function effectively when given modafinil . The drug seems to work on other species, too: At the University of Pennsylvania, scientist Joan Hendricks has even found that modafinil helps sleep-deprived fruit flies perk up. "It has a much gentler effect on promoting wakefulness" than amphetamines and conventional stimulants, said Scammell, the Harvard neurologist. "Many people feel comfortably awake -- they don't feel wound up, jazzed or euphoric. That's what makes it attractive to doctors. We are always worried that amphetamines may not be used properly. The abuse potential [of modafinil] is low." He pointed out that the exact mechanism of modafinil is not understood. For example, while many researchers believe that the medicine doesn't affect the brain's dopamine system -- a neural mechanism known to underlie many addictions -- this hasn't been conclusively demonstrated. About 1 in 10 people on modafinil have headaches, and smaller numbers feel some nausea, he said. Scammell, Mitler and others who study the medicine warn that talk of replacing sleep altogether is foolish. Other chemicals have been similarly touted -- and then found to be harmful. "People were using [amphetamines] to stay awake for a number of days at a time -- there were a lot of problems associated with that," said John Caldwell, a research psychologist at the U.S. Army Aeromedical Research Lab at Fort Rucker, Ala., who has conducted experiments to show that sleep-deprived helicopter pilots perform better when given modafinil. "Who knows what will happen with modafinil?" he said. "We don't know why sleep has the restorative effect it does. Given we don't understand the nature of sleep, I don't think it's a good idea to try to replace it with a drug of any description." LOAD-DATE: April 30, 2002 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2002 The Washington Post 879 of 998 DOCUMENTS San Mateo County Times (San Mateo, CA) February 4, 2002 Monday Colon cancer SECTION: LIVING LENGTH: 537 words The question: For patients with colon cancer, is laparoscopic-assisted surgery preferable to traditional, open-colon surgery? Past studies of laparoscopic-assisted colectomy [LAC] have rarely focused on patients who were being treated for cancer, have assessed only the short-term effects of this minimally invasive technique and have involved only small numbers of patients. This study compared the physical and mental state of 428 patients two days, two weeks and two months after LAC or open surgery. On average, patients who underwent LAC stayed in the hospital almost one day less and needed less pain medication while hospitalized than those who had open surgery. The authors considered these benefits minimal. The two groups had similar experiences regarding factors such as nausea, insomnia and fatigue. Who may be affected by these findings? People with localized colon cancer. Caveats: The researchers did not assess the patients' need for pain relief after their discharge from the hospital. More important, this study did not compare the survival rates of the two groups of patients. [This issue is being evaluated using data from these and other patients, but the results will not be known for several years.] Bottom line: People with localized colon cancer may wish to refrain from asking doctors for LAC until more is known about its risks and benefits. And as an editorial accompanying the study suggests, those who nonetheless prefer LAC may wish to consider entering a clinical trial to help establish the effectiveness and safety of the technique. Find this study: Jan. 16 issue of the Journal of the American Medical Association; abstract online at http://jama.ama-assn.org/ Multiple sclerosis The question: Can modafinil, a drug used to treat narcolepsy, alleviate the fatigue caused by multiple sclerosis [MS]? Past studies have shown that drugs such as amantadine [e.g., Symmetrel], which is used to treat Parkinson's syndrome, and the stimulant pernoline [Cylert] have only minimal effects on the fatigue often experienced by MS patients. This study examined whether modafinil [Provigil] would be more beneficial. The researchers compared the effects of a placebo with those of 200 and 400 milligrams of modafinil in 18 men and 54 women for nine weeks. [The participants were not told when they were using the placebo and when they were receiving the drug.] Most experienced significant relief from fatigue when they were taking 200 milligrams of modafinil; others benefited from the higher dose. Side effects of the drug included mild to moderate cases of headache, nausea and anxiety. Who may be affected by these findings? People with multiple sclerosis who experience fatigue daily. Caveats: Cephalon Inc., the manufacturer of Provigil, funded the study, which was based on self-reports, which may not be accurate. Also, the long-term effects of the drug on MS patients are not known. Bottom line: People with multiple sclerosis may wish to consult a physician about taking modafinil. Find this study: February issue of the Journal of Neurology, Neurosurgery and Psychiatry; abstract online at http://jnnp.bmjjournals.com/ -- Washington Post LOAD-DATE: June 19, 2003 LANGUAGE: ENGLISH Copyright 2002 MediaNews Group, Inc. and ANG Newspapers 880 of 998 DOCUMENTS The Washington Post January 29, 2002 Tuesday Final Edition MULTIPLE SCLEROSIS An anti-sle ... SECTION: HEALTH; QUICK STUDY A WEEKLY DIGEST OF NEW RESEARCH ON MAJOR HEALTH TOPICS; Pg. F09 LENGTH: 775 words MULTIPLE SCLEROSIS * THE QUESTION Can modafinil, a drug used to treat narcolepsy, alleviate the fatigue caused by multiple sclerosis (MS)? * PAST STUDIES have shown that drugs such as amantadine (e.g., Symmetrel), which is used to treat Parkinson's syndrome, and the stimulant pernoline (Cylert) have only minimal effects on the fatigue often experienced by MS patients. * THIS STUDY examined whether modafinil (Provigil) would be more beneficial. The researchers compared the effects of a placebo with those of 200 and 400 milligrams of modafinil in 18 men and 54 women over nine weeks. (The participants were not told when they were using the placebo and when they were receiving the drug.) Most experienced significant relief from fatigue when they were taking 200 milligrams of modafinil; others benefited from the higher dose. Side effects of the drug included mild to moderate cases of headache, nausea and anxiety. * WHO MAY BE AFFECTED BY THESE FINDINGS? People with multiple sclerosis who experience fatigue daily. * CAVEATS Cephalon Inc., the manufacturer of Provigil, funded the study, which was based on self-reports, which may not be accurate. Also, the long-term effects of the drug on MS patients are not known. * BOTTOM LINE People with multiple sclerosis may wish to consult a physician about taking modafinil. * FIND THIS STUDY February issue of the Journal of Neurology, Neurosurgery and Psychiatry; abstract online at http://jnnp.bmjjournals.com/. HAY FEVER * THE QUESTION Does the herb butterbur relieve hay fever symptoms as effectively as do antihistamines? * PAST STUDIES have shown that antihistamines can relieve some of the symptoms of hay fever, such as runny nose and sneezing, but these drugs may also cause drowsiness. * THIS STUDY, which was double-blind, compared the effectiveness of the herbal extract butterbur to cetirizine (Zyrtec) in relieving hay fever symptoms. The researchers randomly assigned 125 people with hay fever to receive daily doses of either butterbur or cetirizine. After two weeks, the people in both groups experienced similar amounts of symptom relief. * WHO MAY BE AFFECTED BY THESE FINDINGS? People who experience hay fever. * CAVEATS Zeller AG of Switzerland, a manufacturer of herbal remedies, funded the study. In addition, the long-term effects of butterbur are not known. Finally, the results are partially based on self-reports of symptoms by the participants. * BOTTOM LINE People with hay fever who would like to avoid the drowsiness caused by antihistamines may wish to consult their doctor about using butterbur. (They should also be aware that supplies of this herb may not have guaranteed purity and potency, and that experts advise users to be sure that the extract has been processed to remove potentially dangerous chemicals called pyrrolizidine alkaloids.) * FIND THIS STUDY Jan. 19 issue of the British Medical Journal or www.bmj.com. COLON CANCER * THE QUESTION For patients with colon cancer, is laparoscopic-assisted surgery preferable to traditional, open-colon surgery? * PAST STUDIES of laparoscopic-assisted colectomy (LAC) have rarely focused on patients who were being treated for cancer, have assessed only the short-term effects of this minimally invasive technique and have involved only small numbers of patients. * THIS STUDY compared the physical and mental state of 428 patients two days, two weeks and two months after LAC or open surgery. On average, patients who underwent LAC stayed in the hospital almost one day less and needed less pain medication while hospitalized than those who had open surgery. The authors considered these benefits minimal. The two groups had similar experiences regarding factors such as nausea, insomnia and fatigue. * WHO MAY BE AFFECTED BY THESE FINDINGS? People with localized colon cancer. * CAVEATS The researchers did not assess the patients' need for pain relief after their discharge from the hospital. More important, this study did not compare the survival rates of the two groups of patients. (This issue is being evaluated using data from these and other patients, but the results will not be known for several years.) * BOTTOM LINE People with localized colon cancer may wish to refrain from asking doctors for LAC until more is known about its risks and benefits. And as an editorial accompanying the study suggests, those who nonetheless prefer LAC may wish to consider entering a clinical trial to help establish the effectiveness and safety of the technique. * FIND THIS STUDY Jan. 16 issue of the Journal of the American Medical Association; abstract online at http://jama.ama-assn.org/. -- Haleh V. Samiei LOAD-DATE: January 29, 2002 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2002 The Washington Post 881 of 998 DOCUMENTS Espicom Business Intelligence January 23, 2002 Modafinil approved for marketing in Mexico LENGTH: 118 words Cephalon's partner, Armstrong Laboratorios ( Organizacion Bago), has received approval to sell and distribute modafinil in Mexico. Armstrong will market modafinil under the brandname, Modiodal. Cephalon controls worldwide rights to modafinil, marketed as Provigil in the US and several other countries. Armstrong has successfully executed a 6-month regulatory approval for modafinil in Mexico. Modafinil is a wake-promoting agent currently approved in several countries for the treatment of excessive daytime sleepiness associated with narcolepsy. The most common side effects associated with the drug in clinical trials include headache, nausea, infection, nervousness, anxiety and insomnia. LOAD-DATE: October 3, 2002 LANGUAGE: ENGLISH Copyright 2002 ESPICOM Business Intelligence Ltd. 882 of 998 DOCUMENTS Reuters Health eLine News January 23, 2002 Wednesday 9:00 PM EST Mexico clears daytime sleepiness drug LENGTH: 170 words DATELINE: WASHINGTON, Jan 23 The Mexican partner of Cephalon Inc., Armstrong Laboratorios de Mexico, has received approval to market Cephalon's daytime sleepiness treatment modafinil in Mexico, the West Chester, Pennsylvania-based concern announced on Tuesday. The drug is marketed under the brand name Provigil in the US and several other countries. In Mexico, it will be sold under the trade name Modiodal. In the US, Provigil was approved in 1998 for the treatment of a sleep disorder called narcolepsy and launched in February 1999. People with the disorder can fall asleep abruptly, possibly putting themselves and others in danger. The most common side effects of the drug are headache, infection, nausea, nervousness, anxiety and insomnia. Modafinil is not recommended for use in individuals with certain types of heart problems. Armstrong is a subsidiary of Organizacion Bago, one of Latin America's largest drug distributors. Cephalon and Armstrong entered the distribution and marketing agreement in May. Details of the deal were not disclosed. LOAD-DATE: July 24, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2002 Reuters Health All Rights Reserved 883 of 998 DOCUMENTS Espicom Business Intelligence January 22, 2002 Modafinil effective treatment for fatigue in MS LENGTH: 363 words Fatigue is one of the most debilitating effects of multiple sclerosis (MS). Researchers at the Ohio State University have now carried out a study to assess the efficacy and safety of Cephalon's Provigil ( modafinil) for the treatment of fatigue in MS. The data, published in the February issue of the Journal of Neurology, Neurosurgery and Psychiatry (2002;72:179-183), suggest that modafinal 200mg/day significantly improves fatigue and is well tolerated in MS patients. A total of 72 patients (74 per cent relapsing-remitting MS, 7 per cent primary-progressive MS, 19 per cent secondary-progressive MS) were enrolled in the 9-week, single-blind, 2-centre Phase II study. The patients were aged 18 to 65 years, and had a diagnosis of MS, a stable disability level 6 on the Kurtzke extended disability status scale (EDSS), and a mean score >4 on the fatigue severity scale (FSS). Exclusion criteria included a diagnosis of narcolepsy, sleep apnoea, or clinically significant major systemic disease and recent use of medications affecting fatigue. All patients received placebo during weeks 1 to 2, 200mg/day modafinil during weeks 3 to 4, 400mg/day modafinil during weeks 5 to 6, and placebo during weeks 7 to 9. Safety was evaluated by unblinded investigators. Efficacy was evaluated by self-rating scales, using the FSS, the modified fatigue impact scale (MFIS), a visual analogue scale for fatigue (VAS-F) and the Epworth sleepiness scale (ESS). After treatment with modafinil 200mg/day for 2 weeks, a significant improvement in fatigue versus placebo run in was demonstrated. Mean scores after treatment with modafinil200mg/daywere: FSS, 4.7 versus 5.5 for placebo (p<0.001); MFIS, 37.7 versus 44.7 (p<0.001); and VAS-F, 5.4 versus 4.5 (p=0.003). Fatigue scores for modafinil 400mg/daywere not significantly improved versus placebo run-in. Mean ESS scores were significantly improved (p<0.001) with modafinil200mg/day(7.2) and 400mg/day (7.0) versus the score at baseline (9.5). Serious adverse events were not found at either dose. The most common adverse events were headache, nausea and asthenia. Sixty-five patients (90 per cent) completed the study. LOAD-DATE: October 3, 2002 LANGUAGE: ENGLISH Copyright 2002 ESPICOM Business Intelligence Ltd. 884 of 998 DOCUMENTS PR Newswire January 22, 2002 Tuesday Cephalon Announces Modafinil Receives Marketing Approval in Mexico SECTION: FINANCIAL NEWS LENGTH: 731 words DATELINE: WEST CHESTER, Pa. Jan. 22 Cephalon, Inc. (Nasdaq: CEPH), an international biopharmaceutical company, announced today that its partner, Armstrong Laboratorios de Mexico S.A.C.V., has received approval to sell and distribute modafinil in Mexico. Armstrong will market modafinil under the brand name, MODIODAL. Cephalon controls worldwide rights to modafinil, marketed as PROVIGIL(R) (modafinil) tablets $(C- IV$) in the United States and several other countries. PROVIGIL is a unique, wake-promoting agent currently approved in several countries for the treatment of excessive daytime sleepiness associated with narcolepsy. The most common side effects associated with PROVIGIL in clinical trials include headache, nausea, infection, nervousness, anxiety and insomnia. "Armstrong has successfully executed a 6-month regulatory approval for modafinil in Mexico," said Frank Baldino, Jr. Ph.D., chairman and CEO of Cephalon. "The Mexican pharmaceutical market is experiencing double-digit growth, thereby providing a dynamic environment for the introduction of modafinil." Armstrong Laboratorios is a subsidiary of the Organizacion Bago, Latin America's leading regional pharmaceutical company. Sales volume for Armstrong's neurology and psychiatry products increased by 29 percent in 2000. The Mexican pharmaceutical market is the tenth largest in the world and has been experiencing greater percentage growth than the U.S. market. Cephalon, Inc. Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products to treat sleep and neurological, disorders, cancer and pain. Cephalon currently employs approximately 1,200 people in the United States and Europe. U.S. sites include the company's headquarters in West Chester, Pennsylvania, and offices and manufacturing facilities in Salt Lake City, Utah. Cephalon's major European offices are located in Guilford, England and in Maisons-Alfort, France. The company currently markets three proprietary products in the United States: PROVIGIL(R) (modafinil) tablets $(C-IV$), GABITRIL(R) (tiagabine hydrochloride) and ACTIQ(R) (oral transmucosal fentanyl citrate) $(C-II$). Full prescribing information on these products is available at www.cephalon.com. Cephalon markets 22 products outside the United States. Cephalon's biotechnology pipeline is focused on the identification of novel molecules that affect cell survival and death. Additional information about Cephalon and its subsidiaries can be obtained by visiting the company's Web site at http://www.cephalon.com. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs, development of potential pharmaceutical products, interpretation of clinical results, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, sales and earnings projections, and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties such as those set forth below and in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion.                      MAKE YOUR OPINION COUNT - Click Here                http://tbutton.prnewswire.com/prn/11690X53813698 SOURCE Cephalon, Inc. CONTACT: Media: Sheryl Williams, +1-610-738-6493 or swilliams@cephalon.com; or Investors: Robert S. (Chip) Merritt, +1-610-738-6376 or cmerritt@cephalon.com, both of Cephalon URL: http://www.prnewswire.com LOAD-DATE: January 23, 2002 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS AND MEDICAL EDITORS PUBLICATION-TYPE: Newswire Copyright 2002 PR Newswire Association, Inc. 885 of 998 DOCUMENTS CBS News Transcripts January 15, 2002 Tuesday SHOW: CBS Morning News (6:30 AM ET) - CBS New drug now used for narcolepsy may someday allow people to stay awake for extended periods without side effects ANCHORS: SUSAN McGINNIS BYLINE: ELIZABETH KALEDIN LENGTH: 476 words SUSAN McGINNIS, anchor: Most people seem to agree there are not enough hours in the day. Well, now scientists are developing a new drug that may someday allow us to burn the candle at both ends and in the middle. Elizabeth Kaledin reports in this morning's Eye on America. ELIZABETH KALEDIN reporting: It's 3:00 in the morning, and Home Depot is hopping. What better time to pick up a new washing machine? Unidentified Man #1: Can I help you? Unidentified Man #2: Yeah. Can I get a cheeseburger... KALEDIN: It's a 24-hour-a-day world, and despite what the clock says, the goal of modern society, it seems, is to expand time to make the difference between day and night obsolete. One little problem? We need to sleep. Professor DAVID DINGES (University of Pennsylvania): We're constantly pounding on this desire to get control of time and to use it, and sleep stands in the way. KALEDIN: Professor David Dinges is at the center of a growing new area of scientific interest... Prof. DINGES: Here, over here. There's a K-complex. KALEDIN: ...how to achieve wakefulness 24 hours a day. Prof. DINGES: There's growing evidence it's not good to go without sleep, and yet that's what everybody wants to do. KALEDIN: Dinges is studying the effects of a drug called Modafinil. Already approved by the FDA to treat the sleep disorder narcolepsy, Modafinil can convince the brain to be awake at any hour. Other older stimulants affect many centers of the brain, often causing the increased heart rate and blood pressure that lead to jitteriness, but Modafinil works only on specific neurotransmitters in the hypothalamus that control wakefulness. Janet Cassidy takes Modafinil twice a day to control narcolepsy and has no side effects. Ms. JANET CASSIDY (Narcoleptic): It's almost like you wouldn't know you'd taken anything. KALEDIN: Modafinil raises the possibility that we may one day be able to eliminate the need for sleep. Imagine the benefits for shift workers, hospital employees, brand-new parents. The American military is particularly interested. At Ft. Rucker in Alabama, researchers are giving Modafinil to Blackhawk helicopter pilots, who often have to fly long missions with no rest. Mr. DAVID TALARCZYK (Pilot): Typically, you're pretty physically and mentally drained. KALEDIN: Pilots here who took the drug and stayed awake as long as 35 hours performed the same as their well-rested peers. Mr. JOHN CALDWELL (US Army Aeromedical Research Center): It's nice to be able to do a research that's going to make our military pilots more effective. KALEDIN: But just because we can fight sleep, should we? Scientists don't know what the long-term health effects might be. It's a question we'll have to sleep on--if we ever go to bed, that is. In New York, I'm Elizabeth Kaledin for Eye on America. LOAD-DATE: January 31, 2002 LANGUAGE: ENGLISH TYPE: Newscast Copyright 2002 CBS Worldwide Inc. All Rights Reserved 886 of 998 DOCUMENTS CBS News Transcripts January 14, 2002 Monday SHOW: CBS Evening News (6:30 PM ET) - CBS New drug to help people stay awake and alert for days ANCHORS: JOHN ROBERTS BYLINE: ELIZABETH KALEDIN LENGTH: 491 words JOHN ROBERTS, anchor: Almost everyone wishes that there were more hours in the day, and while that's not possible, researchers may have found a way to get more out of the hours we have: a new drug to help people stay alert for days without sleep and not feel tired, wired or weird. CBS News medical correspondent Elizabeth Kaledin reports tonight's wide open Eye on America. ELIZABETH KALEDIN reporting: It's 3:00 in the morning, and Home Depot is hopping. What better time to pick up a new washing machine? Unidentified Man #1: Can I help you? Unidentified Man #2: Yeah. Can I get a cheeseburger... KALEDIN: It's a 24-hour-a-day world, and despite what the clock says, the goal of modern society, it seems, is to expand time to make the difference between day and night obsolete. One little problem? We need to sleep. Professor DAVID DINGES (University of Pennsylvania): We're constantly pounding on this desire to get control of time and to use it, and sleep stands in the way. KALEDIN: Professor David Dinges is at the center of a growing, new area of scientific interest... Prof. DINGES: Here, over here. There's a K-complex. KALEDIN: ...how to achieve wakefulness 24 hours a day. Prof. DINGES: There's growing evidence it's not good to go without sleep, and yet that's what everybody wants to do. KALEDIN: Dinges is studying the effects of a drug called Modafinil. Already approved by the FDA to treat the sleep disorder narcolepsy, Modafinil can convince the brain to be awake at any hour. Other older stimulants affect many centers of the brain, often causing the increased heart rate and blood pressure that lead to jitteriness, but Modafinil works only on specific neurotransmitters in the hypothalamus that control wakefulness. Janet Cassidy takes Modafinil twice a day to control narcolepsy and has no side effects. Ms. JANET CASSIDY (Narcoleptic): It's almost like you wouldn't know you'd taken anything. KALEDIN: Modafinil raises the possibility that we may one day be able to eliminate the need for sleep. Imagine the benefits for shift workers, hospital employees, brand-new parents. The American military is particularly interested. At Ft. Rucker in Alabama, researchers are giving Modafinil to Blackhawk helicopter pilots, who often have to fly long missions with no rest. Unidentified Pilot: Typically, you're pretty physically and mentally drained. KALEDIN: Pilots here who took the drug and stayed awake as long as 35 hours performed the same as their well-rested peers. Mr. JOHN CALDWELL (US Army Aeromedical Research Center): It's nice to be able to do a research that's going to make our military pilots more effective. KALEDIN: But just because we can fight sleep, should we? Scientists don't know what the long-term health effects might be. It's a question we'll have to sleep on, if we ever go to bed, that is. In New York, I'm Elizabeth Kaledin for Eye on America. LOAD-DATE: January 31, 2002 LANGUAGE: ENGLISH TYPE: Profile Copyright 2002 CBS Worldwide Inc. All Rights Reserved 887 of 998 DOCUMENTS University Wire January 14, 2002 'Alertness' pill not designed for all-night studying BYLINE: By Shabina S. Khatri, Michigan Daily SOURCE: U. Michigan LENGTH: 432 words DATELINE: Ann Arbor, Mich. Imagine all the benefits of a caffeine pill, but without the harmful consequences. Sound too good to be true? The reality may not be too far off. Studies are being conducted on a drug called Modafinil, which was approved by the Federal Drug Administration in 1998 to treat narcolepsy, a sleep disorder characterized by uncontrollable sleepiness and frequent daytime sleep. Unlike other stimulants, Modafinil, also known as Provigil, has been found to increase alertness and focus in subjects without leaving them feeling wired or anxious. Most studies of the drug have been performed on subjects mimicking the condition of sleep-deprived shift workers, who alternately work day and night shifts. The military has also conducted similar experiments, based on the rationale that soldiers who sleep less can perform better. But is the drug safe enough for healthy, non sleep-deprived individuals who are just looking for a way to stay up at night? Dr. Ronald Chervin, director of the University of Michigan's Sleep Disorders Clinic, doesn't think so. "Modafinil is not a drug that students should take to cram for a test or write a paper," he said. "I have not seen published reports about its use for people without chronic sleep disorders." This lack of information involving the long-term effects of the drug on normal individuals has led many researchers reluctant to praise Modafinil as the newest miracle drug. In addition, Chervin said, "Modafinil does have known side effects, perhaps the most common being headache when patients first start a regular dose." Dr. Naseer Ahmad, an endocrinologist at Beaumont Hospital in Royal Oak, also agrees caution is needed. "This drug is a stimulant used to treat narcolepsy. It keeps your brain active. If not used properly, Modafinil could cause diarrhea, nausea and damage to the liver." LSA junior Anna Boonin, a biopsychology and cognitive science major, admits the idea of this magic pill is tempting but remains skeptical. "There's a risk when you introduce anything into your body. It's nice to think, oh I can take this pill and get all my work done and stay up all night," Boonin said. "But, then what about when you stop taking it? You wouldn't be able to function normally in society," she said. Until extensive research involving sleep deprivation in normal individuals is conducted, Chervin does not foresee Modafinil being sold over the counter. "This drug will not be made public and readily available through some other mechanism than a prescription," he said. (C) 2002 Michigan Daily via U-WIRE LOAD-DATE: January 14, 2002 LANGUAGE: ENGLISH Copyright 2002 Michigan Daily via U-Wire 888 of 998 DOCUMENTS The Associated Press State & Local Wire January 9, 2002, Wednesday, BC cycle NEVADA FOCUS: Las Vegas shift workers often have trouble sleeping BYLINE: By EMILY RICHMOND, Las Vegas Sun SECTION: State and Regional LENGTH: 872 words DATELINE: LAS VEGAS Alex Repp hasn't had a good night's sleep in 17 years. As a pit boss at Harrah's hotel-casino on the Las Vegas Strip, Repp works the casino floor from 8 p.m. to 4 a.m. and drives home through near-empty streets, searching for rest. At home, Repp pulls down the room-darkening shades in his bedroom, unplugs the phone and climbs under the covers. And then he waits for sleep to come. "I'll close my eyes and nothing happens," the 42-year-old said. "Sometimes it takes me three hours to fall asleep, and then I'm only sleeping for two hours. And when I wake up, I'm more tired than when I went to bed." Repp's hope for rest lies in a new study at the Clinical Research Center of Nevada that is trying to uncover a solution for shift-work sleep disorder. The disorder affects Repp and thousands of other shift workers whose bodies can't adjust to the schedule of working while others are off. If there's an answer, researchers figure, it will be in Las Vegas, where about a third of the work force pulls shifts outside the regular 9-to-5. "When you think about shift workers, you think about Las Vegas," said Dr. John Pinto, the study's lead researcher. "We have a unique opportunity to define what happens to shift workers' sleep and how we can help." Getting a good night's sleep is more than satisfying a mother's urging, researchers say. Sleep problems can lead to health problems and contribute to accidents caused by fatigue. "A good night's sleep is a basic necessity, not a luxury," Pinto said. "When you don't get enough sleep it takes a toll on you physically and emotionally." Nearly two-thirds of shift workers surveyed reported difficulty sleeping, and 29 percent said at least a few days a week sleepiness interfered with work and daily activities, according to the National Sleep Foundation. That's compared with 17 percent of regular day workers who reported similar difficulties. The study is trying to use a drug to simulate the effects of sleep on the brain, giving shift-workers - who struggle after an unnatural sleep cycle - the ability to rest. Until recently, most sleep studies have focused on the effects of stimulants to keep people awake. College students pulling all-nighters long ago discovered sugar and caffeine as ways to avoid sleep, Pinto said. There are also prescription stimulants, such as amphetamines, that can boost wakefulness for short periods. But amphetamines, sometimes in the form of speed or crank, have a high potential for addiction. People usually end up "crashing" when such drugs wear off, and experience dangerous side effects such as irregular heartbeat. The new study will focus on the drug modafinil, currently used for the treatment of narcolepsy. Cephalon Inc., a pharmaceutical company and the manufacturer of modafinil, is sponsoring the Las Vegas sleep study. Modafinil is believed to replace orexin, a recently discovered brain protein that is believed to control sleep-wake cycles. Unlike conventional stimulants, modafinil seems to have no effect on people who have enough orexin. "There's no buzz like we see with amphetamine, which means the chances of someone abusing modafinil are reduced," Pinto said. "If you're already awake and you take it, nothing happens." No drug should be viewed as a replacement for sleep, said Dr. Robert Ingham, an assistant professor at the University of Nevada School of Medicine. The idea of replacing sleep and creating soldiers capable of fighting 24 hours a day or factory workers who never go home isn't realistic, he said. Modafinil could be a promising "rescue drug," helping shift workers get through the night while they learn healthier sleep patterns, said Ingham, who is not part of the study. Ingham said most of his patients are insomniacs - unable to fall asleep no matter how hard they try. Las Vegas offers special challenges to insomniacs because there's never a shortage of places to go or things to do besides sleep, Ingham said. The first step toward helping people with sleep disorders is to determine how their circadian clocks are set, Ingham said. Some people are drawn to night work because they naturally feel more alert after dark, Ingham said. Most people are sleepiest from midnight to 6 a.m. "There are definitely night owls and early birds," Ingham said. "And early birds probably shouldn't be shift workers." Repp said he would like to switch to day shifts, but pit bosses are needed mostly at night. Repp, who has six children ranging in age from 9 to 18, said his work and sleep schedule contributed to his divorce and hurt his relationships with friends and family. "You're not around your family as much as you need to be, and when you're trying to sleep, they're walking on pins and needles trying not to wake you up," Repp said. "It's frustrating for them, and frustrating for me." As a participant in the study, Repp will have to use a computerized organizer to record what he eats, how tired he feels and how successful he is at falling, and staying, asleep. "I'll do anything they tell me to if it means my eyes won't feel so heavy all the time," Repp said. "If I could just get a few hours real sleep every day, I would be doing great." LOAD-DATE: January 10, 2002 LANGUAGE: ENGLISH GRAPHIC: AP Photo Copyright 2002 Associated Press All Rights Reserved 889 of 998 DOCUMENTS The Houston Chronicle January 07, 2002, Monday 3 STAR EDITION WAKE-UP CALL; Despite its success, anti-sleep drug raises alarm SOURCE: Staff BYLINE: TODD ACKERMAN, Houston Chronicle Medical Writer SECTION: A; Pg. 1 LENGTH: 1151 words In a world of all-night businesses and time-zone-straddling global trading, it probably had to happen: a drug to keep you awake, alert and performing well without the harsh effects of habit-forming amphetamines. The drug is called Modafinil (Provigil) and, though doctors warn that it shouldn't be used for nonmedical purposes, its success with sleep-disorder patients and sleep-deprived military personnel is causing a buzz that the day is coming soon when biopharmacology redefines what is meant by a good night's sleep. "Pharmacological developments like Modafinil will pose great temptations to society," said David Dinges, a sleep-deprivation researcher at the University of Pennsylvania. "They'll have the potential to satisfy our relentless desire to control time." Modafinil, approved by the Food and Drug Administration in 1998 for narcolepsy, is being studied around the country to determine whether it could be a boon to rescue workers and others who work long hours under intense conditions. A nonaddictive stimulant that has no detectable effect on people already up and alert, it already has been found to enhance the performance of sleep-deprived military pilots. The question, if it proves successful and becomes widely available, is whether it will become the drug of choice for students cramming for exams and Type-A individuals all too willing to sacrifice sleep for achievement. The desire to control time has researchers around the world studying sleep and its mechanisms. After all, people working night shifts have more health and performance problems than people who work during the day, and in situations like war that can mean the difference between life and death. But most of those researchers caution that far more work needs to be done before society starts planning for the day when one need only take a pill to go days without sleeping or to regularly sleep just four hours a night. Too little is known about the value of sleep and too many negative effects have been attributed to a lack of sleep, they say. "We haven't got to the point where we know enough about the body's internal clock to manipulate it without fear of causing damage," said John Byrne, a neurobiologist at the University of Texas Medical School at Houston recently awarded a $ 1.6 million grant from the U.S. Department of Defense to design a mathematical model of the network of genes and proteins that control the clock. "Until then, I think the long-term ingestion of any so-called magic bullet is likely to cause serious side effects." Nevertheless, the clamor for Modafinil has begun. Dr. Richard Castriotta, a UT-Houston professor and medical director of Memorial Hermann's sleep disorders clinic, said he is receiving lots of requests for it from people without sleep disorders, people who want it to make their busy lifestyles more manageable. (He refuses these requests.) Dinges said that one need only consider the growth of Starbucks to imagine how society will react to a "wake-up drug." Calling coffee the beverage of choice in America, he noted that many people drink it mostly because of the caffeine's perceived stimulant effects. Modafinil appears to work much better, researchers say. They report that study subjects say they feel alert without experiencing a "wired" sensation when it takes effect or a "crash" when it wears off, symptoms typically felt when using amphetamines or lots of caffeine. It seems to have no potential for addiction nor have users developed tolerance. It also doesn't affect normal sleep. Users, who have gone as long as 72 hours without sleep in tests, sleep a normal eight hours when they do retire and then wake up without the hangover feeling many stimulants cause. (Modafinil isn't free of side effects. In studies, it has caused mild headaches, dizziness, nausea and other minor symptoms in fairly significant percentages.) "Modafinil might herald a brave new world," said Timothy Monk, a University of Pittsburgh Medical Center professor of psychiatry conducting a NASA-funded study in which subjects on Modafinil and a placebo get 40 percent of their usual sleep over a week's duration. "I hope not. We have knowledge and technology today such that we could substitute vitamins for a lot of eating, but we don't do that. I hope people value sleep as much." Monk, who worries Modafinil could become the Viagra of wakefulness, sees a future in which the drug is good for people with sleep and other disorders and for emergency and night-shift workers. Although now prescribed for narcolepsy and other sleep disorders, physicians are experimenting with it for patients with other disorders, such as multiple sclerosis, Parkinson's disease and depression. It has been shown to alleviate the drowsiness and fatigue that accompany all three. But a more widespread application may be for many of the more than 15 million shift-work employees nationwide, those who work at night and those whose shifts frequently rotate, such as emergency-room workers or paramedics. An estimated 70 percent of these workers suffer from sleep disorders associated with their jobs, according to the American Academy of Sleep Medicine. Modafinil studies on such workers have boded well. A military-funded study by Harvard and the University of Pennsylvania looked at subjects who underwent a 28-hour period of sleep deprivation, then began a four-day period of being awake at night and sleeping from 11 a.m. to 7 p.m. Those on Modafinil did far better on cognitive tests involving memory skills than did their counterparts on placebos. The military is also funding more innovative studies, such as one recently launched at Sea World in San Diego that focuses on dolphins, which never go fully to sleep. In search of methods to sustain cognitive performance in people, scientists are attempting to figure out how the animals' two cerebral hemispheres trade off sleeping while they maintain a basic level of alertness. Still, researchers Byrne and Castriotta say it's a big leap to go from interesting lessons learned from animal studies and strong human showings in controlled experiments to thinking people can "control time" over indefinite periods. Despite our primitive knowledge of sleep, they say the existing evidence shows serious long-term consequences among those who have tried to go long periods without it. "We have potent painkillers, but we only use them after diagnosing the problem because we know pain is a warning that something is wrong," said Castriotta. "We don't understand the reasons for sleep that well, but it's highly unlikely that evolution designed it for anything but an important function. "There may be a coming revolution in which we learn to sleep more efficiently, but anyone who thinks that he or she can go for a long period of time without sleep these days without paying a price will learn the hard way." LOAD-DATE: January 8, 2002 LANGUAGE: ENGLISH GRAPHIC: Photo: John Byrne, a University of Texas neurobiologist seen holding a brain model, says "we haven't got to the point where we know enough about the body's internal clock to manipulate it without fear of causing damage." Byrne is studying genes and proteins that control the body's clock (p. 6); Karl Stolleis / Chronicle Copyright 2002 The Houston Chronicle Publishing Company 890 of 998 DOCUMENTS The Houston Chronicle January 7, 2002, Monday Despite Success, Anti-Sleep Drug Raises Alarm BYLINE: By Todd Ackerman LENGTH: 1177 words In a world of all-night businesses and time-zone-straddling global trading, it probably had to happen: a drug to keep you awake, alert and performing well without the harsh effects of habit-forming amphetamines. The drug is called Modafinil (Provigil) and, though doctors warn that it shouldn't be used for nonmedical purposes, its success with sleep-disorder patients and sleep-deprived military personnel is causing a buzz that the day is coming soon when biopharmacology redefines what is meant by a good night's sleep. "Pharmacological developments like Modafinil will pose great temptations to society," said David Dinges, a sleep-deprivation researcher at the University of Pennsylvania. "They'll have the potential to satisfy our relentless desire to control time." Modafinil, approved by the Food and Drug Administration in 1998 for narcolepsy, is being studied around the country to determine whether it could be a boon to rescue workers and others who work long hours under intense conditions. A nonaddictive stimulant that has no detectable effect on people already up and alert, it already has been found to enhance the performance of sleep-deprived military pilots. The question, if it proves successful and becomes widely available, is whether it will become the drug of choice for students cramming for exams and Type-A individuals all too willing to sacrifice sleep for achievement. The desire to control time has researchers around the world studying sleep and its mechanisms. After all, people working night shifts have more health and performance problems than people who work during the day, and in situations like war that can mean the difference between life and death. But most of those researchers caution that far more work needs to be done before society starts planning for the day when one need only take a pill to go days without sleeping or to regularly sleep just four hours a night. Too little is known about the value of sleep and too many negative effects have been attributed to a lack of sleep, they say. "We haven't got to the point where we know enough about the body's internal clock to manipulate it without fear of causing damage," said John Byrne, a neurobiologist at the University of Texas Medical School at Houston recently awarded a $ 1.6 million grant from the U.S. Department of Defense to design a mathematical model of the network of genes and proteins that control the clock. "Until then, I think the long-term ingestion of any so-called magic bullet is likely to cause serious side effects." Nevertheless, the clamor for Modafinil has begun. Dr. Richard Castriotta, a UT-Houston professor and medical director of Memorial Hermann's sleep disorders clinic, said he is receiving lots of requests for it from people without sleep disorders, people who want it to make their busy lifestyles more manageable. (He refuses these requests.) Dinges said that one need only consider the growth of Starbucks to imagine how society will react to a "wake-up drug." Calling coffee the beverage of choice in America, he noted that many people drink it mostly because of the caffeine's perceived stimulant effects. Modafinil appears to work much better, researchers say. They report that study subjects say they feel alert without experiencing a "wired" sensation when it takes effect or a "crash" when it wears off, symptoms typically felt when using amphetamines or lots of caffeine. It seems to have no potential for addiction nor have users developed tolerance. It also doesn't affect normal sleep. Users, who have gone as long as 72 hours without sleep in tests, sleep a normal eight hours when they do retire and then wake up without the hangover feeling many stimulants cause. (Modafinil isn't free of side effects. In studies, it has caused mild headaches, dizziness, nausea and other minor symptoms in fairly significant percentages.) "Modafinil might herald a brave new world," said Timothy Monk, a University of Pittsburgh Medical Center professor of psychiatry conducting a NASA-funded study in which subjects on Modafinil and a placebo get 40 percent of their usual sleep over a week's duration. "I hope not. We have knowledge and technology today such that we could substitute vitamins for a lot of eating, but we don't do that. I hope people value sleep as much." Monk, who worries Modafinil could become the Viagra of wakefulness, sees a future in which the drug is good for people with sleep and other disorders and for emergency and night-shift workers. Although now prescribed for narcolepsy and other sleep disorders, physicians are experimenting with it for patients with other disorders, such as multiple sclerosis, Parkinson's disease and depression. It has been shown to alleviate the drowsiness and fatigue that accompany all three. But a more widespread application may be for many of the more than 15 million shift-work employees nationwide, those who work at night and those whose shifts frequently rotate, such as emergency-room workers or paramedics. An estimated 70 percent of these workers suffer from sleep disorders associated with their jobs, according to the American Academy of Sleep Medicine. Modafinil studies on such workers have boded well. A military-funded study by Harvard and the University of Pennsylvania looked at subjects who underwent a 28-hour period of sleep deprivation, then began a four-day period of being awake at night and sleeping from 11 a.m. to 7 p.m. Those on Modafinil did far better on cognitive tests involving memory skills than did their counterparts on placebos. The military is also funding more innovative studies, such as one recently launched at Sea World in San Diego that focuses on dolphins, which never go fully to sleep. In search of methods to sustain cognitive performance in people, scientists are attempting to figure out how the animals' two cerebral hemispheres trade off sleeping while they maintain a basic level of alertness. Still, researchers Byrne and Castriotta say it's a big leap to go from interesting lessons learned from animal studies and strong human showings in controlled experiments to thinking people can "control time" over indefinite periods. Despite our primitive knowledge of sleep, they say the existing evidence shows serious long-term consequences among those who have tried to go long periods without it. "We have potent painkillers, but we only use them after diagnosing the problem because we know pain is a warning that something is wrong," said Castriotta. "We don't understand the reasons for sleep that well, but it's highly unlikely that evolution designed it for anything but an important function. "There may be a coming revolution in which we learn to sleep more efficiently, but anyone who thinks that he or she can go for a long period of time without sleep these days without paying a price will learn the hard way." ----- To see more of the Houston Chronicle, or to subscribe to the newspaper, go to http://www.chron.com LOAD-DATE: January 8, 2002 LANGUAGE: ENGLISH KR-ACC-NO: HO-SLEEP-DRUG JOURNAL-CODE: HO Copyright 2002 Knight Ridder/Tribune Business News Copyright 2002 Houston Chronicle 891 of 998 DOCUMENTS The Age (Melbourne, Australia) December 22, 2001 Saturday Late Edition Amazing `alert pill' may lead to abuse BYLINE: STEVE DOW SECTION: NEWS; Pg. 8 LENGTH: 571 words It's the 24-hour sleepless society. Supermarkets and factories operate around the clock. Children are cramming more activities into their leisure time. Round-the-clock gymnasiums are popular. The net result? We're averaging about an hour less sleep a night than we were a decade ago. Teenagers and 20-somethings have eschewed alcohol in favour of all-night amphetamine binges. Why cut the night short when you can dance brightly among the shiny, happy people? Small wonder that 40 per cent of us have sleep disorders, ranging from the intermittent lack of sleep to the chronic. Sleep experts estimate that up to 15 per cent of people have "restless legs" in bed. They're literally running in their dreams. Most sleeping pills leave us groggy. How tempting it would be to pop a "wakefulness pill" to snap us into order during the day. Enter the new wonder drug, modafinil. Modafinil is likely to arrive soon in Australia from Laboratoire Lafon in France via CSL Ltd. It's a wakefulness drug unlike any other, awesomely effective in narcoleptics - that very small group of people who fall asleep at the wrong time. Its brand name is Provigil. Even the connotation of the name "pro" and "vigil" suggest that this new compound, discovered in the early 1980s but only recently put into effect, might hold the key to understanding what it is for us to be awake. But federal health bureaucrats fear that the drug could be misused by shift workers, executives and "party animals". Mostly they fear more taxpayer hip-pocket damage in the wake of cost blow-outs on drugs such as Celebrex and Viagra. Modafinil, United States sleep expert David Dinges recently told The New Yorker, is "the most tempting drug for our society to come along in decades ... It promises to satisfy our relentless desire to control time". The drug works on orexins, a relatively newly identified group of neurotransmitters in the brain. It is known that a deficiency of orexins causes narcolepsy. Unlike traditional stimulants, which work on the central nervous system to release the chemical dopamine to suppress sleep, modafinil takes a novel approach. It stimulates adrenaline sensors in the brain to promote wakefulness. It peaks at 40 minutes to an hour, but remains effective for six to eight hours. It has few side-effects: no heart palpitations, no rush, no hyperactivity, and, in most cases, it promotes much less over-confidence than do amphetamines. But this creates a potential for abuse. Doctors treating children for attention deficit hyperactivity disorder (ADHD) with the amphetamine Ritalin are showing a big interest in modafinil. The Australian and US military, among others, are intensely interested in its battlefield potential. Small wonder that Australian doctors are pushing federal health bureaucrats to strictly limit the type of patient and the type of specialist who can prescribe modafinil. John Swieca, of the Melbourne Sleep Disorders Centre, says modafinil is highly effective in narcoleptics. He admits there is potential for it to "put a Band-Aid over sleep", though party-lovers seeking a buzz might be disappointed. "You won't be able to replace every aspect of sleep," says Mr Swieca, "not in the foreseeable future." And if we eschewed sleep for days on end through currently available pharmacology, would we eventually die? "There's no evidence we would do the same as animals," he says. "But you would get sick through immune dysfunction." LOAD-DATE: July 24, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2001 The Age Company Limited All Rights Reserved 892 of 998 DOCUMENTS Sydney Morning Herald (Australia) December 22, 2001 Saturday Late Edition Experts awake to pros and cons of sleep drug BYLINE: Steve Dow SECTION: NEWS AND FEATURES; Pg. 3 LENGTH: 383 words A revolutionary "wakefulness pill" is poised to go on the Australian market, offering hope for the sleep-deprived but raising concerns it will be misused. Modafinil, which goes by the brand name of Provigil, has proved enormously effective among narcoleptics people who fall asleep at inappropriate times. The drug, which leaves over-the-counter stimulants such as Sudafed, caffeine and guarana in the shade, was discovered in the 1980s, but its efficacy has been established only recently. It will probably soon arrive in Australia from Laboratoire Lafon in France via CSL Ltd. But federal health bureaucrats fear potential misuse and abuse of the drug among shift workers, executives and nightclubbers. The American sleep expert David Dinges recently told The New Yorker that modafinil was "the most tempting drug for our society to come along in decades. It promises to satisfy our relentless desire to control time." It works on a relatively newly identified group of neurotransmitters in the brain called orexins. These are essentially proteins in the hypothalamus. It is now known that a deficiency of orexins causes narcolepsy. Unlike traditional stimulants, such as the common narcolepsy-treating amphetamine Dexedrine, which work on the central nervous system to release dopamine to suppress sleep, the new drug takes a novel approach. Instead, modafinil stimulates adrenaline sensors in the brain to promote wakefulness. It peaks at 40 minutes to an hour, but is effective for six to eight hours. There are significantly fewer side-effects: no heart palpitations, no rush and no hyperactivity. It is far less likely to promote over-confidence than amphetamines. Australian doctors are pushing federal health bureaucrats to strictly limit the type of patient and type of specialist who can prescribe modafinil. Dr John Swieca, of the Melbourne Sleep Disorders Centre, said modafinil is highly effective in narcoleptics. He admitted there was potential for abuse of the drug to "put a Band-Aid over sleep", although party types seeking a buzz might be disappointed. "You won't be able to replace every aspect of sleep. Not in the foreseeable future." Dr David Joffe, of the Royal North Shore Hospital's respiratory and sleep medicine department, said: "The obvious group [for abuse] would be truck drivers." LOAD-DATE: July 24, 2007 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newspaper Copyright 2001 John Fairfax Publications Pty Ltd All Rights Reserved 893 of 998 DOCUMENTS Pittsburgh Post-Gazette (Pennsylvania) December 18, 2001 Tuesday SOONER EDITION PITT CONDUCTING STUDY OF A NONADDICTIVE PILL FOR WAKEFULNESS BYLINE: VIRGINIA LINN, POST-GAZETTE STAFF WRITER SECTION: HEALTH, Pg.D-1 COVER STORY LENGTH: 660 words Imagine a pill that could keep you alert and performing well if you went for days with little sleep. University of Pittsburgh Medical Center is conducting a study funded by NASA on the wake-up pill modafinil. It's one of several studies under way around the country to see if the drug could be a boon to rescue workers, doctors, military personnel, pilots, astronauts and others who have to work long hours under intense conditions. "The ramifications go beyond NASA," said Timothy H. Monk, a UPMC professor of psychiatry who is conducting the study. First used by the French military, modafinil was approved by the Food and Drug Administration in 1998 to treat excessive daytime sleepiness and narcolepsy, a disorder that makes people fall asleep many times a day. Those who have tried it report that they feel alert without the "wired" sensation that comes from using stimulants like amphetamines or too much caffeine. Modafinil isn't free of side effects; it can cause mild headaches, dizziness or other minor symptoms, but it isn't addictive, as amphetamines can be. University of Pennsylvania in Philadelphia is studying the drug's effect on shift workers. The Army also is testing modafinil as a way to help pilots and soldiers perform without sleep. Researchers also see a potential to help millions of people with various disorders that make them sleepy -- everything from multiple sclerosis to depression. The parts of the brain activated by modafinil are the same ones that the brain starts to shut down in sleep-deprived people, said Matthew Miller, a pharmacologist at Cephalon, the biotech company in West Chester, Chester County, that is marketing modafinil. The drug seems to prompt the brain to mimic its well-rested state. Pitt's study began in July 2000, and it is recruiting participants through next summer. Healthy participants between the ages of 20 and 59 are getting only 40 percent of their usual time in bed during testing. "The question is, 'Will modafinil help them function? Will is make them alert enough to do what is required of them?' " Monk said. Broadening the use of the drug, however, raises questions. Would companies push employees to use it so they could work longer hours? Would overachievers use the drug to get a superhuman amount of work done? "There is a spectrum of worries," Monk acknowledged. "I would worry that an employer would force employees to take the drug. I would be very much against that as violating their rights. "At the other end of the scale, there may be a tendency to make modafinil the Viagra of sleep and wakefulness." While there are