A Phase II Dose-Ranging Study Evaluating the Efficacy and Safety of the Orexin Receptor Antagonist Filorexant (MK-6096) in Patients with Primary Insomnia.

Background: Filorexant (MK-6096) is an orexin receptor antagonist; here, we evaluate the efficacy of filorexant in the treatment of insomnia in adults. Methods: A double-blind, placebo-controlled, randomized, two 4-week–period, adaptive crossover polysomnography study was conducted at 51 sites worldwide. Patients (18-<65 years) with insomnia received one of four doses of oral filorexant (2.5, 5, 10, 20 mg) once daily at bedtime during one period and matching placebo in the other period in one of eight possible treatment sequences. Polysomnography was performed on Night 1 and end of Week 4 of each period. Primary endpoint was sleep efficiency (SE) at Night 1 and end of Week 4. Secondary endpoints included wakefulness after persistent sleep onset (WASO) and latency to onset of persistent sleep (LPS). Results: A total of 324 patients received study treatment, 315 received ≥1 dose of placebo and 318 ≥1 dose of filorexant (2.5 mg, n=79; 5 mg, n=78; 10 mg, n=80; 20 mg, n=81). All filorexant doses (2.5/5/10/20 mg) were significantly superior to placebo in improving sleep among patients with insomnia as measured by SE and WASO on Night 1 and end of Week 4. The two higher filorexant doses (10/20 mg) were also significantly more effective than placebo in improving sleep onset as measured by LPS at Night 1 and end of Week 4. Filorexant was generally well tolerated. Conclusions: Orexin receptor antagonism by filorexant significantly improved SE in non-elderly patients with insomnia. Dose-related improvements in sleep onset and maintenance outcomes were also observed with filorexant.