title: A Phase II Dose-Ranging Study Evaluating the Efficacy and Safety of the Orexin Receptor Antagonist Filorexant (MK-6096) in Patients with Primary Insomnia.
abstract: Filorexant (MK-6096) is an orexin receptor antagonist; here, we evaluate the efficacy of filorexant in the treatment of insomnia in adults.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ (Dr Connor, Ms Mahoney, Ms Jackson, Ms Hutzelmann, Dr Zhao, Dr Jia, Dr Snyder, Mr Snavely, Dr Michelson, and Dr Herring); Henry Ford Hospital, Detroit, MI (Dr Roth).Current affiliations: Biogen, Cambridge, MA (E.M.). Janssen Pharmaceutical Research and Development, Raritan, NJ (X.Z.). Eli Lilly and Company, Indianapolis, IN (N.J.) kathryn.connor@merck.com.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Connor
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ (Dr Connor, Ms Mahoney, Ms Jackson, Ms Hutzelmann, Dr Zhao, Dr Jia, Dr Snyder, Mr Snavely, Dr Michelson, and Dr Herring); Henry Ford Hospital, Detroit, MI (Dr Roth).Current affiliations: Biogen, Cambridge, MA (E.M.). Janssen Pharmaceutical Research and Development, Raritan, NJ (X.Z.). Eli Lilly and Company, Indianapolis, IN (N.J.).
authors.forename: Erin
authors.initials: E
authors.lastname: Mahoney
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ (Dr Connor, Ms Mahoney, Ms Jackson, Ms Hutzelmann, Dr Zhao, Dr Jia, Dr Snyder, Mr Snavely, Dr Michelson, and Dr Herring); Henry Ford Hospital, Detroit, MI (Dr Roth).Current affiliations: Biogen, Cambridge, MA (E.M.). Janssen Pharmaceutical Research and Development, Raritan, NJ (X.Z.). Eli Lilly and Company, Indianapolis, IN (N.J.).
authors.forename: Saheeda
authors.initials: S
authors.lastname: Jackson
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ (Dr Connor, Ms Mahoney, Ms Jackson, Ms Hutzelmann, Dr Zhao, Dr Jia, Dr Snyder, Mr Snavely, Dr Michelson, and Dr Herring); Henry Ford Hospital, Detroit, MI (Dr Roth).Current affiliations: Biogen, Cambridge, MA (E.M.). Janssen Pharmaceutical Research and Development, Raritan, NJ (X.Z.). Eli Lilly and Company, Indianapolis, IN (N.J.).
authors.forename: Jill
authors.initials: J
authors.lastname: Hutzelmann
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ (Dr Connor, Ms Mahoney, Ms Jackson, Ms Hutzelmann, Dr Zhao, Dr Jia, Dr Snyder, Mr Snavely, Dr Michelson, and Dr Herring); Henry Ford Hospital, Detroit, MI (Dr Roth).Current affiliations: Biogen, Cambridge, MA (E.M.). Janssen Pharmaceutical Research and Development, Raritan, NJ (X.Z.). Eli Lilly and Company, Indianapolis, IN (N.J.).
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ (Dr Connor, Ms Mahoney, Ms Jackson, Ms Hutzelmann, Dr Zhao, Dr Jia, Dr Snyder, Mr Snavely, Dr Michelson, and Dr Herring); Henry Ford Hospital, Detroit, MI (Dr Roth).Current affiliations: Biogen, Cambridge, MA (E.M.). Janssen Pharmaceutical Research and Development, Raritan, NJ (X.Z.). Eli Lilly and Company, Indianapolis, IN (N.J.).
authors.forename: Nan
authors.initials: N
authors.lastname: Jia
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ (Dr Connor, Ms Mahoney, Ms Jackson, Ms Hutzelmann, Dr Zhao, Dr Jia, Dr Snyder, Mr Snavely, Dr Michelson, and Dr Herring); Henry Ford Hospital, Detroit, MI (Dr Roth).Current affiliations: Biogen, Cambridge, MA (E.M.). Janssen Pharmaceutical Research and Development, Raritan, NJ (X.Z.). Eli Lilly and Company, Indianapolis, IN (N.J.).
authors.forename: Ellen
authors.initials: E
authors.lastname: Snyder
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ (Dr Connor, Ms Mahoney, Ms Jackson, Ms Hutzelmann, Dr Zhao, Dr Jia, Dr Snyder, Mr Snavely, Dr Michelson, and Dr Herring); Henry Ford Hospital, Detroit, MI (Dr Roth).Current affiliations: Biogen, Cambridge, MA (E.M.). Janssen Pharmaceutical Research and Development, Raritan, NJ (X.Z.). Eli Lilly and Company, Indianapolis, IN (N.J.).
authors.forename: Duane
authors.initials: D
authors.lastname: Snavely
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ (Dr Connor, Ms Mahoney, Ms Jackson, Ms Hutzelmann, Dr Zhao, Dr Jia, Dr Snyder, Mr Snavely, Dr Michelson, and Dr Herring); Henry Ford Hospital, Detroit, MI (Dr Roth).Current affiliations: Biogen, Cambridge, MA (E.M.). Janssen Pharmaceutical Research and Development, Raritan, NJ (X.Z.). Eli Lilly and Company, Indianapolis, IN (N.J.).
authors.forename: David
authors.initials: D
authors.lastname: Michelson
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ (Dr Connor, Ms Mahoney, Ms Jackson, Ms Hutzelmann, Dr Zhao, Dr Jia, Dr Snyder, Mr Snavely, Dr Michelson, and Dr Herring); Henry Ford Hospital, Detroit, MI (Dr Roth).Current affiliations: Biogen, Cambridge, MA (E.M.). Janssen Pharmaceutical Research and Development, Raritan, NJ (X.Z.). Eli Lilly and Company, Indianapolis, IN (N.J.).
authors.forename: Thomas
authors.initials: T
authors.lastname: Roth
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ (Dr Connor, Ms Mahoney, Ms Jackson, Ms Hutzelmann, Dr Zhao, Dr Jia, Dr Snyder, Mr Snavely, Dr Michelson, and Dr Herring); Henry Ford Hospital, Detroit, MI (Dr Roth).Current affiliations: Biogen, Cambridge, MA (E.M.). Janssen Pharmaceutical Research and Development, Raritan, NJ (X.Z.). Eli Lilly and Company, Indianapolis, IN (N.J.).
authors.forename: W Joseph
authors.initials: WJ
authors.lastname: Herring
mesh_terms: D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000068796:Orexin Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D017286:Polysomnography; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C573816:MK-6096; D000068796:Orexin Receptor Antagonists; D010880:Piperidines; D011743:Pyrimidines
keywords: dose-ranging study; filorexant; insomnia; orexin receptor antagonist; sleep efficiency