legitimate uses, people can go too far. "We really don't fully understand exactly what all the ramifications are for reducing sleep on a chronic basis," Monk said. "Clearly there are times, at Ground Zero, or [during] some terrible fire or an earthquake, when people for short periods of time -- a couple of weeks, a couple of months -- have to get by with limited amount of sleep. "But there could be serious problems adopting a lifestyle dramatically reducing sleep on a chronic basis for weeks or years." Monk said researchers are still at over how much sleep people must have each day. They agree that people need a minimum of five hours, but it's not clear whether they really need anything beyond that. "I would never prescribe eight hours for everyone. Some do quite well with four or five hours of sleep. But most who are getting five or six hours should be getting seven or eight." Pitt's random, double-blind study uses a placebo pill. Participants stay continuously for seven days in laboratory apartments, then return after two weeks for another seven-day stay. During one stay, they'll be given modafinil, during the other, the placebo. Both parts are critical to make comparisons. Those interested in participating can call Joette Zarotney at 412-383-9851. Compensation is provided. LOAD-DATE: December 18, 2001 LANGUAGE: ENGLISH NOTES: The Philadelphia Inquirer contributed to this report. GRAPHIC: PHOTO: Suzanne Plunkette/Associated Press: Easy availability of a wakefulness drug would have drawbacks as well as benefits. Employers could use it to force employees to work longer hours, and overachievers could use it to get more done during the time they would normally sleep. PHOTO: Charlie Riedel/Associated Press: Possible uses of the wake-up pill under study could be for workers laboring under emergency conditions, such as those at the World Trade Center cleanup site. Copyright 2001 P.G. Publishing Co. 894 of 998 DOCUMENTS Edmonton Journal (Alberta) December 14, 2001 Friday Final Edition New pill won't let you die in your sleep SOURCE: The Edmonton Journal BYLINE: Bill Sass SECTION: Living; Out of My Mind; Pg. C3 LENGTH: 634 words Vivian: "You go too far, Marlowe." Marlowe: "Those are harsh words to throw at a man, especially when he's walking out of your bedroom." Lauren Bacall and Humphrey Bogart dialogue from The Big Sleep - - - So, there I was, looking for a meaningful quote about the qualities of sleep when I ran across this little piece of Bacall-Bogart word play. It contains all the elements of today's topic, sleep and bedrooms, and isn't as overused as Hamlet's whine "To sleep; perchance to dream; aye, there's the rub; For in that sleep of death what dreams may come." Hamlet was a real downer at parties and, I'm willing to bet, he never walked out of Lauren Bacall's bedroom. Anyway, we learned this week that science has found a new way to keep us awake at night beyond its usual methods of inventing atomic ray death bombs and super germs that can cause planet-wide pandemics not even private health care clinics can cure. It's called Modafinil -- an off-white crystalline powder that is practically insoluble in water. You're probably thinking right now: "Oh. It's just another pill. I haven't even used up the pills I bought last week." Well, Bunky, this isn't just another pill. It's 2- [(diphenylmethyl)sulfinyl]acetamide. The molecular formula is C15H15NO2S, in case you want to make your own batch. And if that doesn't put the fear of Aesculapius, the Roman god of medicine in you, then know that Modafinil is a drug powerful enough to keep you awake even if you're sitting in the 4 p.m. news meeting here at News Central. In fact, Professor Michel Jouvet, a world-famous authority on sleep, claimed during an international defence meeting in Paris: "Modafinil could keep an army on its feet and fighting for three days and nights with no major side effects." I suppose that's one major benefit of drug-induced alertness, and one especially good reason to give army recruitment centres a wide berth. For normal people, people who just bought a $1,989 queen size Simmons Adjustable Bed, sleep isn't something to be avoided at all costs. Many people find sleep an attractive option to a news meeting and to be chemically forced into a state of ready alertness borders on the cruel and/or unusual. The real and apparent danger with Modafinil is that it isn't the caffine-stuffed pills we used to take in college the night before the term paper was due. Your heart doesn't race, you don't feel like crawling out of your skin and your roommate doesn't scream at you for keeping him up all night because you spent the past six weeks not doing the stupid term paper. In fact, proponents of the new wonder drug say you don't even realize you're awake and alert until you're in the middle of your second eight-hour stretch at work after your employer figures out one worker who can stay up all night can do the work of three who need periodic rest to keep functionally sane. Researchers say the drug will first be tested on shift workers who report being intensely sleeply when they're supposed to be doing term papers. Is there a downside to all this -- beyond the obvious one of acquiring the ability to stay up all night when the only thing on television is George Foreman Grill infomercials? Well, I'm no scientist, but I do know how to dig up a chilling unattributed scientific-sounding cautionary quote from the Internet when the occasion calls for it: "Prudence should be exercised in drastically curtailing one's sleep. "Prolonged sleeplessness weakens immune function. "Animals tortured in sleep-deprivation experiments eventually die from massive bacterial infections of the blood ..." I guess the upside, then, is we won't die in our sleep. Comments? Questions? Pillow talk? Call Bill Sass, 429-5350. E-mail bsass@thejournal.southam.ca LOAD-DATE: March 27, 2002 LANGUAGE: ENGLISH TYPE: Column Copyright 2001 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 895 of 998 DOCUMENTS Calgary Herald (Alberta, Canada) December 10, 2001 Monday Final EDITION New drug banishes sleepiness BYLINE: Faye Flam SOURCE: Knight Ridder Newspapers SECTION: NEWS, Pg. A4 LENGTH: 231 words DATELINE: PHILADELPHIA In an era where the motto seems to be "if you snooze, you lose," can sleep become optional? Researchers are studying a novel wake-up pill that could allow night-shift workers or long-haul pilots to stay alert for long periods of time, with few apparent side-effects. Those who have tried it report that they feel alert without the "wired" sensation that comes from amphetamines or too much coffee, said David Dinges, a sleep expert at the University of Pennsylvania. Dinges and his colleagues are now recruiting shift workers from the Philadelphia region to conduct broader tests of the drug modafinil. The drug was created to battle narcolepsy, a disorder that makes people fall asleep many times a day. The drug, he said, could be a lifesaver for those who need to perform dangerous tasks or make critical decisions in the wee hours -- doctors, nurses, police officers, and rescue workers. The U.S. army is also testing Modafinil as a way to help pilots and soldiers perform without sleep. "It doesn't appear that the drug has any serious medical downside," said Dinges, who calls modafinil a "revolutionary discovery." But widespread use of the drug raises questions: Would employers use it to push more workers into late-night shift work? Would high-achievers use the drug to get a superhuman amount of work done the way college students have used amphetamines? LOAD-DATE: December 10, 2001 LANGUAGE: ENGLISH TYPE: News Copyright 2001 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 896 of 998 DOCUMENTS Edmonton Journal (Alberta) December 10, 2001 Monday Final Edition New wake-up drug to keep workers alert but not wired: Pill could be boon for pilots, doctors, say sleep experts SOURCE: Knight Ridder BYLINE: Faye Flam SECTION: Top Copy; Pg. A3 LENGTH: 689 words DATELINE: Philadelphia In a time whose motto seems to be "if you snooze, you lose," can sleep become optional? Researchers are studying a novel pill that could allow night-shift workers or long-haul pilots to stay alert for long periods with few apparent side-effects. Those who have tried it report that they feel alert without the "wired" sensation that comes from amphetamines or too much coffee, said David Dinges, a sleep expert at the University of Pennsylvania. Dinges and his colleagues are recruiting shift workers from the Philadelphia region to conduct broader tests of the drug modafinil. The drug was created to battle narcolepsy, a disorder that makes people fall asleep many times a day. Dinges said the drug could be a lifesaver for those who need to perform dangerous tasks or make critical decisions in the wee hours -- doctors, nurses, police officers, and rescue workers. The Army is also testing modafinil as a way to help pilots and soldiers. "It doesn't appear that the drug has any serious medical downside," said Dinges, who calls it a "revolutionary discovery." But the drug raises questions: Would employers use it to push more workers into late-night shift work? Would strivers use it to get a superhuman amount of work done the way college students have used amphetamines? Humans have long looked for ways to control sleep. Thomas Edison thought his electric light would render sleep a thing of the past. The inventor often got by on only four hours of sleep, according to biographers, and expected those who worked for him to follow suit. While modafinil is not addictive, as amphetamines can be, no one knows what consequences people may suffer if they attempt to substitute drugs for sleep. In the sleep lab at the university, Dinges has discovered that, beyond the expected decline in memory and concentration, sleep deprivation can disrupt the way people secrete insulin. Modafinil has been used as an anti-narcolepsy drug in France since the late 1980s. In 1998, the West Chester, Pa.-based firm Cephalon gained approval to market the drug to narcoleptics in the U.S., and soon began to explore wider applications. Researchers see a potential to help millions of people with disorders that make them sleepy -- everything from multiple sclerosis to depression. First, the drug will be tested on shift workers who report being intensely sleepy when they're supposed to be working. Scientists don't really know why people need to sleep as much as they do, but it appears to be an essential and primal part of life. "All animals above worms need sleep," said Matthew Miller, a pharmacologist at Cephalon who has worked on understanding modafinil. Even fruit flies fall asleep during certain hours, their regular circadian rhythm of sleep and wakefulness orchestrated by several genes they share with humans and many other species. Some animals sleep with only one hemisphere of their brains at a time; dolphins do this so they can continue to surface for air. Studying modafinil has begun to reshape scientists' view of sleep and wakefulness, Miller said. Wakefulness was long thought to be controlled largely by a brain chemical called dopamine. Dopamine is involved in vigilance, reward and emotion, Miller said. It helps humans and animals to respond to threats by becoming hypervigilant. By triggering the dopamine system, amphetamines and caffeine not only wake you up, they can raise your pulse and bring on a shot of adrenaline. "If you're sitting in your office, you don't want all those effects," Miller said. Modafinil acts in a completely different way, he said. By giving the drug to dogs and rats and using brain imaging to see how it acts, researchers found that it goes to a deep structure in the brain called the hypothalamus. That part of the brain seems to control the kind of wakefulness that people feel most of the time: alert, but not wired. The parts of the brain activated by modafinil are the same ones that the brain starts to shut down in sleep-deprived people, Miller said. The drug seems to prompt the brain to mimic its well rested state. LOAD-DATE: March 27, 2002 LANGUAGE: ENGLISH GRAPHIC: Photo: AP, File; Inventor Thomas Edison thought his electric light would make sleep unnecessary. TYPE: News Copyright 2001 CanWest Interactive, a division of CanWest Global Communications Corp. All Rights Reserved 897 of 998 DOCUMENTS The Philadelphia Inquirer December 10, 2001, Monday Scientists say new wake-up drug keeps a person alert but not wired BYLINE: By Faye Flam SECTION: DOMESTIC NEWS LENGTH: 1273 words PHILADELPHIA _ In a nation whose motto seems to be "if you snooze, you lose," can sleep become optional? Researchers are studying a novel wake-up pill that could allow night-shift workers or long-haul pilots to stay alert for long periods of time, with few apparent side effects. Those who have tried it report that they feel alert without the "wired" sensation that comes from amphetamines or too much coffee, said David Dinges, a sleep expert at the University of Pennsylvania. Dinges and his colleagues are now recruiting shift workers from the Philadelphia region to conduct broader tests of the drug modafinil. The drug was created to battle narcolepsy, a disorder that makes people fall asleep many times a day. The drug, he said, could be a lifesaver for those who need to perform dangerous tasks or make critical decisions in the wee hours _ doctors, nurses, police officers, and rescue workers. The Army is also testing Modafinil as a way to help pilots and soldiers perform without sleep. "It doesn't appear that the drug has any serious medical downside," said Dinges, who calls modafinil a "revolutionary discovery." But widespread use of the drug raises questions: Would employers use it to push more workers into late-night shift work? Would strivers use the drug to get a superhuman amount of work done the way college students have used amphetamines? Humans have long looked for ways to control sleep. Thomas Edison thought his electric light would render sleep a thing of the past. The inventor often got by on only four hours of sleep, according to biographers, and he expected those who worked for him to follow suit (some say he used electric shocks to discourage slumber). Medicine may not eliminate the need for sleep, either. While modafinil is not addictive, as amphetamines can be, no one knows what consequences people might suffer if they attempt to substitute drugs for sleep. In the sleep lab at the university, Dinges has discovered that, beyond the expected decline in memory and concentration, sleep deprivation can disrupt the way people secrete insulin _ a problem related to diabetes and obesity. Modafinil has been used as an anti-narcolepsy drug in France since the late 1980s. In 1998, the West Chester, Pa.-based company Cephalon gained approval to market the drug to narcoleptics in the United States. Cephalon soon began to explore wider applications. Researchers see a potential to help millions of people with various disorders that make them sleepy _ everything from multiple sclerosis to depression. First, the drug will be tested on shift workers who report being intensely sleepy when they're supposed to be working. Such "shift-work sleep disorder" is not exactly a disease, Dinges said, but more a natural variation in how well different people tolerate a nocturnal schedule. Jennifer Hendrickson, an obstetrician at Hahnemann University Hospital who just finished her residency, knows the rigors of sleeplessness. She often had to stay on call for 36 hours at a time. "The first thing to go _ things become more raw," she said. "Emotions come to the surface." Her medical skills are second nature, she said, but working well with patients can get tough as the hours wear on. She drinks coffee to keep awake at times, but said she would hesitate to take any stronger drug without knowing all the possible side effects. To work as a doctor, "you need to be in command of all your faculties," she said. In tests, people taking modafinil seem to perform much better on many tests of cognitive ability and mood. Scientists don't really know why people need to sleep as much as they do, but it appears to be an essential and primal part of life. "All animals above worms need sleep," said Matthew Miller, a pharmacologist at Cephalon who has worked on understanding modafinil. Even fruit flies fall asleep during certain hours, their regular circadian rhythm of sleep and wakefulness orchestrated by several genes they share with humans and many other species. Some animals sleep with only one hemisphere of their brains at a time; dolphins do this so they can continue to surface for air. Studying modafinil has begun to reshape scientists' view of sleep and wakefulness, said Miller. Wakefulness was long thought to be controlled largely by a brain chemical called dopamine. Dopamine is involved in vigilance, reward and emotion, Miller said. The dopamine system is what helps humans and other animals to respond to threats by becoming hypervigilant. By triggering this dopamine system, amphetamines and caffeine not only wake you up, they can raise your pulse and bring on a shot of adrenaline. That is not always a good thing. "If you're sitting in your office, you don't want all those effects," Miller said. Modafinil acts in a completely different way, he said. By giving the drug to dogs and rats and using brain imaging to see how it acts, researchers found that it goes to a deep structure in the brain called the hypothalamus. That part of the brain seems to control the kind of wakefulness that people feel most of the time: alert, but not wired. "(The drug) produces the kind of wakefulness that seems to be more natural," said Karl Doghramji, a sleep researcher at Thomas Jefferson University Hospital who has studied the new drug. The parts of the brain activated by modafinil are the same ones that the brain starts to shut down in sleep-deprived people, Miller said. The drug seems to prompt the brain to mimic its well-rested state. People who have participated in preliminary tests report that they are unable to feel the effects of the drug, as they would feel the buzz from a strong cup of coffee. Some of the early experiments were done by Dinges and colleagues in Penn's sleep lab. Sixteen healthy volunteers lived in the lab for six days. The subjects went 28 hours without sleep, shifting their schedules so that they slept between 11 a.m. and 7 p.m. At night, they would perform various tasks while being tested for memory, concentration and other abilities. In one test, for example, they were asked to memorize various symbols that stood for numbers, and then type the appropriate number when researchers held up a corresponding symbol. Half the subjects received modafinil, and half got a placebo. Those on the placebo made many more errors in the tests that measured memory and attention. The Army also has tested the drug on sleep-deprived pilots, using flight simulators to test their skills and reactions under various conditions. Again, modafinil seemed to bring test subjects back to their well-rested levels. In other experiments, people were given the drug before they went to sleep, and, surprisingly, they slept fine, Miller said. Somehow the drug makes it easier for people to stay awake but still allows them to fall asleep if they choose to. Cephalon plans to test the drug for many other sleep disorders _ those caused by chronic fatigue syndrome, sleep apnea, multiple sclerosis, and a rare disorder called delayed sleep phase syndrome. Jefferson's Doghramji is interested in testing the drug in patients with depression. While new antidepressants have helped a great deal, he said, many people still feel a deep fatigue that this new drug might combat. But researchers say they don't want modafinil to further deprive a sleep-deprived nation. "There's a desire to control time that's characteristic of our age," Dinges said. "There's a relentless desire to get more done." ___ (c) 2001, The Philadelphia Inquirer. Visit Philadelphia Online, the Inquirer's World Wide Web site, at http://www.philly.com/ LOAD-DATE: December 10, 2001 LANGUAGE: ENGLISH KR-ACC-NO: K4131 JOURNAL-CODE: PH Copyright 2001 Knight Ridder/Tribune News Service Knight Ridder/Tribune News Service 898 of 998 DOCUMENTS The Philadelphia Inquirer December 10, 2001, Monday Researchers Tout Drug that Keeps Sleep at Bay Without Side Effects BYLINE: By Faye Flam LENGTH: 1282 words In a nation whose motto seems to be "if you snooze, you lose," can sleep become optional? Researchers are studying a novel wake-up pill that could allow night-shift workers or long-haul pilots to stay alert for long periods of time, with few apparent side effects. Those who have tried it report that they feel alert without the "wired" sensation that comes from amphetamines or too much coffee, said David Dinges, a sleep expert at the University of Pennsylvania. Dinges and his colleagues are now recruiting shift workers from around the Philadelphia region to conduct broader tests of the drug modafinil. The drug was created to battle narcolepsy, a disorder that makes people fall asleep many times a day. The drug, he said, could be a lifesaver for those who need to perform dangerous tasks or make critical decisions in the wee hours -- doctors, nurses, police officers and rescue workers. Modafinil also is being tested by the Army as a way to help pilots and soldiers perform without sleep. "It doesn't appear that the drug has any serious medical downside," said Dinges, who calls modafinil a "revolutionary discovery." But widespread use of the drug could raise many questions: Would employers use it to push more workers into late-night shift work? Would strivers use the drug to get a superhuman amount of work done the way college students have used amphetamines? Humans have long looked for ways to control sleep. Thomas Edison thought his electric light would render sleep a thing of the past. The inventor often got by on only four hours of sleep, according to biographers, and he expected those who worked for him to follow suit (some say he used electric shocks to discourage slumber). Medicine may not eliminate the need for sleep, either. While modafinil is not addictive, as amphetamines can be, no one knows what consequences people might suffer if they attempt to substitute drugs for sleep. In the sleep lab at Penn, Dinges has discovered that, beyond the expected decline in memory and concentration, sleep deprivation can disrupt the way people secrete insulin -- a problem related to diabetes and obesity. Modafinil has been used as an anti-narcolepsy drug in France since the late 1980s. In 1998, the West Chester-based company Cephalon gained approval to market the drug to narcoleptics in the United States. Cephalon soon began to explore wider applications. Researchers see a potential to help millions of people with various disorders that make them sleepy -- everything from multiple sclerosis to depression. First, the drug will be tested on shift workers who report being intensely sleepy when they're supposed to be working. Such "shift-work sleep disorder" is not exactly a disease, Dinges said, but more a natural variation in how well different people tolerate a nocturnal schedule. Jennifer Hendrickson, an obstetrician at Hahnemann University Hospital who just finished her residency, knows the rigors of sleeplessness. She often had to stay on call for 36 hours at a time. "The first thing to go -- things become more raw," she said. "Emotions come to the surface." Her medical skills are second-nature, she said, but working well with patients can get tough as the hours wear on. She drinks coffee to keep awake at times, but said she would hesitate to take any stronger drug without knowing all the possible side effects. To work as a doctor, "you need to be in command of all your faculties," she said. In tests, people taking modafinil seem to perform much better on many tests of cognitive ability and mood. Scientists don't really know why people need to sleep as much as they do, but it appears to be an essential and primal part of life. "All animals above worms need sleep," said Matthew Miller, a pharmacologist at Cephalon who has worked on understanding modafinil. Even fruit flies fall asleep during certain hours, their regular circadian rhythm of sleep and wakefulness orchestrated by several genes they share with humans and many other species. Some animals sleep with only one hemisphere of their brains at a time; dolphins do this so they can continue to surface for air. Studying modafinil has begun to reshape scientists' view of sleep and wakefulness, said Cephalon's Miller. Wakefulness was long thought to be controlled largely by a brain chemical called dopamine. Dopamine is involved in vigilance, reward and emotion, Miller said. The dopamine system is what helps humans and other animals to respond to threats by becoming hypervigilant. By triggering this dopamine system, amphetamines and caffeine not only wake you up, they can raise your pulse and bring on a shot of adrenaline. That is not always a good thing. "If you're sitting in your office, you don't want all those effects," Miller said. Modafinil acts in a completely different way, he said. By giving the drug to dogs and rats and using brain imaging to see how it acts, researchers found that it goes to a deep structure in the brain called the hypothalamus. That part of the brain seems to control the kind of wakefulness that people feel most of the time: alert, but not wired. "[The drug] produces the kind of wakefulness that seems to be more natural," said Karl Doghramji, a sleep researcher at Thomas Jefferson University Hospital who has studied the new drug. The parts of the brain activated by modafinil are the same ones that the brain starts to shut down in sleep-deprived people, Miller said. The drug seems to prompt the brain to mimic its well-rested state. People who have participated in preliminary tests report that they are unable to feel the effects of the drug, as they would feel the buzz from a strong cup of coffee. Some of the early experiments were done by Dinges and colleagues in Penn's sleep lab. Sixteen healthy volunteers lived in the lab for six days. The subjects went 28 hours without sleep, shifting their schedules so that they slept between 11 a.m. and 7 p.m. At night, they would perform various tasks while being tested for memory, concentration and other abilities. In one test, for example, they were asked to memorize various symbols that stood for numbers, and then type the appropriate number when researchers held up a corresponding symbol. Half the subjects received modafinil, and half got a placebo. Those on the placebo made many more errors in the tests that measured memory and attention. The Army also has tested the drug on sleep-deprived pilots, using flight simulators to test their skills and reactions under various conditions. Again, modafinil seemed to bring test subjects back to their well-rested levels. In other experiments, people were given the drug before they went to sleep, and, surprisingly, they slept fine, Miller said. Somehow the drug makes it easier for people to stay awake but still allows them to fall asleep if they choose to. Cephalon plans to test the drug for many other sleep disorders -- those caused by chronic fatigue syndrome, sleep apnea, multiple sclerosis, and a rare disorder called delayed sleep phase syndrome. Jefferson's Doghramji is interested in testing the drug in patients with depression. While new antidepressants have helped a great deal, he said, many people still feel a deep fatigue that this new drug might combat. But researchers say they don't want modafinil to further deprive a sleep-deprived nation. "There's a desire to control time that's characteristic of our age," Dinges said. "There's a relentless desire to get more done." ----- To see more of The Philadelphia Inquirer, or to subscribe to the newspaper, go to http://www.philly.com LOAD-DATE: December 11, 2001 LANGUAGE: ENGLISH KR-ACC-NO: PH-SLEEP-DRUG JOURNAL-CODE: PH Copyright 2001 Knight Ridder/Tribune Business News Copyright 2001 The Philadelphia Inquirer 899 of 998 DOCUMENTS The Philadelphia Inquirer December 9, 2001 Sunday CITY-D EDITION Rest? No thanks, I'll have a pill; Researchers tout drug that keeps sleep at bay without side effects BYLINE: Faye Flam INQUIRER STAFF WRITER SECTION: NATIONAL; Pg. A01 LENGTH: 1266 words In a nation whose motto seems to be "if you snooze, you lose," can sleep become optional? Researchers are studying a novel wake-up pill that could allow night-shift workers or long-haul pilots to stay alert for long periods of time, with few apparent side effects. Those who have tried it report that they feel alert without the "wired" sensation that comes from amphetamines or too much coffee, said David Dinges, a sleep expert at the University of Pennsylvania. Dinges and his colleagues are now recruiting shift workers from around the Philadelphia region to conduct broader tests of the drug modafinil. The drug was created to battle narcolepsy, a disorder that makes people fall asleep many times a day. The drug, he said, could be a lifesaver for those who need to perform dangerous tasks or make critical decisions in the wee hours - doctors, nurses, police officers and rescue workers. Modafinil also is being tested by the Army as a way to help pilots and soldiers perform without sleep. "It doesn't appear that the drug has any serious medical downside," said Dinges, who calls modafinil a "revolutionary discovery." But widespread use of the drug could raise many questions: Would employers use it to push more workers into late-night shift work? Would strivers use the drug to get a superhuman amount of work done the way college students have used amphetamines? Humans have long looked for ways to control sleep. Thomas Edison thought his electric light would render sleep a thing of the past. The inventor often got by on only four hours of sleep, according to biographers, and he expected those who worked for him to follow suit (some say he used electric shocks to discourage slumber). Medicine may not eliminate the need for sleep, either. While modafinil is not addictive, as amphetamines can be, no one knows what consequences people might suffer if they attempt to substitute drugs for sleep. In the sleep lab at Penn, Dinges has discovered that, beyond the expected decline in memory and concentration, sleep deprivation can disrupt the way people secrete insulin - a problem related to diabetes and obesity. Modafinil has been used as an anti-narcolepsy drug in France since the late 1980s. In 1998, the West Chester-based company Cephalon gained approval to market the drug to narcoleptics in the United States. Cephalon soon began to explore wider applications. Researchers see a potential to help millions of people with various disorders that make them sleepy - everything from multiple sclerosis to depression. First, the drug will be tested on shift workers who report being intensely sleepy when they're supposed to be working. Such "shift-work sleep disorder" is not exactly a disease, Dinges said, but more a natural variation in how well different people tolerate a nocturnal schedule. Jennifer Hendrickson, an obstetrician at Hahnemann University Hospital who just finished her residency, knows the rigors of sleeplessness. She often had to stay on call for 36 hours at a time. "The first thing to go - things become more raw," she said. "Emotions come to the surface." Her medical skills are second-nature, she said, but working well with patients can get tough as the hours wear on. She drinks coffee to keep awake at times, but said she would hesitate to take any stronger drug without knowing all the possible side effects. To work as a doctor, "you need to be in command of all your faculties," she said. In tests, people taking modafinil seem to perform much better on many tests of cognitive ability and mood. Scientists don't really know why people need to sleep as much as they do, but it appears to be an essential and primal part of life. "All animals above worms need sleep," said Matthew Miller, a pharmacologist at Cephalon who has worked on understanding modafinil. Even fruit flies fall asleep during certain hours, their regular circadian rhythm of sleep and wakefulness orchestrated by several genes they share with humans and many other species. Some animals sleep with only one hemisphere of their brains at a time; dolphins do this so they can continue to surface for air. Studying modafinil has begun to reshape scientists' view of sleep and wakefulness, said Cephalon's Miller. Wakefulness was long thought to be controlled largely by a brain chemical called dopamine. Dopamine is involved in vigilance, reward and emotion, Miller said. The dopamine system is what helps humans and other animals to respond to threats by becoming hypervigilant. By triggering this dopamine system, amphetamines and caffeine not only wake you up, they can raise your pulse and bring on a shot of adrenaline. That is not always a good thing. "If you're sitting in your office, you don't want all those effects," Miller said. Modafinil acts in a completely different way, he said. By giving the drug to dogs and rats and using brain imaging to see how it acts, researchers found that it goes to a deep structure in the brain called the hypothalamus. That part of the brain seems to control the kind of wakefulness that people feel most of the time: alert, but not wired. "[The drug] produces the kind of wakefulness that seems to be more natural," said Karl Doghramji, a sleep researcher at Thomas Jefferson University Hospital who has studied the new drug. The parts of the brain activated by modafinil are the same ones that the brain starts to shut down in sleep-deprived people, Miller said. The drug seems to prompt the brain to mimic its well-rested state. People who have participated in preliminary tests report that they are unable to feel the effects of the drug, as they would feel the buzz from a strong cup of coffee. Some of the early experiments were done by Dinges and colleagues in Penn's sleep lab. Sixteen healthy volunteers lived in the lab for six days. The subjects went 28 hours without sleep, shifting their schedules so that they slept between 11 a.m. and 7 p.m. At night, they would perform various tasks while being tested for memory, concentration and other abilities. In one test, for example, they were asked to memorize various symbols that stood for numbers, and then type the appropriate number when researchers held up a corresponding symbol. Half the subjects received modafinil, and half got a placebo. Those on the placebo made many more errors in the tests that measured memory and attention. The Army also has tested the drug on sleep-deprived pilots, using flight simulators to test their skills and reactions under various conditions. Again, modafinil seemed to bring test subjects back to their well-rested levels. In other experiments, people were given the drug before they went to sleep, and, surprisingly, they slept fine, Miller said. Somehow the drug makes it easier for people to stay awake but still allows them to fall asleep if they choose to. Cephalon plans to test the drug for many other sleep disorders - those caused by chronic fatigue syndrome, sleep apnea, multiple sclerosis, and a rare disorder called delayed sleep phase syndrome. Jefferson's Doghramji is interested in testing the drug in patients with depression. While new antidepressants have helped a great deal, he said, many people still feel a deep fatigue that this new drug might combat. But researchers say they don't want modafinil to further deprive a sleep-deprived nation. "There's a desire to control time that's characteristic of our age," Dinges said. "There's a relentless desire to get more done." Faye Flam's e-mail address is fflam@phillynews.com. LOAD-DATE: December 10, 2001 LANGUAGE: ENGLISH GRAPHIC: PHOTO; BONNIE WELLER, Inquirer Staff Photographer Sleep expert David Dinges, overseeing a program at the University of Pennsylvania, calls modafinil a "revolutionary discovery." Copyright 2001 Philadelphia Newspapers, LLC All Rights Reserved 900 of 998 DOCUMENTS ABC News December 5, 2001 Wednesday SHOW: World News Now (2:00 AM ET) - ABC Video sales and rentals; Sleep drug that keeps you alert and is non-addictive ANCHORS: DEREK McGINTY; ALISON STEWART BYLINE: JOHN McKENZIE LENGTH: 542 words TEXT: VIDEO RENTALS 1. LARA CROFT: TOMB RAIDER 2. AMERICA'S SWEETHEARTS 3. SHREK 4. LEGALLY BLONDE 5. SWORDFISH VIDEO SALES 1. SHREK 2. MICKEY'S MAGICAL CHRISTMAS 3. CATS & DOGS 4. DR. DOLITTLE 2 5. BARBIE IN THE NUTCRACKER DEREK McGINTY, co-anchor: And finally this half-hour, a story that everyone watching the show will be interested in. It's about a pill that would make the sleep you're already going without unnecessary; it's a drug that could allow you to stay awake and alert for days. It sounds too good to be true, which means in the long run, it probably won't live up to its billing. But right now it is very tempting. Here's ABC's John McKenzie. JOHN McKENZIE reporting: (VO) It is a tantalizing goal: controlling the night. Sleeping less to accomplish more. A drug that might allow people to stay awake and alert. Unidentified Woman #1: I would use it if I were traveling, if I had to take a red-eye. Unidentified Woman #2: If maybe one of my children or grandchildren were ill and I was, say, going to be in the hospital with them. McKENZIE: (VO) The prescription drug called modafinil is approved for people with a sleeping disorder who cannot stay awake during the day, but it also holds intriguing promise for millions of others who are sleep deprived. Dr. EMMANUEL MIGNOT (Stanford University Medical School): If you take modafinil after sleep deprivation, it can restore you to a normal level of alertness where you can concentrate, you can do things. McKENZIE: (VO) No one knows exactly how it works. But unlike other stimulants, such as caffeine or amphetamines, modafinil shows little sign of being addictive and has few side effects. Dr. NEIL KAVEY (Columbia Presbyterian Medical Center): Modafinil is--has the advantage of not stimulating the cardiovascular system, so people are much less likely to feel palpitations, feel tremulousness, feel their heart racing. Ms. TONI HEATH-RICHARD: I don't feel any buzz at all. McKENZIE: (VO) Toni Heath-Richard uses the drug because breathing problems disrupt her sleep at night. Some doctors are prescribing the drug for daytime drowsiness in people with depression, Parkinson's Disease and Multiple Sclerosis. (OC) But how many other people should have access to the drug? Doctors warn that there's no evidence that modafinil can overcome all the harmful consequences of going without sleep. Dr. KAVEY: Our cardiovascular system needs sleep. Thyroid function, hormone levels, the immune system, glucose metabolism, insulin, all seem to be dependent on sleep for normal function. McKENZIE: (VO) In other words, before doctors can prescribe this stimulant more widely, they need to learn more about how much and how often sleep patterns can be safely disrupted. John McKenzie, ABC News, New York. ALISON STEWART, co-anchor: That stuff is gold around here. McGINTY: What--what do we have to do to get some of that stuff. STEWART: You know, we need to get you some right now, because a certain anchor had a little bit of a--during commercial break had a little bit of an issue. McGINTY: I don't know what you're talking about. I don't think--how is that? STEWART: That's news and snooze for this half-hour! (Commercial break) LOAD-DATE: January 31, 2002 LANGUAGE: ENGLISH TYPE: Newscast Copyright 2001 American Broadcasting Companies, Inc. 901 of 998 DOCUMENTS ABC News December 5, 2001 Wednesday SHOW: World News This Morning (6:00 AM ET) - ABC Modafinil, a new drug to help people with sleep disorders, seems promising ANCHORS: DEREK McGINTY BYLINE: JOHN McKENZIE LENGTH: 373 words DEREK McGINTY, co-anchor: People who spend sleepless nights tossing and turning in bed, usually have trouble keeping their eyes open during the day. Some of them, however, are now turning to a new pill that promises relief. ABC's John McKenzie has the details. JOHN McKENZIE reporting: (VO) It is a tantalizing goal, controlling the night, sleeping less to accomplish more, a drug that might allow people to stay awake and alert. The prescription drug called Modafinil is approved for people with a sleeping disorder who cannot stay awake during the day, but it also holds intriguing promise for millions of others who are sleep-deprived. Dr. EMMANUEL MIGNOT (Stanford University Medical School): If you take Modafinil after sleep deprivation, it can restore you to a normal level of alertness, where you can concentrate, you can do things. McKENZIE: (VO) No one knows exactly how it works, but unlike other stimulants such as caffeine or amphetamines, Modafinil shows little sign of being addictive and has few side effects. Dr. NEIL KAVEY (Columbia Presbyterian Medical Center): Modafinil is--has the advantage of not stimulating the cardiovascular system, so people are much less likely to feel palpitations, feel tremulousness, feel their heart racing. McKENZIE: (VO) Some doctors are prescribing the drug for daytime drowsiness, in people with depression, Parkinson's disease and multiple sclerosis. (OC) But how many other people should have access to the drug? Doctors warn there's no evidence that Modafinil can overcome all the harmful consequences of going without sleep. Dr. KAVEY: Our cardiovascular system needs sleep. Thyroid function, hormone levels, the immune system, glucose metabolism, insulin, all seem to be dependent on sleep for normal function. McKENZIE: (VO) In other words, before doctors can prescribe this stimulant more widely, they need to learn more about how much and how often sleep patterns can be safely disrupted. John McKenzie, ABC News, New York. McGINTY: And coming up on "Good Morning America," the drugs your trusted pharmacist may have left on the shelf far too long. I'm Derek McGinty. Thanks for watching WORLD NEWS THIS MORNING. Have a great day! Bye-bye. LOAD-DATE: January 31, 2002 LANGUAGE: ENGLISH TYPE: Profile Copyright 2001 American Broadcasting Companies, Inc. 902 of 998 DOCUMENTS The Straits Times (Singapore) Pill makes sleep unnecessary December 5, 2001, Wednesday Scientists look at the various uses of modafinil, a stimulant, that has been found to keep a person awake and alert for days NEW YORK -- Imagine a pill that would make sleep unnecessary for fighter pilots on long-range missions, or even the high-powered executives and parents of newborns among us. It might not be too far off. ABC News has reported that scientists are looking at a variety of uses for modafinil, a stimulant that is currently used to treat narcolepsy, a sleep disorder characterised by uncontrollable sleepiness and frequent daytime sleep. Modafinil (sold under the name Provigil) has been found to increase both wakefulness and what researchers call "vigilance", the ability to stay on task, thinking clearly and functioning normally. Other drugs designed to keep people awake, such as amphetamines, or "uppers", are not nearly as good at keeping users mentally sharp, and they often make people jumpy and anxious. "It seems to work dramatically," Dr Thomas Scammell, a sleep expert from the Beth Israel Deaconess Medical Centre in Boston told Good Morning America. Most studies of "normal" volunteers have used military recruits, and the maximum they have kept them up is about four days, with nearly normal performance on mental tasks. But that does not mean that people should start taking pills to stay awake three or four days at a time. "Even if the drug is safe, it seems dangerous to mess with your body's sleep needs," Dr Scammell said. Currently, modafinil is only approved and prescribed for those with narcolepsy. But it is also being studied as an option to treat syndromes where fatigue plays a role, such as multiple sclerosis. Researchers are also exploring the possibility that healthy people could take the pill in order to stay awake, and mentally alert, for days at a time. Though sleep experts acknowledge the drug's effectiveness for narcoleptics, they raise alarms about using it for the average, healthy person who simply wants to do more and sleep less. Dr Joyce Walsleben, director of the Sleep Disorder Centre at the New York University School of Medicine, said that overall, modafinil is good at keeping people awake without side-effects. Sleep research took a big step forward three years ago, when scientists discovered a new family of neurotransmitters called orexins. Studies showed that a deficiency of orexin causes narcolepsy. The military is spending more than US$100 million (S$184 million) on similar research, on the rationale that soldiers who sleep less will give the United States a military edge, said ABC. TEST SUBJECTS: Peak performance for days NEW YORK -- In a recent study, 16 healthy people were placed in a lab where some were given modafinil and the rest took a placebo. First, participants had to stay awake for 28 hours to mimic the sleep-deprived state of shift workers, said the ABC report. Then they began a four-day period of being awake at night and sleeping from 11 am to 7 pm. The volunteer subjects who had taken the modafinil sustained their alertness and the capacity to perform well, while those who had taken the placebo had a higher error rate. SECTION: World, Pg. 9 LENGTH: 531 words LOAD-DATE: December 6, 2001 LANGUAGE: ENGLISH Copyright 2001 Singapore Press Holdings Limited 903 of 998 DOCUMENTS ABC News December 4, 2001 Tuesday SHOW: World News Tonight (6:30 PM ET) - ABC New prescription drug called Modafinil might allow you to stay alert and awake without being addictive and has few side effects ANCHORS: PETER JENNINGS BYLINE: JOHN McKENZIE LENGTH: 459 words PETER JENNINGS, anchor: Finally tonight, the future of sleep which so many of us say we don't get enough of. This is about a pill to keep you awake. One researcher told the New Yorker magazine, 'It is the most tempting drug for our society to come along in decades.' Here's ABC's John McKenzie with medicine on THE CUTTING EDGE. JOHN McKENZIE reporting: (VO) It is a tantalizing goal: controlling the night. Sleeping less to accomplish more. A drug that might allow people to stay awake and alert. Unidentified Woman #1: I would use it if I were traveling, if I had to take a red eye. Unidentified Woman #2: If maybe one of my children or grandchildren were ill and I was, say, going to be in the hospital with them. McKENZIE: (VO) The prescription drug called Modafinil is approved for people with a sleeping disorder who cannot stay awake during the day, but it also holds intriguing promise for millions of other who are sleep deprived. Dr. EMMANUEL MIGNOT (Stanford University Medical School): If you take Modafinil after sleep deprivation, it can restore you to a normal level of alertness where you can concentrate, you can do things. McKENZIE: (VO) No one knows exactly how it works. But unlike other stimulants, such as caffeine or amphetamines, Modafinil shows little sign of being addictive and has few side effects. Dr. NEIL KAVEY (Columbia Presbyterian Medical Center): Modafinil is--has the advantage of not stimulating the cardiovascular system, so people are much less likely to feel palpitations, feel tremulousness, feel their heart racing. Ms. TONI HEATH-RICHARD: I don't feel any buzz at all. McKENZIE: (VO) Toni Heath-Richard uses the drug because breathing problems disrupt her sleep at night. Some doctors are prescribing the drug for daytime drowsiness in people with depression, Parkinson's Disease and multiple sclerosis. (OC) But how many other people should have access to the drug? Doctors warn that there's no evidence that Modafinil can overcome all the harmful consequences of going without sleep. Dr. KAVEY: Our cardiovascular system needs sleep. Thyroid function, hormone levels, the immune system, glucose metabolism, insulin all seem to be dependent on sleep for normal function. McKENZIE: (VO) In other words, before doctors can prescribe this stimulant more widely, they need to learn more about how much and how often sleep patterns can be safely disrupted. John McKenzie, ABC News, New York. JENNINGS: That's our report on WORLD NEWS TONIGHT. Tomorrow on WORLD NEWS, along with the Middle East and Afghanistan, the Coast Guard revives a 19th century tradition with its Christmas ship. I'm Peter Jennings. I hope have you a good evening and you sleep well. Good night. LOAD-DATE: January 31, 2002 LANGUAGE: ENGLISH TYPE: Profile Copyright 2001 American Broadcasting Companies, Inc. 904 of 998 DOCUMENTS ABC News December 3, 2001 Monday SHOW: Good Morning America (7:00 AM ET) - ABC Dr. Thomas Scammell of Beth Israel Deaconess Medical Center discusses the new drug Provigil, approved for treating narcolepsy ANCHORS: CHARLES GIBSON LENGTH: 964 words CHARLES GIBSON, co-host: Twenty of Americans work in round-the-clock businesses, and for anyone on the late shift, just staying awake can be a desperate struggle. But now drug companies are testing a pill. It's on the market with the brand name called Provigil, to see if it can keep you awake for days on end without losing alertness. Joining us from Boston, the prominent sleep researcher Dr. Thomas Scammell of Beth Israel Deaconess Medical Center. He is not part of this study, but he knows this drug very well. It's good to have you with us, Dr. Scammell. Dr. THOMAS SCAMMELL (Beth Israel Deaconess Medical Center): Good morning, Charlie. It's good to be here. GIBSON: Is this designed for people who need to be up for days on end, to be at peak capacity? I'm thinking of people like on a long mission for the military, or is it for someone who's on the late shift and just a little tired? Dr. SCAMMELL: Well, I think this is really for people who have chronic problematic sleepiness. The drug has been approved for use in narcolepsy, a disease where people have daily sleepiness that can often be so difficult that they have trouble holding a job or driving any long distance. As yet, this drug is not being used for people who have more casual sleepiness, such as you and I are familiar with, say due to just, you know, an occasional bit of sleep depravation. GIBSON: But I can see that it would have military implications. Dr. SCAMMELL: I think so. And, in fact, as best as we know, the military is using it on some long-range missions, such as when they need to send a bomber from the United States all the way to Afghanistan and back. GIBSON: Now what's new about it? We have stimulants like caffeine and amphetamines that will keep you awake. Dr. SCAMMELL: Right. Those have been available for decades now. Modafinil only became available to the public about two years ago. And the thing that's so attractive about it for us is that unlike amphetamines or these more traditional drugs, modafinil promotes wakefulness in a much gentler fashion. It doesn't have the jitteriness or the anxiety that many of the amphetamines typically produce. In fact, most people who say--who--who take it say that it feels simply like gentle wakefulness. And amazingly enough, they're able to sleep well at night when they take this during the day. GIBSON: Now you use the word modafinil and I called it Provigil. Dr. SCAMMELL: Right. Modafinil is the generic name and Provigil is the brand name. GIBSON: OK. Now what do we know so far about alertness with this? You say it's sort of gently keeps you awake. But what does it do, for instance, to memory, to coordination, to alertness, to your ability to think, really? Dr. SCAMMELL: As--so far, nobody has demonstrated that those, if you will, higher cognitive functions are any different what people take modafinil. What we do know is that many of the same brain regions that are active during normal, calm wakefulness appear to be active when people take modafinil. This is also seen in animal studies that we've done. And so the studies that have been done generally, you're comparing sleep-deprived people who have taken, say, a placebo pill to sleep-deprived people who have taken modafinil. And it's clear people that people taking the modafinil do have better memory, better attention and they can, for instance, respond more quickly on--on tasks that require that. GIBSON: After being awake for 24, 36 hours? Dr. SCAMMELL: There's been studies--there's been studies were they kept people awake for as much as four days, and remarkably their performance can actually be pretty good if they continue to take the modafinil during that time. GIBSON: Side effects? Downside? Dr. SCAMMELL: There are side effects. About 10 percent of people may have trouble with headaches and occasionally, people may feel queasy. But in contrast to the amphetamines, which generally have fairly frequent side effects, this medicine is very well tolerated. GIBSON: It's now available. I mean, we talked about it being in study phase. But this is now on the market, this drug, right? Dr. SCAMMELL: That's correct. It's on the market. It's approved for use in narcolepsy. Now I can tell you right now, there's so many prescriptions being written for this medicine. It's clear that many patients beyond narcoleptics are taking it. And in my conversations with other doctors, it's clear that patients with depression in sleepiness, multiple sclerosis in sleepiness, Parkinson's disease in sleepiness, have been taking it, and some with some pretty good success. GIBSON: Well, I was just going to say, the potential for abuse here for people who just want it because they want to be awake, I mean, it seems to me there's a huge number of people who will use it as an excuse not to sleep. Dr. SCAMMELL: This is a concern. We--this--this is the first time I think as a society we've had to really deal with this question. Modafinil, because it's such a benign medicine, really is a very tempting one. It's easy to say, well, let me just get by on three nights of, you now, of sleep per--per night during the week and maybe I'll take modafinil to keep myself going during that time. And with a medicine that has almost no side effects, that's really very tempting. Yet I think it really begins to touch upon some very basic questions of why do we sleep and what does sleep accomplish? GIBSON: Well, Dr. Scammell, two people on this broadcast, very curious about this, Diane and me. Modafinil, the generic name, Provigil, the name of the drug under which it's marketed. But of course, bottom line, I know, there is no substitute for sleep. We'll be right back. (Commercial break) LOAD-DATE: January 31, 2002 LANGUAGE: ENGLISH TYPE: Interview Copyright 2001 American Broadcasting Companies, Inc. 905 of 998 DOCUMENTS Espicom Business Intelligence November 28, 2001 Modafinil in trials for SWSD LENGTH: 168 words Researchers at Stanford University Medical Center are beginning a clinical trial onCephalon'sProvigil ( modafinil) for shift work sleep disorder (SWSD), a problem caused by the irregular or nocturnal hours kept by shift workers. Patients suffering from SWSD may experience excessive on-the-job sleepiness, making it difficult to focus. In addition, these people often have difficulties sleeping during off hours, which can compound the problem. Modafinil will be tested to see if it might enable patients to remain alert while at work, without feeling over-stimulated or unable to sleep during off-hours. Modafinil is currently approved by the FDA as a treatment for excessive sleepiness associated with narcolepsy. The research at Stanford is part of a US clinical trial currently accepting volunteers. The 12-week double-blind trial will involve monitoring workers' response to the drug both as they continue their regular work schedule and through several sessions in the sleep laboratory. LOAD-DATE: October 3, 2002 LANGUAGE: ENGLISH Copyright 2001 ESPICOM Business Intelligence Ltd. 906 of 998 DOCUMENTS Espicom Business Intelligence October 12, 2001 Cephalon's modafinil improves wakefulness in patients with obstructive sleep apnea LENGTH: 299 words Results from Cephalon's 327-patient, multi-centre, randomised, double-blind, placebo-controlled, parallel-group study indicate that Provigil ( modafinil) Tablets increased daytime wakefulness in patients suffering from excessive daytime sleepiness (EDS) associated with obstructive sleep apnoea. Obstructive sleep apnoea patients who use continuous positive airway pressure received a once-daily dose of modafinil 200 or 400mg, or placebo, for 12 weeks. Primary endpoint measures were the Maintenance of Wakefulness Test (MWT) and the Clinical Global Impression of Change (CGI-C). Statistically significant improvements in wakefulness and overall clinical condition were found at 12 weeks on the MWT (p<0.0001) and CGI-C (p<0.001) in patients treated with either modafinil dose compared to placebo. Secondary results were measured using a number of endpoints that assess patients' wakefulness and quality of life, including the Epworth Sleepiness Scale, the Functional Outcome of Sleep Questionnaire and the SF36 Health Quality of Life Survey. The results of the secondary measures also were statistically significant in patients treated with either modafinil dose compared to placebo. The most commonly-reported side effects in this study were headache, nausea and anxiety. Modafinil is a unique, wake-promoting agent launched in the US in February 1999. The American Academy of Sleep Medicine regards modafinil as a standard for the treatment of EDS associated with narcolepsy. In controlled clinical trials, modafinil has been found to be generally well tolerated with a low incidence of adverse events relative to placebo. The most commonly observed adverse events associated with the use of modafinil were headache, infection, nausea, nervousness, anxiety and insomnia. LOAD-DATE: October 3, 2002 LANGUAGE: ENGLISH Copyright 2001 ESPICOM Business Intelligence Ltd. 907 of 998 DOCUMENTS PR Newswire May 24, 2001, Thursday Cephalon Announces Marketing and Distribution Agreements For Modafinil in Mexico and Taiwan SECTION: FINANCIAL NEWS LENGTH: 785 words DATELINE: WEST CHESTER, Pa., May 24 Cephalon, Inc. (Nasdaq: CEPH), an international biopharmaceutical company, announced today that it has granted rights to market, sell and distribute modafinil to Armstrong Laboratorios de Mexico S.A.C.V. in Mexico and Sintong Chemical Industrial Co., Ltd. in Taiwan.  