@article{b72c3c9a2ff043aa8ee0b5240678a759,
title = "Phase II proof-of-concept trial of the orexin receptor antagonist filorexant (MK-6096) in patients with major depressive disorder",
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).",
keywords = "Depression, Filorexant, Mk-6096, Orexin receptor antagonist",
author = "Connor, {Kathryn M.} and Paulette Ceesay and Jill Hutzelmann and Duane Snavely and Krystal, {Andrew D.} and Trivedi, {Madhukar H.} and Michael Thase and Christopher Lines and Herring, {W. Joseph} and David Michelson",
note = "Funding Information: This assistance was funded by Merck & Co., Inc., Kenilworth, NJ.The authors are entirely responsible for the scientific content of the paper. Funding Information: K. M. Connor, P. Ceesay, J. Hutzelmann, D. Snavely, C. Lines, W. J. Herring, and D. Michelson are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, and own stock/stock options in Merck. A.D. Krystal has received grants/research support from NIH, Teva, Sunovion, Astellas, Abbott, Neosync, Brainsway, Janssen, ANS St. Jude, Novartis. He has served as a consultant to: Abbott, Astellas, AstraZeneca, Attentiv, BMS,Teva, Eisai, Eli Lilly, GlaxoSmithKline, Jazz, Janssen, Merck, Neurocrine, Novartis, Otsuka, Lundbeck, Roche, Sanofi-Aventis, Somnus, Sunovion, Somaxon, Takeda, Transcept, and Vantia. M. H. Trivedi is or has been an advisor/consultant and received fees from: Abbott Laboratories, Inc., Abdi Ibrahim, Akzo (Organon Pharmaceuticals Inc.), Allergan, Alkermes, Arcadia Pharmaceuticals, AstraZeneca, Axon Advisors, Brintellix, Bristol-Myers Squibb Company, Cephalon, Inc., Cerecor, CME Institute of Physicians, Concert Pharmaceuticals, Inc., Eli Lilly & Company, Evotec, Fabre Kramer Pharmaceuticals, Inc., Forest Pharmaceuticals, GlaxoSmithKline, Health Research Associates, Janssen Global Services, LLC, Janssen Pharmaceutica Products, LP, Johnson & Johnson PRD, Libby, Lundbeck, Meade Johnson, MedAvante, Medtronic, Medscape, Merck, Mitsubishi Tanabe Pharma Development America, Inc., MSI Methylation Sciences Inc., Naurex, Neuronetics, Nestle Health Science-Pamlab Inc., One Carbon Therapeutics Ltd., Otsuka Pharmaceuticals, Pamlab, Parke-Davis Pharmaceuticals, Inc., Pfizer Inc., PgxHealth, Phoenix Marketing Solutions, Rexahn Pharmaceuticals, Ridge Diagnostics, Roche Products Ltd., Sepracor, SHIRE Development, Sierra, SK Life and Science, Sunovion, Takeda, Tal Medical/ Puretech Venture, Targacept, Transcept, VantagePoint, Vivus, and Wyeth-Ayerst Laboratories. In addition, he has received grants/ research support from: Agency for Healthcare Research and Quality (AHRQ), Cyberonics, Inc., National Alliance for Research in Schizophrenia and Depression, National Institute of Mental Health and National Institute on Drug Abuse, National Institute of Diabetes and Digestive Disorders, Johnson & Johnson, Janssen Research and Development. M. Thase has, during the last 3 years, received earning fees as a consultant to Acadia, Alkermes, Allergan (Forest, Naurex), AstraZeneca, Avenir, Cerecor, Eli Lilly & Co, Fabre-Kramer Pharmaceuticals, Inc., Gerson Lehman Group, Guidepoint Global, Johnson & Johnson (Janssen, Ortho-McNeil), H. Lundbeck A/S, MedAvante, Inc, Merck, Moksha8, Nestle (PamLab), Novartis, Otsuka, Pfizer, Shire, Sunovion, and Takeda. During the same timeframe, he has received research grants from Agency for Healthcare Research and Quality, Alkermes, Assurex, Avanir, Forest Pharmaceuticals, Janssen (Johnson & Johnson), Intracellular, the National Institute of Mental Health, Otsuka Pharmaceuticals, and Takeda. He has equity holdings in MedAvante. He receives royalties from the American Psychiatric Foundation, Guilford Publications, Herald House, and W.W. Norton & Company, Inc. His spouse is an employee of Peloton Advantage, which does business with several pharmaceutical companies. Publisher Copyright: {\textcopyright} The Author 2017.",
year = "2017",
month = aug,
day = "1",
doi = "10.1093/ijnp/pyx033",
language = "English (US)",
volume = "20",
pages = "613--618",
journal = "International Journal of Neuropsychopharmacology",
issn = "1461-1457",
publisher = "Cambridge University Press",
number = "8",
}