Investigational Dual Orexin Receptor Antagonist Almorexant Meets Primary Endpoint In Two-week Phase III Study Of Primary Insomnia
Actelion Ltd (SIX: ATLN) announced today that the first phase III study with almorexant (RESTORA 1) has met its primary endpoint, superiority of the dual orexin receptor antagonist almorexant compared to placebo on objective and subjective wake after sleep onset (WASO). The finding was highly significant (p<0.001). In addition, several secondary endpoints of the study were met with statistical significance. In RESTORA 1, the use of almorexant was well-tolerated. However, in this study as well as in the ongoing non-pivotal program, certain safety observations were made that will require further evaluation and assessment in longer-term Phase III studies. The Phase III studies are currently in preparation - in both adults and elderly patients suffering from primary insomnia - and will evaluate long-term efficacy and safety. Professor Jed Black, M.D. and VP Sleep Development at Actelion, commented: "In this two-week study, almorexant has demonstrated clinically meaningful effects on both sleep induction and sleep maintenance for patients suffering from primary insomnia.
Research published in the current issue of the journal, Clinical Science, appears to have found a link between obstructive sleep apnoea and non-alcoholic steatohepatitis. Dr Anne-Christine Piguet and colleagues from the University of Bern, Switzerland, kept mice for a week in low-oxygen atmospheres and found that it led to increased levels of fat and inflammation in their livers. Apnoea means "without breath" and occurs when the muscles in the airways behind the tongue relax in sleep, causing the person to snore and briefly, to stop breathing. Nonalcoholic steatohepatitis (NASH) is a common, often "silent" liver disease occurring in around 40% of the population. It resembles alcoholic liver disease, but occurs in people who drink little or no alcohol. The major feature in NASH is fat in the liver, along with inflammation and damage. NASH can be severe and can lead to cirrhosis, in which the liver is permanently damaged and scarred and no longer able to work properly. Obesity predisposes patients to both fatty liver diseases and obstructive sleep apnoea.
Cephalon Provides Update On Regulatory Review Of NUVIGIL For The Treatment Of Excessive Sleepiness Associated With Jet Lag Disorder
Cephalon, Inc. (Nasdaq: CEPH) 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).
Many alcoholic beverages contain byproducts of the materials used in the fermenting process. These byproducts are called "congeners, " complex organic molecules with toxic effects including acetone, acetaldehyde, fusel oil, tannins, and furfural. Bourbon has 37 times the amount of congeners that vodka has. A new study has found that while drinking a lot of bourbon can cause a worse hangover than drinking a lot of vodka, impairment in people's next-day task performance is about the same for both beverages. Results will be published in the March 2010 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View. "While the toxic chemicals called congeners could be poisonous in large amounts, they occur in very small amounts in alcoholic beverages, " explained Damaris J. Rohsenow, professor of community health at the Center for Alcohol and Addiction Studies at Brown University. "There are far more of them in the darker distilled beverages and wines than in the lighter colored ones.
A study in the Oct. 15 issue of the Journal of Clinical Sleep Medicine found that while a strict diet and exercise program may benefit obese patients with mild to moderate obstructive sleep apnea (OSA), it is unlikely to eliminate the condition. Results show improvement in typical OSA symptoms including snoring, daytime sleepiness, impaired vigilance, poor quality of life and mood after the completion of a 16-week diet and exercise program. Weight loss was significant, with an average loss of 12.3 kg (about 27 pounds), representing 12.9 percent of baseline total body weight. Although weight loss reduced the average apnea-hypopnea index (AHI) by 25 percent from 24.6 to 18.3 breathing pauses per hour of sleep, the change was not statistically significant. Principal investigator Maree Barnes, MBBS, sleep medicine practitioner and senior research fellow at the Institute for Breathing and Sleep at Austin Hospital in Victoria, Australia, said that the exercise program resulted in improved fitness and muscle strength, which is important in obese OSA patients;
New research just released is affirming a long-held maxim: you are what you eat - and, more to the point, what you eat has a profound influence on the brain. The findings offer insight into the neurobiological factors behind the obesity epidemic in the United States and other developed countries. The findings exposed changes in brain chemistry due to diet and weight gain, and were reported at Neuroscience 2009, the Society for Neuroscience's annual meeting and the world's largest source of emerging news about brain science and health. Obesity has been linked to rises in diabetes, stroke, and heart attacks, among other disorders. In the past decade alone, medical spending for obesity is estimated to have increased 87 percent in the United States - reaching $147 billion in 2008 - according to a study funded by the Centers for Disease Control and Prevention. The new research adds another dimension to understanding how obesity rates have more than doubled in the past 30 years. The new findings show that: Disruptions in the sleep/wake cycle lead to weight gain, impulsivity, slower thinking, and other physiological and behavioral changes.
