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Clinical Trial
. 2016 Aug 12;19(8):pyw022.
doi: 10.1093/ijnp/pyw022. Print 2016 Aug.

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

Kathryn M Connor  1 , Erin Mahoney  2 , Saheeda Jackson  2 , Jill Hutzelmann  2 , Xin Zhao  2 , Nan Jia  2 , Ellen Snyder  2 , Duane Snavely  2 , David Michelson  2 , Thomas Roth  2 , W Joseph Herring  2
Affiliations
Clinical Trial

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

Kathryn M Connor et al. Int J Neuropsychopharmacol. .

Abstract

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 to <65 years) 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.

Trial registration: ClinicalTrials.gov NCT01021852.

Keywords: dose-ranging study; filorexant; insomnia; orexin receptor antagonist; sleep efficiency.

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Figures

Figure 1.
Figure 1.
Patient disposition. AE, adverse event; FIL, filorexant; PL, placebo.
Figure 2.
Figure 2.
Difference in least-squares means between filorexant and placebo at night 1 and week 4 for (A) sleep efficiency (SE), (B) wakefulness after sleep onset (WASO), and (C) latency to persistent sleep (LPS). Footnote (A): night 1, P<.001 for all doses; week 4, P≤.001 for filorexant 2.5, 10, and 20mg and P=.004 for filorexant 5mg. Footnote (B): night 1, P<.001 for all doses; week 4, P=.006 for filorexant 2.5mg, P=.020 for filorexant 5mg, P<.001 for filorexant 10 and 20mg. Footnote (C): night 1, P=.022 for filorexant 2.5mg, P<.001 for filorexant 5, 10, and 20mg; week 4, P=.055 for filorexant 2.5mg, P=.060 for filorexant 5mg, P<.001 for filorexant 10mg, P=.015 for filorexant 20mg. LPS, latency to persistent sleep; LSM, least-squares mean; SE, sleep efficiency; WASO, wakefulness after sleep onset.
See this image and copyright information in PMC

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