Phase II Proof-of-Concept Trial of the Orexin Receptor Antagonist Filorexant (MK-6096) in Patients with Major Depressive Disorder

Int J Neuropsychopharmacol. 2017 Aug 1;20(8):613-618. doi: 10.1093/ijnp/pyx033.


Background: We evaluated the orexin receptor antagonist filorexant (MK-6096) for treatment augmentation in patients with major depressive disorder.

Methods: We conducted a 6-week, double-blind, placebo-controlled, parallel-group, Phase II, proof-of-concept study. Patients with major depressive disorder (partial responders to ongoing antidepressant therapy) were randomized 1:1 to once-daily oral filorexant 10 mg or matching placebo.

Results: Due to enrollment challenges, the study was terminated early, resulting in insufficient statistical power to detect a prespecified treatment difference; of 326 patients planned, 129 (40%) were randomized and 128 took treatment. There was no statistically significant difference in the primary endpoint of change from baseline to week 6 in Montgomery Asberg Depression Rating Scale total score; the estimated treatment difference for filorexant-placebo was -0.7 (with negative values favoring filorexant) (P=.679). The most common adverse events were somnolence and suicidal ideation.

Conclusions: The interpretation of the results is limited by the enrollment, which was less than originally planned, but the available data do not suggest efficacy of orexin receptor antagonism with filorexant for the treatment of depression. (Clinical Trial Registry: NCT01554176).

Keywords: MK-6096; depression; filorexant; orexin receptor antagonist.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use*
  • Depressive Disorder, Major / drug therapy*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Orexin Receptor Antagonists / adverse effects
  • Orexin Receptor Antagonists / therapeutic use*
  • Piperidines / adverse effects
  • Piperidines / therapeutic use*
  • Proof of Concept Study
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*
  • Treatment Failure
  • Young Adult


  • Antidepressive Agents
  • MK-6096
  • Orexin Receptor Antagonists
  • Piperidines
  • Pyrimidines

Associated data