Molecules that may hold the key to new ways to fight cancer and other diseases have been found to play an important role in regulating circadian rhythm, says Liheng Shi, a researcher in Texas A&M's Department of Veterinary Integrative Biosciences. Circadian rhythm is the roughly 24-hour cycle of physiological activities of humans, animals and even bacteria, Shi explains. He and colleagues have had their research, currently focusing on the circadian rhythm in chickens' eyes, published in the Journal of Biological Chemistry. Chicken eyes have a lot in common with human eyes. "The prefix 'photo-' in photoreceptors means light, and photoreceptors in animals' eyes receive light signals and then translate them into signals that their brain can understand, and that is how they see, " he explains. Shi notes there are two kinds of photoreceptors - cone photoreceptors and rod photoreceptors, named for the shape they resemble. Some channels that scientists call L-VGCCs are important to the circadian rhythm in chickens' eyes.
Too much light at night can lead to symptoms of depression, according to a new study in mice. Researchers found that mice housed in a lighted room 24 hours a day exhibited more depressive symptoms than did similar mice that had a normal light-dark cycle. However, mice that lived in constant light, but could escape into a dark, opaque tube when they wanted showed less evidence of depressive symptoms than did mice that had 24-hour light, but only a clear tube in their housing. "The ability to escape light seemed to quell the depressive effects, " said Laura Fonken, lead author of the study and a graduate student in psychology at Ohio State University. "But constant light with no chance of escape increased depressive symptoms." The results suggest that more attention needs to be focused on how artificial lighting affects emotional health in humans, according to study co-author Randy Nelson, a professor of neuroscience and psychology at Ohio State. "The increasing rate of depressive disorders in humans corresponds with the increasing use of light at night in modern society, " he said.
A research collaboration led by biologists and neuroscientists at the University of Pennsylvania has found a molecular pathway in the brain that is the cause of cognitive impairment due to sleep deprivation. Just as important, the team believes that the cognitive deficits caused by sleep deprivation, such as an inability to focus, learn or memorize, may be reversible by reducing the concentration of a specific enzyme that builds up in the hippocampus of the brain. It is known that sleep deprivation can have cognitive consequences, including learning and memory deficits, but the mechanisms by which sleep deprivation affects brain function remain unknown. A particular challenge has been to develop approaches to reverse the impact of sleep deprivation on cognitive function. The findings, reported in this week's issue of the journal Nature, could present a new approach to treating the memory and learning deficits of insomnia. A molecular mechanism by which brief sleep deprivation alters hippocampal function is now identified in mice, involving the impairment of cyclic-AMP- and protein-kinase-A-dependent forms of synaptic plasticity, or readiness for cognitive function.
Despite recent advances in anti-inflammatory therapy, many rheumatoid arthritis (RA) patients continue to suffer from pain. Research published in BioMed Central's open access journal, Arthritis Research & Therapy found that inflammation is associated with heightened pain sensitivity at joint sites, whereas increased sleep problems are associated with heightened pain sensitivity at both joint and non-joint sites. Researchers from the Division of Rheumatology and Pain Management Center of Brigham and Women's Hospital, and the Chronic Pain and Fatigue Center of the University of Michigan Medical School, assessed experimental pain sensitivity, disease activity, sleep problems and psychiatric distress in 59 women with RA. The researchers used questionnaires to assess the women's sleep problems and psychiatric distress and measured the levels of C-reactive protein as an indicator of disease activity. They also measured pain sensitivity with pressure pain threshold testing at joint and non-joint sites.