title: Suvorexant in Patients With Insomnia: Results From Two 3-Month Randomized Controlled Clinical Trials.
abstract: BACKGROUND
  Suvorexant is an orexin receptor antagonist for treatment of insomnia. We report results from two pivotal phase 3 trials.
  
  
  METHODS
  Two randomized, double-blind, placebo-controlled, parallel-group, 3-month trials in nonelderly (18-64 years) and elderly (≥65 years) patients with insomnia. Suvorexant doses of 40/30 mg (nonelderly/elderly) and 20/15 mg (nonelderly/elderly) were evaluated. The primary focus was 40/30 mg, with fewer patients randomized to 20/15 mg. There was an optional 3-month double-blind extension in trial 1. Each trial included a 1-week, randomized, double-blind run-out after double-blind treatment to assess withdrawal/rebound. Efficacy was assessed at week 1, month 1, and month 3 by patient-reported subjective total sleep time and time to sleep onset and in a subset of patients at night 1, month 1, and month 3 by polysomnography end points of wakefulness after persistent sleep onset and latency to onset of persistent sleep (LPS). One thousand twenty-one patients were randomized in trial 1 and 1019 patients in trial 2.
  
  
  RESULTS
  Suvorexant 40/30 mg was superior to placebo on all subjective and polysomnography end points at night 1/week 1, month 1, and month 3 in both trials, except for LPS at month 3 in trial 2. Suvorexant 20/15 mg was superior to placebo on subjective total sleep time and wakefulness after persistent sleep onset at night 1/week 1, month 1, and month 3 in both trials and at most individual time points for subjective time to sleep onset and LPS in each trial. Both doses of suvorexant were generally well tolerated, with <5% of patients discontinuing due to adverse events over 3 months. The results did not suggest the emergence of marked rebound or withdrawal signs or symptoms when suvorexant was discontinued.
  
  
  CONCLUSIONS
  Suvorexant improved sleep onset and maintenance over 3 months of nightly treatment and was generally safe and well tolerated.
authors.affiliation: Merck Sharp & Dohme Corporation, Whitehouse Station, New Jersey. Electronic address: william_herring@merck.com.
authors.forename: W Joseph
authors.initials: WJ
authors.lastname: Herring
authors.affiliation: Merck Sharp & Dohme Corporation, Whitehouse Station, New Jersey.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Connor
authors.affiliation: Merck Sharp & Dohme Corporation, Whitehouse Station, New Jersey.
authors.forename: Neely
authors.initials: N
authors.lastname: Ivgy-May
authors.affiliation: Merck Sharp & Dohme Corporation, Whitehouse Station, New Jersey.
authors.forename: Ellen
authors.initials: E
authors.lastname: Snyder
authors.affiliation: Merck Sharp & Dohme Corporation, Whitehouse Station, New Jersey.
authors.forename: Ken
authors.initials: K
authors.lastname: Liu
authors.affiliation: Merck Sharp & Dohme Corporation, Whitehouse Station, New Jersey.
authors.forename: Duane B
authors.initials: DB
authors.lastname: Snavely
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Krystal
authors.affiliation: Sleep Medicine and Research Center, St. Luke's Hospital, St. Louis, Missouri.
authors.forename: James K
authors.initials: JK
authors.lastname: Walsh
authors.affiliation: University of Wisconsin, Madison, Wisconsin.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Benca
authors.affiliation: Atlanta Sleep Medicine Clinic, Atlanta, Georgia.
authors.forename: Russell
authors.initials: R
authors.lastname: Rosenberg
authors.affiliation: Sleep Disorders Institute & Attention Disorders Institute, Oakland University William Beaumont School of Medicine, Sterling Heights.
authors.forename: R Bart
authors.initials: RB
authors.lastname: Sangal
authors.affiliation: Merck Sharp & Dohme Corporation, Whitehouse Station, New Jersey.
authors.forename: Kerry
authors.initials: K
authors.lastname: Budd
authors.affiliation: Merck Sharp & Dohme Corporation, Whitehouse Station, New Jersey.
authors.forename: Jill
authors.initials: J
authors.lastname: Hutzelmann
authors.affiliation: Merck Sharp & Dohme Corporation, Whitehouse Station, New Jersey.
authors.forename: Heather
authors.initials: H
authors.lastname: Leibensperger
authors.affiliation: Merck Sharp & Dohme Corporation, Whitehouse Station, New Jersey.
authors.forename: Samar
authors.initials: S
authors.lastname: Froman
authors.affiliation: Merck Sharp & Dohme Corporation, Whitehouse Station, New Jersey.
authors.forename: Christopher
authors.initials: C
authors.lastname: Lines
authors.affiliation: Henry Ford Hospital Sleep Center, Detroit, Michigan.
authors.forename: Thomas
authors.initials: T
authors.lastname: Roth
authors.affiliation: Merck Sharp & Dohme Corporation, Whitehouse Station, New Jersey.
authors.forename: David
authors.initials: D
authors.lastname: Michelson
mesh_terms: D000368:Aged; D001381:Azepines / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000068796:Orexin Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D017286:Polysomnography; D012890:Sleep / Q000187:drug effects*; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects; D014851:Wakefulness / Q000187:drug effects*
chemical_list: D001381:Azepines; D000068796:Orexin Receptor Antagonists; D014230:Triazoles; C551624:suvorexant
keywords: Insomnia; Orexin; Pharmacotherapy; Randomized controlled trial; Sleep; Suvorexant