Cephalon markets modafinil as PROVIGIL(R) (modafinil) tablets [C-IV] in the United States and several other countries.     PROVIGIL is a unique, wake-promoting agent currently approved in several countries for the treatment of excessive daytime sleepiness associated with narcolepsy.  The most common side effects associated with PROVIGIL in clinical trials include headache, nausea, infection, nervousness, anxiety and insomnia.     "PROVIGIL has experienced major growth in the United States and has the potential for significant growth in other global markets as well," said Frank Baldino, Jr. Ph.D., chairman and CEO of Cephalon.  "Armstrong and Sintong have extensive experience within their respective markets and demonstrate solid results in marketing their own brands and those of other global pharmaceutical companies.  We are confident that they will be successful launching modafinil in Mexico and Taiwan."     Armstrong Laboratorios is a subsidiary of the Organizacion Bago, Latin America's leading regional pharmaceutical company.  Sales volume for Armstrong's neurology and psychiatry products increased by 29 percent in 2000. The Mexican pharmaceutical market is the tenth largest in the world and has been experiencing greater percentage growth than the U.S. market.     Sintong, a diversified pharmaceutical, health care and chemicals company, was established in Taiwan in 1945.  With six regional offices in Taiwan and an extensive sales channel that spans the medical, neurological and psychiatric communities, Sintong is positioned for continued growth in Taiwan.     Cephalon markets modafinil in the United States, the United Kingdom, Ireland, and Italy under the brand name PROVIGIL and promotes the product in Austria and Switzerland under the brand name MODASOMIL(R).  In addition, Cephalon holds exclusive marketing and distribution rights to PROVIGIL in Japan, South Korea, Latin America and Taiwan.     Cephalon, Inc., headquartered in West Chester, Pennsylvania, is an international biopharmaceutical company dedicated to the discovery, development and marketing products for sleep and neurological disorders, cancer and pain. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements.  Forward-looking statements provide Cephalon's current expectations or forecasts of future events.  These may include statements regarding anticipated scientific progress on its research programs, development of potential pharmaceutical products, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, sales and earnings projections, and other statements regarding matters that are not historical facts.  You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning.  Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties such as those set forth below and in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission.  Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect.  Therefore, you should not rely on any such factors or forward-looking statements.  Furthermore, Cephalon does not intend (and it is not obligated) to update publicly any forward-looking statements.  This discussion is permitted by the Private Securities Litigation Reform Act of 1995. NOTE:  Cephalon's press releases are posted on the Internet at the company's Web site at www.cephalon.com.  They are also available by fax 24 hours a day at no charge by calling PR Newswire's Company News On-Call at 800-758-5804, extension 134563.                  MAKE YOUR OPINION COUNT -  Click Here                http://tbutton.prnewswire.com/prn/11690X54347390 SOURCE Cephalon, Inc. CONTACT: Media: Mary Roche, 610-738-6415 or mroche@cephalon.com; or Investors: Mary Beth Alvin, 610-738-6376 or malvin@cephalon.com, both of Cephalon URL: http://www.prnewswire.com LOAD-DATE: May 25, 2001 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS AND MEDICAL EDITORS Copyright 2001 PR Newswire Association, Inc. 908 of 998 DOCUMENTS Reuters Health Medical News May 14, 2001 Monday 5:14 PM EST Modafinil may promote wakefulness in Parkinson-related somnolence BYLINE: By Paula Moyer SECTION: CLINICAL LENGTH: 504 words DATELINE: PHILADELPHIA Modafinil (Provigil), which has been approved for narcolepsy, also benefits patients with somnolence related to Parkinson's disease, Dr. Charles H. Adler of the Mayo Clinic Scottsdale, in Arizona, told participants here at the 53rd annual meeting of the American Academy of Neurology. He reported findings of a small double-blinded, placebo-controlled trial consisting of 21 patients, 20 of whom completed the study. Dr. Adler and his and colleagues found that seven patients treated with modafinil had significant reductions on Epworth Sleepiness Scores (ESS), compared with one patient who received placebo and two patients treated with both modafinil and placebo. Modafinil may also have a role in treating depression-related somnolence, according to Dr. Charles DeBattista of Stanford University School of Medicine. He presented findings in New Orleans at the 154th annual meeting of the American Psychiatric Association, which showed that, in a trial of 14 patients with major depression, 8 of the 11 patients who completed treatment reported an improvement in fatigue and cognition. Cephalon, Inc., the manufacturers of Provigil, provided funding for both studies. The possibility of expanded indications for modafinil is consistent with clinicians' findings, Dr. Thomas Kilkenny of Staten Island Hospital in New York told Reuters Health. Although Dr. Kilkenny was not involved in either study and has no relationship to the manufacturer, he has clinical experience with the use of modafinil in his practice. "I'm surprised it took so long for this to come out," Dr. Kilkenny told Reuters Health. "There are a lot of illnesses that cause fatigue, and this is a novel medication that causes a marked improvement in... wakefulness." Although modafinil's mechanism of action is not fully understood, it may be similar to amphetamines, yet different enough to have a lower risk of amphetamine-type adverse effects, such as addiction and tachycardia. "We do know that modafinil binds to only one of the neuroreceptor sites that amphetamines do," Dr. Kilkenny said, noting that this may be the reason it has fewer adverse effects. In his practice, he often uses modafinil to treat patients with sleep apnea who have residual sleepiness despite conventional treatment. "People sometimes need the extra boost to achieve wakefulness," he told Reuters Health. "I think further studies will [prove] this medication's benefits in fibromyalgia, chronic fatigue and other conditions associated with daytime somnolence." Although some patients on modafinil report nausea and headaches, these adverse effects typically resolve over time, he said. Patients on modafinil do not typically have any escalating need to increase the medication dose. Because there are some drug-drug interactions associated with modafinil, physicians should monitor patients who are on theophylline, diazepam, and some beta-blockers. Patients on oral contraceptives may need a second mode of contraception while on modafinil, Dr. Kilkenny told Reuters Health. LOAD-DATE: July 11, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2001 Reuters Health All Rights Reserved 909 of 998 DOCUMENTS Neurology Alert May 1, 2001 Brief Alert: Modafinil for Myotonic Dystrophy LENGTH: 245 words Brief Alert Modafinil for Myotonic Dystrophy Source: Damian MS, et al. Modafinil for excessive daytime sleepiness in myotonic dystrophy. Neurology. 2001;56: 794-796. Hypersomnia is a prominent feature of myotonic dystrophy (MyD), although, interestingly, it is more often remarked upon by relatives than by patients. Not felt to be true narcolepsy, its cause remains obscure. Modafinil, useful in narcolepsy, may nevertheless be efficacious for excessive daytime sleepiness (EDS) in MyD. In an open label trial, Damian and colleagues describe 8 patients with genetically proven MyD (expanded CTG repeat on chromosome 19q13.13) and 1 with maternally inherited proximal myotonic myopathy (PROMM). Each patient received 200-400 mg/d modafinil for a minimum of 16 weeks. All felt disabled by their EDS prior to the modafinil. With treatment, mean sleep latency (measured by MSLT) significantly increased, mean Epworth Sleepiness Scale score decreased, and all patients felt subjectively better. Modafinil was well tolerated, without significant side effects, blood pressure remained normal, and nighttime sleep was unimpaired. Clearly, it is time to proceed with a placebo-controlled, double-blind, multicenter trial. Commentary With this effective response and the relatively small number of persons who used it, it seems to Damian et al that its duration of effect should first be tested by the enlarging pioneer patients and providing a 6-month test time table.-Michael Rubin LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2001 AHC Media LLC All Rights Reserved 910 of 998 DOCUMENTS PR Newswire November 29, 2000, Wednesday Cephalon Reports That a Recent Study Identifies a Possible Mechanism of Action Of PROVIGIL-Induced Wakefulness SECTION: FINANCIAL NEWS LENGTH: 788 words DATELINE: WEST CHESTER, Pa., Nov. 29 Cephalon, Inc. (Nasdaq: CEPH) reports today that a preclinical study published in the November 15 issue of the Journal of Neuroscience provides further evidence that PROVIGIL(R) (modafinil) activates specific neuronal pathways that are believed to regulate normal wakefulness.  In this study, modafinil strongly activated two well- defined groups of nerve cells located in the hypothalamus that have been implicated in the control of wakefulness - the tuberomammillary nucleus (TMN) and orexin-containing nerve cells.  This mechanism of action is different from the pathways affected by traditional stimulants.     In three separate studies, modafinil was administered to rats at different times of day in combination with physiological recordings of sleep/wake behavior.  The degree of nerve cell activation was then measured in various areas of the brain.  Results of these experiments showed that nerve cells in the TMN were four times more active in rats administered modafinil than in control animals.  In addition, the number of activated orexin-containing nerve cells in the hypothalamus increased threefold in rats administered modafinil.     According to Dr. Thomas Scammell, M.D., Assistant Professor in the Department of Neurology at Beth Israel Deaconess Medical Center and lead author of the study, "This is an exciting finding because it represents the first demonstration of a drug directly activating these regions of the brain. Selective activation of these regions may represent a novel approach to producing wakefulness that is free of amphetamine-like subjective effects."     PROVIGIL(R) (modafinil) Tablets [C-IV] was approved by the Food and Drug Administration (FDA) in December 1998 as a once-a-day therapy to improve wakefulness in patients experiencing excessive daytime sleepiness associated with narcolepsy.  The most frequently reported adverse events observed in clinical trials for narcolepsy were headache, nausea, nervousness, anxiety, infection and insomnia.  The exact mechanism of action of PROVIGIL is not known.     Cephalon, Inc., headquartered in West Chester, Pennsylvania, is an international biopharmaceutical company dedicated to the discovery, development and marketing of products for sleep disorders, neurological disorders, pain management and cancer. This study was supported in part by a grant from Cephalon.     Reference: Scammell TE, Estabrooke IV, McCarthy MT, Chemelli, RM, Yanagisawa M, Miller MS, Saper CB.  Hypothalamic Arousal Regions are Activated during Modafinil-Induced Wakefulness. Journal of Neuroscience, 2000 Nov. 15, 20(22): 8620-8628. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements.  Forward-looking statements provide Cephalon's current expectations or forecasts of future events.  These may include statements regarding anticipated scientific progress on its research programs, development of potential pharmaceutical products, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, sales and earnings projections, and other statements regarding matters that are not historical facts.  You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning.  Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties such as those set forth below and in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission.  Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect.  Therefore, you should not rely on any such factors or forward-looking statements.  Furthermore, Cephalon does not intend (and it is not obligated) to update publicly any forward-looking statements.  This discussion is permitted by the Private Securities Litigation Reform Act of 1995. NOTE:  Cephalon's press releases are posted on the Internet at the company's Web site at www.cephalon.com.  They are also available by fax 24 hours a day at no charge by calling PR Newswire's Company News On-Call at 800-758-5804, extension 134563. SOURCE Cephalon, Inc. CONTACT: Sheryl Williams of Cephalon, 1-800-283-4396, ext. 6493, or swilliam@cephalon.com URL: http://www.prnewswire.com LOAD-DATE: November 30, 2000 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS AND MEDICAL EDITORS Copyright 2000 PR Newswire Association, Inc. 911 of 998 DOCUMENTS Deseret News (Salt Lake City) November 3, 2000, Friday Medication could fight fatigue in M.S. patients SECTION: LIFE; Pg. C06 LENGTH: 175 words SAN DIEGO -- Research presented at a meeting of the American Academy of Neurology indicated multiple sclerosis patients finally have a more effective and safe weapon against fatigue, one of the most impairing and disabling symptoms of the disease. "Fatigue, a common symptom of multiple sclerosis, can be so disabling that it may impair one's ability to work at a time where there is minimal physical disability," according to Kottil Rammohan, M.D., lead author of the study. "Drugs presently used to treat fatigue are only marginally effective. Many of the patients who participated in this study had tried conventional fatigue treatments without benefit, but they responded to modafinil." Modafinil is currently approved for the treatment of narcolepsy, a disorder of excessive daytime sleepiness. As the first non-addicting drug effective in reducing sleepiness and improving alertness, modafinil offers patients a favorable alternative to commonly prescribed stimulants that can cause serious long-term effects and have potential for abuse. LOAD-DATE: November 3, 2000 LANGUAGE: ENGLISH Copyright 2000 The Deseret News Publishing Co. 912 of 998 DOCUMENTS Medical Post October 17, 2000 Modafinil seen as a choice for ADHD: fewer side-effects than traditional stimulants, once daily dosing a plus BYLINE: Ross, Marvin SECTION: Pg. v.36(35) O 17'00 pg 67 ISSN: 0025-7435 LENGTH: 484 words TORONTO - Modafinil may be a useful alternative treatment for children with attention deficit/hyperactivity disorder (ADHD), particularly for once a day dosing or when side-effects limit the use of more traditional stimulants. Dr. Thomas Rugino, a pediatrician from Huntington, West Va., told the participants at the recent American Academy for Celebral Palsy and Developmental Medicine here, that modafinil is currently only indicated for narcolepsy. It is, however, also a stimulant totally unrelated to either methylphenidate or amphetamine. In addition to having a 15-hour effect, it has far fewer side-effects than the traditional stimulants used for ADHD because its uptake in the brain is much more limited. It acts almost entirely in the anterior hypothalamus and does not involve any other area of the brain. Dr. Rugino carried out an open label trial where subjects were evaluated before and after administration of modafinil. Every seven to 10 days, data were collected and dosages adjusted to maximize benefits or reduce side-effects. Fifteen subjects, ages 5 to 15 were enrolled who met DSM-IV criteria for ADHD and who did not suffer from an acute illness, heart or liver problems, uncontrolled seizures, insomnia, manic episodes, psychosis, migraines or were on medications that involved the P450 system or neurotransmitter action. Children who had been on ADHD treatment were able to participate if sufficient time had elapsed for a proper washout. Two children dropped out of the study because they were not compliant, one child became ill and another had an adverse event. All children were evaluated on the Connor's Rating Scales, ADHD Rating Scale IV: School and Home Version and the Test of Variables of Attention (TOVA). Doses began at 100 mg and increased to 400 mg although most children were on 100 mg to 250 mg only. Each child acted as his or her own control and was tested before and after treatment. The average treatment time was 4.6 weeks with highly significant improvements seen for all subjects on all measures. The total TOVA score showed significant improvements but sub-scores did show differences. Impulsivity was much more improved than was inattentiveness. Both the teachers' and the parents' Connor's Ratings showed statistically significant improvements. Weight loss, which is a problem with methylphenidate and amphetamines, was not observed in these children. Side-effects included headaches, feeling disoriented, and an increase in biting of hands. When the medication was given before 8 a.m., parents reported that the effects lasted throughout the day so that a second dose was not required. However, parents did notice that the effects began to wear off as the evening progressed. As the result of this study, Dr. Rugino feels that a double blind placebo controlled trial is warranted to confirm these results. Modafinil, currently indicated for narcolepsy, has fewer side-effects and can last up to 15 hours LOAD-DATE: January 8, 2001 LANGUAGE: ENGLISH ACC-NO: 4969860 DOCUMENT-TYPE: Fulltext; Journal article PUBLICATION-TYPE: Other JOURNAL-CODE: 0945 Copyright 2000 Micromedia Limited All Rights Reserved Canadian Business and Current Affairs Copyright 2000 Maclean Hunter Ltd. 913 of 998 DOCUMENTS OTS Originaltextservice September 20, 2000 Cephalon Launches Modafinil in Switzerland for Treatment of Narcolepsy LENGTH: 777 words DATELINE: West Chester, Pa. Cephalon, Inc. (Nasdaq: CEPH) announced today that it has launched modafinil in Switzerland for the treatment of narcolepsy. Modafinil, which is being promoted by Cephalon in Switzerland under the trade name MODASOMIL(R), is a novel, wake-promoting drug for the treatment of excessive daytime sleepiness (EDS) associated with narcolepsy. Narcolepsy is a chronic sleep disorder of unknown origin and generally begins in young adulthood. The most common symptom of narcolepsy is EDS, which is characterized by frequent irresistible sleep attacks that can last from a few seconds to more than an hour. These attacks can take place any time, such as during conversation, while attending class or while eating. As a result, narcolepsy significantly impacts a person's quality of life. "Swiss neurologists and sleep doctors now have the opportunity to offer their narcolepsy patients a novel, once-a-day, well-tolerated, effective alternative to the stimulants that have traditionally been used to treat this disabling disorder, " said Frank Baldino, Jr., Ph.D., Cephalon's chairman and chief executive officer. "With this launch, modafinil is now available in each of the five European countries in which we have rights to market the drug." Modafinil is a novel, wakefulness-promoting agent. In clinical trials, modafinil was found to significantly improve daytime wakefulness. Patients also experienced a significant improvement in the severity of their disease symptoms and clinical condition. Modafinil has been found to be generally well-tolerated, with a low incidence of adverse events that is relatively comparable to placebo. The most commonly observed adverse events associated with modafinil are headache, infection, nausea, nervousness, anxiety and insomnia. Modafinil is marketed by Cephalon in the United States, the United Kingdom, Ireland, and Italy under the brand name PROVIGIL(R) (modafinil) Tablets C-IV and in Austria and Switzerland under the brand name MODASOMIL. In Switzerland, Mepha AG is the marketing authorization holder for modafinil. In addition, Cephalon has exclusive marketing rights to PROVIGIL in Japan, Latin America, South Korea, and Taiwan. Cephalon, Inc., headquartered in West Chester, Pennsylvania, is an international biopharmaceutical company dedicated to the discovery, development and marketing of products to treat sleep disorders, neurological disorders and cancer. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs, development of potential pharmaceutical products, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, sales and earnings projections, and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties such as those set forth below and in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend (and it is not obligated) to update publicly any forward-looking statements. This discussion is permitted by the Private Securities Litigation Reform Act of 1995. NOTE: Cephalon's press releases are posted on the Internet at the company's Web site at www.cephalon.com. They are also available by fax 24 hours a day at no charge by calling PR Newswire's Company News On-Call at 800-758-5804, extension 134563. ots Original Text Service: Cephalon, Inc. Internet: http://recherche.newsaktuell.de Contact: Sheryl Williams of Cephalon, +1-800-283-4396, ext. 6493, or swilliam@cephalon.com Company News On-Call: http://www.prnewswire.com/comp/134563.html or fax, +1-800-758-5804, ext. 134563 Web site: http://www.cephalon.com LOAD-DATE: September 20, 2000 LANGUAGE: English PUB-TYPE: NewsWire Copyright 2000 News Aktuell - DPA Firmengruppe 914 of 998 DOCUMENTS PR Newswire September 20, 2000, Wednesday Cephalon Launches Modafinil in Switzerland for Treatment of Narcolepsy SECTION: FINANCIAL NEWS LENGTH: 760 words DATELINE: WEST CHESTER, Pa., Sept. 20 Cephalon, Inc. (Nasdaq: CEPH) announced today that it has launched modafinil in Switzerland for the treatment of narcolepsy.  Modafinil, which is being promoted by Cephalon in Switzerland under the trade name MODASOMIL(R), is a novel, wake-promoting drug for the treatment of excessive daytime sleepiness (EDS) associated with narcolepsy.     Narcolepsy is a chronic sleep disorder of unknown origin and generally begins in young adulthood. The most common symptom of narcolepsy is EDS, which is characterized by frequent irresistible sleep attacks that can last from a few seconds to more than an hour.  These attacks can take place any time, such as during conversation, while attending class or while eating.  As a result, narcolepsy significantly impacts a person's quality of life.     "Swiss neurologists and sleep doctors now have the opportunity to offer their narcolepsy patients a novel, once-a-day, well-tolerated, effective alternative to the stimulants that have traditionally been used to treat this disabling disorder, " said Frank Baldino, Jr., Ph.D., Cephalon's chairman and chief executive officer.  "With this launch, modafinil is now available in each of the five European countries in which we have rights to market the drug."     Modafinil is a novel, wakefulness-promoting agent.  In clinical trials, modafinil was found to significantly improve daytime wakefulness.  Patients also experienced a significant improvement in the severity of their disease symptoms and clinical condition.  Modafinil has been found to be generally well-tolerated, with a low incidence of adverse events that is relatively comparable to placebo.  The most commonly observed adverse events associated with modafinil are headache, infection, nausea, nervousness, anxiety and insomnia.     Modafinil is marketed by Cephalon in the United States, the United Kingdom, Ireland, and Italy under the brand name PROVIGIL(R) (modafinil) Tablets [C-IV] and in Austria and Switzerland under the brand name MODASOMIL. In Switzerland, Mepha AG is the marketing authorization holder for modafinil. In addition, Cephalon has exclusive marketing rights to PROVIGIL in Japan, Latin America, South Korea, and Taiwan.     Cephalon, Inc., headquartered in West Chester, Pennsylvania, is an international biopharmaceutical company dedicated to the discovery, development and marketing of products to treat sleep disorders, neurological disorders and cancer. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements.  Forward-looking statements provide Cephalon's current expectations or forecasts of future events.  These may include statements regarding anticipated scientific progress on its research programs, development of potential pharmaceutical products, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, sales and earnings projections, and other statements regarding matters that are not historical facts.  You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning.  Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties such as those set forth below and in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission.  Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect.  Therefore, you should not rely on any such factors or forward-looking statements.  Furthermore, Cephalon does not intend (and it is not obligated) to update publicly any forward-looking statements.  This discussion is permitted by the Private Securities Litigation Reform Act of 1995. NOTE:  Cephalon's press releases are posted on the Internet at the company's Web site at www.cephalon.com.  They are also available by fax 24 hours a day at no charge by calling PR Newswire's Company News On-Call at 800-758-5804, extension 134563. SOURCE Cephalon, Inc. CONTACT: Sheryl Williams of Cephalon, 800-283-4396, ext. 6493, or swilliam@cephalon.com URL: http://www.prnewswire.com LOAD-DATE: September 21, 2000 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS AND MEDICAL EDITORS Copyright 2000 PR Newswire Association, Inc. 915 of 998 DOCUMENTS PR Newswire Europe September 20, 2000, Wednesday CEPHALON LAUNCHES MODAFINIL IN SWITZERLAND FOR TREATMENT OF NARCOLEPSY SECTION: GENERAL LENGTH: 797 words PR Newswire, London, September 20. This press release is transmitted on behalf of Cephalon, Inc. West Chester, Pa., September 20 /PR Newswire/ - Cephalon, Inc. (Nasdaq: CEPH) announced today that it has launched modafinil in Switzerland for the treatment of narcolepsy. Modafinil, which is being promoted by Cephalon in Switzerland under the trade name MODASOMIL(R), is a novel, wake-promoting drug for the treatment of excessive daytime sleepiness (EDS) associated with narcolepsy. Narcolepsy is a chronic sleep disorder of unknown origin and generally begins in young adulthood. The most common symptom of narcolepsy is EDS, which is characterized by frequent irresistible sleep attacks that can last from a few seconds to more than an hour. These attacks can take place any time, such as during conversation, while attending class or while eating. As a result, narcolepsy significantly impacts a person's quality of life. "Swiss neurologists and sleep doctors now have the opportunity to offer their narcolepsy patients a novel, once-a-day, well-tolerated, effective alternative to the stimulants that have traditionally been used to treat this disabling disorder, " said Frank Baldino, Jr., Ph.D., Cephalon's chairman and chief executive officer. "With this launch, modafinil is now available in each of the five European countries in which we have rights to market the drug." Modafinil is a novel, wakefulness-promoting agent. In clinical trials, modafinil was found to significantly improve daytime wakefulness. Patients also experienced a significant improvement in the severity of their disease symptoms and clinical condition. Modafinil has been found to be generally well-tolerated, with a low incidence of adverse events that is relatively comparable to placebo. The most commonly observed adverse events associated with modafinil are headache, infection, nausea, nervousness, anxiety and insomnia. Modafinil is marketed by Cephalon in the United States, the United Kingdom, Ireland, and Italy under the brand name PROVIGIL(R) (modafinil) Tablets [C-IV] and in Austria and Switzerland under the brand name MODASOMIL. In Switzerland, Mepha AG is the marketing authorization holder for modafinil. In addition, Cephalon has exclusive marketing rights to PROVIGIL in Japan, Latin America, South Korea, and Taiwan. Cephalon, Inc., headquartered in West Chester, Pennsylvania, is an international biopharmaceutical company dedicated to the discovery, development and marketing of products to treat sleep disorders, neurological disorders and cancer. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs, development of potential pharmaceutical products, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, sales and earnings projections, and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties such as those set forth below and in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend (and it is not obligated) to update publicly any forward-looking statements. This discussion is permitted by the Private Securities Litigation Reform Act of 1995. NOTE: Cephalon's press releases are posted on the Internet at the company's Web site at www.cephalon.com. They are also available by fax 24 hours a day at no charge by calling PR Newswire's Company News On-Call at 800-758-5804, extension 134563. UNS CONTACT: Sheryl Williams of Cephalon, +1 800-283-4396, ext. 6493, or swilliam@cephalon.com/ Company News On-Call: http://www.prnewswire.com/comp/134563.html or fax, +1 800-758-5804, ext. 134563/ Web site: http://www.cephalon.com / PAP0029 4 GXX BT 660 ONDIGITAL ADDRESS +ZZZ UUK NFL GEN NEX CATCHWORD" UNS GENERAL LOAD-DATE: September 21, 2000 LANGUAGE: ENGLISH Copyright 2000 PR Newswire Europe Limited 916 of 998 DOCUMENTS Case Management Advisor September 1, 2000 Drug promotes better sleep LENGTH: 145 words Drug promotes better sleep Provigil Tablets (modafinil), manufactured by Cephalon in West Chester, PA, increased daytime wakefulness in patients treated with continuous positive airway pressure for sleep apnea. Results of a multicenter, double-blind, placebo-controlled study of 157 sleep apnea patients indicate that patients who were treated with modafinil performed better on validated tests of excessive daytime sleepiness as measured by standardized scales. The most common side effects were headaches, nervousness, nausea, anxiety, and dizziness. Cephalon recently initiated additional clinical trials with modafinil in sleep apnea patients with the intention of pursuing a label extension to include this additional indication. The drug is currently marketed in the United States for the treatment of excessive daytime sleepiness associated with narcolepsy. LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 2000 AHC Media LLC All Rights Reserved 917 of 998 DOCUMENTS The Weekend Australian June 24, 2000, Saturday Wake to a bright new day / STAYING ALIVE BYLINE: Jill Margo SECTION: FEATURES; Pg. R31 LENGTH: 907 words A new drug to combat sleep attacks had its origins in the battlefield TRY to stay awake to the end of this column. If you do, you will have read about the latest alert drug that, in the mildest possible way, seems to stop people nodding off during the day. The international sleep research community is buzzing with news of modafinil, which protects people from sleep attacks -- outwardly benign events that can have disastrous consequences. Sleep attacks are brief, unwanted episodes occurring at inappropriate times. They can last seconds or minutes and usually occur during times of reduced stimulation such as reading, watching television, driving or being driven, or sitting in a meeting. About one in 10 adults suffer from excessive daytime sleepiness and unpredictably drift into sleep. This problem is also one of the primary symptoms of the rare condition narcolepsy. For years people have been using amphetamines or caffeine to overcome such sleepiness. Although amphetamines certainly do the job effectively, they have unpleasant side effects. Drinking several cups of coffee is usually a safer but less effective alternative. Modafinil is said to combine the best of both with the power of amphetamines and the safety profile of caffeine. Although the drug is approved and widely used in Europe and the US, it is not yet officially available in Australia but is bought here via the internet. (The internet has been progressively used to bypass the cautious and protective processes of the country's drug approval authority.) In Europe and the US, modafinil is approved for use in narcolepsy but the French Laboratoire L Lafon, which developed it, is trying to gain approval for wider use. It says the drug can be used to treat attention deficit disorder, sleep apnea, chronic fatigue syndrome and other sleep-wake disorders. Ron Grunstein, of the Royal Prince Alfred Hospital's Sleep Disorder Centre, Sydney, is circumspect. "Modafinil certainly broadens the therapeutic range for the treatment of narcolepsy, is safer than amphetamines and is not psychoactive, but we don't know yet if it's better. Further research is needed," he says. People who suffer excessive daytime sleepiness often have their condition erroneously attributed to slothfulness, depression or a defective character. The condition can strain relationships. It also can impair job performance and, because it occurs so unpredictably, present a serious hazard -- for example, someone falling asleep at the wheel of machinery. Devastating industrial accidents such as the Three Mile Island and the Exxon Valdez disasters in the US were officially attributed to errors of judgment due to sleepiness in the workplace. To protect sleep-deprived military troops from errors of judgment during round-the-clock operations, the military regularly uses stimulants. During the Gulf War, air crews were recommended amphetamines when unduly fatigued through sleep loss. Crack French troops of the Foreign Legion used modafinil during covert operations inside Iraq during the Gulf War. There have since been newspaper reports that Australia's elite troops -- officially cleared to use performance- enhancing chemicals -- have been given the option of modafinil to keep them going on all-night missions. One of Europe's most prominent figures in sleep research, Michel Jouvet, from Lyon University, told an international defence meeting in Paris that "modafinil could keep an army on its feet and fighting for three days and nights with no major side effects". Jouvet was a French resistance fighter and knows about alertness during sustained operations. Defence personnel have been used in several modafinil studies. The military wanted to know if it could effectively counteract fatigue and decline in mental performance due to sleep deprivation in normal populations. One study of about 40 Canadian Force reservists found modafinil appeared to be "a good alternative to amphetamine for counteracting the debilitating mood and cognitive effects of sleep loss during sustained operations". Although amphetamines induce feelings of euphoria, cause a loss of appetite and increase heart rate and blood pressure, modafinil does none of these. Its biggest side effect is a headache and, because it does not induce euphoria, its potential for abuse is low. A later Canadian study, however, found the drug tended to make the defence personnel subjects overconfident when assessing their own cognitive performance during sleep deprivation. Just as the military is interested in broader applications, the drug may have potential as an anti-fatigue agent for truck drivers, airline pilots and others for whom a wakeful state is a critical. The uniqueness of modafinil lies in its ability to stimulate only when stimulation is required. Unlike amphetamines, it is not addictive and does not affect normal sleep patterns. Although amphetamines keep people awake, those on modafinil can revert to their usual sleep pattern if they want to. If they want to remain awake, they will do so with more alertness. It is said that after the initial dose, users comment that they can't discern any effect. Several hours later, however, when they realise how they have remained awake and maintained their attention, they suddenly become aware of the benefit. If you've read this far today without dozing off, you probably don't need it. LOAD-DATE: December 3, 2001 LANGUAGE: ENGLISH JOURNAL-CODE: AUS Copyright 2000 Nationwide News Pty Limited 918 of 998 DOCUMENTS The Weekend Australian June 24, 2000, Saturday Wake to a bright new day / STAYING ALIVE BYLINE: Jill Margo SECTION: FEATURES; Pg. R31 LENGTH: 907 words A new drug to combat sleep attacks had its origins in the battlefield TRY to stay awake to the end of this column. If you do, you will have read about the latest alert drug that, in the mildest possible way, seems to stop people nodding off during the day. The international sleep research community is buzzing with news of modafinil, which protects people from sleep attacks -- outwardly benign events that can have disastrous consequences. Sleep attacks are brief, unwanted episodes occurring at inappropriate times. They can last seconds or minutes and usually occur during times of reduced stimulation such as reading, watching television, driving or being driven, or sitting in a meeting. About one in 10 adults suffer from excessive daytime sleepiness and unpredictably drift into sleep. This problem is also one of the primary symptoms of the rare condition narcolepsy. For years people have been using amphetamines or caffeine to overcome such sleepiness. Although amphetamines certainly do the job effectively, they have unpleasant side effects. Drinking several cups of coffee is usually a safer but less effective alternative. Modafinil is said to combine the best of both with the power of amphetamines and the safety profile of caffeine. Although the drug is approved and widely used in Europe and the US, it is not yet officially available in Australia but is bought here via the internet. (The internet has been progressively used to bypass the cautious and protective processes of the country's drug approval authority.) In Europe and the US, modafinil is approved for use in narcolepsy but the French Laboratoire L Lafon, which developed it, is trying to gain approval for wider use. It says the drug can be used to treat attention deficit disorder, sleep apnea, chronic fatigue syndrome and other sleep-wake disorders. Ron Grunstein, of the Royal Prince Alfred Hospital's Sleep Disorder Centre, Sydney, is circumspect. "Modafinil certainly broadens the therapeutic range for the treatment of narcolepsy, is safer than amphetamines and is not psychoactive, but we don't know yet if it's better. Further research is needed," he says. People who suffer excessive daytime sleepiness often have their condition erroneously attributed to slothfulness, depression or a defective character. The condition can strain relationships. It also can impair job performance and, because it occurs so unpredictably, present a serious hazard -- for example, someone falling asleep at the wheel of machinery. Devastating industrial accidents such as the Three Mile Island and the Exxon Valdez disasters in the US were officially attributed to errors of judgment due to sleepiness in the workplace. To protect sleep-deprived military troops from errors of judgment during round-the-clock operations, the military regularly uses stimulants. During the Gulf War, air crews were recommended amphetamines when unduly fatigued through sleep loss. Crack French troops of the Foreign Legion used modafinil during covert operations inside Iraq during the Gulf War. There have since been newspaper reports that Australia's elite troops -- officially cleared to use performance- enhancing chemicals -- have been given the option of modafinil to keep them going on all-night missions. One of Europe's most prominent figures in sleep research, Michel Jouvet, from Lyon University, told an international defence meeting in Paris that "modafinil could keep an army on its feet and fighting for three days and nights with no major side effects". Jouvet was a French resistance fighter and knows about alertness during sustained operations. Defence personnel have been used in several modafinil studies. The military wanted to know if it could effectively counteract fatigue and decline in mental performance due to sleep deprivation in normal populations. One study of about 40 Canadian Force reservists found modafinil appeared to be "a good alternative to amphetamine for counteracting the debilitating mood and cognitive effects of sleep loss during sustained operations". Although amphetamines induce feelings of euphoria, cause a loss of appetite and increase heart rate and blood pressure, modafinil does none of these. Its biggest side effect is a headache and, because it does not induce euphoria, its potential for abuse is low. A later Canadian study, however, found the drug tended to make the defence personnel subjects overconfident when assessing their own cognitive performance during sleep deprivation. Just as the military is interested in broader applications, the drug may have potential as an anti-fatigue agent for truck drivers, airline pilots and others for whom a wakeful state is a critical. The uniqueness of modafinil lies in its ability to stimulate only when stimulation is required. Unlike amphetamines, it is not addictive and does not affect normal sleep patterns. Although amphetamines keep people awake, those on modafinil can revert to their usual sleep pattern if they want to. If they want to remain awake, they will do so with more alertness. It is said that after the initial dose, users comment that they can't discern any effect. Several hours later, however, when they realise how they have remained awake and maintained their attention, they suddenly become aware of the benefit. If you've read this far today without dozing off, you probably don't need it. LOAD-DATE: March 1, 2002 LANGUAGE: ENGLISH JOURNAL-CODE: AUS Copyright 2000 Nationwide News Pty Limited 919 of 998 DOCUMENTS Reuters Health Medical News June 22, 2000 Thursday Wake-promoting drug shows promise in healthy, sleep-deprived individuals BYLINE: By Jill Stein SECTION: CLINICAL LENGTH: 563 words DATELINE: LAS VEGAS Jun 22 Modafinil, a nonamphetamine approved to treat excessive daytime sleepiness associated with narcolepsy, consistently enhances performance and alertness in healthy individuals who are sleep-deprived, according to preliminary results presented at the 14th annual meeting of the Associated Professional Sleep Societies (APSS). In three separate studies, researchers found that modafinil improved alertness and performance deficits in shift workers and military personnel. "The results are extremely important because of growing numbers of individuals, particularly in the work setting, whose jobs require lengthy bouts of sleep deprivation," Dr. David Dinges, of the University of Pennsylvania, in Philadelphia, said at a symposium where the data were released. "According to the most recent government statistics, at least 2.9 million Americans work on night shifts, and nearly 486,000 work as long-haul truck drivers." "In addition, an estimated 1.5 million Americans are on active military duty, which involves being awake for protracted periods of time during crises and deploying highly lethal systems in hostile environments." At the meeting, Dr. John A. Caldwell, of the US Army Aeromedical Research Laboratory at Fort Rucker, Alabama, presented data from a flight simulator study of six helicopter pilots who underwent two 40-hour periods of continuous wakefulness separated by 1 night of recovery sleep. In one of the two sleep-deprivation periods, three doses of modafinil (200 mg each) were administered; placebo was given during the other deprivation period. Pilots receiving three 200-mg doses of modafinil scored better on tests of performance and physiological arousal during six flight maneuvers than they did while on placebo, and had improved self-ratings of vigor, energy, alertness, talkativeness and confidence. Dr. Nancy Wesensten, of the Walter Reed Army Institute of Research in Washington, DC, announced the results of a study that compared three doses of modafinil (100 mg, 200 mg or 400 mg) to high-dose caffeine (600 mg) and placebo in 50 healthy volunteers undergoing prolonged sleep deprivation. In the trial, the active drug or placebo was administered over 40 hours of sleep deprivation. Alertness, mood, performance and safety were evaluated during a 14-hour period after treatment. Results showed that the 400-mg dose was effective for restoring cognitive performance during prolonged sleep deprivation to near baseline levels. The 200-mg dose was slightly less effective. Dr. Charles A. Czeisler, of the Harvard Medical School, in Boston, Massachusetts, headed a study that monitored sleep and wake times in 16 healthy shift workers for 24 hours per day for 4 days and included one 28-hour period of sleep deprivation. Subjects were randomized to treatment with either 200 mg of modafinil or placebo. Modafinil improved alertness and performance compared with placebo, as measured by standard, validated vigilance scales, and did not interfere with subsequent daytime sleep opportunities. In the three studies, the most common side effects related to modafinil treatment were nausea, headache, vertigo and jitteriness. The investigators emphasized that the side effects may be related to the dosages used in the various studies and added that side effects must be decreased before this medication can be considered for use in shift and military workers. LOAD-DATE: July 11, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2000 Reuters Health All Rights Reserved 920 of 998 DOCUMENTS Community Pharmacy June 2000 Waking up to NARCOLEPSY SECTION: Pg. 28 LENGTH: 1252 words Narcolepsy is a disabling disorder for which there is no cure. But, as Claire Waghorn, pharmacist at Papworth Hospital NHS Trust, explains, the symptoms can be reduced with carefully monitored medication and a daily routine Narcolepsy is a neurological disorder characterised by excessive daytime sleepiness and irresistible sleep attacks. It can occur equally in men and women of any age, although symptoms are often first seen in teenagers and young adults. It is thought to affect around one in 2,500 people in the UK, although it is believed that many thousands of sufferers may still remain undiagnosed. Narcolepsy is a chronic and disabling condition. Treatment may be for life, and there is very rarely remission. Depression, low self-esteem, problems at school and loss of employment are common. There are four classic symptoms of narcolepsy: excessive daytime sleepiness (EDS); cataplexy; sleep paralysis; and hypnagogic/hypnopompic hallucinations. Cataplexy is unique to narcolepsy and this sudden loss of muscle control can range from slight weakness such as a drooping head, sagging jaw or buckling knees, to complete body collapse, usually in association with strong emotion such as anger or laughter. Sleep paralysis creates an inability to move when falling asleep, or upon waking, while the hallucinations are in the form of vivid, dream- like experiences while falling asleep or awakening. Not all people with narcolepsy suffer from every one of these symptoms, although they all experience EDS. There is no cure for narcolepsy, but it is possible to control or reduce symptoms so that patients can lead a more normal life. Treatments Treatment can be non-pharmacological or pharmacological. In the former, the first step is to promote good sleep habits: patients are encouraged to get a full night's sleep, taken at the same time each day, including weekends. Short naps should be planned throughout the day, usually after meals. Regular breaks should be taken from tasks requiring prolonged concentration and work areas should be well-lit and ventilated. Alertness can be improved by taking regular exercise and avoiding vigorous exercise close to bedtime. Caffeine should be avoided within six hours of bedtime, as should alcohol before any activity for which it is important to remain awake. Sufferers should also avoid smoking close to bedtime, whilst in bed or when they feel sleepy. Pharmacological treatment may also be required. Patients often drink large quantities of caffeinated drinks but over- the-counter medicines containing caffeine do not work well and are not recommended for people with narcolepsy. Amphetamines Excessive daytime sleepiness may be controlled by amphetamines and related drugs. Dexamphetamine (Dexedrine) and methylphenidate (Ritalin, which is not licensed in the UK for treatment of narcolepsy) are generalised central nervous system stimulants which decrease the number of sleep attacks, improve task performance, and increase the time taken to fall asleep. These drugs cannot eliminate sleep attacks altogether. The disadvantages of these psychomotor stimulant drugs are that patients can develop autonomic side effects, as well as motor hyperactivity and a sense of euphoria which has led to reports of amphetamine abuse. Common side effects are stomach pain, irritability, nervousness, headaches, psychotic reactions, hypertension, and anorexia. Abruptly withdrawing these stimulants can also cause fatigue, sleep rebound, hypersomnia and psychomotor agitation. Unfortunately, tolerance to the effects of amphetamines may develop in some patients with narcolepsy and some psychomotor stimulants, such as dexamphetamine, have mild anti- cataplectic properties. Both methylphenidate and dexamphetamine are schedule 2 controlled drugs. Non-amphetamines Modafinil is a non-amphetamine, wake-promoting agent. The precise mechanisms through which modafinil promotes wakefulness are unknown. Although the effects of modafinil are reduced by prazosin, an (1- adrenergic receptor) antagonist, modafinil is not a direct or indirect (1-adrenergic) agonist. Modafinil promotes vigilance and wakefulness, and decreases the number of daytime sleep episodes associated with narcolepsy. To date, there have been no reports of problems of abuse with modafinil, and withdrawal has not been associated with any manifestations of drug- related dependency. The drug is generally well tolerated, with the most common adverse effects being nausea, headaches and rhinitis. Although it makes patients more alert, it does not cause the euphoria experienced with the psychomotor stimulants. Further experience is needed to determine whether tolerance to modafinil occurs. Modafinil has no effect on cataplexy symptoms. In vitro studies have shown modafinil to be a potential enzyme inducer and inhibitor of certain enzymes, possibly reducing the effectiveness of some oral contraceptives and anticonvulsants. Shared care guidelines can be developed between the specialist centre and primary care, outlining the use of modafinil and the responsibilities of the hospital and the GP, allowing them to be more involved in the patient's management. The fact that modafinil is not a controlled drug makes for simpler prescribing and dispensing. SSRIs The most effective medications for treating cataplexy are antidepressants, and both tricyclics and selective serotonin reuptake inhibitors (SSRIs) are used. The effectiveness of antidepressants for the treatment of cataplexy is down to their noradrenergic reuptake blocking effects and REM suppressant effects. In general, tricyclics are more effective, but do have more side effects. Clomipramine is the most effective tricyclic antidepressant in cataplexy. Imipramine, protriptyline and the SSRIs fluoxetine and paroxetine, may also be used. Patients who require treatment for both sleepiness and cataplexy may be given psychomotor stimulants and tricyclic antidepressants but will require monitoring as the combination may produce serious adverse effects such as cardiac arrhythmias or hypertension. The antidepressant may also help with the dreams and nightmares experienced by narcolepsy patients. Any pharmacological treatment should be combined with the non-pharmacological measures. SUMMARY * Narcolepsy is a neurological disorder characterised by excessive daytime sleepiness and irresistible sleep attacks * In the UK, an estimated one in 2,500 people suffer from narcolepsy * There is no cure for narcolepsy but symptoms can be reduced by a careful daily routine * Medication, such as amphetamines, can also reduce symptoms but they may produce side effects and dependency * OTC medicines containing caffeine are not recommended for sufferers SLEEP STATISTICS In a recent survey, Stafford-Miller finds that: * 62 per cent of women and 38 per cent of men experience sleepless nights * one person households are more likely to experience sleeplessness * 60 per cent of sufferers experience a sleepless night two to three times a week * Use of OTC sleep aids has increased from 12 per cent in 1995 to 20 per cent in 1999; 24 per cent of users have taken the pharmacist's recommendation * 46 per cent feel that sleep aids are preferable to prescription drugs * 52 per cent believe that OTC drugs are safe and natural; 23 per cent stated that they had no side effects LOAD-DATE: June 5, 2000 LANGUAGE: English PUB-TYPE: Magazine Copyright 2000 CMP Information Ltd 921 of 998 DOCUMENTS Medical Post May 23, 2000 Narcolepsy drug improves fatigue in MS patients BYLINE: Wansbrough, Gillian SECTION: Pg. v.36(20) My 23'00 pg 16 ISSN: 0025-7435 LENGTH: 515 words SAN DIEGO - Modafinil, which is currently approved for the treatment of narcolepsy, may be effective in treating fatigue related to multiple sclerosis. Fatigue in these patients can be so disabling that it can impair their ability to work at a time when there is minimal disability, according to Dr. Kotti Rammohan, a neurologist at Ohio State University in Columbus. In a nine-week, phase II, single-blinded trial at Ohio State and Kaiser Permanente in San Diego, 72 patients received placebo for two weeks, 200 mg modafinil for weeks three and four, 400 mg during weeks four and five, and placebo again for weeks seven through nine. Modafinil is a stimulant used for the treatment of excessive daytime sleepiness in narcolepsy. It has a different profile from the known stimulants of sympathetic amines, and preliminary studies suggest it does not affect dopamine, norepinephrine, serotonin, melatonin or histamine. In a presentation at the meeting here, Dr. Rammohan noted, however, that modafinil's wake-promoting effect can be nullified by the alpha-1 adrenergic receptor antagonists used in MS. In contrast to amphetamines, which promote the global stimulation of the central nervous system, modafinil has very specific stimulatory effects, so the abuse potential is minor. The patients in the study ranged in age from 18 to 65 and had mild to moderate MS (77% were relapsing-remitting) and moderate to severe fatigue. Most had Extended Disability Status Scores of zero to 3, while some scored 6. Many of these patients had tried conventional fatigue treatments such as amantadine without benefit. Exclusion criteria were sleep-related disorders, systemic disorders, hypertension, substance abuse problems, excess caffeine consumption, or use of other medications (including OTC) that would influence sleep. ''The 200 mg dose of modafinil did overcome the placebo effect, but not the 400 mg dose,'' said Dr. Rammohan. ''In fact, when comparing the 400 mg to baseline it has a significant effect but not when compared to the placebo. ''At this point we would not consider 400 mg to be an effective dose.'' Efficacy was evaluated at screening and after each study phase using the Fatigue Severity Scale (FSS), a visual analogue global fatigue scale (VAFS)-a global assessment of how the patient is feeling-and the Modified Fatigue Impact Scale (MFIS), which has physical, cognitive and psychosocial subgroups. Mean total scores on the three scales of increasing fatigue for modafinil 200 mg/day and placebo were 42.4 vs 49.4 on the FSS, 5.5 vs 4.3 on the VAFS, and 37.3 vs 46.2 on the MFIS. The 200 mg dose had the best effect on the MFIS and the VAFS, while both doses were effective on the FSS, ''suggesting the mechanism by which modafinil may act may be different for fatigue as compared to the mechanism involved in sleep.'' Dr. Rammohan suggested this drug may become the first-line treatment against fatigue in MS patients. ''Patients' perceptions of accomplishing daily activities were significantly improved with modafinil treatment,'' he said. The study was funded through a grant from Cephalon, Inc., the makers of modafinil. LOAD-DATE: September 5, 2000 LANGUAGE: ENGLISH ACC-NO: 4856407 DOCUMENT-TYPE: Fulltext; Journal article PUBLICATION-TYPE: Other JOURNAL-CODE: 0945 Copyright 2000 Micromedia Limited All Rights Reserved Canadian Business and Current Affairs Copyright 2000 Maclean Hunter Ltd. 922 of 998 DOCUMENTS PR Newswire May 18, 2000, Thursday Physician Reports First U.S. Study of Modafinil (PROVIGIL(R)) in ADHD SECTION: FINANCIAL NEWS LENGTH: 970 words DATELINE: WEST CHESTER, Pa., May 18 A study presented today at the annual meeting of the American Psychiatric Association (APA) in Chicago described the effects of modafinil and the drug's potential as a treatment for Attention Deficit Hyperactivity Disorder (ADHD). The study conducted by Fletcher B. Taylor, M.D., of Tacoma, WA, compared modafinil to dextroamphetamine, a commonly used amphetamine, and placebo in adults with ADHD.  