Phase II proof-of-concept trial of the orexin receptor antagonist filorexant (MK-6096) in patients with major depressive disorder

Kathryn M. Connor, Paulette Ceesay, Jill Hutzelmann, Duane Snavely, Andrew D. Krystal, Madhukar H. Trivedi, Michael Thase, Christopher Lines, W. Joseph Herring, David Michelson

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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: clinicaltrials.gov: NCT01554176).

Original languageEnglish (US)
Pages (from-to)613-618
Number of pages6
JournalInternational Journal of Neuropsychopharmacology
Volume20
Issue number8
DOIs
StatePublished - Aug 1 2017

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Major Depressive Disorder
Placebos
Therapeutics
Orexin Receptors
Depression
Suicidal Ideation
Antidepressive Agents
Registries
MK-6096
Orexin Receptor Antagonists
Clinical Trials

Keywords

  • Depression
  • Filorexant
  • Mk-6096
  • Orexin receptor antagonist

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Phase II proof-of-concept trial of the orexin receptor antagonist filorexant (MK-6096) in patients with major depressive disorder. / Connor, Kathryn M.; Ceesay, Paulette; Hutzelmann, Jill; Snavely, Duane; Krystal, Andrew D.; Trivedi, Madhukar H.; Thase, Michael; Lines, Christopher; Herring, W. Joseph; Michelson, David.

In: International Journal of Neuropsychopharmacology, Vol. 20, No. 8, 01.08.2017, p. 613-618.

Research output: Contribution to journalArticle

Connor, KM, Ceesay, P, Hutzelmann, J, Snavely, D, Krystal, AD, Trivedi, MH, Thase, M, Lines, C, Herring, WJ & Michelson, D 2017, 'Phase II proof-of-concept trial of the orexin receptor antagonist filorexant (MK-6096) in patients with major depressive disorder', International Journal of Neuropsychopharmacology, vol. 20, no. 8, pp. 613-618. https://doi.org/10.1093/ijnp/pyx033
Connor, Kathryn M. ; Ceesay, Paulette ; Hutzelmann, Jill ; Snavely, Duane ; Krystal, Andrew D. ; Trivedi, Madhukar H. ; Thase, Michael ; Lines, Christopher ; Herring, W. Joseph ; Michelson, David. / Phase II proof-of-concept trial of the orexin receptor antagonist filorexant (MK-6096) in patients with major depressive disorder. In: International Journal of Neuropsychopharmacology. 2017 ; Vol. 20, No. 8. pp. 613-618.
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