BY OUR PHARMA CORRESPONDENT
6 August, 2005: Studies with its investigative new drug showed that Provigil can improve patients’ ability to remain awake and alert, announces Cephalon, Inc, a Pennsylvania-based drug firm.
The results of pivotal phase three study of Provigil (modafinil) in patients with shift work sleep disorder (SWSD) has been published in this week's New England Journal of Medicine. In the first ever clinical study of SWSD, patients taking Provigil showed improvements in their wakefulness, performance and level of attention.
"This study further clarifies the role excessive sleepiness plays in shift work sleep disorder, and the value of Provigil in treating excessive sleepiness," said Dr Paul Blake, Executive Vice President, Worldwide Medical and Regulatory Operations at Cephalon. "We have completed an even larger phase three study in shift work sleep disorder with our second wake-promoting agent, Nuvigil (armodafinil) tablets [C-IV], which currently is being reviewed as part of our request for marketing approval by the Food and Drug Administration.’’
"This is a very important first study demonstrating the value of an effective therapy for shift work sleep disorder and illustrates the need for further research to identify other effective therapies for these patients, whose sleepiness was not completely resolved with treatment," stated Charles A Czeisler, PhD, MD, Professor of Sleep Medicine at Harvard Medical School and lead study author. "Patients with this under-recognized condition are just as sleepy at night as patients with narcolepsy or obstructive sleep apnea during the day."
The three-month, randomized, double-blind, placebo-controlled study sponsored by Cephalon was conducted at 28 centers in the United States between December 2001 and September 2002. All 204 patients treated in the study were pre-screened for SWSD and received 200 milligrams of Provigil or placebo.
Key results of the study show that Provigil significantly improved patients' level of alertness when measured objectively, as compared to patients treated with placebo; reduced patients' level of sleepiness when measured subjectively, as compared to patients treated with placebo; a significant reduction in the number and duration of lapses of attention during 20-minute computerized tests conducted in a sleep lab, as compared to patients treated with placebo. A higher percentage of patients treated with Provigil (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).
According to the American Academy of Sleep Medicine, International Classification of Sleep Disorders (ICSD), shift work sleep disorder is classified as a circadian-rhythm sleep disorder. Working at night and sleeping during the day disrupts circadian rhythms, which control the body's natural cycle of sleeping and waking. Sleep can be disrupted and quality of sleep compromised by having a work schedule that is contrary to natural sleeping patterns. Trying to maintain a healthy pattern of sleep during the daytime is difficult because individuals are trying to sleep when their bodies want them to be awake.
People who frequently rotate shifts or work at night are most at risk for SWSD. The Bureau of Labor Statistics estimates that approximately 6 million Americans work at night on a permanent or rotating basis. However, not every night shift worker suffers from SWSD. A recent study indicates that 10 per cent of night shift workers may meet the criteria for a diagnosis of SWSD. According to the ICSD, a constant or recurrent pattern of sleep interruption that results in symptoms such as insomnia and/or excessive sleepiness is necessary for a diagnosis of SWSD. Other symptoms of SWSD include difficulty concentrating and lack of energy.
In January 2004, the US Food and Drug Administration (FDA) approved Provigil as the first and only medication to treat excessive sleepiness associated with SWSD and with obstructive sleep apnea/hypopnea syndrome (OSA/HS). Provigil is indicated as an adjunct to standard treatment for the underlying airway obstruction in OSA/HS. Now available in more than 20 countries, Provigil was approved in the United States for improving wakefulness in patients with excessive sleepiness associated with narcolepsy in 1998.
Provigil is the first medication in a class of wake-promoting agents. The medication is believed to work selectively through the sleep-wake centers to activate the cortex of the brain. Activation of the cortex is essential for wakefulness. The exact mechanism of action of Provigil is not known. Provigil promotes wakefulness without causing the generalized stimulation to the brain associated with central nervous system (CNS) stimulants.
The safety of Provigil has been demonstrated in clinical trials enrolling more than 3,500 patients. Provigil has been shown to have no effect on the patients' ability to follow their normal sleep schedule. Studies have demonstrated that the sleep of patients taking Provigil was of similar quality and quantity to individuals on placebo.
In clinical trials, Provigil was well tolerated, with an incidence of adverse events generally comparable to placebo. Most adverse events were mild to moderate. The most frequently reported adverse events were headache, nausea, nervousness, stuffy nose, diarrhea, back pain, anxiety, trouble sleeping, dizziness and upset stomach.
While the drug does treat the symptom of excessive sleepiness, it does not treat the underlying disorder, and it may not completely resolve sleepiness. Patients with excessive sleepiness, including those taking Provigil, should be frequently reassessed for their degree of sleepiness and, if appropriate, advised to avoid driving or other potentially dangerous activities. Physicians should also be aware that patients may not acknowledge sleepiness or drowsiness until directly questioned about drowsiness or sleepiness during specific activities, Cephalon alerted.
Founded in 1987, Cephalon, Inc is an international biopharmaceutical company involved in 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. US sites include the company's headquarters in Frazer, Pennsylvania, and offices, laboratories or manufacturing facilities in 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, Gabatril (tiagabine hydrochloride), Actiq (oral transmucosal fentanyl citrate) [C-II] and Trisenox (arsenic trioxide) injection and more than 20 products internationally.
BY OUR PHARMA CORRESPONDENT