Results of the study demonstrated that an average daily dose of approximately 200 mg of modafinil produced a statistically and clinically significant reduction (30 percent or more) in the symptoms of ADHD as measured by the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) ADHD Behavior Checklist for Adults, compared to placebo.  Modafinil is marketed as PROVIGIL(R) (modafinil) Tablets [C-IV] in several countries, including the United States, by Cephalon, Inc. (Nasdaq: CEPH) for the treatment of excessive daytime sleepiness associated with narcolepsy.     The double-blind, placebo-controlled, cross-over study included 22 adult patients meeting the DSM-IV diagnostic criteria for ADHD.  In this study, dextroamphetamine at an average daily dose of approximately 20 mg also reduced the symptoms of ADHD with an effect similar to that of modafinil.  Both medications were well tolerated.  Compared to placebo, the most commonly reported side effects for both modafinil and dextroamphetamine were insomnia, irritability, muscle tension and appetite suppression.     Dr. Taylor indicated that he and his colleagues initiated the study because some of their patients wanted an alternative therapy.  Today, stimulants, including amphetamine, methylphenidate and pemoline are the most established treatments for ADHD.  Treatment of ADHD with traditional stimulants is often associated with troublesome side effects, tolerance and the potential for abuse.   In addition, some patients do not respond to currently available therapies. According to Dr. Taylor, "Modafinil, with its low potential for abuse, may represent a valuable treatment option for adults with ADHD."     ADHD affects an estimated 5 to 7 million adults and children in the United States.  Dr. Taylor noted that while 30 to 70 percent of children with ADHD will retain the diagnosis through adulthood, in his study 70 percent of the participants had a relative with ADHD, usually their child.     "We are pleased by the results of this independent study and hope to corroborate these findings with data from our own studies in adults with ADHD," stated Frank Baldino, Jr., Ph.D., chairman and chief executive officer of Cephalon.     Cephalon currently is conducting studies with PROVIGIL in adults with ADHD at seven academic medical centers in the United States.  In addition, Cephalon has initiated a pharmacokinetic study and intends to initiate a dose-ranging study in children by mid-year, as a prelude to a Phase 3 study in children with ADHD.     PROVIGIL was approved by the Food and Drug Administration (FDA) in December 1998 as a once-a-day therapy to improve wakefulness in patients experiencing excessive daytime sleepiness due to narcolepsy.  The most frequently reported adverse events observed in clinical trials for narcolepsy were headache, nausea, nervousness, anxiety, infections and insomnia.     Cephalon, Inc., headquartered in West Chester, Pennsylvania, is an international biopharmaceutical company dedicated to the discovery, development and marketing of products to treat neurological disorders, sleep disorders and cancer. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements.  Forward-looking statements provide Cephalon's current expectations or forecasts of future events.  These may include statements regarding anticipated scientific progress on its research programs, development of potential pharmaceutical products, interpretation of clinical results, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, sales and earnings projections, and other statements regarding matters that are not historical facts.  You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties such as those set forth below and in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission.  Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect.  Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend (and it is not obligated) to update publicly any forward-looking statements.  This discussion is permitted by the Private Securities Litigation Reform Act of 1995. NOTE:  Cephalon's press releases are posted on the Internet at the company's Web site at http://www.cephalon.com.  They are also available by fax 24 hours a day at no charge by calling PR Newswire's Company News On-Call at 800-758-5804, extension 134563. SOURCE Cephalon, Inc. CONTACT: Sandra Menta (Investors), 610-738-6376, or Sheryl Williams (Media), 610-738-6493, both of Cephalon, or Michael Kaplan (Media) of Makovsky & Co, Inc., 212-508-9673, for Cephalon URL: http://www.prnewswire.com LOAD-DATE: May 19, 2000 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS AND MEDICAL EDITORS Copyright 2000 PR Newswire Association, Inc. 923 of 998 DOCUMENTS PR Newswire May 2, 2000, Tuesday Narcolepsy Drug Helps Control Fatigue in Patients With MS SECTION: FINANCIAL NEWS LENGTH: 500 words DATELINE: COLUMBUS, Ohio, May 2 A drug used to treat some of the symptoms of the sleeping disorder narcolepsy also appears to help control fatigue in-patients with multiple sclerosis.     Researchers found that a 200 milligram-per-day dose of the drug modafinil, sold under the brand name Provigil, successfully controlled fatigue in-patients with MS, a disease that attacks the nervous system.  "About 70 percent of all MS patients suffer from fatigue," said Kottil Rammohan, an associate professor of neurology at Ohio State University.  "It's one of the most disabling symptoms of MS."     Other symptoms of MS include blurred vision, tremors and weakness, particularly in the legs.  Rammohan will present the study's findings on May 1 at the annual meeting of the American Academy of Neurology in San Diego.     Provigil is currently approved to treat excessive daytime sleepiness, which is one of the major symptoms of patients with narcolepsy.     During a nine-week trial, the researchers studied 72 patients with severe fatigue and MS.  The patients received a placebo during the first two weeks and again during the final three weeks of the study.  During weeks three and four, each patient received 200 milligrams of modafinil; during weeks five and six, the dosage was increased to 400 mg daily.     After each phase of treatment, the researchers asked each patient to evaluate their level of fatigue and sleepiness.  Overall, patients reported significantly less fatigue when they took the 200-mg dose compared to the placebo.  However, when patients took the 400-mg dose, some of them experienced side effects that "probably overshadowed any favorable effects on fatigue by the drug," Rammohan said.     In this study, the most common side effects of the 200-mg dosage were headaches (19 percent of patients); nervousness (14 percent); and loss of physical strength (12 percent).  "None of the side effects reported by patients were serious, however," Rammohan said.     In addition to helping control fatigue, and unlike similar drugs, modafinil has little potential for abuse, according to Rammohan.     "There's some stimulant effect with this drug," he said.  "But modafinil targets select areas of the brain -- the areas presumably important to fatigue and to wakefulness.  Stimulants such as Ritalin and amphetamines cause the whole brain to light up in terms of activity."     Rammohan conducted the study with Charles Pollak, D. Joanne Lynn and Haikady Nagaraja, all at Ohio State; and Jay Rosenberg and Andrew Blumenfeld, both with Kaiser Permanente in San Diego.  This study was funded by a grant from the National Institutes of Health, and by Cephalon, Inc. (Nasdaq: CEPH), the manufacturer of Provigil. SOURCE Cephalon Inc. CONTACT: Kottil Rammohan, M.D., Lead Investigator, of OSU School of Medicine, 614-329-7556; or Holly Wagner, Associate Editor of OSU Communications, 614-292-8310 URL: http://www.prnewswire.com LOAD-DATE: May 3, 2000 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS AND MEDICAL EDITORS Copyright 2000 PR Newswire Association, Inc. 924 of 998 DOCUMENTS Reuters Health eLine News May 2, 2000 Tuesday Narcolepsy drug helps relieve fatigue of multiple sclerosis LENGTH: 340 words DATELINE: SAN DIEGO May 2 A medication approved to treat the sleep disorder narcolepsy may help improve fatigue in patients with multiple sclerosis (MS), according to study results reported here at the American Academy of Neurology annual meeting. The drug is known as modafinil, according to Dr. Kottil W. Rammohan, of Ohio State University in Columbus. Multiple sclerosis is caused by a destruction of nerve fibers in the brain and spinal cord, which result in muscle weakness, dizziness and vision problems. "More than 75% of MS patients have chronic disabling fatigue irrespective of the severity of their MS, and current treatments are, for the most part, ineffective," Rammohan said. "The findings suggest that modafinil may be superior in terms of effectiveness, safety and tolerability, and lack of potential for abuse." In a 9-week study, 72 patients with MS took alternating doses of modafinil or an inactive placebo. The patients were aged 18 to 65 and were experiencing fatigue that was not relieved by treatment with the drugs amantadine and pemoline, which are conventionally used to treat fatigue. The trial excluded patients with narcolepsy, a condition in which people suffer from episodes of an uncontrollable desire to sleep. The results showed that modafinil improved fatigue on each of three assessment scales. Overall, 85% of patients were able to distinguish the active medication from placebo solely on the basis of their improvement in fatigue. The most common side effects were headache, nervousness and weakness, which occurred more frequently with a higher dose of the drug. Only four patients withdrew from the study because of side effects related to modafinil. Patients said they preferred the lower dose of the drug because it was better tolerated. Rammohan said studies are planned that will examine the use of modafinil in chronic fatigue syndrome and fatigue associated with chemotherapy. The present trial was conducted at Kaiser Permanente Medical Center in San Diego and funded by Cephalon, Inc., the company that manufactures modafinil. LOAD-DATE: July 21, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2000 Reuters Health All Rights Reserved 925 of 998 DOCUMENTS United Press International May 2, 2000, Tuesday Health Tips BYLINE: By LIDIA WASOWICZ, UPI Science Writer SECTION: GENERAL NEWS LENGTH: 625 words 0- DRUG EASES MS FATIGUE: Multiple sclerosis patients can get a boost from a new drug. The drug modafinil can help them overcome a serious side effect of their condition, tiredness, a study indicates. The report, presented at the American Academy of Neurology's 52nd Annual Meeting in San Diego, points out that fatigue is a common symptom of multiple sclerosis and that it can be disabling. Lead study author Dr. Kottil Rammohan, neurologist at Ohio State University in Columbus, said: "Drugs used to treat fatigue are only marginally effective. Many of the patients who participated in this study had tried conventional fatigue treatments without benefit, but they responded to modafinil." Modafinil is approved for the treatment of narcolepsy, a disorder of excessive daytime sleepiness. 0- GENE THERAPY BOOSTS AGING BRAIN: Gene therapy could rejuvenate aging brain networks, researchers report. The study of monkeys shows age-related deterioration in critical brain networks night be restored with such treatment. The study, presented at the American Academy of Neurology's 52nd Annual Meeting in San Diego, supports another trial testing gene therapy against Alzheimer's disease. Researchers from the University of California, San Diego, found normal aging in monkeys causes a 28 percent decline in the density of certain brain networks originating from nerve cells called neurons deep in the brain. The scientists could restore these connections by transplanting brain cells genetically programmed to release a protein called "nerve growth factor." "It would be inappropriate to suggest that this approach could be used to treat the course of normal aging, but it is not a far stretch to suggest that this may be useful in the treatment of Alzheimer's disease," said Dr. Mark Tuszynski, researcher at the Center for Neural Repair at UCSD and principal study author. 0- WORKPLACE CAN HELP SMOKERS QUIT: If you're trying to quit smoking, you'll be better off working in a place that frowns on the unhealthy habit, a study shows. Researchers at the University of California, Berkeley, found smokers employed in locations with strong anti-smoking workplace ordinances were 38 percent more likely to quit over a six-month period than those in regions with no such laws. The study, published in the American Journal of Public Health, was conducted in California before the state had a statewide workplace smoking law. "The benefits of workplace smoking ordinances for non-smokers are well known," said study co-author Joel Moskowitz, director of UC Berkeley's Center for Family and Community Health in the School of Public Health. "This is the first time we've seen such a big benefit for smokers also." 0- STRESS INCREASES COLITIS RISK: A study shows long-term stress increases the risk of ulcerative colitis, a potentially serious disease of the digestive tract. The disease differs from irritable bowel syndrome, which is non-inflammatory. It causes an inflammation of the inner lining of the colon and rectum. The study finally gives scientific evidence for what patients and doctors have been saying all along. "Despite the tenacity of the stress-exacerbation hypothesis, there is little evidence in its favor," said lead author Dr. Susan Levenstein of the San Camillo-Forlanini Hospital in Rome, Italy, who conducted the research while at the Nuovo Regina Margherita Hospital in Rome. Previous studies testing the effects of stress-reduction techniques and psychotherapy found these therapies had little impact on ulcerative colitis, but Levenstein suggests better results might be found if psychologically oriented therapies are offered to select patients who are likely to benefit rather than being given indiscriminately. 0- LOAD-DATE: May 3, 2000 LANGUAGE: ENGLISH Copyright 2000 U.P.I. 926 of 998 DOCUMENTS United Press International May 1, 2000, Monday Sleep disorder drug beats fatigue in MS BYLINE: By ED SUSMAN, UPI Science News SECTION: GENERAL NEWS LENGTH: 540 words DATELINE: SAN DIEGO, May 1 Doctors said Monday a drug now used for treatment of narcolepsy -- a sleep disorder -- appears to help most patients who suffer from disabling fatigue due to multiple sclerosis (MS). "Patients told us that when they took modafinil is was like a load lifting from their shoulders," said Dr. Kottil Rammohan, associate professor of neurology at Ohio State University, Columbus. Modafinil has been approved for the treatment of narcolepsy in the US and abroad. Rammohan's study is the first to show effectiveness in fatigue associated with MS. "Fatigue is a common problem and among the most disabling symptoms of MS," Rammohan said at the annual meeting of the American Academy of Neurology in San Diego. "Modafinil (Provigil, manufactured by Cephalon, Inc., West Chester, Penn.) is a novel wake-promoting agent that is effective and well tolerated for the treatment of excessive daytime sleepiness in patients with narcolepsy." In the study, 72 confirmed MS patients suffering from fatigue participated in the 9-week treatment regimen. First they were given dummy pills for two weeks and then received 200 milligrams of modafinil for two weeks, then 400 mg for two weeks and then placebo pills again for three weeks. Although the study was designed so that patients were supposed to be unaware of when they were receiving the active drug, Rammohan said, "About 85 percent of the patients knew when they were getting modafinil because their fatigue improved so markedly." Two drugs that are currently used to treat fatigue in MS patients, amantadine and pemoline, have not been shown to have a significant impact on fatigue as measured by standard scales, Rammohan said. "These drugs are only marginally effective," he said. "Many of the patients who participated in this study have tried conventional fatigue treatments without benefit, but they responded to modafinil." The study results impressed Dr. Robin Brey, associate professor of radiology at the University of Texas Health Science Center at San Antonio. "I have begun to prescribe modafinil to my patients. Fatigue in MS is possibly the most disabling condition in MS. It comes on suddenly as with other MS symptoms. My patients describe this fatigue as if they were hitting a wall," Brey said. "This is truly exciting," she said. "It's going to help a lot of people." Rammohan said that his patients found the 200 mg dose of the drug was preferred by his patients. "The higher dose made the patients feel jittery and uncomfortable," he said at a press briefing. On standard scales of fatigue, patients were able to record a one point improvement in their scores. Rammohan said the study would have considered a half-point improvement a success. the fatigue scale ranges from 1 to 7, with 7 being the worst fatigue experience. Most patients were at a 5-6 level and taking the drug lowered that by a point. "Generally the 200 mg dose of modafinil was very well tolerated by patients," Rammohan said. "Modafinil has no major toxicity and has a favorable long-term use in Europe." Rammohan said further studies of modafinil in fatigue associated with cancer chemotherapy, chronic fatigue syndrome and other fatigue conditions are planned by the manufacturer. LOAD-DATE: May 2, 2000 LANGUAGE: ENGLISH Copyright 2000 U.P.I. 927 of 998 DOCUMENTS Reuters Health Medical News March 14, 2000 Tuesday Modafinil improves excessive daytime sleepiness in narcolepsy SECTION: CLINICAL LENGTH: 363 words DATELINE: WESTPORT Mar 14 Modafinil, a unique wake-promoting agent, safely reduces excessive daytime sleepiness in patients with narcolepsy, according to a report in the March 14th issue of Neurology. Dr. Paul T. Gross, of the Lahey Clinic in Burlington, Massachusetts, and colleagues with the US Modafinil in Narcolepsy Multicenter Study Group, investigated the safety and effectiveness of 9 weeks of modafinil therapy (200 mg/day or 400 mg/day) in 271 patients diagnosed with narcolepsy according to International Classification of Sleep Disorders criteria. At the end of 9 weeks, improvements in mean sleep latency were greater in the modafinil groups than in the placebo group, the authors report. As measured by the Multiple Sleep Latency Test, mean sleep latency was 5.1 minutes in the modafinil 400-mg/day group, compared with 4.9 minutes in the 200-mg/day group and 3.5 minutes in the placebo group. Similarly, mean sleep latency as measured by the Maintenance of Wakefulness Test "improved for each modafinil treatment group (200 mg and 400 mg) compared with placebo at every follow-up visit (weeks 3, 6, and 9)," the investigators note. Upon discontinuation of medication, the patients' sleepiness returned and, in the case of the 400-mg group, briefly rebounded above the baseline level, the results indicate. "The percent of patients with improved clinician assessment of illness...was greater for modafinil 200 mg (46/80 patients, 58%) and 400 mg treatment groups (51/83 patients, 61%) compared with placebo (32/84 patients, 38%) at week 9," the authors observe. Overall, there were no significant differences in the number of adverse experiences among the three patient groups, the investigators indicate, though more patients in the modafinil groups experienced nausea and, in the 200-mg group, rhinitis. There appeared to be no withdrawal symptoms or abuse potential with modafinil. "Thus," the authors conclude, "modafinil is not only a well-tolerated and effective treatment for [excessive daytime sleepiness] associated with narcolepsy, its minimal side-effect profile during dosing and withdrawal represent clinical advantages over existing therapeutics." SOURCE: Neurology 2000;54:1166-1175. LOAD-DATE: July 11, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2000 Reuters Health All Rights Reserved 928 of 998 DOCUMENTS Reuters Health eLine News March 14, 2000 Tuesday New drug helps narcolepsy patients stay awake LENGTH: 439 words DATELINE: NEW YORK Mar 14 Modafinil, a new, nonaddicting drug with few side effects, significantly improves the excessive daytime sleepiness experienced by people with narcolepsy, report US researchers. Narcolepsy is a disorder of the sleep-wake cycle. Patients with this disorder suddenly fall into deep sleep, and experience abnormal daytime sleepiness. Narcolepsy affects about 1 in every 2,000 people, and often first appears in the teenage years. Currently, narcolepsy is treated with amphetamines and amphetamine-like drugs, but this may lead to side effects such as palpitations, anxiety and nausea, or to dependence on these drugs. In a search for an alternative treatment, Dr. Paul T. Gross from Lahey Clinic in Burlington, Massachusetts, and other members of the US Modafinil in Narcolepsy Multicenter Study Group tested the safety and effectiveness of modafinil therapy in 271 narcolepsy patients. The results of the study, funded by the drug's manufacturer Cephalon, Inc., are published in the March 14th issue of the journal Neurology. The researchers tested the drug by asking patients to sit quietly in a darkened room and try to stay awake. During a 9-week study, they tested two doses of the drug -- 200 mg and 400 mg -- against a placebo ("dummy") pill. They found that those taking modafinil could stay awake longer than those taking placebo -- 5 minutes, compared with 3.5 minutes. Similarly, other tests of the tendency to fall asleep quickly "improved for each modafinil treatment group (200 mg and 400 mg) compared with placebo at every follow-up visit (weeks 3, 6, and 9)," the investigators note. Patients taking the drug also reported feeling less sleepy during the day. But once the patients stopped taking the medication, their sleepiness returned. Overall, there were no major differences in the number of side effects, the investigators indicate, although more patients in the modafinil groups experienced nausea and, in the 200 mg group, nasal symptoms. There appeared to be no withdrawal symptoms or potential for drug abuse with modafinil. "Thus," the authors conclude, "modafinil is not only a well-tolerated and effective treatment for excessive daytime sleepiness associated with narcolepsy, its minimal side-effect profile during dosing and withdrawal represent clinical advantages over existing therapeutics." "While modafinil significantly improves alertness and has advantages over existing therapies, we must keep in mind that no treatment for narcolepsy can completely resolve its symptoms," Gross said in a news release. "Further research and study of this life-altering disorder is required." SOURCE: Neurology 2000;54:1166-1175. LOAD-DATE: July 21, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 2000 Reuters Health All Rights Reserved 929 of 998 DOCUMENTS PR Newswire September 30, 1999, Thursday - 14:17 Eastern Time Cephalon Updates Investors on Product Development Programs SECTION: Financial News LENGTH: 1057 words DATELINE: NEW YORK, Sept. 30 Cephalon, Inc. (Nasdaq: CEPH) president and chief executive officer, Frank Baldino, Jr., Ph.D., today provided an update on the company's lead product, PROVIGIL(R) (modafinil) Tablets C-IV, its marketing strategy for GABITRIL(R) (tiagabine hydrochloride), and its advancing pipeline in the fields of neurology and oncology. In remarks delivered to investors attending the Warburg Dillon Read Global Health Care Conference in New York, Dr. Baldino reported on increasing sales of PROVIGIL and its acceptance in the U.S. narcolepsy market since the product's launch in February. He noted that the company has been conducting clinical studies this year to validate the potential use of PROVIGIL in the treatment of other disorders such as sleep apnea, fatigue in multiple sclerosis, and attention deficit hyperactivity disorder (ADHD). The company expects to complete several of these studies by year-end, and will report trial results as they become available. Results from a small study with PROVIGIL in patients with hypersomnia will be presented next week at the World Federation Sleep Research Society meeting in Germany. Dr. Baldino also reported on a recently published study demonstrating that administration of modafinil (PROVIGIL) resulted in significant improvements in several quality of life measurements, and also showed that narcolepsy imposes a serious burden on a person's quality of life. This study entitled: "The Health-Related Quality of Life Effects of Modafinil in the Treatment of Narcolepsy," was published in the September 15th issue of the journal Sleep. According to Dr. Joyce Walsleben, Ph.D., Assistant Professor of Medicine at NYU School of Medicine and Director of the NYU Sleep Disorders Center at Bellevue Hospital Center, and an author of the multi-center study, "This study shows that this therapy could significantly improve a number of quality-of- life parameters, such as social functioning and mental health." Dr. Baldino stated that Cephalon has expanded its sales force to 90 territory sales specialists, to market PROVIGIL and GABITRIL, a product of Abbott Laboratories, to neurologists in the United States. Dr. Baldino believes that the company's experienced sales force can increase the market share of GABITRIL in the partial seizure marketplace over the next several years, and noted that the company will co-develop the product with Abbott to maximize the product's potential in treating partial seizures as well as in treating other neurological conditions. Commenting on the company's advancing pipeline in neurology and oncology, Dr. Baldino reviewed the company's recent collaboration with H. Lundbeck A/S, which focuses on the discovery, development and marketing of products for the treatment of neurodegenerative diseases. The company discovered a novel class of orally active, small molecules, which in preclinical studies, has been shown to promote neuronal survival in animal models of Parkinson's disease and Alzheimer's disease; data from these studies will be presented at the Society for Neuroscience meeting in Miami at the end of November. This past July, the companies advanced the program's lead molecule, CEP-1347, into Phase 1 development for the treatment of Parkinson's disease. Dr. Baldino also provided an update on the company's oncology program with TAP Holdings in prostate and other cancers. Prostate cancer is the second leading cause of cancer death in men, and current therapies for this disease treat hormone-dependent tumors. The company's lead molecule, CEP-701, in preclinical studies, slowed tumor growth in the prostate, and if effective in man, has the potential to impact both hormone-dependent and hormone- independent tumor growth. Results of the Phase 1 studies showed that CEP-701 is well tolerated; this compound is scheduled to enter Phase 2 development later this year for the treatment of prostate cancer. Cephalon, Inc., headquartered in West Chester, PA, is an international biopharmaceutical company dedicated to the discovery, development and marketing of products to treat neurological disorders, sleep disorders and cancer. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide the company's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs, development of potential pharmaceutical products, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, sales and earnings projections, and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. The company's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties such as those set forth below and in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you are cautioned not to place too much reliance on any such factors or forward-looking statements. Furthermore, Cephalon does not intend (and it is not obligated) to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise. This discussion is permitted by the Private Securities Litigation Reform Act of 1995.     NOTE:  Cephalon's press releases are posted on the Internet at the company's Web site at http://www.cephalon.com.  They are also available by fax 24 hours a day at no charge by calling PR Newswire's Company News On-Call at 800-758-5804, extension 134563. SOURCE  Cephalon, Inc.      CONTACT: Sandra Menta of Cephalon, 610-738-6376 LOAD-DATE: October 1, 1999 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS EDITOR Copyright 1999 PR Newswire Association, Inc. 930 of 998 DOCUMENTS PR Newswire May 25, 1999, Tuesday - 08:32 Eastern Time Cephalon Announces Availability of Modafinil in Austria SECTION: Financial News LENGTH: 883 words DATELINE: WEST CHESTER, Pa., May 25 Cephalon, Inc. (Nasdaq: CEPH) today announced the availability of modafinil in Austria for the treatment of narcolepsy. Modafinil, which is being promoted by Cephalon in Austria under the tradename MODASOMIL(R), is the first pharmaceutical product registered in Austria by the Ministry for Work, Health and Social Issues for treatment of this disorder. Modafinil also is marketed by Cephalon in the United States, the United Kingdom and Ireland under the tradename PROVIGIL(R) (modafinil) Tablets C-IV for the treatment of excessive daytime sleepiness associated with narcolepsy. Narcolepsy is a chronic, lifelong, neurological sleep disorder that can strike people of both sexes and all races, with symptoms generally first appearing during adolescence. The symptoms of narcolepsy include sleep paralysis, sudden loss of muscle control known as cataplexy, and vivid hallucinations at the onset of sleep known as hypnagogic hallucinations. The most common and debilitating symptom of narcolepsy, however, is excessive daytime sleepiness, which is characterized by uncontrollable sleep attacks that significantly impair a person's ability to perform basic daily activities. "The introduction of MODASOMIL is a breakthrough in the treatment of excessive daytime sleepiness in narcolepsy patients in Austria," stated Univ.- Prof. Dr. Bernd Saletu, Chairman of the Austrian Sleep Research Association. Uwe Maschek, Ph.D., Cephalon's country manager, Germany, stated: "We welcome the opportunity to establish Cephalon's sales and marketing capabilities in Austria, and look forward to bringing this important new therapy to physicians and their patients who suffer from this undertreated, disabling sleep disorder." Cephalon began marketing modafinil (PROVIGIL) in the United States and Ireland this past February, and has been marketing the product in the United Kingdom since March 1998. The company received rights from Merckle GmbH to market modafinil in Austria and in Switzerland, where marketing approval is being pursued. Cephalon granted rights to Dompe SpA to market modafinil in Italy, and to Azwell Pharmaceuticals to develop and commercialize the product in Japan. Cephalon also is pursuing regulatory clearance to market the product in Mexico. Modafinil is a unique, wake-promoting agent. In landmark clinical trials involving more than 550 patients with narcolepsy, modafinil was found to be efficacious in improving daytime wakefulness. Patients also demonstrated overall clinical improvement in the severity of their disease symptoms. Modafinil has been found to be generally well-tolerated, with a low incidence of adverse events relative to placebo. In controlled clinical trials, most adverse events were mild to moderate. The most commonly observed were headache, infection, nausea, nervousness, anxiety, and insomnia. No specific symptoms of withdrawal were observed after discontinuation of therapy.     Cephalon, Inc., headquartered in West Chester, PA, is an international biopharmaceutical company dedicated to the discovery, development and marketing of products to treat neurological disorders, sleep disorders and cancer.     In addition to historical facts or statements of current condition, this press release may contain forward-looking statements.  Forward-looking statements provide our current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on our research programs, development of potential pharmaceutical products, prospects for regulatory approval, manufacturing development and capabilities, market prospects for our products, sales and earnings projections, and other statements regarding matters that are not historical facts.  You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning.  Our performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties such as those set forth below and in our reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission.  Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect.  Therefore, you are cautioned not to place too much reliance on any such factors or forward- looking statements.  Furthermore, we do not intend (and we are not obligated) to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise.  This discussion is permitted by the Private Securities Litigation Reform Act of 1995.     NOTE:  Cephalon's press releases are posted on the Internet at the company's Web site at http://www.cephalon.com.  They are also available by fax 24 hours a day at no charge by calling PR Newswire's Company News On-Call at 800-758-5804, extension 134563. SOURCE  Cephalon, Inc.      CONTACT: Sandra Menta of Cephalon (U.S.), 610-738-6376, or Carmen Bischof of Welldone PR (Austria), 011-43-1-402-134-114 LOAD-DATE: May 26, 1999 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS AND MEDICAL EDITORS Copyright 1999 PR Newswire Association, Inc. 931 of 998 DOCUMENTS Internal Medicine Alert March 15, 1999 Modafinil for the Treatment of Narcolepsy LENGTH: 1185 words Pharmacology Update Modafinil for the Treatment of Narcolepsy By William T. Elliott, MD, FACP and James Chan, PharmD, PhD Cephalon inc. has received approval to market modafinil (Provigil), the first nonamphetamine drug approved by the FDA for the treatment of excessive daytime sleepiness associated with narcolepsy. Narcolepsy is a disorder that afflicts about 125,000 Americans and is characterized by inability to stay awake or alert in the daytime, sleep attacks, disrupted nocturnal sleep, and cataplexy. Prior treatment for this disorder has consisted primarily of amphetamine type drugs-agents that are commonly associated with side effects and eventual development of tolerance. While it is known that modafinil is not an amphetamine, the exact mechanism of action of the drug is not known. It apparently does not appear to bind to receptors associated with sleep/wake regulation, such as norepinephrine, serotonin, dopamine, GABA, melatonin, or benzodiazepine.1 Indications Modafinil is indicated to improve wakefulness in patients with excessive daytime sleepiness associated with narcolepsy. Dosage The recommended dose of modafinil is 200 mg as a single dose in the morning. There is no consistent evidence that doses greater than 200 mg confer any additional benefit.1 Patients with severe hepatic impairment should reduce the dose by half.1 In the elderly population, consideration should be given to use the lowest effective dose. Modafinil is supplied as 100 mg and 200 mg tablets. The drug is placed into DEA Schedule IV. Potential Advantages The major advantage of modafinil over other drugs, such as amphetamines and methylphenidate, used for narcolepsy is its apparent lower abuse potential. Modafinil is Schedule IV while amphetamine and methylphenidate are Schedule II. In clinical trials (9 weeks with open label up to 40 weeks), modafinil reduced daytime sleepiness, was generally well tolerated, did not affect sleep, and tolerance did not appear to be problematic.1,2,3 The improvement in average sleep latencies was about 58% based on Maintenance of Wakefulness Test (MWT). Potential Disadvantages While modafinil does not appear to have the same abuse potential as amphetamine, it may produce effects similar to other CNS stimulants such as euphoric effects and alteration in mood and/or perception. In addition, monkey studies suggest that modafinil is reinforcing in a manner similar to cocaine.1 Cocaine is one of the most strongly reinforcing self-administered drugs. A clinical study suggested that modafinil produced psychoactive and euphoric effects and feelings consistent with methylphenidate. Patients should be observed for signs of misuse or abuse.1 Albeit rare, chest pain, palpitations, dyspnea, and transient ischemic T-wave changes have been observed in association with mitral valve prolapse or left ventricular hypertrophy. Modafinil is not recommended in patients with a history of left ventricular or ischemic ECG changes, chest pain, arrhythmia, or significant manifestations of mitral valve prolapse in association with CNS stimulants.1 In vitro studies suggest that modafinil has the potential to inhibit cytochrome P450 2C19, suppress the expression of 2C9, and slightly induce 1A2, 2B6, and 3A4. If coadministration of modafinil and drugs that are substrates for one or more of these isoenzymes is clinically indicated, the patient should be monitored for potential toxicity or reduced effectiveness. In clinical trials, common side effects of modafinil relative to placebo include headache (50% vs 40%), nausea (13% vs 4%), and diarrhea (8% vs 4%).1 Five percent of patients discontinue therapy in these trials. Comments Modafinil is the first nonamphetamine or non-methylphenidate drug approved for the treatment of excessive daytime sleepiness associated with narcolepsy. Effectiveness was established in two U.S. multicenter, placebo-controlled, double-blind, nine-week trials in more than 550 patients. The primary measures of efficacy were sleep latency as assessed by the MWT and the change in the patient's overall disease status, determined by evaluators, as measured by the Clinical Global Impression of Change (CGI-C). MWT assesses the ability of the subject to remain awake without using extraordinary measures. It measures latency (in minutes) to sleep onset averaged over four test sessions at two-hour intervals. Modafinil improved average sleep latency from 5.07 to 5.35 for placebo to 8.18 to 8.28 for the 200 mg dose. For CGI-C, 58% to 64% of patients improved compared to 37% to 38% for placebo. There are currently no comparative trials between modafinil and current agents such as amphetamine or methylphenidate, and, therefore, comparative efficacy cannot be assessed. A survey of several agents used to treat narcolepsy suggests that modafinil may be less effective than dextroamphetamine or methylphenidate based on MWT.4 The wholesale cost of modafinil is about $7 per day for a 200 mg dose. Clinical Implications Narcolepsy is a neurologic disorder of unknown cause characterized by excessive somnolence, cataplexy, sleep paralysis, disrupted nocturnal sleep, and hypnagogic hallucinations.5 It affects 2-10 individuals per 10,000 and has a gradual onset between the ages of 15 and 35. Sleep paralysis is a paralysis of voluntary muscles that occurs at the entry into or emergence from sleep.6 Hypnagogic hallucinations are visual hallucinations with auditory and tactile components that occur during onset and emergence from sleep. Cataplexy is a sudden loss of muscle tone (often dropping of the jaw) triggered by strong emotions such as laughter.6 The symptoms of this condition have serious personal, social, and economic implications as the ability of the individual to function in normal daily activity can be significantly compromised. Excessive daytime sleepiness is generally the most prominent symptom of narcolepsy. Current pharmacologic treatment includes dextroamphetamine, methylphenidate, and pemoline. These drugs have potential for the development of tolerance and unwanted side effects. Modafinil offers an alternative with milder side effects and may have a lower abuse potential. Long-term safety and efficacy remains to be established. As with other stimulants, it does not affect cataplexy, which is generally managed with tricyclic antidepressants.5,6 Modafinil is only FDA-approved for use in narcolepsy. Efficacy and safety in improving vigilance in healthy sleep- derived individuals has not been established. Results from a trial of modafinil in sleep apnea patients are expected early next year. References 1. Provigil Product Information. Cephalon, Inc. December 1998. 2. US Modafinil in Narcolepsy Multicenter Study Group. Ann Neurol 1998;43(1):88-97. 3. Broughton RJ, et al. Neurology 1997;49(2):441-451. 4. Mitler MM, et al. Sleep 1991;14(3):218-220. 5. Adams RD, Maurice V, Ropper AH. Sleep and its Abnormalities. In: Principles of Neurology. 6th ed. McGraw-Hill; 1997:380-402. 6. Fry JM. Sleep Disorders. In: Merritt's Textbook of Neurology. 9th ed. William & Wilkens; 1995:875-881. LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 1999 AHC Media LLC All Rights Reserved 932 of 998 DOCUMENTS The Detroit News March 14, 1999 Sunday Final Edition Youth's sleep disorder treated with new drug: New Warren center tries out Modafinil for the first time SECTION: METRO; Technician Judy Munro and Ed Shuman of Fraser, who suffers sleep apnea, demonstrate how electrodes are attached to monitor patients at the Sleep Disorders Center at Bi-County Community Hospital. Todd McInturf / The Detroit News; Pg. 5B LENGTH: 443 words WARREN -- A Macomb County teen-ager is making medical history, of sorts, at Bi-County Community Hospital. The 17-year-old is the first patient at the hospital's new Sleep Disorders Center -- and possibly in Macomb County -- to receive the new sleep drug, Modafinil. Modafinil is used to treat severe cases of the sleep disorder narcolepsy, which is characterized by sudden overwhelming waves of profound sleepiness. Narcolepsy sometimes comes after a good night's sleep, said Renee Shimmel, spokeswoman for Bi-County Hospital in Warren. The drug went on the market March 1 in Michigan after its approval in January by the U.S. Food and Drug Administration. Bi-County's narcolepsy patient "has the most severe case I've ever seen," said Dr. Leon Rosenthal, director of the Sleep Disorders Center which opened five weeks ago. "We're still adjusting the dosage, so it's too early to tell how effective it will be," Rosenthal said. "Advance studies have been very positive. The drug has been available in France for many years with good results." Rosenthal is proceeding cautiously in prescribing Modafinil because of the high cost of the medication: $3 a pill. Most patients take one pill each day. He expects the price to drop as Modafinil becomes more popular. Narcolepsy patients will be on the medication for years, Rosenthal said. Other symptoms include a sudden loss of muscle control triggered by laughter, vivid dreams when falling asleep and a temporary sensation of being unable to move upon going to sleep. The teen-ager, whose identity was not released, is one of about 25 patients being treated for various sleep disorders at the new center. More than a dozen of the patients have spent the night at the center where doctors monitor their inability to sleep. "The most prevalent sleep disorder is insomnia," Rosenthal said. "That affects about one-third of the population. Only 20 percent to 30 percent are easy to treat. Insomnia is not easy to treat. For about one third it becomes chronic and is a long-lasting problem and that's when the sleep lab becomes involved." One of Rosenthal's patients, Amy Ofiara, 24, a graphics designer from Troy, has been battling narcolepsy for eight years. "I was falling asleep in class," Ofiara said. When various tests failed to diagnose her problem, Ofiara overnighted at the Henry Ford sleep disorders center, and that's when her problem was pinpointed. Ofiara said that she takes the medication Cylert to help her stay awake and Vivactil to help her sleep soundly. Sleep disorders treated by doctors at the Bi-County Community Hospital Sleep Disorders Center in Warren include: LOAD-DATE: January 21, 2003 LANGUAGE: ENGLISH Copyright 1999 The Detroit News All Rights Reserved 933 of 998 DOCUMENTS PR Newswire February 16, 1999, Tuesday - 09:05 Eastern Time The Narcolepsy Network Welcomes the Introduction of Modafinil for the  Treatment of Narcolepsy; Availability Provides New Hope For Patients With Debilitating Sleep Disorder SECTION: Domestic News LENGTH: 526 words DATELINE: FAIRFIELD, N.J., Feb. 16 The Narcolepsy Network welcomes the Introduction of Modafinil for the treatment of excessive daytime sleepiness associated with narcolepsy. Marketed by Cephalon, Inc. as Provigil it is the first new non-amphetamine treatment in 40 years available to patients for this indication. "The narcolepsy community has been awaiting the availability of modafinil with anticipation and hope," says Howard Wolfe, Executive Director of the national non-profit group, Narcolepsy Network. "For many persons suffering with this condition, modafinil promises a more normal life both at work and with their families." Narcolepsy is a chronic neurological disorder suffered by approx. 1 out of 1000 Americans. The most common symptom is excessive daytime sleepiness (EDS) which can cause sudden "sleep attacks" that are for the most part, irresistible.     Other key symptoms may include     -- cataplexy -- a sudden loss of muscle control ranging from slight        weakness to total collapse;     -- sleep paralysis -- an inability to talk or move when falling asleep or        waking up;     -- hypnagogic hallucinations -- vivid or frightening dreams and sounds        when falling asleep and;     -- Automatic behavior, performing familiar routines while asleep.     Current treatment for narcolepsy most often includes stimulants to increase alertness, antidepressants to control cataplexy, and behavior modifications such as regularly scheduled naps.     Narcolepsy can have a significant impact on a person's daily life, both personally and professionally.  The "sleep attacks" and cataplexy experienced by many persons with narcolepsy can be embarrassing, disruptive and even dangerous.  In some cases, the symptoms are so severe that the affected individuals are unable to drive safely or earn a living.     Narcolepsy affects men, woman and children of any age with symptoms usually appearing after puberty begins.  It is not a psychological disorder, although depression and low self-esteem may occur in persons with narcolepsy who are untreated, feel misunderstood, or have difficulty coping with their disorder.     "We urge persons who are suffering with EDS or any other symptoms of narcolepsy to consult their physician or sleep specialist immediately. Although there is no cure for narcolepsy, there are treatments available to minimize the symptoms," said Howard Wolfe.     The Narcolepsy Network is a national non-profit organization founded in 1986.  Its members include individuals with narcolepsy, their friends and family and health professionals.  Its goals are to educate the public, facilitate early diagnosis, encourage research, assist support groups, protect the rights of those with narcolepsy and to serve as a resource center.  For additional information write or call:     Narcolepsy Network     227 Fairfield Rd., Suite 310B     Fairfield, NJ 07004     973 276-0115     973 227-8224 fax     E-Mail narnet@aol.com     www.websciences.org/narnet SOURCE  The Narcolepsy Network      CONTACT: Howard Wolfe of The Narcolepsy Network, 973-276-0115, or narnet@aol.com LOAD-DATE: February 17, 1999 LANGUAGE: ENGLISH DISTRIBUTION: TO NATIONAL AND MEDICAL EDITORS Copyright 1999 PR Newswire Association, Inc. 934 of 998 DOCUMENTS PR Newswire February 2, 1999, Tuesday - 08:31 Eastern Time Cephalon Launches PROVIGIL(R) (modafinil) in the Republic of Ireland SECTION: Financial News LENGTH: 949 words DATELINE: WEST CHESTER, Pa., Feb. 2 Cephalon, Inc. (Nasdaq: CEPH) announced today the availability of PROVIGIL(R) ( modafinil) tablets in the Republic of Ireland for the treatment of narcolepsy. PROVIGIL is the first pharmaceutical product licensed by the Irish Medicines Board for treatment of this disorder. The company's European subsidiary, Cephalon U.K. Ltd., which currently markets the drug in the United Kingdom, also will market PROVIGIL to sleep specialists and neurologists in Ireland. Narcolepsy is a chronic, neurological, lifelong sleep disorder that generally begins in young adulthood. Often, 10 to 15 years may pass between onset of symptoms and proper diagnosis of the disorder. The most common symptom is excessive daytime sleepiness, which is characterized by uncontrollable sleep attacks. These attacks impair a person's ability to perform basic daily activities, significantly impacting their quality of life. "PROVIGIL is an extremely significant step forward in the treatment of this disorder," stated Dr. Catherine Crowe, consultant in sleep disorders medicine in Dublin. "Narcolepsy is a very handicapping condition, which unfortunately is not well recognized. We know there are many people in Ireland who are living with narcolepsy but who are currently undiagnosed. PROVIGIL gives us the opportunity to provide an effective, well-tolerated medical treatment for the first time. Once a diagnosis is made, we believe it will make a real difference." Frank Baldino, Jr., Ph.D., Cephalon's president and chief executive officer, said, "PROVIGIL is the first licensed agent to be available in Ireland to help manage this undertreated, disabling disorder. This event reflects Cephalon's commitment to the PROVIGIL franchise, and more broadly to addressing unmet medical needs worldwide. We expect to be marketing PROVIGIL in five countries by the end of this year." Dr. Baldino continued, "We are currently marketing PROVIGIL in the United Kingdom and we look forward to launching PROVIGIL in the U.S. later this month." U.S. clinical trials involving more than 550 patients found PROVIGIL to be efficacious in improving daytime wakefulness. Patients demonstrated overall clinical improvement in the severity of their disease symptoms. PROVIGIL has been found to be generally well-tolerated, with a low incidence of adverse events relative to placebo. In controlled clinical trials, most adverse events were mild to moderate. The most frequently reported adverse events that occurred at a higher rate for PROVIGIL-treated patients than for placebo- treated patients were headache, infection, nausea, nervousness, anxiety and insomnia. No specific symptoms of withdrawal were observed after discontinuation of PROVIGIL therapy. Cephalon has exclusive rights to market modafinil in the United States, the United Kingdom, Ireland, Japan, Italy and Mexico. In December 1998, Cephalon received approval to market PROVIGIL(R) (modafinil) Tablets C IV in the United States to improve wakefulness in patients with excessive daytime sleepiness (EDS) associated with narcolepsy and has been marketing the drug in the United Kingdom since March 1998. The company granted rights to Azwell Inc. to develop and market modafinil in Japan, and to Dompe Biotech S.p.A., which is currently pursuing regulatory clearance to promote and distribute the product in Italy. Cephalon also holds exclusive rights to promote the product in Austria and Switzerland; commercial launch in Austria is planned for later this year and approval to market the drug in Switzerland is currently being pursued. Cephalon, Inc., headquartered in West Chester, PA, is an international biopharmaceutical company dedicated to the discovery, development and marketing of products to treat neurological disorders and cancer.     In addition to historical facts or statements of current condition, this press release may contain forward-looking statements.  Such statements may be identified by, among other things, the use of forward-looking terminology such as "believes," or by discussions of strategy or intention, and may include statements regarding present or anticipated scientific progress, development of potential pharmaceutical products, manufacturing development and capabilities, sales and marketing capabilities, and other statements regarding matters that are not historical facts, or otherwise involve beliefs or predictions.  The company's performance and financial results could differ materially from those reflected in the forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties such as those set forth in documents filed by the company with the SEC (including, but not limited to, its most recent reports on Form 8-K, Form 10-Q and Form 10-K).  Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect.  Therefore, current or prospective investors are cautioned not to place undue reliance on any such forward-looking statements.  Furthermore, the company has no intent, and disclaims any obligation, to update any such factors or forward-looking statements to reflect future events or developments.     NOTE:  Cephalon's press releases are posted on the Internet at the company's Web site at http://www.cephalon.com.  They are also available by fax 24 hours a day at no charge by calling PR Newswire's Company News On-Call at 800-758-5804, extension 134563. SOURCE  Cephalon, Inc.      