Neurocrine Biosciences, Inc. announced preliminary positive results from two of the Company's Phase III clinical trials. The trials reported today evaluated the two formulations of indiplon, immediate release and modified release, in elderly patients with chronic insomnia. Neurocrine has now completed Phase I, II and III clinical trials in over 7000 subjects to date in one of the most comprehensive clinical programs in insomnia to address the multiple needs of younger and older adult patients with insomnia such as sleep initiation, sleep maintenance, middle of the night awakenings, and long-term administration. Neurocrine is moving forward to complete regulatory documents for submitting its New Drug Applications (NDAs) for the immediate release and modified release formulations.
The Company reported preliminary efficacy and safety results from its Phase III trial with two dose levels (20 mg and 30 mg) of indiplon modified release in approximately 340 elderly patients with chronic insomnia who have sleep maintenance difficulties. Efficacy results with indiplon modified release demonstrated highly statistically significant improvements as measured objectively over eight hours by polysomnography (PSG) in Wake After Sleep Onset (WASO) after the first two nights of dosing at both doses (p<0.0001). Further analysis of WASO data based on seven hours of recording was highly statistically significant for both doses at all time points (p<0.001). Other secondary sleep maintenance and initiation endpoints including Total Sleep Time (TST), Sleep Efficiency (SE), Wake Time During Sleep (WTDS), and Latency to Persistent Sleep (LPS) were also statistically significantly improved over placebo at all time points for both doses. Patient reported Sleep Quality also showed significant improvement over placebo. There was no evidence of tolerance observed at either dose for sleep maintenance or sleep initiation. Safety results were similar to what had been observed in other indiplon modified release studies.
The study was a randomized, double-blind, placebo-controlled, parallel-group, multi-center, in-patient, out-patient Phase III clinical trial conducted in 30 sleep centers in the U.S. Patients received nightly administration of one of two dose levels of indiplon or placebo over a 35-day period.
Neurocrine also reported additional safety results from its Phase III clinical trial with two doses (5 mg and 10 mg) of the immediate release formulation of indiplon in approximately 120 elderly patients for six months of treatment. Safety results demonstrated that the incidence of adverse events was similar to what had been observed in long-term studies conducted previously with indiplon. Results also demonstrated that with administration of indiplon immediate release, the majority of patients reported sleep benefit during the six-month treatment period. The study was a Phase III double-blind, out-patient extension study to assess the long-term safety of indiplon immediate release in elderly patients who had successfully completed a previously conducted Phase III two-week out-patient study with indiplon immediate release.
"The results of this study with indiplon modified release demonstrated more favorable efficacy to date for PSG monitored sleep maintenance studies as compared with results presented for other similar compounds. We believe that our four Phase III MR trials will satisfy the registration requirements for demonstrating sleep maintenance. The results today showed significant clinical benefit with both indiplon immediate release and modified release in helping elderly patients initiate and maintain sleep," said Dr. Henry Pan, executive vice president and chief medical officer for Neurocrine Biosciences. "These data support earlier results demonstrating the safety and efficacy of the product in our comprehensive clinical program in over 7000 subjects, including 5000 younger and older adult patients with chronic and transient insomnia in our Phase III program alone."
Indiplon is a unique non-benzodiazapine agent that acts on a specific site of the GABA-A receptor. Indiplon has been shown to bind selectively to the specific subtype of GABA-A receptors within the brain believed to be responsible for promoting sleep. Two formulations of indiplon, immediate release and modified release, are being evaluated in clinical trials to address different types of sleep problems. Indiplon was licensed from DOV Pharmaceutical in 1998.