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

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The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)


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 toyears) with insomnia received 1 of 4 doses of oral filorexant (2.5, 5, 10, 20mg) once daily at bedtime during one period and matching placebo in the other period in 1 of 8 possible treatment sequences. Polysomnography was performed on night 1 and end of week 4 of each period. The primary endpoint was sleep efficiency at night 1 and end of week 4. Secondary endpoints included wakefulness after persistent sleep onset and latency to onset of persistent sleep.

RESULTS: A total of 324 patients received study treatment, 315 received ≥1 dose of placebo, and 318 ≥1 dose of filorexant (2.5mg, n=79; 5mg, n=78; 10mg, n=80; 20mg, n=81). All filorexant doses (2.5/5/10/20mg) were significantly superior to placebo in improving sleep among patients with insomnia as measured by sleep efficiency and wakefulness after persistent sleep onset on night 1 and end of week 4. The 2 higher filorexant doses (10/20mg) were also significantly more effective than placebo in improving sleep onset as measured by latency to onset of persistent sleep at night 1 and end of week 4. Filorexant was generally well tolerated.

CONCLUSIONS: Orexin receptor antagonism by filorexant significantly improved sleep efficiency in nonelderly patients with insomnia. Dose-related improvements in sleep onset and maintenance outcomes were also observed with filorexant.

Medical Subject Headings

Adolescent; Adult; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Orexin Receptor Antagonists; Piperidines; Polysomnography; Pyrimidines; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Young Adult

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