CONTACT: Scott Melville (media), 610-738-6270, or Sandra Menta (investors), 610-738-6376, both of Cephalon, Inc. (U.S.), or Anne Marie Rodriguez of Sante Communications (Europe), 011-44-1-71-379-7377 LOAD-DATE: February 3, 1999 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS AND MEDICAL EDITORS Copyright 1999 PR Newswire Association, Inc. 935 of 998 DOCUMENTS NBC News Transcripts January 27, 1999, Wednesday SHOW: DATELINE NBC (8:00 PM ET) WAKE UP CALL; NEW DRUG FOR NARCOLEPSY MAY TEMPT ABUSE FROM NON- NARCOLEPTICS BYLINE: BOB ARNOT LENGTH: 1088 words WAKE UP CALL Announcer: Here now is Jane Pauley. JANE PAULEY: In tonight's Healthline, are you exhausted? Millions of Americans are, but for some the problem is not too little sleep, but having no control over when they fall asleep. It's a disorder called narcolepsy and it can be dangerous. But there's a new drug that's giving people who suffer from narcolepsy new hope of living a normal life. Here's chief medical correspondent Dr. Bob Arnot. BOB ARNOT reporting: (Voiceover) It's a feeling most of us have learned to dread. It's late, the lines of the road blur past, our eyelids heavy, we fight to resist sleep and stay awake on the road. Now imagine feeling this way, struggling against sleepiness 16, 18, even 20 hours a day. Welcome to the world of the narcoleptic. (Blurred view of driving down road; clock; patient in hospital bed) Ms. MARIE SIMMONS: You're fighting to stay awake, but you're being pulled into, kind of, quicksand. It's a pull that's stronger than you. ARNOT: (Voiceover) For Marie Simmons, the need for sleep had been constant, a need that hits narcoleptics any time of day and can last nearly all day. (Maria Simmons stretching; Simmons working out) Ms. SIMMONS: (Voiceover) I've fallen asleep eating dinner in a restaurant... (Simmons working out) Ms. SIMMONS: ...even at the gym while in the process of exercising. ARNOT: (Voiceover) Marie's fatigue got so bad, a nine-to-five job was out of the question. She went to work at home as a therapist. But even then, she had to fight to conceal her secret. (Simmons hugging man and leaving) Ms. SIMMONS: I fell asleep while seeing a client, and that really scared me. ARNOT: (Voiceover) This is what the disease can look like, in dogs studied at Stanford University, Pluto is a normal, healthy, Doberman pinscher, except for one thing--bring out his favorite toy, and instead of playing, Pluto collapses, awake, but completely paralyzed. It's the same thing you and I experience in the middle of deep sleep, but for Pluto and this dachshund named Bo, the slightest excitement triggers an attack. The roots of narcolepsy lie deep in the brain, where special cells control our sleep. Every morning, those cells sound an alarm that keeps us awake throughout the day. In narcoleptics, the signal is too weak, causing sudden and unpredictable attacks of sleepiness. Until now, treatment meant amphetamine type drugs, Marie tried those, but they made her jumpy and anxious. (Researcher playing with Pluto; Pluto paralyzed; Bo paralyzed; diagram of brian indicating normal alarm and weakened alarm in narcoleptic; pills) Ms. SIMMONS: (Voiceover) Although I was more alert... (Pills being dropped into pan) Ms. SIMMONS: ...the cure was almost as bad as the disease. Dr. JED BLACK: A lot of our patients are not able to work and have to be on disability because of the sleepiness. ARNOT: (Voiceover) Dr. Jed Black is Marie's doctor and runs the sleep lab at Stanford University. (Jed Black; Black talking to researcher) Dr. BLACK: (To researcher) Has he fallen asleep on any of his naps? ARNOT: (Voiceover) He told her about a revolutionary new drug called modafinil, a drug that promised to push back the night for her and many of the estimated 125,000 Americans with narcolepsy. Four years ago, she became one of the first in the US to try the drug as part of a clinical trial (Black pointing to medical chart; Simmons opening modafinil bottle; modafinil bottle; pill; bottle of modafinil) ARNOT: Modafinil works differently from any drug before it. Unlike stimulants, modafinil appears to work by turning up the volume on those so-called alarm cells in the brain, without any of the jitteriness and nervousness caused by amphetamines. (Voiceover) After nearly giving up hope of a normal life, Marie was anxious for anything that would help. She didn't have to wait long. She still remembers the very first dose. (Simmons working out) Ms. SIMMONS: You know, it was like I was sleepwalking and I just woke up. ARNOT: (Voiceover) Dr. Black admits Marie's response was the most dramatic he saw. But he says half the patients he studied responded as well or better to modafinil as they had to stimulants. The drug is already approved for narcoleptics in some European countries, where it is tightly controlled. But in the US, FDA approval means doctors could prescribe it to anyone, so-called off-label use. That has Dr. Black and others worried about potential abuse of Modafinil by non-narcoleptics. It's not tough to see how millions of busy people might find a pill that allows you to go days without sleep hard to resist. (Empty hospital bed; medical chart; pillow; patient in hospital bed; modafinil bottle; pills; modafinil bottle; people sleeping) Dr. BLACK: (Voiceover) It's potentially going to happen. (Modafinil bottle) Dr. BLACK: People will be feeling pressured to use this to--to stay awake to--to--to be more productive. ARNOT: (Voiceover) What happens when healthy people take the drug? Well, just such a study was done in 1994 by the Canadian military, which was looking for ways to fight fatigue on the battle field. You're looking at lab video from that first experiment. When a small group of Canadian soldiers took modafinil, they managed to stay awake for 64 hours. All the while performing repetitive tasks on a computer. Most surprising of all, after the study, the volunteers seemed perfectly fine. It was as if they hadn't lost any sleep at all. A remarkable result, but one that only heightened fears of abuse. But for Marie Simmons, the benefits are clear. Modafinil allowed her the ability to return to full time work as a nurse. And four years after beginning treatment, she still thinks about the little pill that made such a big difference. (Soldiers; soldiers walking; soldier looking through binoculars; soldier on telephone; lab video showing man working at desk; lab video showing two men looking at computer screens; lab video showing man sitting at computer; lab video showing man working at desk; lab video showing two men leaving computers; Simmons working out; Simmons leaving work out) Ms. SIMMONS: It was like having a second life. It was wonderful to be able to do the many things that I was still interested in but I had just withdrawn from. PAULEY: So, what are the worries about this drug? Doctors say the fundamental concern is that people will be tempted to use this drug instead of sleep. They stress that no drug can ever replace sleep, which is beneficial in many ways we understand and many ways we don't. Announcer: Coming up--he helped police when he identified a murder suspect. Did his courage cost him his life? Mr. CARLOS COLLAZO: If he wouldn't have picked out a photo, I believe he would have still been here with us, swimming, you know, playing basketball. Announcer: Who was looking out for B.J. Brown? Plus--whose fault is it that the president and Monica are still on our minds? It's DATELINE's Question of the Week. (Announcements) Announcer: DATELINE NBC, winner for the last two years of top honors from the Investigative Reporters and Editors awards. The years most honored newsmagazine, DATELINE, will be right back. (Announcements) LOAD-DATE: January 28, 1999 LANGUAGE: English TYPE: Profile Copyright 1999 National Broadcasting Co. Inc. 936 of 998 DOCUMENTS U.S. Newswire January 12, 1999 8:57 Eastern Time New Excessive Daytime Sleepiness Treatment Brings Hope of Reaching Undiagnosed SECTION: NATIONAL DESK, MEDICAL WRITER LENGTH: 1473 words DATELINE: WASHINGTON, Dec. 12 The recent announcement that a new wake-promoting medication, modafinil, will soon be available to consumers has triggered public discussion about potential "off-label" uses.    Approved by the Food and Drug Administration (FDA) Dec. 28 for the treatment of excessive daytime sleepiness (EDS) associated with narcolepsy, modafinil is considered to be a novel therapy. It is being marketed in the United States by Cephalon Inc. (Nasdaq: CEPH), as Provigil.    Millions of Americans experience daytime sleepiness, but only a fraction suffer from narcolepsy.  According to a 1998 National Sleep Foundation (NSF) survey, thirty-seven percent of Americans report being so sleepy during the day that their fatigue interferes with daily activities. Daytime sleepiness has numerous causes; it is most frequently the result of sleep deprivation.  For example, in the same survey, one-third of Americans reported getting six or fewer hours of sleep per night during the work week, in spite of the fact that the average person needs eight hours of sleep.    "Excessive daytime sleepiness (EDS) for any reason is a cause for concern," said NSF President Lorraine Wearley, Ph.D. "At this time, however, we must focus our concerns on helping the estimated 200,000 Americans who have narcolepsy. This is a chronic, neurological condition that can be extremely debilitating if left untreated."    Wearley urged that discussions about use of modafinil maintain a clear distinction between EDS related to narcolepsy and EDS caused by other condition s or as a side effect of medications, which can often be helped significantly through lifestyle changes or other treatments.    As Common as MS, But Only 25 Percent Diagnosed    The National Center on Sleep Disorders Research, part of the National Institutes of Health, estimates that only 50,000 of the estimated 200,000 Americans with narcolepsy -- as few as one in four -- have been diagnosed. Narcolepsy, therefore, is considered to be at least as common as multiple sclerosis or Parkinson s disease, but is by far less well known.    "The interest in this new medication provides an opportunity to help individuals and their family members better understand narcolepsy," Wearley added, "and to encourage people to discuss with their physician any symptoms they might be experiencing."    The most common symptom of narcolepsy is EDS, specifically, a feeling of overwhelming sleepiness during the daytime, even after a full night's rest. Other symptoms may include:    -- cataplexy, a sudden loss of muscle control ranging from slight weakness to total collapse, which is typically triggered by a strong emotion or laughter;    -- sleep paralysis, a temporary sensation of being unable to talk or move upon falling asleep or waking up; and    -- hypnagogic or hypnopompic hallucinations, vivid and often frightening dreams or sensations experienced when falling asleep or upon awakening.    Diagnosis is complicated by the fact that these symptoms differ in age of onset and severity among people with narcolepsy, and they can be experienced independently of narcolepsy. Furthermore, most narcoleptics do not experience all of these symptoms.  For example, cataplexy was once considered a hallmark of the disease, but researchers now recognize that individuals with narcolepsy may experience no or very slight episodes of this symptom.    "The popular perception of narcolepsy among those who have heard or seen anything about the disease in general, is that of a cataplectic or very sudden sleep attack," Wearley commented. "Although these are indeed common symptoms, a person does not need to have a full body collapse or even bang their head onto a table during an attack to have narcolepsy."    Diagnosis Often Takes Years, Several Consultations    Proper diagnosis of narcolepsy requires a careful medical history and laboratory testing, usually given under the direction of a sleep specialist. However, many individuals are reluctant to talk with their health care providers about their symptoms -- and therefore possibly delay diagnosis -- because they believe that nearly all sleep problems are psychological in nature. Or, they may fear that their concerns might be misunderstood or will not be taken seriously.    Unfortunately, these concerns are not unfounded. Many narcoleptic patients were previously misdiagnosed with psychiatric problems or told that their sleepiness was due to the effect of an unrelated medication.  Patients and health professionals need to persistently evaluate the individual's symptoms, their cause, and how they are affected by recommended treatments.    The National Commission on Sleep Disorders reported in 1992 that, on average, patients had to consult five physicians before being diagnosed with narcolepsy. In addition, the mean length of time between the onset of symptoms and the diagnosis of narcolepsy is 15 years.    "This is our frustration and our challenge," said Wearley.  "We have an effective new treatment, but the reality is that many clinicians are unable to identify and diagnose narcolepsy, and patients end up losing their jobs, relationships, and other important elements of their lives instead of receiving the treatment they need."    Treatment Options    Medications to help alleviate excessive daytime sleepiness play a central role in helping narcoleptics cope and lead a more "normal" life. In addition, depending on the patient s symptoms, medications to help control other symptoms, such as cataplexy, might also be needed. Finally, behavioral techniques, such as daytime naps, may help some patients as an adjunctive therapy.    Scientists have not yet identified the precise pharmacological process that occur with the use of modafinil.  However, they agree that the new drug is distinct from but has similar "wake-promoting actions" as other central nervous system (CNS) stimulants used to reduce the effects of excessive daytime sleepiness in narcoleptics, according to FDA-approved product labeling.  U.S. clinical trials also demonstrated that modafinil is less likely to cause nervousness or withdrawal-like symptoms than other wake- promoting medications. The studies confirmed findings from longer-term use of the medication in France.    Modafinil is expected to be available in mid-February.  The Drug Enforcement Agency has recommended that it be classified as a schedule IV medication. Modafinil therefore may be more readily accessible to patients than most similarly prescribed stimulants, such as amphetamines, which are registered as schedule II medications. For example, patients may be able to purchase modafinil after their provider calls in a prescription to a pharmacy; for schedule II medications, patients must personally deliver a hand-signed prescription to the pharmacy before it can be filled.    ------    For more information about narcolepsy and how to locate a local sleep center, visit the Web site of the National Sleep Foundation (NSF) at www. sleepfoundation.org, or call 202-347-3471. Request a brochure about narcolepsy by sending a self-addressed, stamped ($.55) envelope to NSF, 729 Fifteenth Street, N.W., Washington, D.C., 20005. to participate in NSF's National Narcolepsy Registry, a confidential and voluntary database of genetic information from individuals diagnosed with narcolepsy and their families. Scientific evidence suggests that genetics play a key role in the onset of this condition. Thus, the registry was developed to help researchers find the cause of narcolepsy and to enhance their understanding of the genetics of sleep in general.    Another resource for people with narcolepsy is the Narcolepsy Network, a self-help organization.  The organization can be contacted at 277 Fairfield Ave., Suite 310B, Fairfield, N.J., 07004 or by calling 973-276-0115.    ------    Founded in 1990, the National Sleep Foundation (NSF) is an independent, nonprofit organization that promotes public understanding of sleep and sleep disorders, and supports sleep-related research and education and advocacy to improve public health and safety.    ------    Note to Editors: The National Sleep Foundation is able to provide additional background information on narcolepsy, sleep disorders and sleep deprivation, and related issues. Contact with sleep experts nationwide can also be arranged. Call 202-347-3471 for assistance.    ------    Editors: Some computer systems do not recognize the "at" sign. It is an important component of e-mail addresses and should be used in place of the symbol (At) in the contact information above. LOAD-DATE: January 12, 1999 LANGUAGE: ENGLISH Copyright 1999 PR Newswire Association LLC All Rights Reserved 937 of 998 DOCUMENTS The Lancet Lancet 1999; 353 (9147): 131 January 9, 1999 FDA approves first new narcolepsy drug in USA in decades AUTHOR: Ault, Alicia SECTION: News: Policy and People LENGTH: 274 words    Just before the new year, the US FDA approved the first new therapy for narcolepsy in 40 years-Cephalon's (West Chester, Pennsylvania, USA) modafinil (Provigil). About 125 000 Americans have narcolepsy, which is marked by persistent drowsiness and sudden attacks of sleepiness.    Modafinil is not an amphetamine, but promotes wakefulness. "It really is, to our knowledge, the first selective wake promoting agent," says Cephalon senior director of pharmacology Matt Miller. The drug's mechanism of action is not well understood, but in cat studies, it worked discretely in the hypothalamus, says Miller.    Modafinil was discovered by the French pharmaceutical company Laboratoire L Lafon and is already approved in France, the UK, and Ireland. Unlike conventional stimulants used to treat narcolepsy, modafinil does not cause withdrawal. It does not work through dopamine or bind to other relevant receptors for sleep-wake regulation, so there is no hyperactivity and minimal cardiovascular effects, says Miller.    Even so, because it works in the brain, the US Drug Enforcement Administration will put modafinil on its list of controlled substances. In trials, patients taking once-daily doses of modafinil had a statistically significantly greater ability to stay awake, and an improvement in symptom severity. Patients rated themselves as having less propensity to fall asleep during the day. The drug did not affect night-time sleep, said Cephalon. But the company added that insomnia was a common adverse event. Other side-effects included headache, infection, nausea, nervousness, and anxiety. A 200 mg daily dose was approved. LANGUAGE: ENGLISH Copyright 1999 by The Lancet Ltd 938 of 998 DOCUMENTS Austin American-Statesman (Texas) December 29, 1998 Narcolepsy drug gets FDA approval with restrictions BYLINE: By Rick Weiss SECTION: News; Pg. A7 LENGTH: 370 words WASHINGTON -- The Food and Drug Administration has approved a drug that keeps people with debilitating sleepiness awake and attentive yet has few of the side effects associated with caffeine, amphetamines and other commonly used stimulants. The drug, modafinil, was approved by the FDA for people with a serious sleep disorder called narcolepsy, which affects one out of 1,000 to 2,000 people and is characterized by sudden, overwhelming waves of intense sleepiness. It will be available only by prescription, under the brand name Provigil, and will be listed by the Drug Enforcement Administration as a "schedule IV" substance, which means it will be regulated more tightly than most prescription drugs. Despite those restrictions, several experts said they would not be surprised if the pills quickly gain popularity among some of the millions of people in this country who suffer from daytime sleepiness caused by problems more mundane than narcolepsy, such as overwork and stress-related insomnia. The drug may find a "gray market" among truck drivers, emergency room doctors, soldiers in battle, college students and others whose jobs demand that they remain alert for days with little or no sleep. Preliminary studies on Canadian soldiers found that modafinil increased wakefulness and vigilance in those who went without sleep for almost three days, without the agitation or the "rebound" fatigue that typically follows long stretches of amphetamine-induced wakefulness. No one knows yet whether modafinil is safe or effective for the vast majority of the world's fatigued. But clues may arise long before clinical trials are devised to study the question. Doctors who are licensed to prescribe scheduled drugs are allowed to prescribe those drugs for patients who do not have the disorder for which the FDA approved them. But they must be able to justify to federal officials their reasoning for writing such "off-label" prescriptions. Experts said only time would tell whether doctors will feel comfortable prescribing modafinil to sleepy, non-narcoleptics. If the DEA determines that the drug is being overprescribed or abused, the agency can reschedule it to a more restrictive level. LOAD-DATE: January 7, 1999 LANGUAGE: ENGLISH Copyright 1998 The Austin American-Statesman 939 of 998 DOCUMENTS Portland Press Herald (Maine) December 29, 1998, Tuesday, Narcolepsy drug gets FDA nod, with limits; The drug is only approved for people with this serious sleep disorder, but many believe it will be used more widely. BYLINE: The Washington Post SECTION: FRONT, Pg. 3A LENGTH: 637 words DATELINE: WASHINGTON The Food and Drug Administration (FDA) has approved a novel drug that keeps people with debilitating sleepiness awake and attentive yet has few of the side effects associated with caffeine, amphetamines and other commonly used stimulants. The drug, modafinil, was approved by the FDA for people with a serious sleep disorder called narcolepsy, which affects 1 out of 1,000 to 2,000 people and is characterized by sudden, overwhelming waves of intense sleepiness. It will be available only by prescription, under the brand name Provigil, and will be listed by the Drug Enforcement Administration (DEA) as a "schedule IV" substance, which means it will be regulated more tightly than most prescription drugs. Despite those restrictions, several experts said they would not be surprised if the pills quickly gained popularity among some of the millions of people in this country who suffer from daytime sleepiness caused by problems more mundane than narcolepsy, such as overwork and stress-related insomnia. The drug may also find a "gray market" following among truck drivers, emergency room doctors, soldiers in battle, college students and others whose jobs demand them to remain alert for days on end with little or no sleep. Preliminary studies on Canadian soldiers found that modafinil increased wakefulness and vigilance in soldiers who went without sleep for almost three days, without the agitation or the "rebound" fatigue that typically follows long stretches of amphetamine-induced wakefulness. No one knows yet whether modafinil is safe or effective for the vast majority of the world's fatigued. But clues may arise long before clinical trials are devised to study the question. Doctors who are licensed to prescribe scheduled drugs are allowed to prescribe those drugs for patients who do not have the disorder for which the FDA approved them. But they must be able to justify to federal officials their reasoning for writing such "off-label" prescriptions. Experts said only time would tell whether doctors will feel comfortable prescribing modafinil to sleepy, non-narcoleptics. If the DEA determines that the drug is being overprescribed or abused, the agency can reschedule it to a more restrictive level. Frank Baldino, president of West Chester, Pa.-based Cephalon, Inc., which will market modafinil, emphasized that the drug has been proven safe and effective only in narcoleptics. But he acknowledged that the company is pursuing research to test the drug's usefulness for other sleep-related disorders, including sleep apnea, a nighttime breathing disorder that disrupts sleep in an estimated 12 million Americans. And he said the company has been negotiating with branches of the U.S. armed forces to set up clinical tests of the drug's value in combat situations. The company announced modafinil's approval Monday, after getting word from the FDA on Dec. 24. Its stock jumped 12 percent, rising $ 1 to close at $ 9.18 3/4 on the Nasdaq Stock Exchange. Although scientists still don't know how modafinil works, it appears to interact much more specifically with the brain's sleep-wake centers than do other wakefulness-inducing drugs, such as amphetamines, which have many undesirable side effects. "The amphetamines are a problem because you get a little overactivated," said Emmanuel Mignot, an associate professor of psychiatry and director of the center for narcolepsy at Stanford University. "There is a time when it overshoots and people get a little speedy and irritable and after that they crash." Modafinil, Mignon said, is much better tolerated. "It is much smoother and milder. They feel awake without feeling overagitated, and there is no effect on the cardiovascular system that we can tell." The drug is expected to become available in February. LOAD-DATE: October 29, 1999 LANGUAGE: ENGLISH Copyright 1998 Blethen Maine Newspapers, Inc. 940 of 998 DOCUMENTS Reuters Health Medical News December 29, 1998 Tuesday FDA grants approval of first nonamphetamine for treatment of narcolepsy SECTION: REGULATORY LENGTH: 366 words DATELINE: WESTPORT Dec 29 Cephalon, of West Chester, PA, received its first US approval late last week, when the Food and Drug Administration granted approval of modafinil (Provigil) for treatment of narcolepsy. This is the first nonamphetamine approved for use in this condition. Modafinil's mechanism of action is "not well understood," Dr. Russell Rosenberg of Northside Hospital in Atlanta told Reuters Health. "It's a wake-promoting agent, it works on that part of the brain." It does not work along the same pathways as amphetamines, he added. FDA granted approval based on results of two phase III trials that involved more than 550 patients with narcolepsy who received either modafinil or placebo. Dr. Rosenberg was an investigator with the first of those. Dr. Rosenberg said that modafinil lacks the adverse effects often seen with amphetamines, such as jitteriness, anxiety and heart palpitations. The new drug also does not cause hepatotoxicity, which can occur with amphetamine use. "It's a unique drug. It will offer a great advantage for patients with narcolepsy," Dr. Rosenberg commented. According to Cephalon, 5% of patients who were part of the drug's clinical studies had to discontinue therapy due to adverse events. Company spokesmen said that most of the adverse events, which included headache, infection, nausea, nervousness, anxiety and insomnia, were mild to moderate in severity. The FDA approval is for the once-daily 200 mg dose of modafinil. According to a company press release posted on PR Newswire, the company expects the agent to be classified as a Schedule IV controlled substance. According to the DEA, a Schedule IV drug is one that "...has a low potential for abuse relative to the drugs or other substances in Schedule III," which are drugs that might lead to moderate or low physical dependence or high psychological dependence. Other Schedule IV drugs include Xanax and Valium. Off-label uses of modafinil may include treatment of excessive daytime sleepiness and other symptoms of sleep disorders, according to Dr. Rosenberg. "We're just scratching the surface of the population at risk," he said. Cephalon's shares climbed 1-1/8 to 9-5/16 in mid-afternoon trading on Monday. LOAD-DATE: July 9, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 1998 Reuters Health All Rights Reserved 941 of 998 DOCUMENTS The Washington Post December 29, 1998, Tuesday, Final Edition Narcolepsy Drug Wins Approval Of FDA; Regulators on Alert For 'Off-Label' Use Rick Weiss, Washington Post Staff Writer SECTION: A SECTION; Pg. A01 LENGTH: 1000 words The Food and Drug Administration has approved a novel drug that keeps people with debilitating sleepiness awake and attentive yet has very few of the side effects associated with caffeine, amphetamines and other commonly used stimulants. The drug, modafinil, was approved by the FDA for people with a serious sleep disorder called narcolepsy, which affects at least one in every 2,000 people and is characterized by sudden, overwhelming waves of intense sleepiness. It will be available only by prescription, under the brand name Provigil, and will be listed by the Drug Enforcement Administration (DEA) as a "schedule IV" substance, which means it will be regulated more tightly than most prescription drugs. Despite those restrictions, several experts said they would not be surprised if the pills quickly gained popularity among some of the millions of people in this country who suffer from daytime sleepiness caused by problems more mundane than narcolepsy, such as overwork and stress-related insomnia. The drug may also find a "gray market" following among truck drivers, emergency room doctors, soldiers in battle, college students and others whose jobs demand that they remain alert for days on end with little or no sleep. Preliminary studies on Canadian soldiers found that modafinil increased wakefulness and vigilance in those who went without sleep for almost three days, without the agitation or the "rebound" fatigue that typically follows long stretches of amphetamine-induced wakefulness. No one knows yet whether modafinil is safe or effective for the vast majority of the world's fatigued. But clues may emerge long before clinical trials are devised to study the question. Doctors who are licensed to prescribe scheduled drugs are allowed to prescribe those drugs for patients who do not have the disorder for which the FDA approved them. But they must be able to justify to federal officials their reasoning for writing such "off-label" prescriptions. Experts said only time would tell whether doctors will feel comfortable prescribing modafinil to sleepy, non-narcoleptic people. If the DEA determines that the drug is being overprescribed or abused, the agency can reschedule it to a more restrictive level. Frank Baldino, president of West Chester, Pa.-based Cephalon, Inc., which will market modafinil, emphasized that the drug has been proven safe and effective only in narcoleptics. But he acknowledged that the company is pursuing research to test the drug's usefulness for other sleep-related disorders, including sleep apnea, a nighttime breathing disorder that disrupts sleep in an estimated 12 million Americans. And he said the company has been negotiating with branches of the U.S. armed forces to set up clinical tests of the drug's value in combat situations. The company announced modafinil's approval yesterday, after getting word from the FDA on Dec. 24. Its stock jumped 12 percent, rising $ 1 to close at $ 9.18 3/4 on the Nasdaq Stock Market. Modafinil was discovered by French researchers many years ago and has been approved in France since 1994, where it is sold under more restrictive conditions than it will be in the United States. Cephalon, which holds the license to market the drug in the United States and seven European countries, conducted additional clinical trials involving 550 people at 39 medical centers in the United States to gain the FDA's approval. Although scientists still don't know how modafinil works, it appears to interact much more specifically with the brain's sleep-wake centers than do other wakefulness-inducing drugs, such as amphetamines, which have a panoply of effects on the brain, the heart and other organs and so have many undesirable side effects. Especially problematic, amphetamines influence dopamine centers in the brain, which are involved in craving and addiction, explaining in part why those drugs are so often abused. "The amphetamines are a problem because you get a little overactivated," said Emmanuel Mignot, an associate professor of psychiatry and director of the center for narcolepsy at Stanford University. "There is a time when it overshoots and people get a little speedy and irritable and after that they crash." Modafinil, Mignon said, is much better tolerated. "It is much smoother and milder. They feel awake without feeling overagitated, and there is no effect on the cardiovascular system that we can tell." Merrill M. Mitler, a professor in the department of neuropharmacology at Scripps Research Institute in La Jolla, Calif., said he was very excited about the drug's approval for narcolepsy, which he described as "a miserable disorder." "They've been relegated to using drugs that have been developed for other conditions like obesity and attention deficit disorder," Mitler said, adding that most of those drugs are "schedule II" compounds that can only be prescribed in person in a doctor's office. "Provigil has been developed for narcoleptics with their needs in mind, and can be prescribed by telephone to the pharmacist, which is much more convenient for the patient." In Cephalon's studies, about 60 percent of patients who took 200 milligrams of modafinil daily for nine weeks showed a significant decline in symptoms. These included general daytime sleepiness, the tendency to suddenly fall asleep without warning, sleep paralysis (in which the mind is awake but the body is paralyzed as if asleep), and catalexy (a peculiar symptom of narcolepsy in which a paralytic, sleep-like state is triggered by laughter or other emotional events). By contrast, about 37 percent of those who took inactive placebos improved. The trials did not directly compare modafinil against amphetamines. But side effects from modafinil -- mostly headaches, infection, nausea, nervousness, anxiety and insomnia -- were less common and less severe than typically seen with amphetamines. The drug is expected to become available in February. LOAD-DATE: December 29, 1998 LANGUAGE: ENGLISH Copyright 1998 The Washington Post 942 of 998 DOCUMENTS PR Newswire December 28, 1998, Monday - 17:39 Eastern Time The National Sleep Foundation Welcomes FDA Approval of Modafinil  For the Treatment of Narcolepsy. SECTION: Washington Dateline LENGTH: 371 words DATELINE: WASHINGTON, Dec. 28 The National Sleep Foundation (NSF) welcomes the Food and Drug Administration (FDA) approval of modafinil, a new treatment for persons with narcolepsy, a serious neurological sleep disorder that affects an estimated 200,000 Americans. This chronic sleep disorder, with no known cause, is often disabling and is characterized by excessive daytime sleepiness, cataplexy (a sudden loss of muscle tone triggered by strong emotion), sleep paralysis upon falling asleep or awakening, and hypnagogic hallucinations (vivid dreams upon falling asleep). "We are exceedingly pleased that a new treatment option will soon be available for people who suffer from narcolepsy," said Lorraine L. Wearley, Ph.D., NSF President. "Modafinil represents the first new non-amphetamine drug in 40 years to be designed for excessive daytime sleepiness associated with narcolepsy." Modafinil is being marketed by Cephalon, Inc. as Provigil(R). It will be available in tablet form by prescription after final scheduling by the U.S. Drug Enforcement Administration. Founded in 1990, the National Sleep Foundation is an independent, nonprofit organization that promotes public understanding of sleep and sleep disorders, and supports sleep-related education, research and advocacy to improve public health and safety. NSF publishes public education brochures and a professional newsletter on narcolepsy. In addition, NSF supports the National Narcolepsy Registry, a confidential and voluntary database of genetic information from individuals diagnosed with narcolepsy and their families. Scientific evidence suggests that genetics play a key role in the onset of this condition. Thus, the registry was developed to help researchers find the cause of narcolepsy and to enhance their understanding of the genetics of sleep in general. For more information or to receive a brochure about narcolepsy, the registry, or other sleep disorders, please call 202-347-3471, fax 202-347-3472 or visit the NSF Web site at www.sleepfoundation.org. SOURCE  National Sleep Foundation      CONTACT: National Sleep Foundation, 202-347-3471; Pat Britz, ext. 203, or Susan Sagusti, ext. 208; e-mail, natsleep@erols.com LOAD-DATE: December 29, 1998 LANGUAGE: ENGLISH DISTRIBUTION: TO HEALTH/MEDICAL EDITOR Copyright 1998 PR Newswire Association, Inc. 943 of 998 DOCUMENTS Reuters Health eLine News December 28, 1998 Monday FDA approves narcolepsy drug LENGTH: 266 words DATELINE: NEW YORK Dec 28 Cephalon, Inc., of West Chester, Pennsylvania, received its first US approval late last week, when the Food and Drug Administration (FDA) granted approval of modafinil (Provigil) for the treatment of narcolepsy. This is the first non-amphetamine approved for use in narcolepsy -- an illness characterized by sudden, uncontrollable sleep attacks. Modafinil's mechanism of action is "not well-understood," investigator Russell Rosenberg of Northside Hospital in Atlanta, Georgia, told Reuters Health. "It's a wake-promoting agent, it works on that part of the brain." It does not work along the same pathways as amphetamines, he added. FDA granted approval based on results of two trials that involved more than 550 patients with narcolepsy who received modafinil or (an inactive) placebo. Rosenberg was an investigator on the first of those trials. He said that modafinil is not associated with the adverse effects that amphetamines often cause, such as jitteriness, anxiety and heart palpitations. The new drug does not promote the liver toxicity that can occur with amphetamine use. "It's a unique drug. It will offer a great advantage for patients with narcolepsy," Rosenberg commented. Other uses of modafinil not yet approved by the FDA may include treatment of excessive daytime sleepiness and other symptoms of sleep disorders. "We're just scratching the surface of the population at risk," he said. The most common side effects of the drug are headache, infection, nausea, nervousness, anxiety and insomnia. Modafinil is not recommended for use in individuals with certain types of heart problems. LOAD-DATE: July 23, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 1998 Reuters Health All Rights Reserved 944 of 998 DOCUMENTS PR Newswire December 3, 1998, Thursday - 08:34 Eastern Time Cephalon to Promote Modafinil in Austria and Switzerland. SECTION: Financial News LENGTH: 777 words DATELINE: WEST CHESTER, Pa., Dec. 3 Cephalon, Inc. (Nasdaq: CEPH) announced today that its U.K. subsidiary, Cephalon UK Ltd., has gained exclusive rights from Merckle GmbH to promote modafinil in Austria and Switzerland. Financial terms of this ten-year agreement were not disclosed. Cephalon already has exclusive rights to market and sell modafinil in the United States, the United Kingdom, Ireland, Japan, Italy and Mexico. Modafinil is approved to be marketed in Austria and launch is planned for early next year. Approval to market modafinil in Switzerland is currently being pursued. Cephalon will promote modafinil in these territories to neurology and psychiatry specialists who treat patients suffering from narcolepsy. Narcolepsy is a chronic, lifelong sleep disorder commonly characterized by excessive daytime sleepiness or uncontrollable sleep attacks that can hamper a person's ability to perform basic daily activities. "Our agreement with Merckle allows us not only to capitalize on our investment in this important product, but broadens our efforts in increasing awareness of, and offering a new treatment for, a disabling disease that is currently managed by few or inadequate therapies," stated Uwe Maschek, Ph.D., Cephalon's country manager, Germany. In clinical trials, modafinil has been shown to be effective in promoting daytime wakefulness, and well tolerated with low abuse potential. The most commonly observed adverse experiences with modafinil, which occurred more frequently than placebo, were headache, nausea and diarrhea. Cephalon licensed rights to modafinil from Laboratoire L. Lafon, the French pharmaceutical company which discovered the drug and markets it in France. Cephalon has received market authorization for modafinil in the United Kingdom and the Republic of Ireland. The company is currently marketing modafinil in the United Kingdom for the treatment of narcolepsy and will launch the product in Ireland early next year. Cephalon has received an approvable letter for modafinil from the U.S. Food and Drug Administration and also is pursuing regulatory clearance to market the drug in Mexico. The company granted rights to AZWELL Inc. (a newly formed entity of Nippon Shoji Kaishi Ltd. and Showa Pharmaceutical Co., Ltd.) to develop and market modafinil in Japan, and to Dompe Biotech S.p.A. who is currently pursuing regulatory clearance to promote and distribute the product in Italy. Cephalon, Inc., headquartered in West Chester, PA, is an international biopharmaceutical company dedicated to the discovery, development and marketing of products to treat neurological disorders and cancer. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Such statements may be identified by, among other things, the use of forward-looking terminology such as "believes," or by discussions of strategy or intention, and may include statements regarding present or anticipated scientific progress, development of potential pharmaceutical products, manufacturing development and capabilities, sales and marketing capabilities, and other statements regarding matters that are not historical facts, or otherwise involve beliefs or predictions. The company's performance and financial results could differ materially from those reflected in the forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties such as those set forth in documents filed by the company with the SEC (including, but not limited to, its most recent reports on Form 8-K, Form 10-Q and Form 10-K). Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, current or prospective investors are cautioned not to place undue reliance on any such forward-looking statements. Furthermore, the company has no intent, and disclaims any obligation, to update any such factors or forward-looking statements to reflect future events or developments. NOTE: Cephalon's press releases are posted on the Internet at the company's Web site at http://www.cephalon.com. They are also available by fax 24 hours a day at no charge by calling PR Newswire's Company News On-Call at 800-758-5804, extension 134563. SOURCE  Cephalon, Inc.      CONTACT: Scott Melville (media), 610-738-6270, or Sandra Menta (investor), 610-738-6376, both of Cephalon, or Anne Marie Rodriguez of Sante Communications (Europe), 011-44-1-71-379-7377 LOAD-DATE: December 4, 1998 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS AND MEDICAL EDITORS Copyright 1998 PR Newswire Association, Inc. 945 of 998 DOCUMENTS The New York Times November 3, 1998, Tuesday, Late Edition - Final New Hope for the Losers in the Battle to Stay Awake BYLINE: By ERICA GOODE SECTION: Section F; Page 1; Column 2; Health & Fitness LENGTH: 1677 words It is midafternoon on the eastern coast of a chronically sleep-deprived nation and if you listen carefully, you can hear the whoosh of cappuccino makers and the ripping open of No-Doz boxes and the yawns of night-shift workers and the sighs of pilots as they check their watches to see how much longer they must keep their aircraft aloft. These are the sounds of the struggle to stay awake, a major enterprise in a country that long ago exchanged the effortless biological cycle of sleeping and waking for the tyranny of electric lights, job-plus-kids living, graveyard shifts and packages that absolutely, positively have to be there overnight. About two-thirds of workplace accidents in the United States are caused by human error, studies show, many of them the result of a failure of alertness at critical times. Jet-lag sufferers, all-night workers, the elderly and the multitude of Americans with disorders like sleep apnea and narcolepsy wage a continual battle against excessive daytime sleepiness. And staying awake supports a multibillion-dollar industry that serves up a variety of stimulants, legal and illegal, and sleep promoters, offering hope that a good night's sleep will bring alertness the next day. Yet the search for artificial compounds to enhance wakefulness is a chronicle of limited success. Caffeine, for all its appeal, is not especially potent, and in high doses can be unpleasant, causing irritability, tremor and excessive urination. Amphetamines, the wonder drugs of the 1950's and 60's, quickly opened a Pandora's box of side effects and abuse. The drugs keep people awake, but they also produce euphoria and the jitters, revving up the central nervous system and causing the heart rate and blood pressure to jump. And once the effects wear off, users soon crave more of the drug. Fearful of lawsuits, drug companies largely stopped trying to improve alertness, and for 20 years have devoted their efforts to developing new sleep-promoting drugs, seeking to maximize high quality sleep while minimizing day-after hangovers. That may soon change. By Dec. 31, the Food and Drug Administration is to decide whether a new compound called modafinil can be marketed as a treatment for excessive sleepiness associated with narcolepsy, a severe sleep disorder that afflicts about one in 1,000 Americans. Approval of the drug would also open the door to "off-label" use, allowing doctors to prescribe it for other conditions. If modafinil goes on the market, many sleep scientists believe, it could usher in a new era of wakefulness compounds and help researchers unlock the mysteries of sleep and waking. But at the same time, the arrival of the drug is likely to raise profound questions about how, as a society, Americans choose to cope with their perpetual lack of sleep and their constant campaign to stay awake. Modafinil, to be sold under the trade name Provigil, is licensed to Cephalon Inc., a small pharmaceutical company in West Chester, Pa. Since its discovery by French scientists in the late 1970's, the compound has stirred interest among sleep researchers because it appears to work entirely differently from other alertness drugs. "This is the first drug in history to selectively promote wakefulness in a way analogous to how the brain normally wakes up," said Dr. Dale Edgar, associate professor of psychiatry and behavioral science at Stanford University, who conducted preclinical trials of Provigil for Cephalon and has done other animal studies of the drug financed by the Air Force Office of Research. "Modafinil is certainly not a real substitute for getting sleep. That would be a misuse of this drug. But I personally believe it has great promise for a much wider range of sleep disorders." In human trials, modafinil appears more effective than caffeine without causing the anxiety, euphoria and cardiovascular effects of amphetamines. Four years of on-the-market experience in France, where the drug is sold as Mododial, and clinical trials financed by Cephalon in this country have revealed few side effects. The most common complaints are mild headache and slight nausea, and these are infrequent. Preliminary studies suggest that modafinil is nonaddictive and that it does not induce tolerance in users. Dr. Jed Black, director of the Sleep Disorders Clinic at Stanford and a participant in the clinical trials, said subjects taking the drug reported feeling "naturally alert, like they'd taken a good nap and felt good." And modafinil does not seem to touch off rebound sleepiness -- the "crash" familiar to amphetamine users -- after it is discontinued. If all this sounds too good to be true, it could turn out to be. Many promising drugs have shown serious problems once they became widely prescribed. The diet drugs Fen-phen, withdrawn from the market after patients developed heart valve problems, are a case in point. "You've got to have the drug out there, and you've got to see what it does," said Dr. Philip Smith, director of the Johns Hopkins University Sleep Disorders Center, who was not involved in the Provigil trials. "It would really mean something to have a medication that can stimulate the brain and keep it awake without juicing the whole system. But the proof is in the pudding." Clinical trials of new drugs are typically small (558 patients at 39 sleep disorder clinics around the country took part in two trials of Provigil), and the studies are almost always financed by the drug company that wants to market the compound, a fact that some experts believe limits the usefulness of the research. And while France has four years of experience with Mododial, prescription of the drug there is tightly controlled, and its users have been limited to patients suffering from narcolepsy or from idiopathic hypersomnia, another relatively rare sleep disorder. Many questions about modafinil remain to be answered. Scientists do not know, for example, how long the drug can keep people awake, and they are only beginning to discover its effects on judgment, reaction time and other aspects of cognitive and physical performance. In one study, by Dr. Ross Pigeau, Dr. Joseph Baranski and their colleagues at the Canadian Defence and Civil Institute of Environmental Medicine, 41 military reservists were deprived of sleep for 64 hours, given modafinil, an amphetamine or a dummy medication and were required to perform a repeated series of cognitive tasks. Those given on modafinil or amphetamines performed significantly better than those given a placebo. But the modafinil group, while experiencing fewer side effects than the amphetamine group, was also more likely to be overconfident, overestimating abilities after performance declined -- a problem that, if it proved common, could severely limit the drug's use in the general population. The biggest unanswered question about modafinil, however, is: How does it work? Central nervous system stimulants like amphetamines achieve their effects by increasing levels of chemical messengers in areas of the brain associated with arousal, and also with pleasure and locomotor activity. In particular, amphetamines act on a brain chemical called dopamine, which scientists believe is responsible for the euphoria the drugs produce and also their potential for abuse. Modafinil, in contrast, does not appear to affect dopamine, or if it does, it does so only very weakly. Nor does the drug seem to target other neurotransmitters -- adrenaline and serotonin, for example -- affected by amphetamines. Caffeine blocks the action of the chemical substance adenosine, which scientists believe promotes sleep. But modafinil, studies have found, seems indifferent to adenosine as well. Instead, work by Dr. Michel Jouvet, a French sleep researcher, and his colleagues suggests that modafinil increases cellular activity in an area of the brain adjacent to the suprachiasmatic nucleus, or SCN, the body's circadian clock. And this fits nicely with scientists' best guess as to how the brain maintains wakefulness, a theory developed by Dr. Edgar of Stanford. According to Dr. Edgar's theory, the sleep-wake cycle represents a battle between oppositional forces: the SCN, on the one hand, and the pressure to sleep on the other. The SCN, through communication with other brain areas, acts like an alarm ringing throughout the day to fight back sleepiness and maintain wakefulness. In the morning, when sleep pressure for humans is low, the SCN does not need to work very hard to keep a person awake. But as the day goes on, sleep pressure builds, and the bell rings louder and louder to fight off fatigue. At night, the clock's output diminishes, the clock stops ringing and the built-up sleep pressure rushes in, swooping the tired day warrior into the Land of Nod. Modafinil, Dr. Edgar and others believe, may act by somehow invoking the clock's natural alerting mechanism, keeping the alarm "ringing" well beyond the time when it normally shuts off. And if this is the case, modafinil and other drugs like it would offer the possibility of literally doing away with sleep, fooling the body into staying "naturally" awake for long periods. Would such a drug be a cure for shift workers and jet lagged travelers and overworked mothers with bills to pay and reports to file? Who would be permitted to take it? Police officers? Soldiers? Airplane pilots? These are questions, says Dr. David Dinges, chief of the Division of Sleep and Chronobiology in psychiatry at the University of Pennsylvania, that society will have to address sooner or later, as the new generation of wake-promoting drugs emerges. "We are on an inexorable march to uncovering the biology of wakefulness and manipulating it," Dr. Dinges said. Modafinil may not live up to expectations. "But when such a drug does arrive, it will change the world. Is it O.K. for us to become a nation that doesn't sleep? Until we know what sleep is for, and why it is so overwhelming, we're not going to be able to say it's O.K. to find a substitute for it." LOAD-DATE: November 3, 1998 LANGUAGE: ENGLISH GRAPHIC: Chart: "Fighting To Stay Awake" Dr. Dale Edgar describes sleep and wakefulness as a battle of oppositional forces where the desire to sleep, which builds from the moment one awakens, is countered by signals from the brain's internal clock. In the evening, when the clock stops ringing, we sleep. Day Pressure to sleep builds.Alerting signals counter, staving off immediate sleep. Night Signals from the body's clock diminish, and sleep occurs. Sleep pressure decreases. THE BRAIN'S INTERNAL CLOCK -- A tiny portion of the brain called the suprachiasmatic nuclei (or SCN) sends out disinhibitory signals that counter the inhibiting signals that result in sleepiness. Copyright 1998 The New York Times Company 946 of 998 DOCUMENTS Village Voice (New York, NY) August 11, 1998 CITY NEVER SLEEPS BYLINE: mark schoofs SECTION: Columns; Pg. 61 LENGTH: 827 words When Ross Pigeau, a researcher with the Canadian military, first heard about a new drug that can keep people awake as effectively as amphetamines but without the jitters, ''it just sounded too good to be true,'' he recalls. But after studying the drug, called modafinil, and trying it himself, Pigeau is a believer, and he ticks off the benefits: ''Apparently not addictive, apparently no withdrawal, and very few side effects. Someone tried to OD on modafinil by taking almost a whole bottle, and he just had a night without sleep.'' So far, the drug has caught the attention only of National Public Radio and a smattering of other media outlets. Perhaps that's because the Food and Drug Administration is expected to approve modafinil, probably by the end of the year, for a rare illness which French doctors have for several years been using the drug to treat: narcolepsy, a disorder in which people fall asleep suddenly in the middle of the day. But once a drug is approved, doctors can prescribe it for almost any reason, however frivolous, such as enabling a healthy person to pull an all-nighter. The Canadian military--like the French and American armed forces, which have also studied the drug--wanted to be able to keep soldiers awake for long stretches. So in Pigeau's experiment, healthy subjects were kept awake for three days while adhering to a grueling work regimen that permitted only one 15-minute break every two hours. Modafinil improved performance just as much as amphetamines, but it didn't give people a high; they simply felt awake. What's more, when test subjects were finally allowed to get some shut-eye, those on modafinil had sleep cycles that were normal. The only drawback--which Pigeau terms ''very interesting''--is that people on modafinil were consistently overconfident, estimating their proficiency to be better than it actually was. So will workaholics flock to the drug? ''We are all concerned about that,'' sighs Joyce Walsleben, director of the New York University Sleep Disorders Center, where modafinil has been studied. She worries that people will ''think it is a magic bullet so they can do without sleep.'' That's a dangerous misconception, because the drug does not keep people operating at peak performance. When Pigeau gave his subjects modafinil after they had been awake for two nights, the drug only restored them to the level of performance they had following their first night without sleep--and that was a whopping 35 percent below their rested performance. Imagine people driving cars, flying planes, or wielding scalpels at such perilously subpar levels--yet overconfident about their ability--and suddenly Walsleben's worry seems a lot more urgent. No one knows the function of sleep--a complex biological phenomenon quite distinct from mere resting--but it must be extremely important. Sleep renders animals unconscious, and thus easy prey, yet all mammals, birds, and reptiles sleep. What's more, they have evolved elaborate adaptations to do so. Horses sleep while standing, birds while perching, and dolphins while swimming. And dolphins even sleep with one-half of their brain at a time. Allan Rechtschaffen, a professor at the University of Chicago and one of the foremost authorities on sleep, found that rats deprived of sleep die in two to three weeks. Yet despite extensive study, neither he nor anyone else has been able to determine the cause of death. In humans, says Rechtschaffen, the record for staying awake ''is 11 days, by one high school student who did it as a science project.'' But no lasting physiological harm was detected. Of course, while people are sleep-deprived, their irritability soars and sense of humor plummets. ''There is often some hallucination,'' adds Pigeau. ''It's very subtle: they'll say, 'Did you hear that sound?' or 'I think I saw something running across the floor.''' Even mild sleep loss has been shown to impair creative or complex thinking. No one knows how or why sleep deprivation causes these problems, much less what sleep is ultimately for. But the inquiry can be flipped on its head: ''What is wakefulness for?'' asks Merrill Mitler, a clinical professor at the University of California at San Diego and a consultant to Cephalon, which is developing modafinil for the U.S. market. Chuckling slyly, he offers an off-the-cuff answer to his own question: wakefulness is for eating, drinking, and procreating. Maybe that's true, but it hardly gets at why we value being awake. In a similar way, even if the Darwinian, biological function of sleep is found, it may have only limited relevance to our experience of sleep. And that personal, almost existential understanding of sleep may be the best bulwark against the abuse of caffeine substitutes. Most people hate feeling sleep-deprived and love feeling well rested. No drug on the horizon can equal that natural high. Research assistance: Tyler Schnoebelen, Sam Bruchey LOAD-DATE: August 05, 1998 LANGUAGE: ENGLISH Copyright 1998 VV Publishing Corporation 947 of 998 DOCUMENTS Village Voice (New York, NY) August 11, 1998 CITY NEVER SLEEPS BYLINE: mark schoofs SECTION: Columns; Pg. 61 LENGTH: 827 words When Ross Pigeau, a researcher with the Canadian military, first heard about a new drug that can keep people awake as effectively as amphetamines but without the jitters, ''it just sounded too good to be true,'' he recalls. But after studying the drug, called modafinil, and trying it himself, Pigeau is a believer, and he ticks off the benefits: ''Apparently not addictive, apparently no withdrawal, and very few side effects. Someone tried to OD on modafinil by taking almost a whole bottle, and he just had a night without sleep.'' So far, the drug has caught the attention only of National Public Radio and a smattering of other media outlets. Perhaps that's because the Food and Drug Administration is expected to approve modafinil, probably by the end of the year, for a rare illness which French doctors have for several years been using the drug to treat: narcolepsy, a disorder in which people fall asleep suddenly in the middle of the day. But once a drug is approved, doctors can prescribe it for almost any reason, however frivolous, such as enabling a healthy person to pull an all-nighter. The Canadian military--like the French and American armed forces, which have also studied the drug--wanted to be able to keep soldiers awake for long stretches. So in Pigeau's experiment, healthy subjects were kept awake for three days while adhering to a grueling work regimen that permitted only one 15-minute break every two hours. Modafinil improved performance just as much as amphetamines, but it didn't give people a high; they simply felt awake. What's more, when test subjects were finally allowed to get some shut-eye, those on modafinil had sleep cycles that were normal. The only drawback--which Pigeau terms ''very interesting''--is that people on modafinil were consistently overconfident, estimating their proficiency to be better than it actually was. So will workaholics flock to the drug? ''We are all concerned about that,'' sighs Joyce Walsleben, director of the New York University Sleep Disorders Center, where modafinil has been studied. She worries that people will ''think it is a magic bullet so they can do without sleep.'' That's a dangerous misconception, because the drug does not keep people operating at peak performance. When Pigeau gave his subjects modafinil after they had been awake for two nights, the drug only restored them to the level of performance they had following their first night without sleep--and that was a whopping 35 percent below their rested performance. Imagine people driving cars, flying planes, or wielding scalpels at such perilously subpar levels--yet overconfident about their ability--and suddenly Walsleben's worry seems a lot more urgent. No one knows the function of sleep--a complex biological phenomenon quite distinct from mere resting--but it must be extremely important. Sleep renders animals unconscious, and thus easy prey, yet all mammals, birds, and reptiles sleep. What's more, they have evolved elaborate adaptations to do so. Horses sleep while standing, birds while perching, and dolphins while swimming. And dolphins even sleep with one-half of their brain at a time. Allan Rechtschaffen, a professor at the University of Chicago and one of the foremost authorities on sleep, found that rats deprived of sleep die in two to three weeks. Yet despite extensive study, neither he nor anyone else has been able to determine the cause of death. In humans, says Rechtschaffen, the record for staying awake ''is 11 days, by one high school student who did it as a science project.'' But no lasting physiological harm was detected. Of course, while people are sleep-deprived, their irritability soars and sense of humor plummets. ''There is often some hallucination,'' adds Pigeau. ''It's very subtle: they'll say, 'Did you hear that sound?' or 'I think I saw something running across the floor.''' Even mild sleep loss has been shown to impair creative or complex thinking. No one knows how or why sleep deprivation causes these problems, much less what sleep is ultimately for. But the inquiry can be flipped on its head: ''What is wakefulness for?'' asks Merrill Mitler, a clinical professor at the University of California at San Diego and a consultant to Cephalon, which is developing modafinil for the U.S. market. Chuckling slyly, he offers an off-the-cuff answer to his own question: wakefulness is for eating, drinking, and procreating. Maybe that's true, but it hardly gets at why we value being awake. In a similar way, even if the Darwinian, biological function of sleep is found, it may have only limited relevance to our experience of sleep. And that personal, almost existential understanding of sleep may be the best bulwark against the abuse of caffeine substitutes. Most people hate feeling sleep-deprived and love feeling well rested. No drug on the horizon can equal that natural high. Research assistance: Tyler Schnoebelen, Sam Bruchey LOAD-DATE: August 11, 1998 LANGUAGE: ENGLISH Copyright 1998 VV Publishing Corporation 948 of 998 DOCUMENTS The Philadelphia Inquirer JULY 13, 1998 Monday SF EDITION NEW DRUG HOLDS PROMISE FOR HELPING NARCOLEPTICS / WILL OTHERS - MERELY STRESSED OUT AND SLEEP-DEPRIVED - ALSO TRY TO OBTAIN IT? BYLINE: Shankar Vedantam, INQUIRER STAFF WRITER SECTION: FEATURES MAGAZINE: HEALTH & SCIENCE; Pg. D01 LENGTH: 951 words While most of America isn't sleeping enough, some people - those with a chronic condition called narcolepsy - are sleeping too much, dozing off several times a day, even getting some dangerous shut-eye while they drive. Soon, there may be help for them. A new medicine marketed by Cephalon, a West Chester-based pharmaceutical company, promises powerful help to fight daytime sleepiness. Sleep doctors are unanimous: This is great news for those with narcolepsy. The question, however, is whether hyperactive, stressed-out, sleep-deprived America will also seek the drug in order to stay awake even longer. Although doctors warn about the dangers of not sleeping, the new drug could add to the stay-awake arsenal of night-shift workers, truck drivers and students. The medicine will almost certainly have to be prescribed by a doctor and be sold under strict supervision, but that hasn't stopped other drugs from being misused in the past. "All you have to do is look at the history of Fen-phen and other drugs that were originally described as being appropriate for one use and ended up being prescribed by physicians for patients who were not appropriate," said Joan Goldberg, a spokeswoman at the National Sleep Foundation, a nonprofit organization in Washington that monitors America's sleep debt. "Anybody involved in the health business wants to see treatments are used by the right people for the right reasons," she said. The Food and Drug Administration has not yet made a ruling on the drug modafinil , which Cephalon wants to sell under the brand name Provigil. The drug has cleared testing hurdles, and a decision is expected by the end of the year. "It's important that we caution anyone who has an interest in this product that the data only address its potential use in treating daytime sleepiness associated with narcolepsy," said Cephalon spokesman Jason Rubin. Would the company dissuade people who were not narcoleptics from using the medicine? "I can't answer that question," he said. "If the drug is approved for excessive daytime sleepiness [as a result of narcolepsy] we would have the freedom to promote the product for that indication alone," not for other uses. While the FDA approves a drug for a specific condition, doctors can prescribe medicines "off-label" for other reasons if they feel such use would help patients. Rubin guessed that there were about 125,000 patients with narcolepsy in the United States. Goldberg and the National Sleep Foundation put the number at 200,000. It is difficult to diagnose narcolepsy because its primary symptom - sleepiness - is not in itself abnormal. Predictably, the number of Americans who are sleep-deprived is far larger than the group of narcoleptics. "The average person needs eight hours of sleep and the average person gets seven hours of sleep," said Goldberg. "At least one-third of Americans are suffering from significant sleep loss during the work week." About one in five people said that their sleep deprivation interfered with their daily activities a few days a month, according to the 1998 results of a survey by the foundation. About one in three people said that their sleepiness interfered with their job, family duties, relationships and recreation. Modafinil has several advantages over other stimulants. In studies conducted in the United States and Europe, the drug has been shown to be safe. It seems to work well long-term, and does not produce the psychological highs of stimulants such as coffee or amphetamines. "It won't be abused because it doesn't make people feel good," said Calvin Stafford, director of the Sleep Disorder Center at Crozer Chester Medical Center, who helped conduct trials of modafinil in America. "It doesn't appear to have the roller-coaster effect," he said. "You don't feel wired." Other stimulants cause people to "have periods where the drug levels are high and they are bright but then they begin to get drowsy. Modafinil is long-acting," he said. "I can't say what will happen out there without supervision. It is my hope people won't use it to stay up for finals, but we have certainly seen such behavior with other stimulants. We can't guarantee it won't happen with any new drug." No one is quite sure how modafinil works. One of its fascinating effects is it seems to remove the need for sleep. "We always thought when you take away sleep you have to pay back, but that does not seem to happen with this medication," said Karl Doghramji, director of the Sleep Disorders Center at Thomas Jefferson University. "With amphetamines you have a post-drug crash. Once you stop taking them, you have tremendous sleepiness. "What these pills help us do is make sure we get sleep only for six to eight hours a night," he said. "It ensures that during the time we are awake we stay awake, but also makes sure the sleep at night is good." Sleep is as central to human health as food and water. Cognitive functions and judgment rapidly decline with sleep deprivation, and the body quickly goes downhill. "It is not possible to really define all the aspects of what happens to a person when they are sleep-deprived," said June Fry, director of the sleep disorders center at the Allegheny University of the Health Sciences. "They are more susceptible to disease, especially viruses and communicable diseases. It affects their immune systems, their hormone balances, all their circadian rhythms." Fry said doctors didn't know what would happen to healthy people if they used modafinil to stay awake, but said it was pretty certain not to be good for them. "The only appropriate treatment for sleep deprivation," she said, "is sleep." LOAD-DATE: October 24, 2002 LANGUAGE: ENGLISH Copyright 1998 Philadelphia Newspapers, LLC All Rights Reserved 949 of 998 DOCUMENTS Internal Medicine Alert June 29, 1998 Modafinil for Narcolepsy LENGTH: 819 words Modafinil for Narcolepsy ABSTRACT & COMMENTARY Synopsis: If its relatively low side effects continue, modafinil appears to be the first non-toxic drug that can improve the disturbing symptoms of narcolepsy. Source: U.S. Modafinil in Narcolepsy Study Group. Ann Neurol 1998;43:88-97. Narcolepsy affects approximately 100,000 persons in the United States, with a sizable fraction of the sufferers experiencing repeated, semi-disabling, excessive daytime sleepiness. A measurably fewer number suffer from cataplexy, fractioned nocturnal sleep, hypnagogic hallucinations, and sleep paralysis. The illness is usually inherited and associated with one of several HLA DRZ or DQB1 haplotype groups plus other factors. Haplotype specificity, however, does not guarantee expression of the disorder. Disabling daytime sleepiness provides narcolepsy's dominant dysfunction, for which amphetamines bring only modest improvement, often with considerable unwanted side effects. Investigators have suggested that the disease results from insufficient CNS dopamine release plus an increase in muscarinic acetylcholine receptors generating hypersensitivity to acetylcholine. Against this therapeutically unfavorable backdrop, a new wake-provoking stimulus called modafinil, 2 ([diphenylmethyl] sulfinyl) acetamide has been introduced. Modafinil stimulates CNS targets known to respond to amphetamine and methylphenidate. Effects in animals indicate that modafinil increases wakefulness but induces little amphetamine-like excitation of motor function. To test the value of modafinil, 283 persons aged 18-68 years were randomized into three cohorts: placebo (n = 92), 200 mg daily (n = 96), and 400 mg daily (n = 95). This report provides preliminary results, and a successive open-label trial is in progress. Participants graded the patient's post-therapy dozing response as: 1) never, 2) slight chance, 3) moderate, or 4) high. All categories were applied during times of relatively inactive behavior. Objective evaluations included Sleep Latency Testing (SLT) and Maintenance of Wakeful Test (MWT). Severity of disease was evaluated by a clinician's Clinical Global Impression (CGI). Nocturnal polysomnography was applied before each assessment. Mean age of the cohort was 42 years, and sex numbered 43 men and 51 women in each cohort. Mean length of disease amounted to 22 years; 95% had daytime sleep attacks, 88% had cataplexy, 71% had interrupted nighttime sleep, 69% hallucinated, and 64% experienced sleep paralysis. Results were appraised at three, six, and nine weeks following onset of the trial. Self-reported sleepiness (ESS) events were similar at onset and, in the placebo group, at nine weeks. Otherwise, at week nine both modafinil cohorts showed less sleepiness than controls (P < 0.001), with the 400 mg group significantly better than the 200 mg group (P < 0.001). Sleep latency was similar between the two modafinil groups but was significantly better than controls (P < 0.001). Maintenance of wakefulness was better than control in both modafinil groups (P < 0.001) but not different between the two groups. Also, more subjects in the modafinil groups remained awake longer than in the control group. Blinded clinical assessment rated modafinil-taking patients as measurably improved compared to the controls. Complications were relatively low: one of the 200 mg dose cohort withdrew, as did 11 (12%) of the 400 mg group. The only symptom significantly higher than placebo was headache. A subsequent open-label trial continues beyond the above blind control studies. In that trial, clinical global impression showed 84% improvement by week two of taking modafinil with the number rising to 91% by week 40. Both times had significance at the P < 0.001 level. The authors indicate that "adverse experiences were mostly mild to moderate." In the open trial, however, 25% of patients withdrew because of side effects or lack of efficacy. COMMENT BY FRED PLUM, MD If its relatively low side effects continue, modafinil appears to be the first non-toxic drug that can improve the disturbing symptoms of narcolepsy. The drug clinically appears to reduce daytime sleepiness, and the result of latency tests supported that conclusion. The general clinical appraisal of the participating neurologists also concluded that wakefulness improved in the treated group. At this writing, the reporting participating neurologists estimate that overall efficacy of modafinil against narcolepsy amounts to about 55%, with Pemoline providing about an equal help but with amphetamine or methylphenidate each improving symptoms by about 80%. The latter level, however, produces a relatively high incidence of unwanted symptoms. As the authors conclude, " modafinil is a pharmacologically and clinically promising compound for treating pathological daytime somnolence." (Dr. Plum is Neurologist-in-Chief, New York Hospital-Cornell Medical Center.) LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 1998 AHC Media LLC All Rights Reserved 950 of 998 DOCUMENTS Reuters Health Medical News June 12, 1998 Friday Nippon Shoji to market Cephalon's modafinil in Japan SECTION: INDUSTRY LENGTH: 168 words DATELINE: WESTPORT Jun 12 Nippon Shoji Kaisha, based in Osaka, Japan, will market in Japan Cephalon's modafinil for the treatment of narcolepsy, according to a Cephalon press release posted on PR Newswire. Cephalon will receive milestone payments and royalties based on sales of the product in Japan. Nippon Shoji will continue development of the drug in Japan an seek regulatory approval. West Chester, Pennsylvania-based Cephalon licensed rights to modafinil in France to Laboratoire L. Lafon. The drug has been approved for marketing in the UK and Ireland, and Cephalon received an approvable letter from the Food and Drug Administration in the US. The company is also currently pursuing regulatory clearance to market modafinil in Mexico and Italy. Dr. Frank Baldino, Jr., president and CEO of Cephalon, commented, "Japan is a significant component of the worldwide pharmaceutical marketplace. We are delighted to partner with Nippon Shoji to bring to Japan what we believe may be an important new therapy for this disabling disease." LOAD-DATE: July 9, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 1998 Reuters Health All Rights Reserved 951 of 998 DOCUMENTS PR Newswire June 11, 1998, Thursday - 08:35 Eastern Time Cephalon Grants Nippon Shoji Rights to Modafinil in Japan. SECTION: Financial News LENGTH: 467 words DATELINE: WEST CHESTER, Pa., June 11 Cephalon, Inc. (Nasdaq: CEPH) announced today that it has entered into an agreement with Nippon Shoji Kaisha, Ltd. (NSK) for the development and marketing of modafinil in Japan. Under the terms of the agreement, Cephalon will receive milestone payments and royalties based upon NSK product sales. Nippon Shoji plans to initially develop and seek regulatory approval for modafinil for the treatment of narcolepsy, which is a chronic, lifelong sleep disorder that hampers a person's ability to perform basic daily activities. "Japan is a significant component of the worldwide pharmaceutical marketplace," said Frank Baldino, Jr., Ph.D., Cephalon's president and chief executive officer. "We are delighted to partner with Nippon Shoji to bring to Japan what we believe may be an important new therapy for this disabling disease." Cephalon licensed rights to modafinil in certain territories from Laboratoire L. Lafon, the French pharmaceutical company which discovered and markets the drug in France. Cephalon received market authorization for modafinil in the United Kingdom and the Republic of Ireland. The company is currently marketing modafinil in the United Kingdom for the treatment of narcolepsy and plans to market the drug in Ireland upon clearance of U.S. manufacturing arrangements. Cephalon has received an approvable letter from the U.S. Food and Drug Administration. Additionally, the company is pursuing regulatory clearance to market modafinil in Mexico and Italy. Nippon Shoji Kaisha, Ltd., headquartered in Osaka, Japan, is an integrated supplier of medical products. Nippon Shoji actively markets and produces pharmaceutical products, diagnostics and medical devices. Cephalon, Inc., headquartered in West Chester, PA, is an international biopharmaceutical company that discovers, develops and markets products to treat neurological disorders. This news release may contain forward-looking statements that involve risks and uncertainties. A full discussion of Cephalon's operations and financial condition, including factors that may affect the company's business and future prospects, is contained in documents the company files with the SEC, such as form 10-Q and 10-K reports. These documents identify important factors that could cause the company's actual performance to differ from current expectations. NOTE: Cephalon's press releases are posted on the Internet at the company's Web site at http://www.cephalon.com. They are also available by fax 24 hours a day at no charge by calling PR Newswire's Company News On-Call at 800-758-5804, extension 134563. SOURCE  Cephalon, Inc.      CONTACT: Jason Rubin (US) of Cephalon, 610-738-6302, or Shun-Ichi Miyake (Japan) of Nippon Shoji Kaisha, 011-81-69-42-6192 LOAD-DATE: June 12, 1998 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS EDITOR Copyright 1998 PR Newswire Association, Inc. 952 of 998 DOCUMENTS Community Pharmacy June 1998 Sleep Problems - Waking up to narcolepsy SECTION: Pg. 20 LENGTH: 1780 words Will the introduction of a new narcolepsy treatment help control the disease nightmare for many sufferers? Assistant editor Clare Evans finds out. Narcolepsy is a chronic and life-long debilitating sleep disorder. As many as approximately 2,500 diagnosed narcolepsy patients in the UK currently receive treatment although, due to the difficulties in correctly diagnosing the disease, this is thought to be simply the tip of the iceberg. The characteristic feature of narcolepsy is excessive daytime sleepiness (EDS), but patients may also be affected by a range of other symptoms. These include: - cataplexy (sudden loss of muscle tone) - sleep paralysis (the inability to move during the process of falling asleep or while awakening) - dreamlike imagery or sound known as visual or auditory hallucinations. Only 11 per cent of people with narcolepsy suffer from all four symptoms. Excessive daytime sleepiness (EDS) EDS is the most disabling and difficult to treat symptom of narcolepsy. Sufferers are constantly tired, resulting in recurrent, uncontrollable bouts of sleep throughout the day. EDS is overpowering and sufferers may become irritable if sleep is resisted or prevented. Attacks typically last for up to 30 minutes. Up to 80 per cent of narcoleptics also experience changes in alertness throughout the day lasting a few seconds through to several minutes. During this time they can undertake irrational and potentially dangerous tasks, of which they have no recollection. These can include putting things in the oven or driving to an unplanned, or even unknown, destination. Cataplexy Almost three quarters of narcolepsy sufferers develop cataplexy. Attacks involve sudden decreases in, or loss of, muscle tone which can affect a single muscle or the whole body. They may last for less than a minute to over 20 minutes and include a range of symptoms including slurred or lost speech, dropping arms and a sagging jaw. Cataplexy triggers include strong emotion such as laughter, surprise, fear, anger, anticipation and excitement. Sleep paralaysis Some patients experience the sudden inability to move or speak during the transition period between sleeping and waking. Sleep paralysis attacks may also be accompanied by breathing problems - the person may feel as if their chest is constricted, when their breathing actually continues as normal. The reported prevalence of sleep paralysis among narcoleptics varies between one quarter and two thirds of sufferers, possibly due to the fact that few sufferers seek advice for the condition. Hypnagogic/hynopompic hallucinations Many narcoleptics experience dreamlike imagery or sounds while dozing or awakening. These experiences are clinically known as visual or auditory hallucinations and can occur just before falling asleep (hypnagogic), or just after awakening (hypnopompic). Narcoleptics also demonstrate a different sleep pattern to non- narcolepsy sufferers. Rapid eye movement (REM) occurs approximately 90 minutes into a non-sufferers sleep and it is here that dreaming occurs. In narcoleptics, REM occurs much earlier, generally within 10 minutes of falling asleep. As a result of the rapid onset of dreaming, the sufferer may experience hallucinations. Other reported symptoms of the narcoleptic syndrome include facial twitching, headaches, insomnia, poor concentration and problems with memory. Prevalence Narcolepsy can develop at any age and it affects both sexes equally. Symptoms commonly present during adolescence, although 6 per cent of sufferers are affected before they reach the age of 10. The cause of narcolepsy is unknown. Genetic pre-disposition may play a part; 98 per cent of sufferers carry the human leucocyte antigen HLA- DR2, but, as 25 per cent of the total population also carry it, the antigen itself is not the cause. Symptomatic narcolepsy has been reported in association with traumatic illnesses such as brain tumours, stroke, and head trauma, although cases are rare and may resolve with specific treatment. Diagnosis Diagnosing narcolepsy is often difficult. Many sufferers avoid visiting their GP for fear of being perceived as lazy; others have their symptoms mistakenly attributed to other illnesses such as hypothyroidism and multiple sclerosis. The diagnosis of narcolepsy is usually confirmed at a specialist sleep centre through laboratory tests. These include: - Polysomnography: a multiple set of physiological tests including EEG, ECG, measures of oxygen saturation, and respiratory flow and effort - Multiple Sleep Latency Test (MSLT): a measure of sleepiness levels. The patient is given the opportunity to sleep at two hourly intervals, four or five times throughout the day under supervision. If the time it takes the person to fall asleep is eight minutes or less it suggests that they may be suffering narcolepsy. The speed of achieving REM sleep is also observed. - Maintenance of Wakefulness Test (MWT): Patients are placed in comfortable conditions in a darkened room during the day and asked to try and remain awake. This test can also be used to measure the effects of treatment. Treatment options Since the 1930s, amphetamines have been used to treat the EDS symptom of narcolepsy. Acting on the central nervous system (CNS), use results in increased alertness, improved mood and euphoria. Most sufferers initially respond to treatment and find their sleepiness controlled to an acceptable degree. However, side-effects including irritability, headache, palpitations, nausea, muscle jerks, tremor, psychosis and anorexia, plus a strong association with dependence, has limited amphetamine use, many patients discontinuing treatment of their own accord. Three in 10 patients develop tolerance to amphetamines, the dose having to be increased to have the same therapeutic effect. There is also great potential for abuse. A new treatment Now, though, there is an alternative to amphetamines. Provigil (modafinil) from Cephalon is a non-amphetamine, wake-promoting agent that is claimed to increase wakefulness and restore a normal pattern of daytime alertness. Clinical studies show that modafinil significantly reduces all measures of sleepiness on physiological and clinical scales, as well as the patient's own self assessment of sleepiness, without affecting night- time sleep.(1) Although the exact mechanism of action is unknown, modafinil is known to bind to specific receptors on the anterior hypothalamus - the area of the brain thought to be responsible for wakefulness - instead of stimulating the CNS receptors as with amphetamines.(2) This specificity also reduces the incidence of adverse-effects, with headache the only reported significant side-effect. (2,3) Dr John Shneerson, director of the Sleep Disorders Centre, Papworth NHS Trust, finds modafinil to be equally as effective as dexamphetamine in treating narcolepsy, although it provides a smoother onset, and cessation, of action and is longer-acting. He also believes there may be a positioning for combining modafinil with amphetamine treatment at this sleep centre using this combination. Although the concomitant use of amphetamines and modafinil is not recommended by Cephalon, it is something that the company may address in the future. Pharmacologically, modafinil differs from amphetamines in that it does not cause mood 'highs' and 'lows', it appears to retain efficacy in long-term use and has low potential for abuse.(4) But the company recommends that people who are stable and well- controlled on amphetamines should remain on them. "People should not be changed to modafinil just because it is there", says a company spokesperson. The drug is also contra-indicated for use during pregnancy and lactation, in children and in patients with moderate to severe hypertension, left ventricular hypertrophy, chest pain or arrhythmias. It may impair the effectiveness of oral contraceptives containing less than 50mcg of ethinyl oestradiol and care should also be taken with its co-administration with anticonvulsants. To date there has been no definite drug-drug reactions involving modafinil use.(5) When a patient is changing from amphetamine to modafinil therapy, the amphetamine dose should be reduced over a period of two to three days until zero. The patient should then remain drug-free for a period of two to three days to allow complete excretion. Modafinil can then be gradually introduced in titrated doses until the patient's symptoms are stable. Don Pincham, who chairs the UK Narcolepsy Association (UKAN) believes the launch of modafinil has finally highlighted the problems with treating the disease. "Provigil is not a wonder drug and it won't suit everyone. But for those who can take it, it promises a tremendous improvement in their quality of life as the side-effects of amphetamines can be as bad as the illness itself. "One of the real benefits is that Provigil is the only drug designed specifically for narcolepsy and public awareness of the disease has been greatly raised as a result." The references for this article are available from the editor SUMMARY - Narcolepsy can develop at any age and affects both sexes equally - There are 2,500 diagnosed narcolepsy sufferers in the UK currently receiving treatment - In addition to excessive daytime sleepiness, patients may also suffer from cataplexy, sleep paralysis and visual or auditory hallucinations - Amphetamines have been the mainstay of narcolepsy treatment since the 1930s - Provigil (modafinil) is a non-amphetamine wake-promoting agent THE NARCOLEPTIC SYNDROME The 1990 International Classification of Sleep Disorders defines the narcoleptic syndrome as: 'a disorder of unknown aetiology which is characterised by excessive daytime sleepiness that typically is associated with cataplexy and other REM sleep phenomena such as sleep paralysis and hypnagogic hallucinations' INTERNATIONAL CLASSIFICATION OF SLEEP DISORDERS To help improve the accuracy of narcolepsy diagnosis, there is a set international minimum. This is: B+C or A+D+E+G A Excessive sleepiness or sudden muscle weakness B Recurrent daytime sleep episodes 3 months or more C Cataplexy D Sleep paralysis, hypnagogic hallucinations, etc E Polysomnographic:  Sleep latency 10 minutes or less  REM sleep latency 20 minutes or less  MSLT Mean sleep latency 8 minutes or less  Two or more SOREMPS* F HLA-DR2 positive G Exclude medical and psychiatric disorders * Sleep Onset Rapid Eye Movement Periods LOAD-DATE: February 9, 1999 LANGUAGE: English PUB-TYPE: Magazine Copyright 1998 CMP Information Ltd 953 of 998 DOCUMENTS PR Newswire May 15, 1998, Friday - 08:07 Eastern Time Cephalon Receives Authorization to Market PROVIGIL(R) (modafinil)  In the Republic of Ireland. SECTION: Financial News LENGTH: 474 words DATELINE: WEST CHESTER, Pa., May 15 Cephalon, Inc. (Nasdaq: CEPH) announced today that its UK subsidiary, Cephalon UK Ltd., has received authorization from the Irish Medicines Board (IMB) to market PROVIGIL(R) (modafinil) tablets in the Republic of Ireland for the treatment of narcolepsy. Narcolepsy is a chronic, neurological, lifelong sleep disorder that generally begins in young adulthood. The most common symptom is excessive daytime sleepiness, which is characterized by uncontrollable sleep attacks. These attacks hamper a person's ability to perform basic daily activities. As a result, narcolepsy significantly impacts a person's quality of life. Cephalon intends to manufacture PROVIGIL tablets in the United States and launch the drug in the Republic of Ireland upon IMB approval of the U.S. manufacturing arrangements. "This is the first non-amphetamine agent licensed for the treatment of narcolepsy in Ireland," said Frank Baldino, Jr., Ph.D., Cephalon's president and chief executive officer. "Our European sales and marketing organization looks forward to making PROVIGIL available to the neurology community in Ireland for patients suffering from this disabling disease." Cephalon licensed modafinil from Laboratoire L. Lafon, the French pharmaceutical company which discovered and markets the drug in France. Cephalon has exclusive rights to market modafinil in the United States, Japan, the United Kingdom, Ireland, Mexico and Italy. In March 1998, Cephalon commenced marketing of PROVIGIL for the treatment of narcolepsy in the United Kingdom. Cephalon has a marketing application currently pending in the United States to market PROVIGIL for the treatment of excessive daytime sleepiness associated with narcolepsy. Cephalon, Inc., headquartered in West Chester, PA, is an international biopharmaceutical company that discovers, develops and markets products to treat neurological disorders. This news release may contain forward-looking statements that involve risks and uncertainties. A full discussion of Cephalon's operations and financial condition, including factors that may affect the company's business and future prospects, is contained in documents the company files with the SEC, such as form 10-Q and 10-K reports. These documents identify important factors that could cause the company's actual performance to differ from current expectations.     NOTE:  Cephalon's press releases are posted on the Internet at the company's Web site at http://www.cephalon.com.  They are also available by fax 24 hours a day at no charge by calling PR Newswire's Company News On-Call at 800-758-5804, extension 134563. SOURCE  Cephalon, Inc.      CONTACT: Sandra Menta (US) of Cephalon, 610-738-6376, or Anne Marie Rodriguez (Europe) of Sante Communications, 011-44-171-379-7377 LOAD-DATE: May 16, 1998 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS AND MEDICAL EDITORS Copyright 1998 PR Newswire Association, Inc. 954 of 998 DOCUMENTS Neurology Alert May 1, 1998 Modafinil for Treatment of Narcolepsy LENGTH: 820 words Modafinil for Treatment of Narcolepsy ABSTRACT & COMMENTARY Source: U.S. Modafinil in Narcolepsy Study Group. Randomized trial of modafinil for the treatment of pathological somnolence in narcolepsy. Ann Neurol 1998;43:88-97. Narcolepsy affects approximately 100,000 persons in the United States, with a sizable fraction of the sufferers experiencing repeated, semi-disabling, excessive daytime sleepiness. A measurably fewer number suffer from cataplexy, fractioned nocturnal sleep, hypnagogic hallucinations, and sleep paralysis. The illness is usually inherited and associated with one of several HLA DRZ or DQB1 haplotype groups plus other factors. Haplotype specificity, however, does not guarantee expression of the disorder. Disabling daytime sleepiness provides narcolepsy's dominant dysfunction, for which amphetamines bring only modest improvement, often with considerable unwanted side effects. Investigators have suggested that the disease results from insufficient CNS dopamine release plus an increase in muscarinic acetylcholine receptors generating hypersensitivity to acetylcholine. Against this therapeutically unfavorable backdrop, a new wake-provoking stimulus called modafinil, 2 ([diphenylmethyl] sulfinyl) acetamide has been introduced. Modafinil stimulates CNS targets known to respond to amphetamine and methylphenidate. Effects in animals indicate that modafinil increases wakefulness but induces little amphetamine-like excitation of motor function. To test the value of modafinil, 283 persons aged 18-68 years were randomized into three cohorts: placebo (n = 92), 200 mg daily (n = 96), and 400 mg daily (n = 95). This report provides preliminary results, and a successive open-label trial is in progress. Participants graded the patient's post-therapy dozing response as: 1) never, 2) slight chance, 3) moderate, or 4) high. All categories were applied during times of relatively inactive behavior. Objective evaluations included Sleep Latency Testing (SLT) and Maintenance of Wakeful Test (MWT). Severity of disease was evaluated by a clinician's Clinical Global Impression (CGI). Nocturnal polysomnography was applied before each assessment. Mean age of the cohort was 42 years, and sex numbered 43 men and 51 women in each cohort. Mean length of disease amounted to 22 years; 95% had daytime sleep attacks, 88% had cataplexy, 71% had interrupted nighttime sleep, 69% hallucinated, and 64% experienced sleep paralysis. Results were appraised at three, six, and nine weeks following onset of the trial. Self-reported sleepiness (ESS) events were similar at onset and, in the placebo group, at nine weeks. Otherwise, at week nine both modafinil cohorts showed less sleepiness than controls (P < 0.001), with the 400 mg group significantly better than the 200 mg group (P < 0.001). Sleep latency was similar between the two modafinil groups but was significantly better than controls (P < 0.001). Maintenance of wakefulness was better than control in both modafinil groups (P < 0.001) but not different between the two groups. Also, more subjects in the modafinil groups remained awake longer than in the control group. Blinded clinical assessment rated modafinil-taking patients as measurably improved compared to the controls. Complications were relatively low: one of the 200 mg dose cohort withdrew, as did 11 (12%) of the 400 mg group. The only symptom significantly higher than placebo was headache. A subsequent open-label trial continues beyond the above blind control studies. In that trial, clinical global impression showed 84% improvement by week two of taking modafinil with the number rising to 91% by week 40. Both times had significance at the P < 0.001 level. The authors indicate that "adverse experiences were mostly mild to moderate." In the open trial, however, 25% of patients withdrew because of side effects or lack of efficacy. COMMENTARY If its relatively low side effects continue, modafinil appears to be the first non-toxic drug that can improve the disturbing symptoms of narcolepsy. The drug clinically appears to reduce daytime sleepiness, and the result of latency tests supported that conclusion. The general clinical appraisal of the participating neurologists also concluded that wakefulness improved in the treated group. At this writing, the reporting participating neurologists estimate that overall efficacy of modafinil against narcolepsy amounts to about 55%, with Pemoline providing about an equal help but with amphetamine or methylphenidate each improving symptoms by about 80%. The latter level, however, produces a relatively high incidence of unwanted symptoms. As the authors conclude, " modafinil is a pharmacologically and clinically promising compound for treating pathological daytime somnolence." Modafinil is currently available in Europe and, I'm told, is well along the way for FDA approval in the United States, possibly by late April or May 1998. -fp LOAD-DATE: May 28, 2010 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newsletter Copyright 1998 AHC Media LLC All Rights Reserved 955 of 998 DOCUMENTS The Practitioner April 1998 New product information SECTION: Pg. 314 LENGTH: 223 words PROVIGIL (Modafinil, Cephalon UK) Modafinil is a non-amphetamine wake promoting agent used for the treatment of narcolepsy. It is also a non-controlled drug. Phase III clinical trials show that treatment with the non-controlled modafinil reduces all measures of sleepiness on physiological and clinical scales, as well as patients' own self-assessments of sleepiness, without affecting night-time sleep. Cephalon UK, tel 0800 783 4869. COLAZIDE (Balsalazide, Astra Pharmaceuticals) Balsalazide provides faster symptom relief and complete remission in a greater proportion of patients with ulcerative colitis than delayed- release mesalazine, according to studies. Improved rates of sigmoidoscopic healing have also been shown. Balsalazide may be a suitable alternative for patients who fail mesalazine therapy, says the manufacturer. Astra Pharmaceuticals, tel 01923 266191. MUSE (Alprostadil, Astra Pharmaceuticals) The Medicated Urethral System for Erection or MUSE? is a sterile single- use transurethral system thatdelivers alprostadil directly to the male urethra. In the form of a small pellet (1.4mm across by 3mm or 6mm in length depending on the strength) contained in a narrow applicator, the treatment is inserted by pressing a button on theapplicator. Astra Pharmaceuticals, tel 01923 266191. LOAD-DATE: September 22, 1998 LANGUAGE: English PUB-TYPE: Magazine Copyright 1998 CMP Information Ltd 956 of 998 DOCUMENTS Pharma Marketletter March 5, 1998 Cephalon's Provigil Launched In UK LENGTH: 155 words Cephalon has launched Provigil (modafinil) in the UK for the treatment of narcolepsy. This represents the first nonamphetamine-based therapy for this indication to be made available in the UK and is the first narcolepsy drug to be approved there for 40 years. The recommended daily dose of modafinil is 200mg-400mg to be taken as two divided doses in the morning and at noon, or as a single dose in the morning. The cost to the National Health Service is L60 ($ 98.78) for 30 x 100mg tablets, said a spokesperson for the company. Modafinil has been available in France, under the brand name Modiodal, through originator Laboratoire Lafon since 1994. Cephalon has exclusive marketing rights in Japan, Mexico, Italy, Ireland and the USA, and marketing applications are pending in the latter two countries. In December last year, the company received an "approvable" letter from the US Food and Drug Administration. LOAD-DATE: November 22, 2002 LANGUAGE: ENGLISH Copyright 1998 Marketletter Publications Ltd. 957 of 998 DOCUMENTS The Independent (London) March 4, 1998, Wednesday Wonder wake-up boosts alertness BYLINE: Jeremy Laurance Health Editor SECTION: NEWS; Page 6 LENGTH: 439 words A WAKE-UP pill that increases alertness and boosts memory in people who are sleep-deprived was launched yesterday. It is more effective than coffee but lacks the side-effects of amphetamine-based stimulants. But it will not be available to party-goers, students or armies preparing for a long march - yet. Modafinil is a new pharmacological compound with a unique effect on the brain that is not fully understood. It has been licensed in the UK as a treatment for narcolepsy, a rare disorder marked by an intense and overwhelming need to sleep that can strike at any time. Surveys show a third of people get less sleep than they need, which is blamed on the invention of electricity. By extending the waking day, modafinil could provide the pharmaceutical equivalent of the electric light bulb. Unlike amphetamines, which stimulate the nervous system, modafinil appears to target the hypothalamus, the area of the brain thought to be responsible for wakefulness. Tests in normal volunteers have shown it boosts cognitive performance, especially memory, and reaction times in the sleep-deprived. Its main advantage over amphetamines is that it does not produce the euphoria associated with those drugs and is thought not to be addictive. Yet tests on normal volunteers show it can keep people going through the night without causing rebound depression or sleepiness. Dr Colin Markland, medical director of Cephalon UK, which is marketing the drug, to be called Provigil, in Britain, said there were no plans to explore its potential as an alertness pill. "All our activities have been in the area of narcolepsy. If we wanted to seek another indication for the drug we would have to go back and conduct other studies." Military organisations in France, where the drug was first licensed in 1994, the US and Britain are understood to have shown interest. There would be an obvious military advantage in a pill that could help armies fight through the day and march through the night. Dr Markland that in the four years the drug had been available in France there had been no evidence of abuse but this would be monitored in Britain. It is available on prescription only and costs pounds 60 for 30 tablets of 100g. The normal dose for treating narcolepsy would be 200g to 400g a day, costing up to almost pounds 3,000 a year. If proved safe and effective, modafinil might become a treatment for jet-lag or for disrupted sleep caused by shift work. But by far its biggest potential market could be in the treatment of insomnia - by preventing sleep during the day and thus promoting it at night. LOAD-DATE: March 04, 1998 LANGUAGE: ENGLISH Copyright 1998 Independent Print Ltd 958 of 998 DOCUMENTS PR Newswire March 4, 1998, Wednesday - 08:38 Eastern Time Cephalon Launches PROVIGIL(R) (modafinil) in the United Kingdom. SECTION: Financial News LENGTH: 557 words DATELINE: WEST CHESTER, Pa., March 4 Cephalon, Inc. (Nasdaq: CEPH) announced today the availability of PROVIGIL(R) ( modafinil) tablets in the United Kingdom for the treatment of narcolepsy. The drug will be marketed to sleep specialists and neurologists in the United Kingdom by Cephalon's U.K. subsidiary, which is based in Guildford, England. "As the first non-amphetamine treatment for narcolepsy available in the U.K., PROVIGIL offers patients a new therapeutic alternative for the management of daytime sleepiness associated with this debilitating disease," said Frank Baldino, Jr., Ph.D., Cephalon's president and chief executive officer. "The launch of PROVIGIL demonstrates our continued commitment to the sleep community." Dr. Adrian Williams, Director of the Sleep Disorders Center at St. Thomas' Hospital in London describes the introduction of PROVIGIL as "a major step forward in the treatment of narcolepsy. It is very exciting to be able to offer patients a novel, effective and well tolerated medicine." Narcolepsy is a chronic, neurological, lifelong sleep disorder that generally begins in young adulthood. The most common symptom is excessive daytime sleepiness, which is characterized by uncontrollable sleep attacks. These attacks hamper a person's ability to perform basic daily activities. As a result, narcolepsy significantly impacts a person's quality of life. The most commonly observed adverse experiences associated with the use of PROVIGIL, which occurred more frequently than placebo were: headache, nausea and diarrhea. Cephalon licensed modafinil from Laboratoire L. Lafon, the French pharmaceutical company which discovered and markets the drug in France. Cephalon has exclusive rights to market modafinil in the United States, Japan, the United Kingdom, Ireland, Mexico and Italy. Cephalon has a marketing application currently pending in the United States to market PROVIGIL for the treatment of excessive daytime sleepiness associated with narcolepsy. In December 1997, Cephalon received a letter from the U.S. FDA indicating that the company's application is approvable, upon the satisfactory completion of product labeling and response to the agency's comments. A marketing application is also pending in Ireland. Cephalon, Inc., headquartered in West Chester, PA, is an international biopharmaceutical company that discovers, develops and markets products to treat neurological disorders.     This news release may contain forward-looking statements that involve risks and uncertainties.  A full discussion of Cephalon's operations and financial condition, including factors that may affect the company's business and future prospects, is contained in documents the company files with the SEC, such as form 10-Q and 10-K reports.  These documents identify important factors that could cause the company's actual performance to differ from current expectations.     NOTE:  Cephalon's press releases are available by fax 24 hours a day at no charge by calling PR Newswire's Company News On-Call at 800-758-5804, extension 134563.  They are also posted on the Internet at http://www.prnewswire.com. SOURCE  Cephalon, Inc.      CONTACT: U.S., Kori Beer of Cephalon, 610-738-6532, or Europe, Jacinta Collins of Sante Communications, 011-44-171-379-7377 LOAD-DATE: March 5, 1998 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS EDITOR Copyright 1998 PR Newswire Association, Inc. 959 of 998 DOCUMENTS Reuters Health Medical News March 4, 1998 Wednesday UK Medicines Control Agency Approves Modafinil For Narcolepsy SECTION: REGULATORY LENGTH: 222 words DATELINE: LONDON Mar 4 Britain's Medicines Control Agency has approved modafinil (Provigil) for treatment of narcolepsy in the UK, according to Cephalon UK Ltd. Modafinil was developed by the private French company, Laboratoire Louis Lafon, which launched the drug in France in 1994. Britain is the second European country to market the medication, officials from Cephalon said at a news briefing on Tuesday. "This drug is the first alternative to amphetamines and amphetamine-like drugs. It is the only drug specifically developed for the treatment of narcolepsy," Dr. Colin G. Markland, medical director of Cephalon UK, told the briefing. Cephalon has received rights from Lafon to market the drug in Britain as well as in the US, Mexico, Japan, Ireland and Italy, according to Jason Rubin, vice president for corporate communications of Cephalon, Inc. Company officials said that they expect the medication to be approved by the Food and Drug Administration in late spring or early summer. The Medicines Control Agency has licensed modafinil in tablet form at a dosage of 100 mg per tablet. For adults, the recommended daily dose is 200-400 mg. "Provigil may be taken as two divided doses in the morning and at noon, or as a single dose in the morning according to physician assessment of the patient and the patient's response," the agency said in a statement. LOAD-DATE: July 9, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 1998 Reuters Health All Rights Reserved 960 of 998 DOCUMENTS Pharma Marketletter October 23, 1997 Provigil Cleared In UK LENGTH: 101 words Cephalon has been granted a license to market its narcolepsy drug Provigil ( modafinil) in the UK. This is first time that Cephalon has had a product approved, and the company said it planned to launch it as soon as manufacturing arrangements are finalized with the UK authorities. Modafinil is the first narcolepsy drug to be approved there for 40 years. Cephalon licenses modafinil from the French firm Laboratoires Lafon (which already sells it in its home market) for sale in the UK, Japan, Mexico, the USA and Ireland, and marketing applications are pending in the latter two countries. LOAD-DATE: January 7, 2003 LANGUAGE: ENGLISH Copyright 1997 Marketletter Publications Ltd. 961 of 998 DOCUMENTS PR Newswire October 20, 1997, Monday - 10:38 Eastern Time Cephalon Granted Approval to Market Provigil in the United Kingdom SECTION: Financial News LENGTH: 500 words DATELINE: WEST CHESTER, Pa., Oct. 20 Cephalon, Inc. (Nasdaq: CEPH) announced today that its U.K. subsidiary has been granted a license by the Medicines Control Agency (MCA) to market PROVIGIL(R) ( modafinil) Tablets in the United Kingdom for the treatment of narcolepsy. Narcolepsy is a chronic, lifelong sleep disorder that generally begins in young adulthood. The most common symptom is excessive daytime sleepiness, which is characterized by uncontrollable sleep attacks. These attacks hamper a person's ability to perform basic daily activities. As a result, narcolepsy significantly impacts a person's quality of life. Currently, amphetamines are the only agents licensed to treat this disease in the United Kingdom. Modafinil is a novel, non-amphetamine agent that Cephalon is developing for the treatment of excessive daytime sleepiness associated with narcolepsy under a license from Laboratoire L. Lafon, the French pharmaceutical company which discovered and currently markets the drug in France. Cephalon has exclusive rights to market modafinil in the United States, Japan, the United Kingdom, Ireland and Mexico. Marketing applications are currently pending in the United States and Ireland. Cephalon intends to manufacture PROVIGIL tablets in the United States and launch the drug in the United Kingdom upon MCA approval of these manufacturing arrangements. "The receipt of the company's first product license is an important milestone for Cephalon," said Frank Baldino, Jr., Ph.D., Cephalon's president and chief executive officer. "PROVIGIL is the first new therapy to treat narcolepsy in the United Kingdom in over 40 years. Our U.K. sales and marketing organization has been established and is enthusiastic about bringing PROVIGIL to the neurology community for patients suffering from this debilitating disease." Cephalon, Inc., headquartered in West Chester, PA, is an international biopharmaceutical company that discovers, develops and markets products to treat neurological disorders. The company is developing products for the treatment of ALS, narcolepsy, peripheral neuropathies, Alzheimer's disease and stroke, and currently copromotes three products in the United States for the treatment of neurological conditions. This news release may contain forward-looking statements that involve risks and uncertainties. A full discussion of Cephalon's operations and financial condition, including factors that may affect the company's business and future prospects, is contained in documents the company files with the SEC, such as form 10-Q and 10-K reports. These documents identify important factors that could cause the company's actual performance to differ from current expectations. NOTE: Cephalon's press releases are available by fax 24 hours a day at no charge by calling PR Newswire's Company News On-Call at 800-758-5804, extension 134563. They are also posted on the Internet at http://www.prnewswire.com SOURCE  Cephalon, Inc.      CONTACT: Jason Rubin of Cephalon, 610-738-6302, or U.K. media, Liz Shanahan of Sante Communications, 0171-379-7377, for Cephalon LOAD-DATE: October 21, 1997 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS EDITOR Copyright 1997 PR Newswire Association, Inc. 962 of 998 DOCUMENTS Manufacturing Chemist June 1997 CENTRAL STIMULANT - MODAFINIL SECTION: Pg. 41 LENGTH: 277 words Narcolepsy is an uncommon condition characterised by recurrent, unpredictable and irresistible episodes of sleep, often with hallucinations and muscle weakness. The attacks may occur several times a day, and are similar to those that occur in idiopathic daytime sleepiness. These conditions have not always been recognised, and it is thought that they may be the cause of some otherwise inexplicable motoring and industrial accidents. For treatment, reliance has been placed on the amphetamines and methylphenidate, which are effective but carry the risk of inducing drug dependence. A new alternative is modafinil. * Although its action is not yet fully understood, it is known to differ from that of other central stimulants. It is thought to decrease the brain level of the neurotransmitter GABA, but its action probably involves the serotonic and adrenergic receptor systems. In clinical studies, modafinil was given in morning doses of 200mg, which brought about a significant reduction in the frequency of sleep attacks in narcoleptic patients as well as improved alertness during the first part of the day. Sudden withdrawal of the drug after a course of treatment did not result in any symptoms of drug dependence. The amount and quality of night-time sleep remained unaffected, so modafinil appears to be a distinct advance in the treatment of narcolepsy and idiopathic hypersomnia. It enables patients to play a more normal part in social and occupational activities, and further studies are in progress to assess the possible value of the drug in Parkinson's disease and sleep apnoea. Drugs of Today 23 (Suppl. 