title: Suvorexant in Patients with Insomnia: Pooled Analyses of Three-Month Data from Phase-3 Randomized Controlled Clinical Trials.
abstract: Suvorexant is an orexin receptor antagonist approved for treating insomnia at a maximum dose of 20 mg. Phase-3 trials evaluated two age-adjusted (non-elderly/elderly) dose-regimes of 40/30 mg and 20/15 mg with the primary focus on 40/30 mg. We report here results from pooled analyses of the 20/15 mg dose-regime, which was evaluated as a secondary objective in the trials.
  
  
  
  Prespecified analysis of pooled data from two identical randomized, double-blind, placebo-controlled, parallel-group, 3-month trials in non-elderly (18-64 years) and elderly (≥ 65 years) patients with insomnia. Patients were randomized to suvorexant 20/15 mg (non-elderly/elderly), suvorexant 40/30 mg (non-elderly/elderly), or placebo; by design, fewer patients were randomized to 20/15 mg. Efficacy was assessed by self-reported and polysomnography (PSG; subset of patients) sleep maintenance and onset endpoints.
  
  
  
  Suvorexant 20/15 mg (N = 493 treated) was effective compared to placebo (N = 767 treated) on patient-reported and PSG sleep maintenance and onset endpoints at Night-1 (PSG endpoints) / Week-1 (subjective endpoints), Month-1 and Month-3, except for effects on PSG sleep onset at Month-3. Suvorexant 20/15 mg was generally well tolerated, with 3% of patients discontinuing due to adverse events over 3 months vs. 5.2% on placebo. Somnolence was the most common adverse event (6.7% vs. 3.3% for placebo). There was no systematic evidence of rebound or withdrawal signs or symptoms when suvorexant was discontinued after 3 months of nightly use.
  
  
  
  Suvorexant 20/15 mg improved sleep onset and maintenance over 3 months of nightly treatment and was generally safe and well tolerated.
  
  
  
  ClinicalTrials.gov trial registration numbers: NCT01097616, NCT01097629.
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: W Joseph
authors.initials: WJ
authors.lastname: Herring
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Connor
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Ellen
authors.initials: E
authors.lastname: Snyder
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Duane B
authors.initials: DB
authors.lastname: Snavely
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Jill
authors.initials: J
authors.lastname: Hutzelmann
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Deborah
authors.initials: D
authors.lastname: Matzura-Wolfe
authors.affiliation: University of Wisconsin, Madison, WI.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Benca
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Krystal
authors.affiliation: Sleep Medicine and Research Center, St. Luke's Hospital, St. Louis, MO.
authors.forename: James K
authors.initials: JK
authors.lastname: Walsh
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Christopher
authors.initials: C
authors.lastname: Lines
authors.affiliation: Henry Ford Hospital Sleep Center, Detroit, MI.
authors.forename: Thomas
authors.initials: T
authors.lastname: Roth
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: David
authors.initials: D
authors.lastname: Michelson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001381:Azepines / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000068776:Sleep Aids, Pharmaceutical / Q000627:therapeutic use*; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D001381:Azepines; D000068776:Sleep Aids, Pharmaceutical; D014230:Triazoles; C551624:suvorexant
keywords: insomnia; orexin; pharmacotherapy; randomized controlled trial; sleep; suvorexant