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Phase 3 Trial That Measures Efficacy and Tolerability of Ocinaplon Initiated
This clinical trial is a randomized, double-blind, placebo-controlled, outpatient study assessing the efficacy and tolerability of ocinaplon. After a seven-day placebo lead-in, qualifying patients will be randomized into one of three groups and dosed over a 28-day period with either placebo, 30 mg of ocinaplon twice a day or 60 mg of ocinaplon once a day. The primary endpoint is statistically significant improvement in Hamilton Anxiety Rating Scale scores as compared to placebo.
Dr. Warren Stern, DOV's Senior Vice President of Drug Development, stated, "The initiation of the ocinaplon Phase III program is an important step in the development of this novel anxiolytic, as we hope to confirm the efficacy we demonstrated in earlier studies and establish safety, particularly with regard to hepatic function, in this larger-scale trial. In two previous placebo- controlled Phase II studies in which ocinaplon was administered for either 14 or 28 days, GAD patients treated with ocinaplon exhibited a statistically significant reduction in anxiety after one week of dosing. The magnitude of anxiety reduction measured after four weeks of ocinaplon administration was greater than what has previously been seen with benzodiazepines, SSRIs or SNRIs, classes of drugs commonly prescribed for the treatment of anxiety. In addition, the incidence of daytime drowsiness, a common side effect associated with benzodiazepine anxiolytics, was no different in ocinaplon and placebo-treated patients. Furthermore, termination of ocinaplon administration did not result in rebound anxiety, a condition observed with benzodiazepines related to their propensity for producing dependence."
Ocinaplon is DOV's product candidate for the treatment of anxiety disorders, including GAD, the first indication for which the Company intends to seek FDA approval. Anxiety can be defined in broad terms as a state of unwarranted or inappropriate worry, often accompanied by restlessness, tension, distraction, irritability and sleep disturbances and is made up of various disorders, including GAD, panic disorder and phobias. GAD is the most common of the anxiety disorders, with a lifetime prevalence of approximately 5%. Every year, it is estimated that approximately 15 million people in the U.S. suffer solely from an anxiety disorder.
The Company believes ocinaplon, a non-benzodiazepine, can address significant unmet needs for the treatment of anxiety disorders. Ocinaplon appears to selectively modulate a specific subset of GABAA receptors that DOV believes are involved in the mediation of anxiety. Preclinical studies have demonstrated that ocinaplon produces an anti-anxiety effect at doses 20 to 40 times lower than doses that produce sedation and muscle relaxation and 10 times lower than doses that produce amnesia. In preclinical studies, ocinaplon was also shown to be 15 times less likely than Valium to potentiate the sedating effects of alcohol. By contrast, benzodiazepines often produce these side effects at doses approximating those that produce an anti-anxiety effect.
To date, 11 clinical trials on ocinaplon have been conducted, including nine Phase I trials. In these clinical trials, ocinaplon was shown to be safe and well-tolerated at the maximum doses used, with no evidence of sedation or any other side effects typically associated with benzodiazepines. To date, 477 subjects have been treated with ocinaplon.
In DOV's two Phase II double-blind, placebo-controlled clinical trials, ocinaplon exhibited the following characteristics:
-- efficacy at least comparable to what has been reported for benzodiazepines;
-- rapid onset of action;
-- a favorable side effect profile not significantly different from placebo; and
-- no "rebound" anxiety following treatment cessation.
Source: DOV Pharmaceutical, Inc.