1) LOAD-DATE: November 11, 1997 LANGUAGE: English PUB-TYPE: Magazine Copyright 1997 CMP Information Ltd 963 of 998 DOCUMENTS Pharma Marketletter January 13, 1997 Cephalon Files Modafinil Application In USA LENGTH: 276 words US biopharmaceutical company Cephalon Inc has now filed a New Drug Application with the US Food and Drug Administration for marketing approval of modafinil, its treatment for excessive daytime sleepiness associated with narcolepsy. Modafinil was discovered by the French company Laboratoire Lafon, which has granted exclusive marketing rights to Cephalon for the USA, Japan, the UK, Ireland and Mexico. It is already approved and marketed in France for the treatment of narcolepsy and idiopathic hypersomnia. The FDA submission contains results of 14 clinical trials with modafinil conducted by Cephalon, including two double-blind, placebo-controlled Phase III studies involving 558 patients with narcolepsy. The Phase III studies were conducted at 39 sleep centers in the USA and were designed to assess the patient's ability to stay awake using a number of laboratory and clinical measures. The studies also measured the patient's well-being, as assessed by an independent clinician, and the patient's quality of life. First NDA Filing By Cephalon For Cephalon this is an important milestone, according to its president and chief executive, Frank Baldino; it is the company's first NDA filing. Dr Baldino also noted: "to our knowledge, this is the most comprehensive clinical investigation ever undertaken in the study of narcolepsy." Narcolepsy, a chronic, lifelong sleep disorder, affects around 125,000 people in the USA alone. Therapies to treat excessive daytime sleepiness associated with the disease have been limited to amphetamine and other stimulants. Modafinil was designated an orphan drug by the FDA in March 1993. LOAD-DATE: January 7, 2003 LANGUAGE: ENGLISH Copyright 1997 Marketletter Publications Ltd. 964 of 998 DOCUMENTS Reuters Health Medical News January 1, 1997 Wednesday Cephalon Submits NDA For Narcolepsy Drug SECTION: REGULATORY LENGTH: 174 words DATELINE: WESTPORT Jan 1 Cephalon, based in West Chester, PA, announced yesterday that it has filed an NDA with the FDA for clearance to market modafinil. Modafinil is designed to treat patients with excessive daytime sleepiness associated with narcolepsy. According to a company press release posted on PR Newswire, the NDA contained data from 14 clinical studies of modafinil. Dr. Frank Baldino, Jr., president and CEO of Cephalon, said, "As our first NDA submission, this event marks an important milestone for Cephalon. To our knowledge, this is the most comprehensive clinical investigation ever undertaken in the study of narcolepsy." The drug was developed by French pharmaceutical firm Laboratoire L. Lafon, which currently markets modafinil in France to treat patients with narcolepsy and idiopathic hypersomnia. Cephalon has exclusive rights to market the drug in the U.S., U.K., Ireland, Mexico and Japan. According to Cephalon, if modafinil is approved for marketing in the U.S., it would be the first new chemical entity for narcolepsy in more than 20 years. LOAD-DATE: July 9, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 1997 Reuters Health All Rights Reserved 965 of 998 DOCUMENTS PR Newswire December 31, 1996, Tuesday - 08:01 Eastern Time Cephalon Submits New Drug Application For Modafinil to U.S. Food and Drug Administration SECTION: Financial News LENGTH: 599 words DATELINE: WEST CHESTER, Pa., Dec. 31 Cephalon, Inc. (Nasdaq: CEPH) announced today that the company has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration for clearance to market modafinil for use in treating excessive daytime sleepiness associated with narcolepsy. The NDA contains results of 14 clinical studies with modafinil conducted by Cephalon, including two double-blind, placebo-controlled multicenter Phase 3 trials involving 558 patients with narcolepsy. The Phase 3 studies were conducted at 39 sleep centers in the United States and were designed to assess the patient's ability to stay awake using a number of laboratory and clinical measures. The studies also measured the patient's overall well-being, as assessed by an independent clinician, and the patient's quality of life. "As our first NDA submission, this event marks an important milestone for Cephalon," said Frank Baldino, Jr., Ph.D., Cephalon's president and chief executive officer. "To our knowledge, this is the most comprehensive clinical investigation ever undertaken in the study of narcolepsy. We are grateful to the patients who participated in these studies, and appreciate the dedication of the physicians and Cephalon employees who are working to improve the lives of patients with this chronic and debilitating disease." Modafinil is a novel oral medication that is approved and marketed in France for the treatment of narcolepsy and idiopathic hypersomnia. Cephalon received exclusive rights to market modafinil in the United States, Japan, the United Kingdom, Ireland and Mexico from Laboratoire L. Lafon, the French pharmaceutical company which developed and currently markets the drug in France. If approved in the United States, modafinil would be the first new chemical entity available to treat narcolepsy in more than 20 years. Narcolepsy is a chronic, lifelong sleep disorder afflicting approximately 125,000 people in the United States. The most common symptom is excessive daytime sleepiness. Narcolepsy generally begins in young adulthood. Therapies to treat the excessive daytime sleepiness associated with the disease have been limited to amphetamine and other stimulants. The FDA designated modafinil an orphan drug in March 1993 for the treatment of excessive daytime sleepiness in narcolepsy. Cephalon is an international biopharmaceutical company that discovers, develops and markets products to treat neurological disorders. The company is developing products for the treatment of ALS, narcolepsy, peripheral neuropathies, Alzheimer's disease, head and spinal injury, and stroke, and currently copromotes two products in the United States for the treatment of neurological conditions. This news release may contain forward-looking statements that involve risks and uncertainties. The results of the modafinil clinical trials have not been reviewed by the FDA and there can be no assurance that the FDA will consider that these results demonstrate sufficient safety and efficacy data to allow the filing of an NDA to obtain marketing clearance or if the filing is allowed, to obtain marketing clearance. A full discussion of Cephalon's operations and financial condition, including factors that may affect the company's business and future prospects, is contained in documents the company files with the SEC, such as form 10-Q and 10-K reports.  These documents identify important factors that could cause the company's actual performance to differ from current expectations. SOURCE  Cephalon, Inc.      CONTACT: Jason Rubin or Kori Beer of Cephalon, 610-344-0200 LOAD-DATE: January 1, 1997 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS EDITOR Copyright 1996 PR Newswire Association, Inc. 966 of 998 DOCUMENTS Financial Post Daily August 9, 1996 Draxis files for use of sleep-disorder drug SECTION: Pg. v.9(108) August 9, 1996 pg 47 LENGTH: 89 words Pharmaceutical company Draxis Health has filed a new drug submission with Canada's health protection branch to market the sleep disorder drug Modafinil. In February, Draxis reported statistically significant results for its clinical study of the drug in treatment of narcolepsy, which affects 0.05% to 0.1% of Canadians. No new drug for narcolepsy had been approved in Canada since 1959. Modafinil is used in France, and Draxis has an exclusive licence from Laboratoire L. Lafon to market and sell the product in Canada. *** END OF DOCUMENT *** LOAD-DATE: July 08, 1999 LANGUAGE: ENGLISH ACC-NO: 3680885 DOCUMENT-TYPE: Fulltext; News article PUBLICATION-TYPE: Other JOURNAL-CODE: 0341 Copyright 1996 Micromedia Limited All Rights Reserved Canadian Business and Current Affairs 967 of 998 DOCUMENTS Canada NewsWire August 8, 1996, Thursday   DRAXIS FILES NEW DRUG SUBMISSION FOR MODAFINIL IN CANADA SECTION: Financial News LENGTH: 481 words DATELINE: TORONTO, Aug. 8 DRAXIS Health Inc. (Toronto Stock Exchange: DAX; Nasdaq: DRAXF) today announced that it has filed a New Drug Submission with Canada's Health Protection Branch to market Modafinil in Canada for use in treating narcolepsy, a sleep disorder characterized by uncontrolled episodes of falling asleep at unexpected times or in unexpected circumstances.  In February 1996 DRAXIS reported statistically significant results for its one-year-long, double-blind, randomized, placebo-controlled, cross-over clinical study of 200 milligram and 400 milligram dosages of Modafinil in the treatment of narcolepsy. The primary sleep disorder affects approximately 0.05 percent to 0.1 percent of the population or approximately 14,800 to 29,600 Canadians. No new treatment for narcolepsy has been approved in Canada since 1959.  "We are very excited about the prospects for Modafinil," Dr. Martin Barkin, M.D., stated in making the announcement. "Our clinical trials showed that Modafinil produced a highly statistically significant benefit in reducing excessive daytime sleepiness in patients with narcolepsy and had a good tolerance profile. We also believe that Modafinil has a low potential for abuse, which gives it a further advantage. Subject to receiving health regulatory approval, Modafinil will be a significant addition to the DRAXIS line of neurological products."  Modafinil is approved for the treatment of narcolepsy in France. DRAXIS has an exclusive license from Laboratoire L. Lafon to market and sell Modafinil in Canada. The licensee for the United States, United Kingdom and Japan is Cephalon Inc.(Nasdaq: CEPH). DRAXIS Health Inc., based in Toronto, is an emerging Canadian pharmaceutical company focused on neurological, dermatological and veterinary markets in Canada and the United States. Products under development include Modafinil for narcolepsy and proprietary liposomed topical products for both the prescription and over-the-counter markets. The company's U.S. units include a division offering products exclusively to podiatrists and a 50 percent interest in a consumer products company specializing in cosmeceuticals and nutriceuticals. DRAXIS holds a controlling interest in Deprenyl Animal Health, Inc. (TSE: DAH; Nasdaq OTC Bulletin Board: DAHI), which has filed for U.S. approval of its proprietary compound Aniprylr for canine Cushing's disease.  Factors that could cause forward-looking statements in this news release to differ materially from actual results are discussed in the company's Form 20F and other periodic filings with the U.S. Securities and Exchange Commission and Canada's securities authorities.  To receive additional information on DRAXIS Health Inc., via fax at no charge, dial 1-800-PRO-INFO and enter code DRAXF.     SOURCE  Draxis Health, Inc.     -30- For further information: Dr. Martin Barkin, M.D., DRAXIS Health Inc. (905) 677-5500, or U.S. Investor Relations: The Financial Relations Board -- Jeffrey D. Bogart, (212) 661-8030, or Canadian Investor Relations: Small-Cap Equity Investor Relations Ltd. -- Robert Grahovar, (416) 368-7459 LOAD-DATE: August 8, 1996 LANGUAGE: ENGLISH Copyright 1996 Canada NewsWire Ltd. 968 of 998 DOCUMENTS PR Newswire August 8, 1996, Thursday - 09:28 Eastern Time Draxis Files New Drug Submission for Modafinil in Canada SECTION: Financial News LENGTH: 476 words DATELINE: TORONTO, Aug. 8 DRAXIS Health Inc. (Toronto Stock Exchange: DAX; Nasdaq: DRAXF) today announced that it has filed a New Drug Submission with Canada's Health Protection Branch to market Modafinil in Canada for use in treating narcolepsy, a sleep disorder characterized by uncontrolled episodes of falling asleep at unexpected times or in unexpected circumstances. In February 1996 DRAXIS reported statistically significant results for its one-year-long, double-blind, randomized, placebo-controlled, cross-over clinical study of 200 milligram and 400 milligram dosages of Modafinil in the treatment of narcolepsy. The primary sleep disorder affects approximately 0.05 percent to 0.1 percent of the population or approximately 14,800 to 29,600 Canadians. No new treatment for narcolepsy has been approved in Canada since 1959. "We are very excited about the prospects for Modafinil," Dr. Martin Barkin, M.D., stated in making the announcement. "Our clinical trials showed that Modafinil produced a highly statistically significant benefit in reducing excessive daytime sleepiness in patients with narcolepsy and had a good tolerance profile. We also believe that Modafinil has a low potential for abuse, which gives it a further advantage. Subject to receiving health regulatory approval, Modafinil will be a significant addition to the DRAXIS line of neurological products." Modafinil is approved for the treatment of narcolepsy in France. DRAXIS has an exclusive license from Laboratoire L. Lafon to market and sell Modafinil in Canada. The licensee for the United States, United Kingdom and Japan is Cephalon Inc.(Nasdaq: CEPH). DRAXIS Health Inc., based in Toronto, is an emerging Canadian pharmaceutical company focused on neurological, dermatological and veterinary markets in Canada and the United States. Products under development include Modafinil for narcolepsy and proprietary liposomed topical products for both the prescription and over-the-counter markets. The company's U.S. units include a division offering products exclusively to podiatrists and a 50 percent interest in a consumer products company specializing in cosmeceuticals and nutriceuticals. DRAXIS holds a controlling interest in Deprenyl Animal Health, Inc. (TSE: DAH; Nasdaq OTC Bulletin Board: DAHI), which has filed for U.S. approval of its proprietary compound Aniprylr for canine Cushing's disease. Factors that could cause forward-looking statements in this news release to differ materially from actual results are discussed in the company's Form 20F and other periodic filings with the U.S. Securities and Exchange Commission and Canada's securities authorities. To receive additional information on DRAXIS Health Inc., via fax at no charge, dial 1-800-PRO-INFO and enter code DRAXF. SOURCE  Draxis Health, Inc.      CONTACT: Dr. Martin Barkin, M.D., DRAXIS Health Inc. 905-677-5500, or U.S. Investor Relations: The Financial Relations Board -- Jeffrey D. Bogart, 212-661-8030, or Canadian Investor Relations: Small-Cap Equity Investor Relations Ltd. -- Robert Grahovar, 416-368-7459 LOAD-DATE: August 9, 1996 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS EDITOR Copyright 1996 PR Newswire Association, Inc. 969 of 998 DOCUMENTS Biotechnology Newswatch August 5, 1996 Narcolepsy research gets wake-up call: first new drug in two decades BYLINE: By Steve Carrell SECTION: Pg. 13 LENGTH: 346 words The first new narcolepsy treatment in more than two decades made a solid showing in studies presented at the recent Association of Professional Sleep Societies (APSS) convention. The results triggered a publicity wave lasting weeks after researchers presented results of their multi-center studies on modafinil (Provigil). The next news on Cephalon, Inc.'s drug may come when the firm files modafinil's New Drug Application, probably late this year. Narcolepsy affects an estimated 125,000 people nationwide. But there's widespread agreement the ailment is under-diagnosed, and the lag between onset and diagnosis often spans 10 years. So the actual patient population could be 250,000 or more, said Marguerite Utley, a board member of the Cincinnati-based Narcolepsy Network. Cephalon showcased the material at a company-sponsored symposium during the busy meeting, which is the combined conventions of the American Sleep Disorders Association and the Sleep Research Society. U.S. researchers presented partial results of two Phase III trials with a total of 558 patients. Discussants covering results of the first trial included principal investigator Merrill Mitler, director of sleep research at the Scripps Clinic and Research Foundation in La Jolla, Calif. Cephalon officials summarized the second study during a briefing for stock analysts. In the studies, modafinil kept patients awake 50 percent to 75 percent longer than placebo, as measured by the Mean Wakefulness Time (MWT) test. On the physicians' Clinical Global Impressions scale, modafinil patients scored 20 - 40 points higher than placebo patients. Both tests produced statistically significant and clinically meaningful scores, researchers said. Speakers at the symposium also noted that side effects, mainly headache, were minimal and easily controllable and abuse potential is low. Such data helped make Cephalon a ''strong buy'' recommendation, said stock analyst Joyce Lonergan, who attended the meetings. She works for the investment banking firm Cowen & Co. in Boston. URL: http://www.platts.com LOAD-DATE: August 27, 1996 LANGUAGE: ENGLISH Copyright 1996 McGraw-Hill Inc. 970 of 998 DOCUMENTS The New York Times June 11, 1996, Tuesday, Late Edition - Final Research Suggests Sleep Seizures May Be Linked to Immune System BYLINE: By WARREN E. LEARY SECTION: Section C;   Page 3;   Column 4;   Science Desk;   Medical Science Page LENGTH: 1590 words DATELINE: WASHINGTON AFTER decades of slow progress in understanding narcolepsy, a disorder characterized by sudden seizures of sleepiness, researchers say it may be linked to the immune system and may also be as prevalent in women as it is in men. Scientists say they are beginning to see narcolepsy as a disorder with both genetic and environmental components, even though the exact cause remains unknown. Studies of identical twins, for example, indicate that in only about 20 percent of cases do both develop narcolepsy. This, experts say, indicates the incurable condition must be triggered by some environmental factors. Research with humans and animals also suggests that the condition may involve genetic factors. And although no one has proved it, some suggest that narcolepsy may be a type of autoimmune disease, in which the body attacks some part of itself, that is unlike any other form of that disorder. Dr. Emmanuel Mignot, director of the Stanford University Center for Narcolepsy, said Japanese scientists first discovered a gene associated with the condition. That gene was near a location for another gene for a human leucocyte antigen, or H.L.A. Other H.L.A. genes, which are involved with control of the immune system, were identified at Stanford to have an association with narcolepsy. However, while these H.L.A. genes are found in more than 95 percent of narcolepsy patients, and serve as markers to help diagnose the disease, experts said, they also are found in 25 percent of those without the disease. Finding an H.L.A. association suggests that the immune system is involved in the pathology of the disease, or that an unidentified susceptibility gene is situated very close to the H.L.A. gene, Dr. Mignot said. "Most diseases with an H.L.A. association are autoimmune by nature, but all attempts to prove narcolepsy is an autoimmune disease have failed," Dr. Mignot said in an interview. "It looks like an autoimmune disease, but does not manifest itself as one. I believe it is a new type of autoimmune disease that may affect a very limited area of the brain, but there is no proof -- yet." The best animal models for narcolepsy are dogs, some of which naturally develop a form of the disease that appears almost identical to the human variety. A colony of 30 narcoleptic Doberman pinschers at Stanford is the largest in the country. Dogs have leucocyte antigen genes similar to those in humans. Those genes in the narcoleptic Dobermans also did not appear to be involved with the canine disease, Stanford researchers said. However, they said, studies indicate the canine narcolepsy gene is linked with a gene that may be responsible for switching on antibodies, another indication that the immune system is involved. While research continues on the basic science of narcolepsy, doctors treating the condition are excited about a new drug that appears to help patients stay alert without being a stimulant. Modafinil, being developed under the name Provigil by Cephalon Inc. of West Chester, Pa., appears to help patients stay awake with far fewer side effects than current drugs, researchers say. At the annual meeting of the Associated Professional Sleep Societies this month in Washington, researchers reported that a clinical trial of modafinil at 21 medical centers in the nation showed the drug to be "significantly effective." The 273 narcoleptic patients involved took the drug once a day in doses of 200 or 400 milligrams or received a dummy pill for nine weeks followed by a two-week observation period. Laboratory tests showed patients taking modafinil stayed awake at least 50 percent longer than those receiving the dummy drug, researchers said. Patient evaluations by independent doctors not participating in the study indicated that 60 percent of patients receiving the higher dose and 57 percent of those on the lower-dose regimen showed improvement in disease symptoms, as against 37 percent for those taking the fake drug. The company, which said the results were similar to those of an earlier trial conducted with 285 patients at 18 centers, said it would review the results with the Food and Drug Administration and apply to market the drug in the United States. In 1993, the Food and Drug Administration designated modafinil as an orphan drug, one given special licensing protection to encourage its development for a condition for which there is not a large market. Dr. June M. Fry of the Medical College of Pennsylvania and Hahnemann University, in Philadelphia, called it "exciting that we are on the brink of a new medication for our patients." Modafinil was not tested in the most severe cases and may not work for everyone, said Dr. Fry, a leader in the study. Dr. Dale M. Edgar of Stanford University Medical School, another principal in the study, said no one was sure how modafinil worked. But the drug, developed in France, is not like the amphetamine-like stimulants most often used now. Even with progress in basic research and treatment, narcolepsy researchers say progress is being hampered by a shortage of research money and a lack of understanding of how devastating narcolepsy can be to sufferers. "Narcolepsy is a significant problem and is often a disabling disease," said Dr. Michael S. Aldrich, director of the University of Michigan's Sleep Disorders Center in Ann Arbor. "But because it involves sleep, which people see as benign, and doesn't cause death or put people in wheelchairs, its been underemphasized." Experts say the Federal Government only spends about $2.5 million a year on research into narcolepsy, which afflicts 125,000 to 250,000 Americans. That is less than one-tenth the amount for multiple sclerosis, which afflicts about as many people. People with narcolepsy, who are constantly tired and easily fatigued, have bouts of excessive daytime sleepiness lasting from a few seconds to more than 30 minutes. They fall asleep not only in normally restful situations, but also at inappropriate times, sometimes during conversations or while driving a car. In up to 80 percent of cases, these sleep seizures are accompanied by a decrease or loss of muscle control called cataplexy, which can cause the head or jaw to droop or the whole body to collapse, the National Sleep Foundation says. Narcoleptics also experience hypnagogic hallucinations, dreamlike visual and auditory hallucinations that come on quickly while dozing and falling asleep. More than 60 percent of narcoleptics also suffer with bouts of sleep paralysis, a frightening symptom that keeps a patient from moving for several minutes, often upon falling to sleep or awaking. Narcolepsy has an incidence of 1 to 2 cases per 2,000 people in the United States, Europe and Japan. Symptoms generally begin to appear between the onset of puberty and the age of 25 and the chronic condition gets progressively worse. Specialists say diagnosis and initial treatment are often delayed for years because patients and doctors do not readily recognize daytime sleepiness as a sign of disease. Until as recently as five years ago, many believed narcolepsy was four times more common in men than women. However, while some experts still believe men are slightly more susceptible than women, most specialists now believe the wide gender gap never existed. Dr. Meeta Goswami, director of the Narcolepsy Institute at Montefiore Medical Center in the Bronx, and other experts say the condition is most noticeable in the workplace and until more women started working outside the home, many female sufferers were missed. The psychological and social consequences of narcolepsy can be severe, experts said, and are usually worse the later it takes to diagnose the problem. "Those who are diagnosed early know they have a treatable disease and adjust for it," said Dr. Goswami, whose center has state financing to offer support services to narcoleptics throughout New York City. "People who have gone for years not knowing what was wrong tend to have low self-esteem, feelings of hopelessness and worthlessness, and social problems. Major social consequences of narcolepsy include a higher-than-normal divorce rate and clinical depression, which has to be treated separately." People who are not familiar with narcolepsy often interpret the symptoms as signs sufferers are uninterested, disrespectful or lazy, which can be detrimental to careers and social lives, Dr. Goswami said. Dr. Merrill M. Mitler, director of sleep research at the Scripps Clinic and Research Center in San Diego, said most patients with narcolepsy were successfully treated with amphetamine-like compounds such as methylphenidate and dextroamphetamine, or other stimulants, like Pemoline and Ritalin, to ward off sleepiness. Many patients also receive antidepressant drugs to counteract cataplexy, hallucinations and sleep paralysis. More than 80 percent of patients can be successfully treated with drugs that sharply reduce their symptoms, Dr. Mitler said, but doses may have to be modified or medications changed over time as their bodies get used to the treatments. Dr. Aldrich, of the University of Michigan, said some patients also responded to sleep therapy along with drugs. With this, doctors prescribe a sleep regimen of set bedtimes and daytime naps which helps some patients get through the day with fewer unexpected sleep episodes. "Naps can't be the whole answer, but sometimes they can help," he said, "Narcoleptics do worse if they don't get enough sleep. It just compounds the problem." LOAD-DATE: June 11, 1996 LANGUAGE: ENGLISH GRAPHIC: Photo: Emotional excitement induces cataplexy, a rapid eye movement sleep with muscle relaxation, in both human and canine narcolepsy. When a narcoleptic dog like this Doberman pinscher is excited by food, the most powerful emotional stimulus for dogs, a cataplectic attack occurs, and the dog finally collapses (lower right). (Courtesy of the Sleep Disorder Center, Stanford University) Copyright 1996 The New York Times Company 971 of 998 DOCUMENTS Pharma Marketletter March 25, 1996 Positive Results From Second PhII Modafinil Study LENGTH: 63 words Cephalon of the USA has reported positive results from its second Phase III study of Provigil (modafinil), the narcolepsy treatment licensed from Lafon of France. The 273-patient study found that modafinil was able to increase patients' ability to stay awake, measured by the maintenance of wakefulness test and clinical global impression of change, compared to placebo. LOAD-DATE: January 7, 2003 LANGUAGE: ENGLISH Copyright 1996 Marketletter Publications Ltd. 972 of 998 DOCUMENTS Reuters Health Medical News March 15, 1996 Friday [] - Cephalon Says Modafinil Effective In Patients With Narcolepsy LENGTH: 108 words DATELINE: WEST CHESTER, Pa. Mar 14 Cephalon Inc said on Thursday that results from its second Phase III clinical trial of its modafinil product, Provigil, in patients with narcolepsy showed that Provigil increased patients' ability to stay awake. Cephalon said the results follow positive findings from its first U.S. Phase III clinical study of Provigil. Cephalon is planning to review the findings of both Phase III studies with the FDA and to submit a New Drug Application to the agency for clearance to market Provigil in the United States. The FDA designated modafinil an orphan drug in March, 1993, for the treatment of excessive daytime sleepiness in patients with narcolepsy. LOAD-DATE: July 9, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 1996 Reuters Health All Rights Reserved 973 of 998 DOCUMENTS PR Newswire March 14, 1996, Thursday - 07:58 Eastern Time CEPHALON ANNOUNCES SECOND POSITIVE PHASE III MODAFINIL STUDY IN NARCOLEPSY SECTION: Financial News LENGTH: 831 words Cephalon, Inc. (Nasdaq: CEPH) announced today that results from its second Phase III clinical trial of Provigil(TM) (modafinil) in patients with narcolepsy demonstrated that Provigil had a significant benefit in increasing patients' ability to stay awake as measured by the maintenance of wakefulness test (MWT), and in improving patients' overall condition as measured by the clinical global impression of change (CGI-C), the two primary endpoints of the study. The double-blind, placebo-controlled study of 273 patients with narcolepsy was conducted at 21 medical centers in the United States. Patients were randomized to receive once-daily doses of placebo, 200 or 400 milligrams of Provigil for nine weeks, followed by a two-week observation period. The MWT is a daytime laboratory test of a person's ability to stay awake over time. Patients who received 200 or 400 mg of Provigil stayed awake approximately 50 percent longer than patients who received placebo (p<0.001). WEST CHESTER, Pa., March 14 The CGI-C is a seven-point scale used in many clinical trials to evaluate changes in a patient's overall disease status from the time of study entry. These impressions of change range from very much worse to no change to very much improved. In this study, CGI-C assessments were made by independent clinicians who did not participate in any other aspects of the study. Sixty percent of patients who received 400 mg of Provigil (p<0.001) and 57 percent of those who received 200 mg of Provigil (p<0.001) demonstrated improvement on this scale compared to 37 percent of patients who received placebo. In February, Cephalon reported positive findings from the first U.S. Phase III clinical study of Provigil, which was conducted at 18 medical centers in the United States and involved 285 patients with narcolepsy. In that study, patients randomized to receive 200 or 400 milligrams of Provigil stayed awake up to 61 percent (p<0.001) and 76 percent (p<0.001) longer, respectively, than those who received placebo. Also, for the CGI-C, 72 percent of patients who received 400 mg of Provigil (p<0.001) and 65 percent of those who received 200 mg of Provigil  (p<0.001) demonstrated improvement compared to 37 percent who received placebo. "Patients with narcolepsy face tremendous physical, social and economic challenges as a result of their inability to stay awake," said Michael F. Murphy, M.D., Ph.D., senior vice president of worldwide clinical research at Cephalon. "The primary objective of these studies was to evaluate modafinil's effects on excessive daytime sleepiness, the most common symptom of this disease. The results of these studies offer clear evidence, from both laboratory tests and physician assessments, that modafinil provides clinically important benefits to the patient." Provigil was well-tolerated at both doses. The most frequent adverse event reported in both studies was headache. In the first study, headache was transient and usually mild, with approximately 15 percent greater incidence in the drug group compared to placebo. In the second study, there were no significant differences in the incidence of headache between the drug and placebo groups. The only consistently observed adverse event related to drug in both studies was dry mouth, which occurred in approximately 5 percent of patients in the drug group. The efficacy and safety results of both Phase III studies of Provigil, as well as findings from preclinical and other clinical studies of the drug, will be reported by investigators at the Association of Professional Sleep Societies annual meeting on May 31, 1996, in Washington, D.C. Cephalon is planning to review these findings with the U.S. Food and Drug Administration and to submit a New Drug Application to the FDA for clearance to market Provigil in the United States. Narcolepsy is a chronic, lifelong sleep disorder afflicting approximately 125,000 people in the United States. The four most common symptoms are excessive daytime sleepiness, cataplexy, sleep paralysis and hypnagogic hallucinations. Narcolepsy generally begins in young adulthood. Therapies to treat the disease have been limited to amphetamine and other stimulants. Cephalon licensed exclusive rights to market modafinil in the United States, Japan, the United Kingdom, Ireland and Mexico from Laboratoire L. Lafon, a French pharmaceutical company which developed and currently markets the drug in France. The FDA designated modafinil an orphan drug in March 1993 for the treatment of excessive daytime sleepiness in narcolepsy. Cephalon discovers, develops and markets products to treat neurological disorders. The company's principal focus is on neurological disorders such as ALS, narcolepsy, peripheral neuropathies, Alzheimer's disease, head and spinal injury, and stroke. // CONTACT: Jason Rubin or Mary Fisher of Cephalon, 610-344-0200 LOAD-DATE: March 15, 1996 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS AND MEDICAL EDITORS Copyright 1996 PR Newswire Association, Inc. 974 of 998 DOCUMENTS Pharma Marketletter March 4, 1996 Modafinil Filed In Canada By End-96? LENGTH: 157 words Draxis Health, the firm which holds Canadian rights to the narcolepsy drug modafinil, expects to file for approval of the drug by year-end. Modafinil was originally developed by France's Lafon, and is licensed by Cephalon in the USA, the UK and Japan (Marketletters passim). Draxis has reported the results of a 75-patient study of modafinil, which reveals that in patients who had received no prior treatment with stimulants, a decrease in daytime sleepiness was reported in 80% of those taking modafinil 400mg/day, 66% of those taking 200mg/day and 34% of those on placebo. In previously-treated patients, the values were 53%, 50% and 25% respectively. Modafinil was found to have no adverse effects on mood, with a single exception. At the 400mg/day dose, the drug increased tension-anxiety compared to placebo. However, the scores were still well below pre-study values. Vigor-activity scores were increased by modafinil. LOAD-DATE: January 7, 2003 LANGUAGE: ENGLISH Copyright 1996 Marketletter Publications Ltd. 975 of 998 DOCUMENTS Business Wire February 28, 1996, Wednesday DRAXIS' Modafinil trial results are statistically significant; new treatment for Narcolepsy LENGTH: 771 words DATELINE: MISSISSAUGA, Ontario Feb. 28, 1996--DRAXIS Health Inc. (TSE:DAX;NASDAQ:DRAXF) Wednesday reported statistically significant results of its one-year long double-blind randomized placebo-controlled cross-over clinical study of Modafinil 200 mg and Modafinil 400 mg in the treatment of Narcolepsy. Seventy-five patients were each studied over a six-week period during which each patient was given placebo, 200 mg or 400 mg of Modafinil in divided doses. The primary end points were sleep latency (the time from lights out to sleep onset) during the Maintenance of Wakefulness Test (a daytime sleep laboratory test) and daily sleep episodes recorded in the patient dairy. Modafinil significantly increased the mean sleep latency (the time taken to fall asleep). The 200 mg dose was 40% better than placebo (p=.002) and the 400 mg dose was 54% better than placebo (p=.001). The 200 mg dose reduced the mean number of periods of sleep and severe somnolence by 24% (p=.013) and the 400 mg dose by 27% (p=.008). Among those patients taking no stimulant medication prior to the study, a comparative decrease in excessive daytime somnolence was reported by 80% of the patients while on Modafinil 400 mg, 66% while on Modafinil 200 mg and 34% while on placebo. Among those patients treated with stimulants prior to the study the comparative differences were 53%, 50% and 25% for Modafinil 400 mg, Modafinil 200 mg and placebo respectively. Conversely, patients previously treated who reported deterioration while on the study were for placebo 58%, Modafinil 200 mg 25%, and Modafinil 400 mg 33%. Using the Epworth Sleepiness Scale, Modafinil 200 mg (p=.018) and 400 mg (p=.009) both decreased the likelihood of falling asleep. The Profile of Mood States (POMS) test was used to evaluate changes in mood, specifically tension-anxiety, anger-hostility, confusion-bewilderment, vigor-activity, and fatigue-inertia. Modafinil had no adverse effects on mood, with a single exception. Modafinil 400 mg slightly increased tension-anxiety compared to placebo (p=.028); but the scores were still well below both the pre-study scores and published normal scores for this factor. Vigor-activity increased after Modafinil 200 mg (p=.018) and 400 mg (p=.012). Neither dose of Modafinil interfered with the patient's ability to sleep voluntarily during the day nor did either dose interfere with the quantity or quality of nocturnal sleep. Only one patient dropped out of the study due to side effects of Modafinil. The principle side effects were headache, nausea, dry mouth, heartburn, diarrhea, and dizziness. The side effects were generally limited to the first few days of treatment. Narcolepsy is a primary sleep disorder characterized by uncontrolled episodes of falling asleep at unexpected times and conditions. It affects approximately 0.05% to 0.1% of the population or approximately 14,800 to 29,600 Canadians. No new treatment for Narcolepsy has been approved in Canada since 1959. The full results of this study will be used by the company to complete its submission for regulatory approval in Canada. This file is expected to be ready for submission to Canadian Health Regulatory authorities towards the end of 1996. Modafinil is approved for the treatment of Narcolepsy in France. DRAXIS has an exclusive license to market and sell Modafinil in Canada. The licensor for the US, UK and Japan is Cephalon Inc. (NASDAQ:CEPH). DRAXIS, is a marketing and research company that operates Canadian Neurological, Dermatological, and Veterinary pharmaceutical divisions, a U.S. consumer marketing company, and offers products exclusively through U.S. podiatrists. CONTACT: DRAXIS Health Inc.                         Kendall McAlister, Coordinator, External Relations                         905/677-5500; Fax 905/677-5502                         or                         Canadian Investor Relations                         Small-Cap Equity Investor Relations Ltd.                         Robert Grahovar                         416/535-4146                         or                         U.S. Investor Relations                         RKC Communications                         Robert Kneeley, 954/351-1976 LOAD-DATE: February 29, 1996 LANGUAGE: ENGLISH DISTRIBUTION: Business Editors Copyright 1996 Business Wire, Inc. 976 of 998 DOCUMENTS Canada NewsWire February 28, 1996, Wednesday Attention Business/Health Editors:  DRAXIS' MODAFINIL TRIAL RESULTS ARE STATISTICALLY SIGNIFICANT  NEW TREATMENT FOR NARCOLEPSY SECTION: Financial News LENGTH: 632 words DATELINE: MISSISSAUGA, Ont., Feb. 28 DRAXIS Health Inc. (TSE:DAX; NASDAQ:DRAXF) today reported statistically significant results of its one-year long double-blind randomized placebo-controlled cross-over clinical study of Modafinil 200 mg and Modafinil 400 mg in the treatment of Narcolepsy.  Seventy-five patients were each studied over a six-week period during which each patient was given placebo, 200 mg or 400 mg of Modafinil in divided doses.  The primary end points were sleep latency (the time from lights out to sleep onset) during the Maintenance of Wakefulness Test (a daytime sleep laboratory test) and daily sleep episodes recorded in the patient diary. Modafinil significantly increased the mean sleep latency (the time taken to fall asleep). The 200 mg dose was 40% better than placebo (p equals .002) and the 400 mg dose was 54% better than placebo (p equals .001). The 200 mg dose reduced the mean number of periods of sleep and severe somnolence by 24% (p equals .013) and the 400 mg dose by 27% (p equals .008). Among those patients taking no stimulant medication prior to the study, a comparative decrease in excessive daytime somnolence was reported by 80% of the patients while on Modafinil 400 mg, 66% while on Modafinil 200 mg and 34% while on placebo. Among those patients treated with stimulants prior to the study the comparative differences were 53%, 50% and 25% for Modafinil 400 mg, Modafinil 200 mg and placebo respectively. Conversely, patients previously treated who reported deterioration while on the study were for placebo 58%, Modafinil 200 mg 25%, and Modafinil 400 mg 33%.  Using the Epworth Sleepiness Scale, Modafinil 200 mg (p equals .018) and 400 mg (p equals .009) both decreased the likelihood of falling asleep.  The Profile of Mood States (POMS) test was used to evaluate changes in mood, specifically tension-anxiety, anger-hostility, confusion-bewilderment, vigor-activity, and fatigue-inertia. Modafinil had no adverse effects on mood, with a single exception. Modafinil 400 mg slightly increased tension-anxiety compared to placebo (p equals .028); but the scores were still well below both the pre-study scores and published normal scores for this factor. Vigor-activity increased after Modafinil 200 mg (p equals .018) and  400 mg (p equals .012).  Neither dose of Modafinil interfered with the patient's ability to sleep voluntarily during the day nor did either dose interfere with the quantity or quality of nocturnal sleep.  Only one patient dropped out of the study due to side effects of Modafinil. The principle side effects were headache, nausea, dry mouth, heartburn, diarrhea, and dizziness. The side effects were generally limited to the first few days of treatment. Narcolepsy is a primary sleep disorder characterized by uncontrolled episodes of falling asleep at unexpected times and conditions. It affects approximately 0.05% to 0.1% of the population or approximately 14,800 to 29,600 Canadians. No new treatment for Narcolepsy has been approved in Canada since 1959.  The full results of this study will be used by the Company to complete its submission for regulatory approval in Canada. This file is expected to be ready for submission to Canadian Health Regulatory authorities towards the end of 1996.  Modafinil is approved for the treatment of Narcolepsy in France. DRAXIS has an exclusive license to market and sell Modafinil in Canada. The licensor for the US, UK and Japan is Cephalon Inc. (NASDAQ:CEPH).  DRAXIS is a marketing and research company that operates Canadian Neurological, Dermatological, and Veterinary pharmaceutical divisions, a U.S. consumer marketing company, and offers products  exclusively through U.S. podiatrists.  -30- For further information: Contacts at DRAXIS - Kendall McAlister, Coordinator, External Relations, Tel: (905) 677-5500, Fax: (905) 677-5502; Canadian Investor Relations - Robert Grahovar, Small-Cap Equity Investor Relations Ltd., Tel: (416) 535-4146; U.S. Investor Relations - Robert Kneeley, RKC Communications, Tel: (954) 351-1976 LOAD-DATE: February 28, 1996 LANGUAGE: ENGLISH Copyright 1996 Canada NewsWire Ltd. 977 of 998 DOCUMENTS PR Newswire February 12, 1996, Monday Correction Appended - 07:32 Eastern Time CEPHALON ANNOUNCES MODAFINIL PHASE III TRIAL RESULTS SECTION: Financial News LENGTH: 340 words Cephalon, Inc. (Nasdaq: CEPH) announced today that a review of data from the first of two Phase II clinical trials of Provigil(TM) (modafinil) in patients with narcolepsy demonstrated that Provigil had a highly statistically significant benefit in reducing excessive daytime sleepiness as measured by the maintenance of wakefulness test (MWT) and a physician-perceived measure of benefit to the patient (CGI-C), the two primary endpoints of the study. A number of adverse experiences were reported in the study, with headache being the most frequently reported side effect potentially attributable to the drug. WEST CHESTER, Pa., Feb. 12 The double-blind, placebo-controlled, nine-week study of 285 patients with narcolepsy was conducted at 18 medical centers in the United States. Cephalon is continuing to analyze the efficacy and safety results of the Phase III trial, which will be reported by clinical investigators at an appropriate medical meeting later this year. Cephalon has not yet reviewed these findings with the U.S. Food and Drug Administration. Positive findings from two Phase III studies are expected to be required for submission of a new Drug Application to the FDA for clearance to market Provigil in the United States. The second Phase III study of Provigil has not yet been completed. Cephalon licensed exclusive rights to market Provigil in the United States, Japan, the United Kingdom, Ireland and Mexico from Laboratoire L. Lafon, a French pharmaceutical company which developed and currently markets the drug in France. The FDA designated modafinil an orphan drug in March 1993 for the treatment of excessive daytime sleepiness in narcolepsy. Cephalon discovers, develops and markets products to treat neurological disorders. The company's principal focus is on neurological disorders such as ALS, narcolepsy, peripheral neuropathies, Alzheimer's disease, head and spinal injury, and stroke. CONTACT: Jason Rubin or Mary Fisher of Cephalon, 610-344-0200 LOAD-DATE: February 13, 1996 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS AND MEDICAL EDITORS CORRECTION-DATE: February 12, 1996, Monday CORRECTION: In NYM033, Cephalon Announces Modafinil Phase III Trial Results, moved earlier today, the first graph, third line, should read "first of two Phase III clinical trials" rather than "Phase II" as incorrectly transmitted by PR Newswire.; Copyright 1996 PR Newswire Association, Inc. 978 of 998 DOCUMENTS Canada NewsWire February 8, 1996, Thursday Attention Business/Financial Editors:  DRAXIS HEALTH INC. REPORTS $ 0.10 FOURTH QUARTER  $ 16.6 MILLION IN CASH RESERVES SECTION: Financial News LENGTH: 3892 words DATELINE: MISSISSAUGA, Ont., Feb. 8     ----------------------------------------------------------------     HIGHLIGHTS FROM CONSOLIDATED STATEMENT OF OPERATIONS     For the three month period                 For the year ended             ended                              December 31, 1995        December 31, 1995     1995       1994                            1995       1994     $ 3,725,161 $ 4,258,756   REVENUES       $ 16,630,712 $ 17,086,116     ---------------------                  ------------------------    (1,696,378) 1,332,573  INCOME (LOSS)        564,992   4,944,540     --------------------  FROM OPERATIONS  ------------------------                           GAIN ON SALE OF     3,067,425     ---     DUSA OPTION        3,067,425      ---     --------------------                   ------------------------     1,883,016     ---     GAIN ON DILUTION   1,833,016      ---     -------------------- OF DUSA INVESTMENT------------------------                          EQUITY SHARE OF NET                        DEVELOPMENT STAGE COSTS                             OF AFFILIATED      (204,706)  (507,241)     COMPANIES    (1,533,325)  (2,095,430)     ---------------------                  ------------------------    $ 2,089,854  $ 147,524     NET INCOME     $ 2,417,404   $ 1,099,392     ---------------------                  ------------------------                          AFTER TAX EARNINGS         $ 0.10      $ 0.01      PER SHARE         $ 0.12        $ 0.06     ----------------------------------------------------------------           ---------------------------------------------------                 CONSOLIDATED BALANCE SHEET HIGHLIGHTS                                            December 31                                          1995         1994             CASH AND TREASURY BILLS  $ 16,605,970  $ 11,691,434             WORKING CAPITAL          $ 16,359,182  $ 12,511,905             -------------------------------------------------     Draxis Health Inc. (TSE: DAX: NASDAQ: DRAXF) today reported earnings of $ 2.1 million or $ 0.10 per share for the three month period ended December 31, 1995, on the strength of a non-operating gain of $ 3,067,425 on the sale of its option to purchase two million shares of DUSA Pharmaceuticals, Inc. ("DUSA") back to DUSA and a non-operating gain of $ 1,833,016 on the dilution of the Company's investment in DUSA as a result of that company's recent public offering.     In commenting on the sale of the Company's option, Dr. Martin Barkin, DRAXIS' CEO stated, "The $ 3 million received from the sale of our DUSA option has further added to the Company's already solid cash position. Draxis ended the year with no debt and cash reserves of $ 16.6 million.     The Company's significant investments in the fourth quarter to upgrade the infrastructure of IHS and launch the Company's Podiatric product in the United States contributed to the $ 1.7 million loss on operations in the quarter. The Company also incurred increased R&D costs for the development of LipoTECA and Modafinil. Additional product launch costs are expected in 1996 related to these launches and the launch of Anipryl in Canada and the Skin Care line into the United States.     Modafinil     Clinical trials on Modafinil have now been fully enrolled. The Company expects to start analyzing the data in February and file its New Drug Submission for approval to market the drug in Canada, in June. Modafinil is licensed to Draxis by Laboratoire L. Lafon of France. The drug is being developed in the United States by Cephalon Inc. (NASDAQ: CEPHIN).     Kerasal     The launch of Kerasal, the Company's keratolytic agent, into the United States market has been received by the podiatric community with a high level of enthusiasm. The Company anticipates that sales of Kerasal will contribute to revenue growth in 1996.     LipoTECA     The Company completed the first multicenter, double-blind, placebo-controlled, 65-patient clinical trial of LipoTECA at the end of 1995. Preliminary analysis of the final results on the effect of the topical drug LipoTECA indicate statistically significant difference against placebo in the treatment of abnormal scar formations known as keloids. Dr. J.P. Bosse, who made a presentation at the North-Western Plastic Surgeon Society conference on January 29, 1996 stated, "Until now, there has not been a satisfactory treatment for keloids. LipoTECA cream will not cure all keloids, but it is the most effective topical treatment that I have come to evaluate in my 30 years of practice as a plastic surgeon." The estimated potential worldwide market for LipoTECA is approximately $ 300 million. DRAXIS holds the worldwide rights for LipoTECA.     FINANCIAL POSITION     - Cash and treasury bills increased to $ 16.6 million at December       31, 1995; an increase of $ 4.9 million over September 30, 1995;     - Working capital increased to $ 16.4 million at December 31,       1995; an increase of $ 2.6 million over September 30, 1995;     - Shareholders' equity increased to $ 29.8 million at December       31, 1995; an increase of $ 2.0 million over September       30, 1995.     DEPRENYL ANIMAL HEALTH, INC. ("DAHI")     DRAXIS recent marketing agreement has positioned it to increase its stake in DAHI from a current 44% to up to 52% by conversion of its loans into DAHI shares. Draxis will commence distribution in Canada as soon as sufficient supplies are received into inventory. Anipryl was filed with the United States with the FDA in September 1995.     DUSA PHARMACEUTICALS, INC. ("DUSA")     On December 14, 1995, DUSA raised U.S. $ 16.5 million, before expenses, in a public offering of 3 million shares of common stock, thus reducing DRAXIS' equity position from 20.00% to 12.76%. DRAXIS holds the Canadian rights to any ALA PDT (photodynamic therapy) products developed by DUSA.     OUTLOOK     In 1995, DRAXIS' mandate was to position itself for growth through the acquisition, licensing or development of new products and the creation of new markets. The Company has accomplished this through the introduction of Kerasal into the United States, the acquisition of a 50% interest in Innovative Health Systems of Indianapolis, and the licensing and introduction of Anipryl in Canada. As a result of these activities, the Company expects sales growth in 1996 despite full genericization of Eldepryl, and will commit funds to additional marketing and selling expenses necessary to support that sales growth.     DRAXIS Health Inc. is a Canadian pharmaceutical company specializing in the areas of neurology, dermatology, podiatry and veterinary medicine. It also has two operating companies in the United States; a consumer market company and a company offering products exclusively to United States podiatrists.     ---------------------------------------------------------------                           DRAXIS HEALTH INC.                      CONSOLIDATED BALANCE SHEET                     (stated in Canadian dollars)                             (unaudited)                                                December 31                                             1995          1994     ASSETS     Current Assets      Cash and treasury bills           $ 16,605,970  $ 11,691,434      Marketable securities                   -            766,609      Accounts receivable                  1,485,953     1,806,793      Income taxes recoverable               170,221       255,389      Inventory                              704,551     1,014,038      Current portion of long-term       receivables                              -          364,676      Prepaid expenses                       796,342       946,446                                          -----------   -----------                                          19,763,037    16,845,385                                          -----------   -----------     Long-term receivables                 4,992,186     5,573,271     Long-term investments                 3,930,858     3,202,896     Fixed assets                            544,556       452,584     Goodwill                              1,663,447     1,897,647     Licenses and other deferred charges   4,157,776     5,090,298                                          -----------   -----------                                        $ 35,051,860  $ 33,062,081                                          -----------   -----------                                          -----------   -----------     LIABILITIES     Current Liabilities      Accounts payable and       accrued charges                  $   1,569,289  $   1,805,852      Royalties payable                    1,334,566     1,527,628      Current portion of license       obligation                            500,000     1,000,000                                          -----------   -----------                                           3,403,855     4,333,480                                          -----------   -----------     License obligation                         -          500,000                                          -----------   -----------     Deferred income taxes                 1,799,100     1,070,100                                          -----------   -----------     SHAREHOLDERS' EQUITY     Capital stock                        18,665,861    18,392,861     Contributed surplus                   9,701,004     9,701,004     Retained earnings (deficit)           1,482,040      (935,364)                                          -----------   -----------                                          29,848,905    27,158,501                                          -----------   -----------                                        $ 35,051,860  $ 33,062,081                                          -----------   -----------                                          -----------   -----------         Exchange rate as at         balance sheet date               U.S. $ 0.73    U.S. $ 0.71                                          -----------   -----------     ---------------------------------------------------------------     ---------------------------------------------------------------                          DRAXIS HEALTH INC.                 CONSOLIDATED STATEMENT OF OPERATIONS                     (stated in Canadian dollars)                             (unaudited)     FOR THE THREE MONTH PERIOD               FOR THE YEAR ENDED        ENDED DECEMBER 31                        DECEMBER 31        1995      1994                        1995         1994                             REVENUES     $ 3,401,211 $ 4,005,870    Sales        $ 15,433,813 $ 16,242,892                             Interest        323,950    252,886    income         1,196,899     843,224     ---------- -----------                ----------- ------------      3,725,161  4,258,756                  16,630,712  17,086,116                              OPERATING      5,421,539  2,926,183    EXPENSES      16,065,720  12,141,576     ---------- -----------                ----------- ------------                              INCOME FROM     (1,696,378) 1,332,573    OPERATIONS       564,992   4,944,540     ---------- -----------                ----------- ------------                          OTHER INCOME (EXPENSE)                           Gain(loss) on sales         64,497    (37,544)   of securities    549,296      58,630                          DUSA Pharmaceuticals, Inc.                           Gain on sale      3,067,425         -    of option       3,067,425       -                           Gain on dilution      1,833,016         -    of investment   1,833,016     219,363         -        (202,188)   Other              -        (287,671)     ---------- -----------                 ----------- -----------                           INCOME BEFORE INCOME                           TAXES AND UNDERNOTED      3,268,560  1,092,841        ITEMS      6,014,729   4,934,862                             PROVISION FOR        974,000    438,076   INCOME TAXES    2,064,000   1,740,040     ---------- -----------                ----------- ------------                             INCOME BEFORE                              UNDERNOTED      2,294,560    654,765      ITEMS        3,950,729   3,194,822                            EQUITY SHARE OF                            NET DEVELOPMENT                            STAGE COSTS OF                              AFFILIATED       (204,706)  (507,241)   COMPANIES     (1,533,325) (2,095,430)      ---------- ----------                ------------ -----------                            NET INCOME FOR     $ 2,089,854   $ 147,524    THE YEAR      $ 2,417,404  $ 1,099,392     ---------- -----------                ----------- ------------                            EARNINGS PER          $ 0.10      $ 0.01     SHARE             $ 0.12       $ 0.06     ---------- -----------                ----------- ------------                           WEIGHTED AVERAGE                           NUMBER OF SHARES     20,126,718 20,019,297   OUTSTANDING    20,058,062  19,927,427     ---------- -----------                ----------- ------------     ---------------------------------------------------------------     ---------------------------------------------------------------                          DRAXIS HEALTH INC.                CONSOLIDATED STATEMENT OF CASH FLOWS                    (stated in Canadian dollars)                             (unaudited)     FOR THE THREE MONTH PERIOD                FOR THE YEAR ENDED        ENDED DECEMBER 31                          DECEMBER 31     1995           1994                        1995        1994                         Cash Flows from (used in)                           Operating Activities                             Net Income for     $ 2,089,854   $ 147,524    the year      $ 2,417,404  $ 1,099,392                    Non cash transactions reflected                            in net income                           Depreciation and        502,465    (33,676)  amortization    1,051,066     632,389                           Amortization of         58,550     58,550   goodwill          234,200     234,200                            Deferred income        658,080     48,000      taxes          729,000     110,100                            Equity share of                            net development                             stage costs of                              affiliated        204,706    507,241     companies     1,533,325   2,095,430                            (Gain) loss on                              sale of        (64,497)    37,544    securities      (549,296)    (58,630)                            Shares issued in                               lieu of            -          -       salary           14,500      12,500                          Gain on sale of option                               in DUSA                           Pharmaceuticals,     (3,067,425)       -         Inc.       (3,067,425)         -                            Gain on dilution                            of investment in                          DUSA Pharmaceuticals     (1,833,016)        -        Inc.       (1,833,016)    (219,363)     ----------------------                  -----------------------     (1,451,283)   765,183                     529,758   3,906,018                             Changes in current                             assets and current                            liabilities impacting                              cash flows from      1,679,302  2,018,532      operations    1,751,879  2,401,594     ----------------------                  -----------------------                           Net cash flows from                                operating        228,019  2,783,715     activities    2,281,637   6,307,612     ----------------------                  -----------------------                          Cash flows from (used                         in) Investing Activities                         Decrease (increase) in other        418,699     50,000  deferred charges     8,487      (4,600)                             Acquisition of        (23,086)       466    fixed assets    (219,003)   (119,370)                            License milestone           -            -       payments    (1,000,000) (2,000,000)                           Acquisition of subsid-                            iary and affiliated           -         1,224     companies      (428,271)   (297,639)     ----------------------                  -----------------------                           Net  Cash flows from                           (used in) Investing        395,613     51,690     Activities    (1,638,787) (2,421,609)     ----------------------                  -----------------------                           Cash Flows from (used                          in) Financing Activities                                Long-term      1,213,229    (842,644)    receivables     945,761  (3,034,417)                            Exercise of stock             -         -         options        258,500         -                            Proceeds from                            sale of option                            in DUSA Pharma-      3,067,425        -     ceuticals, Inc.  3,067,425         -                         Income taxes paid on sale                          of Company shares owned             -         -       by subsidiary      -     (1,663,205)                         Issuance of shares for                               subsidiary             -      (1,224)   acquisitions        -        297,639     ----------------------                  -----------------------                         Net cash flows from                         (used in) financing       4,280,654  (843,868)   activities     4,271,686  (4,399,983)     ----------------------                  -----------------------                         Net Increase (decrease)                           in cash and treasury       4,904,286 1,991,537       bills       4,914,536    (513,980)                            Cash and treasury                          bills at beginning of      11,701,684 9,699,897      year        11,691,434  12,205,414     ----------------------                 ------------------------                            Cash and treasury                             bills at end of     $ 16,605,970 $ 11,691,434     year      $ 16,605,970  $ 11,691,434     -----------------------                ------------------------     ----------------------                 ------------------------     -30- For further information: Edward L. Foster, CA, Vice President and CFO; Kendall McAlister, Coordinator, External Relations, TEL: (905) 677-5500, FAX: (905) 677-5502 LOAD-DATE: February 8, 1996 LANGUAGE: ENGLISH Copyright 1996 Canada NewsWire Ltd. 979 of 998 DOCUMENTS Reuters Health Medical News January 10, 1996 Wednesday [] - Cephalon To Study More Uses For Modafinil LENGTH: 135 words DATELINE: SAN FRANCISCO Jan 10 Cephalon Inc. chief executive Frank Baldino said his company plans to begin studies this year to determine if its drug, Modafinil, can be used to treat other disorders in addition to narcolepsy. "We're going to launch studies this year and hopefully apply in 1997 for approval," with the FDA, Baldino told the audience at the recent Hambrecht & Quist healthcare conference. Baldino said one of the possible additional uses may be in treating sleep disorders in patients with multiple sclerosis. "There's tremendous opportunity here, especially with this low-abuse potential," Baldino said. Results from the first phase of a two-part study showed that the risk of abuse with Modafinil by patients was low, he said. The company is currently conducting Phase III trials of Modafinil for treatment of narcolepsy. LOAD-DATE: July 9, 2008 LANGUAGE: ENGLISH PUBLICATION-TYPE: Newswire Copyright 1996 Reuters Health All Rights Reserved 980 of 998 DOCUMENTS PR Newswire September 28, 1995, Thursday - 08:36 Eastern Time CEPHALON EXPANDS MARKETING TERRITORY FOR MODAFINIL SECTION: Financial News LENGTH: 443 words Cephalon, Inc. (Nasdaq: CEPH) announced today the expansion of its marketing territory for modafinil to include Japan, the third largest pharmaceutical market in the world, in exchange for milestone and royalty payments to Laboratoire L. Lafon. With this agreement, Cephalon now has the exclusive right to market modafinil in the United States, the United Kingdom, Ireland, Mexico and Japan. "This territory expansion allows us to strengthen our presence in Japan, capitalize on our investment in this important product and underscore our global commercial strategy," said Frank Baldino, Jr., Ph.D., Cephalon's president and chief executive officer. "We are pleased to broaden our relationship with Lafon, and look forward to identifying an appropriate partner for this new program in Japan." WEST CHESTER, Pa., Sept. 28 Cephalon originally licensed modafinil from Lafon in February 1993 with an initial focus on its development in narcolepsy. Other potential applications for modafinil include several sleep disorders, cerebrovascular conditions and the fatigue associated with a variety of neurological diseases. Lafon currently markets modafinil in France for the treatment of narcolepsy and idiopathic hypersomnia. Cephalon is currently conducting two Phase III clinical studies of modafinil for the treatment of the excessive daytime sleepiness associated with narcolepsy. The U.S. Food and Drug Administration designated modafinil an orphan drug in March 1993 for this indication. Narcolepsy is a disabling, chronic, lifelong sleep disorder afflicting approximately 125,000 people in the United States. It is characterized by uncontrollable sleep attacks that can last from a few seconds to more than one hour. These attacks can take place at any time, and hamper a person's ability to perform basic daily activities. Symptoms of narcolepsy can appear suddenly or develop slowly over many years. The four most common symptoms are excessive daytime sleepiness, cataplexy, sleep paralysis and hypnagogic hallucinations. In most cases excessive daytime sleepiness is the only symptom. Current therapies to treat symptoms of the disease include amphetamines and other stimulants which have potential for abuse. Cephalon is a leader in the discovery and development of products to treat neurological disorders. The company's principal focus is on neurological diseases such as amyotrophic lateral sclerosis (Lou Gehrig's disease), peripheral neuropathies, narcolepsy, Alzheimer's disease, head and spinal injury and stroke. // CONTACT: Jason Rubin or Mary Fisher of Cephalon, 610-344-0200 LOAD-DATE: September 29, 1995 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS EDITOR Copyright 1995 PR Newswire Association, Inc. 981 of 998 DOCUMENTS Pharma Marketletter May 22, 1995 Eight-Year-Old Cephalon Integrates For Success LENGTH: 1045 words In the precarious biotechnology industry, too often the news has centered on yet another firm gambling all on a core technology which falls at the last hurdle and reveals very little of value in the following field. Highly-publicized failures have led to a drying-up of investor cash, with more and more start-up firms foregoing their independence, and looking to the pharmaceutical majors for support. A notable exception to this rule is neurological disease specialist Cephalon, which in the eight years since its inception, has grown into an integrated biopharmaceutical firm, with research, manufacturing and latterly sales/marketing capabilities. Chief executive of the company Frank Baldino said at the Hambrecht & Quist meeting in London this month that he believes it is this integrative approach which allows him to manage risk effectively. Cephalon has two products in very late-stage clinical development, one of which, a licensed-in product called modafinil for narcolepsy, has a high chance of reaching the market as it is already launched in France by its developer, Laboratoires Lafon. The other product, Myotrophin (insulin-like growth factor) for amyotrophic lateral sclerosis, has just one more hurdle to jump (see later). In addition, Cephalon has already set up a sales and marketing operation for the comarketing of an opioid analgesic, Stadol NS, (butorphenol tartrate) with Bristol-Myers Squibb, which will bring in near-term revenues and perhaps more importantly be in place for when Cephalon's own products reach the market. Dr Baldino said that analysts estimate that Stadol could generate sales of over $ 100 million in fiscal 1995, of which the neurology opportunity is "at least 15-20%." Dr Baldino noted that there are four key requirements for success in drug development; a well-designed study, proven safety, bioavailability, and efficacy. For modafinil, all four of these criteria have been satisfied, while for Myotrophin three have been satisfied, with the outstanding efficacy data scheduled for presentation at a neurological conference in France on June 10. This data will come from a North American Phase II/III study of the drug, which has now been concluded and the code broken. A similar European Phase II/III trial should end later this summer, with data available before the end of the year. Approximately 450 patients have been involved in both studies. The drug may also have applications outside of ALS; Cephalon has a Phase II program ongoing with the drug in peripheral neuropathies. Three specific indications are being pursued in the first instance, namely chemotherapy-induced neuropathy, post-polio syndrome and diabetic neuropathy. The first two of these will be investigated at sites in the USA, while the latter is in trials in the UK. In the future, other neuropathies may be added into the program, eg, small-fiber painful neuropathy and Guillain-Barre syndrome. The two pivotal trials of modafinil should both be reported in 1995, said Dr Baldino. Protocol 301 is fully accrued and the code should be broken in the summer, while for protocol 302 accrual is scheduled for completion in October. Modafinil has been studied in over 1,000 patients by Lafon, and the data reveals that the drug can achieve a significant decrease in daytime sleep attacks. Already on the market in France, modafinil dossiers have been filed with the European Union Committee for Proprietary Medicinal Products. Cephalon has marketing rights in the UK, Ireland, the USA and Mexico. Like Myotrophin, modafinil potentially has a far greater target population than its first indication would suggest (approximately 125,000 people suffer from narcolepsy in the USA with a similar number affected in Europe). "The real opportunity with modafinil goes beyond narcolepsy," said Dr Baldino. A prime example is Alzheimer's disease. Although modafinil will not affect the cognitive performance in these patients, it has beneficial effects on vigilance and awareness which may have marked effects on AD patients. Most of these patients are not institutionalized because of their cognitive deficits, rather they are institutionalized because they cannot focus on anything, are apathetic and have a short attention span. Similarly, patients with multiple sclerosis are fatigued, and this is exacerbated by treatment with interferon products such as Chiron/Schering's Betaseron (interferon beta). Modafinil could be used to treat this fatigue, which affects 250,000 people in the USA. "The point I'm trying to make to you today is that modafinil is not a niche product for narcolepsy. It's a very big product, and I think it will be the biggest product in our portfolio within the next three years," said Dr Baldino. Other potential indications include hypersomnia, and also children with attention-deficit disorder. The latter patients are currently treated with amphetamine drugs and methylphenidate HCl, which also happen to be the two classes which are used to treat narcoleptics in the USA and Europe. Modafinil will have considerable advantages over them, particularly as it does not appear to have abuse potential. Further back in the pipeline, Dr Baldino commented on a series of programs, targeting several diseases, which focus on three core technologies; protease inhibitors, neurotrophic factors and receptor tyrosine kinase effectors. The latter program is centering, amongst other things, on the development of small molecule mimics of neurotrophic factors, and Cephalon is due to publish an account of this work in a journal in the next few months. The programs are also throwing out a lot of compounds which may have applications in non-core diseases, and these are being licensed out as the opportunities occur (eg, a prostate cancer drug was licensed to TAP Holdings last year). In the future, Cephalon has promised Wall Street an Investigational New Drug every year, and Dr Baldino is confident this is achievable. Certainly funding is not an obstacle - the company is financially strong, with more than $ 110 million in cash (and $ 10 million in a partnership fund for the development of Myotrophin), as well as projected product revenues of more than $ 30 million in fiscal 1995. LOAD-DATE: January 7, 2003 LANGUAGE: ENGLISH Copyright 1995 Marketletter Publications Ltd. 982 of 998 DOCUMENTS PR Newswire February 21, 1995, Tuesday - 08:39 Eastern Time CEPHALON ANNOUNCES 1994 FINANCIAL RESULTS SECTION: Financial News LENGTH: 1102 words DATELINE: WEST CHESTER, Pa., Feb. 21 Cephalon, Inc. (Nasdaq: CEPH) today reported a net loss of $36.1 million, or $2.13 per share, for the year ended December 31, 1994, compared to a loss of $19.2 million, or $1.77 per share, reported for 1993. For the quarter ended December 31, 1994, the company reported a loss of $9.9 million, or $.54 per share, compared to a loss of $6.3 million, or $.53 per share for the same period in 1993. "In 1994 clinical research represented a significant portion of our expenditures," said Frank Baldino, Jr., Ph.D., Cephalon's president and chief executive. "The increase in clinical research expense last year reflected our progress toward the completion of the Myotrophin(TM) (rhIGF-1) clinical development program in North America and Europe in patients with amyotrophic lateral sclerosis (ALS), and the initiation of Phase III clinical trials of modafinil for the treatment of excessive daytime sleepiness associated with narcolepsy. The Myotrophin ALS studies are now fully enrolled, and enrollment in the modafinil studies is actively proceeding. These studies are expected to be completed later this year." Revenues for 1994 increased 28 percent to $21.7 million compared to $16.9 million for 1993. The increase in revenue resulted principally from revenues under agreements with TAP Pharmaceuticals, SmithKline Beecham and Cephalon Clinical Partners, L.P. Cephalon incurred operating expenses of $60.8 million in 1994 compared to $38.0 million in 1993. The increase in expenses resulted primarily from increases in research and development activities, including expenses associated with clinical testing of Myotrophin and modafinil. Research and development expenses totaled $13.0 million during the fourth quarter and $51.6 million for the year, compared to $9.2 million for the quarter and $33.2 million for the year in 1993. The fourth quarter 1994 expense also reflected accrual of a $1.1 million license fee payment due in 1995 for modafinil as required under the company's agreement with Laboratoire L. Lafon. Selling, general and administrative expenses increased 91 percent to $9.2 million in 1994, primarily due to the addition of a 30-person neurology sales organization to support sales of Stadol NS(R) (butorphanol tartrate) under the company's co-promotion agreement with Bristol-Myers Squibb, as well as growth in various support functions. As of December 31, 1994, Cephalon had approximately $114 million in cash and marketable securities, and approximately $12 million available from Cephalon Clinical Partners, L.P. to fund Myotrophin's clinical development in North America and Europe. Cephalon discovers, develops and markets products to treat neurological disorders. The company's principal focus is on neurological diseases such as amyotrophic lateral sclerosis (Lou Gehrig's disease), narcolepsy, peripheral neuropathies, Alzheimer's disease, head and spinal injury, and stroke.                     CEPHALON, INC. AND SUBSIDIARIES                   Consolidated Statement of Operations                 (Amounts in Thousands, Except Per Share)                                Three Months Ended      Year Ended                                     Dec. 31,            Dec. 31,                                 1994        1993     1994      1993     Revenues                  $5,924      $3,640   $21,681   $16,922     Expenses:     Research and development  13,020       9,187    51,613    33,158     Selling, general and      administrative            3,735       1,095     9,180     4,794     Total                     16,755      10,282    60,793    37,952     Loss from operations     (10,831)     (6,642)  (39,112)  (21,030)     Interest income (net)        916         369     3,047     1,794     Loss                     ($9,915)    ($6,273) ($36,065) ($19,236)     Loss per share            ($0.54)     ($0.53)   ($2.13)   ($1.77)     Weighted average shares      outstanding              18,278      11,869    16,929    10,885                           Selected Cash Flow Data                            (Amounts in Thousands)                                Three Months Ended      Year Ended                                     Dec. 31,            Dec. 31,                                 1994        1993     1994      1993     Cash, cash equivalents      and investments         $121,781    $50,033   $49,438   $43,847     Cash (used for) provided      by operations             (3,564)       923   (25,850)  (10,600)     Capital expenditures       (2,567)    (1,962)  (10,677)   (6,932)     Sale leaseback of      property & equipment      11,750          0    11,750         0     Cash (used for) provided      by financing activities  (12,942)       444    89,797    23,123     Cash, cash equivalents      and investments         $114,458    $49,438  $114,458   $49,438                         Selected Balance Sheet Data                            (Amounts in Thousands)                                               Dec. 31,      Dec. 31,                                                1994           1993     Cash, cash equivalents and investments   $114,458       $49,438     Total assets                              140,173        78,108     Long-term debt, including current portion  18,991        11,570     Accumulated deficit                       (71,679)      (35,614)     Stockholders' equity                      112,767        63,105     //     /EDITORS' ADVISORY:  Cephalon's press releases are available at no charge through PR Newswire's Company News On-Call fax service.  For a menu of available Cephalon press releases or to retrieve a specific release, call 800-758-5804, ext. 134563./      CONTACT: Jason Rubin of Cephalon, 610-344-0200, ext. 302 LOAD-DATE: February 22, 1995 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS EDITOR Copyright 1995 PR Newswire Association, Inc. 983 of 998 DOCUMENTS APPLIED GENETICS NEWS September, 1994 Narcolepsy Drug Enters Phase III SECTION: BIOPROCESS TECHNOLOGY; Vol. 15, No. 2 LENGTH: 94 words Narcolepsy is a disabling disease, characterized by uncontrollable sleep attacks. In the U.S., about 125,000 have the disorder. Cephalon (145 Brandywine Parkway, West Chester, PA 19380-4245; tel. 215-344-0200) is now starting Phase III clinical trials of its treatment for narcolepsy, a drug called modafinil. Modafinil is a synthetic compound that acts selectively on the part of the central nervous system that controls sleep and wakefulness. If approved for marketing, modafinil will be the first new treatment for narcolepsy in more than 30 years. LOAD-DATE: March 22, 1997 LANGUAGE: ENGLISH Copyright 1994 Business Communications Co. 984 of 998 DOCUMENTS Pharma Marketletter August 15, 1994 Cephalon Starts Phase III Modafinil Trials LENGTH: 328 words Cephalon has begun Phase III clinical trials of modafinil, its treatment for narcolepsy. The sleep disorder affects around 125,000 people in the USA, according to the company. The company says it plans to conduct the two double-blind trials, which will evaluate modafinil's efficacy in reducing the number of daytime sleep attacks, at more than 40 leading sleep research centers across the USA. After initial screening, patients will receive modafinil or placebo daily for nine weeks. Cephalon licenses modafinil from Laboratoires Lafon of France, and has exclusive rights to market the product in the USA, the UK, Republic of Ireland and Mexico. Cephalon also says it is expecting data analysis of Phase II/III studies of its lead product Myotrophin (recombinant human insulin-like growth factor-1) for amyotrophic lateral sclerosis to be completed in the first quarter of 1995. Comarketing Agreement With B-MS Meantime, Cephalon has entered into an agreement with Bristol-Myers Squibb under which Cephalon will extend direct marketing of the opioid nasal spray Stadol NS (butorphanol) to neurologists via a newly-formed specialty sales force. The analgesic is currently marketed to general practitioners and to a lesser extent obstetricians/gynecologists. After training by B-MS, the Cephalon sales force will promote Stadol NS primarily for use in migraine headache, and detailing could begin as early as October. The drug has a broad-ranging indication - the management of pain when the use of an opioid analgesic is appropriate, including postsurgical, musculoskeletal, dental and trauma pain as well as migraines. The agreement is renewable and on an initial three-year contract, reports the Pink Sheet, and will split revenues on a 50/50 basis after a base sales level is reached. Sales of Stadol NS were estimated to be $ 50 million in 1993. Cephalon said it is seeking other agreements similar to the one it has struck with B-MS. LOAD-DATE: January 7, 2003 LANGUAGE: ENGLISH Copyright 1994 Marketletter Publications Ltd. 985 of 998 DOCUMENTS PR Newswire August 4, 1994, Thursday - 08:01 Eastern Time CEPHALON BEGINS PHASE III MODAFINIL CLINICAL TRIALS SECTION: Financial News LENGTH: 443 words DATELINE: WEST CHESTER, Pa., Aug. 4 Cephalon, Inc. (Nasdaq: CEPH) announced today the start of Phase III clinical trials of modafinil for the treatment of narcolepsy, a chronic, debilitating sleep disorder which affects 125,000 Americans. Modafinil is a synthetic compound which acts selectively on the part of the central nervous system that controls sleep and wakefulness. "Narcolepsy is a disabling disease with serious economic and social consequences for patients and their families," said Frank Baldino, Jr., Ph.D., Cephalon's president and chief executive officer. "Modafinil has received marketing approval for narcolepsy and idiopathic hypersomnia in France. If approved for marketing in the United States, modafinil would be the first new treatment option for U.S. patients with narcolepsy in more than thirty years." Narcolepsy is characterized by uncontrollable sleep attacks. As a result, narcolepsy significantly impacts a person's ability to perform basic daily activities. Symptoms of the disorder can appear all at once or develop slowly over many years. The four most common symptoms are excessive daytime sleepiness, cataplexy, sleep paralysis and hypnagogic hallucinations. In most cases excessive daytime sleepiness is the only symptom. Narcolepsy usually begins in young adulthood. Current therapies to treat symptoms of the disease include amphetamines and other stimulants which may have potential for abuse. Cephalon plans to conduct two multi-center, double-blind, placebo- controlled trials at more than forty leading sleep research centers nationwide to evaluate modafinil's efficacy in reducing day-time sleep attacks. After initial screening, patients will receive modafinil or placebo daily for nine weeks. Modafinil is the second Cephalon product to enter late-stage clinical development. Last year, the company began Phase II/III trials with Myotrophin(TM) (rhIGF-1) in patients with amyotrophic lateral sclerosis (ALS). Cephalon has exclusive rights to market modafinil in the United States, the United Kingdom, Ireland and Mexico. The U.S. Food and Drug Administration designated modafinil an orphan drug in March 1993 for the treatment of excessive daytime sleepiness in narcolepsy. Cephalon is a leader in the discovery and development of products to treat neurological disorders. The company's principal focus is on neurological diseases such as amyotrophic lateral sclerosis (Lou Gehrig's disease), peripheral neuropathies, Alzheimer's disease, head and spinal injury and stroke. // CONTACT: Mary Fisher, Corporate Communications of Cephalon, 610-344-0200 LOAD-DATE: August 5, 1994 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS EDITOR Copyright 1994 PR Newswire Association, Inc. 986 of 998 DOCUMENTS Pharma Marketletter September 6, 1993 US MODAFINIL TRIAL STARTED LENGTH: 81 words Cephalon has initiated clinical studies in the USA on its narcolepsy treatment, modafinil. The study, involving healthy volunteers, will support dose selection for pivotal Phase III efficacy trials. In January, Cephalon obtained development and marketing rights in the USA and Mexico for modafinil from Laboratoires Lafon of France. Now, under an extension to the existing agreement, Cephalon also gains an expansion of its marketing rights to include the UK and Ireland. LOAD-DATE: January 13, 2003 LANGUAGE: ENGLISH Copyright 1993 Marketletter Publications Ltd. 987 of 998 DOCUMENTS PHILADELPHIA INQUIRER August 18, 1993, Wednesday CEPHALON TO BEGIN TRIALS SECTION: Section D; Page 3, Column 1 LENGTH: 40 words West Chester, Pa-based Cephalon Inc says it will begin US clinical trials of modafinil for treatment of narcolepsy; company will expand marketing for modafinil to include United Kingdom and Ireland (S) LANGUAGE: ENGLISH JOURNAL-CODE: PHI Copyright 1993 The New York Times Company: Abstracts 988 of 998 DOCUMENTS PR Newswire August 17, 1993, Tuesday - 08:02 Eastern Time CEPHALON BEGINS MODAFINIL CLINICAL TRIAL IN UNITED STATES; EXPANDS MARKETING TERRITORY TO U.K. AND IRELAND SECTION: Financial News LENGTH: 463 words DATELINE: WEST CHESTER, Pa., Aug. 17 Cephalon, Inc. (NASDAQ: CEPH) announced today the initiation of U.S. clinical trials of modafinil for the treatment of narcolepsy as well as the expansion of its marketing territory for modafinil to include the United Kingdom and Ireland. Cephalon is initiating the U.S. studies in healthy volunteers to support dose selection for pivotal efficacy trials. Phase III pivotal studies in patients with narcolepsy are planned to begin at leading U.S. sleep centers following the completion of the current study. In January 1993, Cephalon licensed modafinil from Laboratoire L. Lafon of Paris for development in the United States and Mexico. Under a recent amendment to that agreement, Cephalon now has the exclusive right to market mondafinil in the United Kingdom and Ireland upon approval in those countries. "We are pleased to begin the clinical development program for modafinil on schedule," said Cephalon President and CEO Frank Baldino Jr., Ph.D. "The expansion of our territory for modafinil into the United Kingdom and Ireland represents an important potential market opportunity for the company and underscores our intent to develop products around the globe." Modafinil is a synthetic compound developed by Lafon that acts selectively on the alpha adrenergic system in the brain. Researchers believe this system is involved with narcolepsy, a debilitating sleep disorder that affects more than 125,000 people in the United States. In 1992 Lafon received regulatory approval for modafinil in France, and expects to seek regulatory approval of modafinil in other European countries later this year. Narcolepsy is generally characterized by an uncontrollable propensity to fall asleep and has no known cure. Current therapies that treat disease symptoms, such as amphetamine-type stimulants, may be addictive or have other side effects. If approved, modafinil would be the first new product in the United States to address this disorder in many years. Founded in 1951, Lafon is a privately owned, research-based, mid- size ethical pharmaceutical company located in France. Lafon research specializes in discovery and development of innovative compounds, especially in CNS and cardiovascular therapies. Cephalon is a leader in the discovery and development of products to treat neurological diseases and disorders. The company's principal focus is on neurodegenerative diseases such as amyotrophic lateral sclerosis (Lou Gehrig's disease), peripheral neuropathy, Alzheimer's disease, head and spinal cord injury, and stroke. // CONTACT: Jason Rubin or Lyn Hyduke of Cephalon, 215-344-0200; or Karen Bergman of Burns McClellan, 212-505-1919, for Cephalon; or Bill Mattson for Laboratoire L. Lafon, 314-469-7600 LOAD-DATE: August 18, 1993 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS AND MEDICAL EDITORS Copyright 1993 PR Newswire Association, Inc. 989 of 998 DOCUMENTS Pharma Marketletter July 26, 1993 MERCKLE GAINS LICENSE FROM LAFON LENGTH: 342 words German pharmaceutical company Merckle and France's Laboratoire Lafon have reached agreement for the former to acquire the exclusive right to develop, market and sell modafinil in Germany, Switzerland, Austria and the former Soviet Union as well as selected eastern European countries. Lafon, a privately-owned research-based drugmaker specializing in the discovery and development of innovative drugs, especially in the cardiovascular and central nervous system arena, and Merckle, specializing in similar areas as well as sports medicine, respiratory and pulmonary products, and likewise privately-owned, are two partners in the Euro-Alliance Group, which was formed in 1990 as a cooperation agreement which encourages the partners to collaborate on the licensing and development of their pipeline products amongst themselves. All the EuroAlliance partners maintain autonomy and continue to focus on their home countries, where they maintain strong positions. Modafinil is a synthetic compound discovered and developed by Lafon. It acts selectively on the alpha adrenergic system in the brain. This system has been shown by leading scientists to be involved in the etiology of narcolepsy (a debilitating, lifelong sleep disorder that is estimated to affect over 50,000 people in Germany alone), and for which there is no cure. Results from a four-year series of European studies in nearly 1,000 patients demonstrates that modafinil significantly reduces daytime sleep attacks and drowsiness, which endanger and reduce the quality of life of patients suffering this condition. The compound has shown no significant adverse effects, compared with current therapies, which are often addictive and may have other unpleasant side effects. Modafinil was approved by the French Ministry of Health as safe and effective in February 1992, and commercialization there will commence once pricing and reimbursement has been agreed. The compound has also been licensed to Cephalon for marketing in the USA and Mexico (Marketletter July 5). LOAD-DATE: January 13, 2003 LANGUAGE: ENGLISH Copyright 1993 Marketletter Publications Ltd. 990 of 998 DOCUMENTS Pharma Marketletter July 19, 1993 CEPHALON FILES US IND FOR MODAFINIL LENGTH: 137 words Cephalon has filed an Investigational New Drug Application in the USA for modafinil, its new compound for the treatment of narcolepsy. The company licensed the drug from French pharmaceutical firm Laboratoires Lafon (Marketletter July 5). Modafinil has already been approved for the treatment of this condition in France. Cephalon chief executive Frank Baldino said that the company had filed the IND in order to carry out additional studies required to supplement the data generated in the European clinical trial program for the drug. Phase III studies in the USA should be starting by the end of the year, he added. Earlier this year, the US Food and Drug Administration granted orphan drug designation for modafinil in the treatment of narcolepsy. Cephalon has rights to the drug in the USA and Mexico. LOAD-DATE: January 13, 2003 LANGUAGE: ENGLISH Copyright 1993 Marketletter Publications Ltd. 991 of 998 DOCUMENTS Business Wire July 6, 1993, Tuesday Cephalon Inc. files Investigational New Drug Application for the use of modafinil for the treatment of narcolepsy LENGTH: 423 words DATELINE: WEST CHESTER, Pa. Inc. (NASDAQ:CEPH) Tuesday announced that the company filed an Investigational New Drug (IND) application with the United States Food and Drug Administration (FDA) for clinical trials of modafinil which is being developed for the treatment of narcolepsy. Narcolepsy is a debilitating disorder which often originates in adolescence and is most notably characterized by uncontrollable daytime sleep attacks. These attacks can take place during conversation, while eating, and even while driving, and significantly impact the patient's ability to perform daily activities. Narcolepsy affects more than 125,000 people in the United States. "We continue to make excellent progress towards our goal of submitting a New Drug Application (NDA) for modafinil," stated Dr. Frank Baldino Jr., president and CEO of Cephalon. "We filed this IND to allow us to perform the additional clinical studies required by the FDA to supplement the data package used to obtain market approval for modafinil in France. The modafinil program is advancing as anticipated and we are targeting the end of this year for the initiation of Phase III clinical studies." Modafinil represents an important development in the treatment of narcolepsy. Data from over 1,000 patients in Europe demonstrated that modafinil significantly reduced daytime sleep attacks and drowsiness seen in this disorder, while showing no significant adverse side effects. Modafinil received regulatory approval in France for the treatment of narcolepsy in February 1992. Earlier this year the FDA granted orphan drug designation for modafinil in the treatment of narcolepsy. Cephalon has the exclusive right to develop, market and sell modafinil in the U.S. and Mexico. Cephalon Inc. discovers and develops pharmaceutical products for the treatment of neurological diseases and disorders. The company's primary focus is on neurodegenerative diseases, which are characterized by the death of neurons, the specialized conducting cells of the nervous system. The company has concentrated its research programs on the prevention of neuronal death in several disorders, including amyotrophic lateral sclerosis and peripheral neuropathy, Alzheimer's disease, head and spinal cord injury and stroke. CONTACT: Cephalon Inc., West Chester             Lyn Hyduke, corporate communications, 215/344-0200             by             Burns McClellan, New York             Karen L. Bergman, 212/505-1919 LANGUAGE: ENGLISH DISTRIBUTION: Business Editors/Health Editors Copyright 1993 Business Wire, Inc. 992 of 998 DOCUMENTS Business Wire May 5, 1993, Wednesday Cephalon announces first-quarter financial results LENGTH: 1033 words DATELINE: WEST CHESTER, Pa. Inc. (NASDAQ:CEPH) Wednesday reported its financial results for the first quarter ended March 31, 1993. Revenues for the quarter were $2 million. No revenues were reported for the same period in 1992. The company had a net loss of $5.8 million (64 cents per share) for the quarter, as compared with a loss of $3 million (34 cents per share) reported for the same 1992 period. The results for the 1993 period reflect a $1 million charge to earnings for a payment made to Laboratoire L. Lafon upon the execution of an agreement providing Cephalon with exclusive rights to develop, market and sell modafinil for the treatment of narcolepsy in the United States and Mexico. In the March 31, 1993 quarter, the company incurred operating expenses of $6.4 million, compared with $3.9 million during the same period last year. The increase in expenses results primarily from the payment to Lafon, and the increases in research and development costs, including costs associated with the development of Myotrophin, which entered pivotal Phase II/III clinical testing for the treatment of amyotrophic lateral sclerosis (ALS) during this first quarter 1993. "The licensing of modafinil provides Cephalon with another product in late stage clinical development. We are excited about its potential use in treating narcolepsy, a debilitating, lifelong disorder that adversely affects over 125,000 Americans. It fits well within that segment of our product pipeline directed toward the niche neurology marketplace," stated Dr. Frank Baldino Jr., president and CEO of Cephalon. Modafinil is a synthetic compound that acts selectively on the alpha adrenergic system in the brain. This system has been shown by leading scientists in the field to be involved in the etiology of narcolepsy. Current therapies to treat narcolepsy, such as amphetamine-like stimulants and antidepressants, are often addictive and have other undesirable side effects. In European studies, conducted over a four-year period, modafinil significantly reduced daytime sleep attacks and drowsiness seen in this disorder, while showing no significant adverse side effects. Subsequent to these trials, modafinil was judged by the French Ministry of Health to be safe and effective, receiving regulatory approval in France. In April of this year Cephalon completed a secondary offering of 2.3 million shares of common stock which resulted in net proceeds to the company of approximately $20.5 million in funds. At April 30, 1993, Cephalon had access to over $85 million, both on and off the balance sheet, including approximately $33 million available from Cephalon Clinical Partners L.P. to fund Myotrophin's clinical development in the United States and Europe. Cephalon discovers and develops pharmaceutical products for the treatment of neurological diseases and disorders. The company's primary focus is on neurodegenerative diseases, which are characterized by the death of neurons, the specialized conducting cells of the nervous system. The company has concentrated its research and development efforts on the prevention of neuronal death in several disorders, including ALS and peripheral neuropathy, Alzheimer's disease, head and spinal cord injury and stroke. -0-                       cephalon Inc. and Subsidiaries                    Consolidated Statement of Operations                  (Amounts in thousands, except per share)                                (Unaudited)                                          Three Months Ended                                               March 31,                                          1993          1992 Revenues                               $ 1,975       $  -- Expenses: Research and development                 7,384         3,252 General and administrative                 976           623                                          8,360         3,875 Loss from operations                    (6,385)       (3,875) Interest income (net)                      559           877 Loss                                   [5,826)      [2,998) Loss per share                       (64 cents)    (34 cents) Weighted average  shares outstanding                      9,103         8,855                       Selected Balance Sheet Data                         (Amounts in thousands)                                        March 31,       Dec. 31,                                          1993            1992                                       (Unaudited) Cash, cash equivalents  & investments                         $ 36,492        $ 43,847 Total assets                             64,859          71,061 Long-term debt, net of current portion   12,010          12,010 Accumulated deficit                     (22,204)        (16,378) Stockholders' equity                   $ 51,232        $ 56,733 CONTACT: Cephalon Inc., West Chester             Lyn Hyduke, 215/344-0200             or             Burns McClellan Inc., New York             Karen L. Bergman (media), 212/505-1919             Emily Calmer Magowan (investors), 212/505-1919 LANGUAGE: ENGLISH DISTRIBUTION: Business Editors & Health/Medical Writers Copyright 1993 Business Wire, Inc. 993 of 998 DOCUMENTS Business Wire March 25, 1993, Thursday Cephalon, Inc. receives orphan drug status for modafinil LENGTH: 400 words DATELINE: WEST CHESTER, Pa. , Inc. (NASDAQ:CEPH) Thursday announced the Company was granted orphan drug designation for modafinil in the treatment of narcolepsy from the Food and Drug Administration. Narcolepsy affects 125,000 people in the United States. Cephalon received the exclusive right to develop, market and sell modafinil in the United States and Mexico from Laboratoire L. Lafon of Paris, France in February of this year. "This is the first step in our development program for modafinil," stated Dr. Frank Baldino, Jr., President and Chief Executive Officer of Cephalon. " Modafinil represents a product opportunity that fits our strategic objectives within the neurology field. We are rapidly advancing this potential product though the development process and expect to file an IND later this year." Narcolepsy is a debilitating disorder which often originates in late childhood and is most notably characterized by uncontrollable daytime sleep attacks. These attacks take place during conversation, while eating, even while driving, and significantly impact the patient's ability to perform daily activities. Currently, there is no cure for narcolepsy, and current therapies that treat disease symptoms, such as amphetamine-like stimulants, are often addictive and have other undesirable side effects. Results of a four-year series of European studies in more than 1,000 patients demonstrated that modafinil significantly reduced daytime sleep attacks and drowsiness seen in this disorder, while showing no significant adverse side effects. Modafinil received regulatory approval in France for the treatment of narcolepsy in February 1992. Cephalon, Inc. discovers and develops pharmaceutical products for the treatment of neurological diseases and disorders. The Company's primary focus is on neurodegenerative diseases, which are characterized by the death of neurons, the specialized conducting cells of the nervous system. The Company has concentrated its research programs on the prevention of neuronal death in several disorders, including ALS and peripheral neuropathy, Alzheimer's disease, head and spinal cord injury and stroke. CONTACT: Cephalon Inc., West Chester             Lyn Hyduke, 215/344-0200             or             Burns McClellan, New York             Karen L. Bergman, 212/505-1919 LANGUAGE: ENGLISH DISTRIBUTION: Business, Health & Medical Editors Copyright 1993 Business Wire, Inc. 994 of 998 DOCUMENTS PHILADELPHIA INQUIRER February 2, 1993, Tuesday CEPHALON GETS DRUG RIGHTS SECTION: Section C; Page 3, Column 1 LENGTH: 43 words Laboratoire L Lafon, of Paris, France, has granted Cephalon Inc, of West Chester, Pa, exclusive right to develop, market and sell modafinil in US and Mexico; Modafinil is a compound developed by Lafon to treat narcolepsy (S) LANGUAGE: ENGLISH JOURNAL-CODE: PHI Copyright 1993 The New York Times Company: Abstracts 995 of 998 DOCUMENTS PR Newswire February 1, 1993, Monday - 09:11 Eastern Time CEPHALON LICENSES NOVEL PRODUCT TO TREAT NARCOLEPSY  FROM LABORATOIRE L. LAFON SECTION: Financial News LENGTH: 630 words DATELINE: WEST CHESTER, Pa. and PARIS, Feb. 1 Cephalon, Inc. (NASDAQ: CEPH) of West Chester, Pennsylvania and Laboratoire L. Lafon of Paris announced today an agreement under which Cephalon receives the exclusive right to develop, market and sell modafinil in the United States and Mexico. The announcement came jointly from Frank Baldino, Jr., Ph.D., President and CEO of Cephalon, and Francois Lafon, CEO of Lafon. Modafinil is a synthetic compound developed by Lafon that acts selectively on the alpha adrenergic system in the brain. This system has been shown by leading scientists in the field to be involved with the etiology of narcolepsy, a debilitating, lifelong sleep disorder that is estimated to affect over 125,000 Americans. Results of a four-year series of European studies in more than 1,000 patients demonstrated that modafinil significantly reduced daytime sleep attacks and drowsiness seen in this disorder, while showing no adverse side effects. Subsequent to these trials, modafinil was judged by the French Ministry of Health to be safe and effective, receiving regulatory approval for narcolepsy in France in February 1992. Product sales in France will be initiated by Lafon upon receipt of pricing and reimbursement approval. "The acquisition of marketing rights for modafinil fits within the company's strategic objective to license in product opportunities directed toward neurologists," stated Dr. Frank Baldino, Jr. "Modafinil is a product with proven safety in man that has already gained French regulatory approval. The company is planning to perform a Phase III study in the U.S. to facilitate the filing of an NDA for marketing approval for the treatment of narcolepsy." Narcolepsy is a sleep disorder which has severe negative impacts on public safety, sense of self-worth, social image and the ability to retain a job. Symptoms of this disease often originate in late childhood and are most notably characterized by an uncontrollable propensity to fall asleep during the day. There is no cure for narcolepsy. Current therapies that treat disease symptoms, such as amphetamine-type stimulants, are often addictive and may have other side  effects. Cephalon's results for the first quarter of 1993 will include a charge to earnings to reflect the payment made to Lafon upon execution of the agreement. Additionally, under the agreement Cephalon will purchase supplies of modafinil from Lafon and fund modafinil's clinical development in the U.S. and Mexico. The agreement also provides for royalty and certain other payments to Lafon. Mr. Francois Lafon commented that, "We are pleased to be working with a dynamic and focused company like Cephalon for the U.S. development and commercialization of modafinil." Founded in 1951, Lafon is a privately owned, research based, mid-size ethical pharmaceutical company in France. Lafon research specializes in discovery and development of innovative compounds, especially in CNS and cardiovascular therapies. Cephalon, Inc. is a leader in the development of products to treat neurological diseases and disorders. The company's primary focus is on neurodegenerative diseases which are characterized by the death of neurons, specialized conducting cells of the nervous system. The company has concentrated its research and development efforts on the prevention of neuronal death in several disorders, including Alzheimer's disease, amyotrophic lateral sclerosis, head and spinal cord injuries, peripheral neuropathy, retinopathy, and stroke. CONTACT: Lyn Hyduke, assistant director of corporate communications of Cephalon, Inc., 215-344-0200; Karen L. Bergman of Burns McClellan, 212-505-1919, for Cephalon, Inc.; or Bill Mattson, 314-469-7600, for Laboratoire L. Lafon LOAD-DATE: February 2, 1993 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS AND MEDICAL EDITORS Copyright 1993 PR Newswire Association, Inc. 996 of 998 DOCUMENTS Canada NewsWire November 19, 1992, Thursday CANADIAN LICENSE FOR NEW NEUROLOGY DRUG ACQUIRED BY DEPRENYL RESEARCH LIMITED FROM LABORATOIRE L. LAFON OF FRANCE SECTION: Financial News LENGTH: 247 words DATELINE: TORONTO, Nov. 19 Laboratoire L. Lafon of Paris, France and Deprenyl Research Limited (TSE: DEP; NASDAQ: DEPLF) announced today that they have concluded an agreement whereby Deprenyl Research has acquired an exclusive license to market Modafinil in Canada. Modafinil, recently approved in France, is a new drug for Narcolepsy, a disorder which affects an estimated 26,000 Canadians according to Sleep-Wake Disorders Canada, a national patient group.  The drug received extensive testing in Europe including testing on French military personnel during the Gulf war. Modafinil regulates wakefulness without cardiovascular effects in patients with sleeping disorders. It is an original new drug with a novel mechanism of action entirely unrelated to amphetamines or methylphenidate (Ritalin(R)). Modafinil has been shown to have a very good safe profile and a low abuse potential. Dr. Roger Mailhot, Deprenyl's Vice President Scientific Affairs, indicated that Deprenyl expects to submit the drug to Canadian regulatory authorities within the next ninety days. Deprenyl Research Limited is a Canadian pharmaceutical company which currently markets three neurologic drugs for Parkinson's disease. It is carrying out and sponsoring research in Alzheimer's disease, Epilepsy, Multiple Sclerosis and other neurologic disorders. The Company recently launched in Canada four of its drugs from its dermatologic division through its affiliate Lipopharm Inc. of Montreal, Quebec. For further information: AT THE COMPANY, Martin Barkin, MD, President & CEO, Deborah Worobec, Investor Relations (416) 537-4372, (416) 537-1653 fax; UNITED STATES CONTACT: O'Connor Biro & Associates, Jim Tolan, Senior Vice President (708) 498-2284, (708) 498-3144 fax LOAD-DATE: November 19, 1992 LANGUAGE: ENGLISH DISTRIBUTION: Attention Business Editors Copyright 1992 Canada NewsWire Ltd. 997 of 998 DOCUMENTS PR Newswire November 19, 1992, Thursday - 09:03 Eastern Time CANADIAN LICENSE FOR NEW NEUROLOGY DRUG ACQUIRED BY DEPRENYL RESEARCH LIMITED FROM LABORATOIRE L. LAFON OF FRANCE SECTION: Financial News LENGTH: 247 words DATELINE: TORONTO, Nov. 19 Laboratoire L. Lafon of Paris, France and Deprenyl Research Limited (TSE: DEP; NASDAQ: DEPLF) announced today that they have concluded an agreement whereby Deprenyl Research has acquired an exclusive license to market Modafinil in Canada. Modafinil, recently approved in France, is a new drug for narcolepsy, a disorder which affects an estimated 26,000 Canadians, according to Sleep-Wake Disorders Canada, a national patient group.  The drug received extensive testing in Europe including testing on French military personnel during the Gulf war. Modafinil regulates wakefulness without cardiovascular effects in patients with sleeping disorders. It is an original new drug with a novel mechanism of action entirely unrelated to amphetamines or methylphenidate (Ritalin R). Modafinil has been shown to have a good safety profile and a low abuse potential. Dr. Roger Mailhot, Deprenyl's vice president-scientific affairs, indicated that Deprenyl expects to submit the drug to Canadian regulatory authorities within the next ninety days. Deprenyl Research Limited is a Canadian pharmaceutical company which currently markets three neurologic drugs for Parkinson's disease. It is carrying out and sponsoring research in Alzheimer's disease, epilepsy, multiple sclerosis and other neurologic disorders. The company recently launched in Canada four of its drugs from its dermatologic division through its affiliate Lipopharm Inc. of Montreal, Quebec. LOAD-DATE: November 20, 1992 LANGUAGE: ENGLISH DISTRIBUTION: TO BUSINESS EDITOR Copyright 1992 PR Newswire Association, Inc. 998 of 998 DOCUMENTS Pharma Marketletter November 2, 1992 MODAFINIL APPROVED IN FRANCE LENGTH: 253 words Despite fears of misuse, the French regulatory authorities have granted marketing approval to Laboratoires L Lafon for modafinil, the so-called "anti-sleep pill" publicized during the Gulf war, where it was tested on French military personnel. Modafinil, a member of the adrafanil group of compounds, will have relatively limited indications once launched, namely narcolepsy and idiopathic hypersomnia. The fear of misuse of the compound has led to its inclusion in the context of new legislation covering the prescription of certain drugs. Under this legislation, modafinil will be included in the List I category (formerly Schedule A), and while prescribable by physicians working in office practice and hospital doctors, prescriptions must be made out using a dangerous substances pad. Nevertheless, the prescriptions will remain renewable on a monthly basis for a maximum of one year. The suggested dosing regimen for the product in the recommended indications is two to four tablets per 24 hours, given in the morning and at noon. Evening doses, while not recommended, have not been linked to insomnia. The most common adverse reaction reported, with an overall incidence of about 6%, is tension and agitation. These reactions come about as a result of modafinil's mode of action, as a stimulator of the central noradrenergic system. The price of modafinil has not yet been determined, and awaits consideration by the Medications Transparency Committee of documentation concerning the drug. LOAD-DATE: January 13, 2003 LANGUAGE: ENGLISH Copyright 1992 Marketletter Publications Ltd.