title: Effects of Suvorexant, an Orexin Receptor Antagonist, on Respiration during Sleep In Patients with Obstructive Sleep Apnea.
abstract: OBJECTIVE
  To investigate the respiratory effects of suvorexant, an orexin receptor antagonist for treating insomnia, in patients with obstructive sleep apnea (OSA).
  
  
  METHODS
  This was a randomized, double-blind, placebo-controlled, 2-period (4 days per period), crossover, sleep laboratory study. Twenty-six patients aged 18-65 years with mild (apnea-hypopnea index [AHI] ≥ 5 and < 15) to moderate (AHI ≥ 15 and < 30) OSA were randomized to receive suvorexant 40 mg or placebo in period-1 and then crossed over to the other treatment in period-2. Breathing during sleep was measured by AHI (primary endpoint) and oxygen saturation assessed by pulse oximetry (SpO2, secondary endpoint). The study was powered to rule out a mean increase in AHI between suvorexant and placebo of 5 or greater on Day 4.
  
  
  RESULTS
  There was a small increase in mean AHI (2.66) in OSA patients after multiple doses of suvorexant relative to placebo, with the upper 90% CI bound slightly exceeding 5.00 (0.22, 5.09). No increase in mean AHI was observed after a single dose of suvorexant versus placebo (mean difference = -0.47 [-3.20, 2.26]), and there was no treatment effect on mean SpO2 during total sleep time after single or multiple doses (Day 1: mean difference = -0.04 [-0.49, 0.42]; Day 4: mean difference = -0.06 [-0.45, 0.33]). There was inter- and intra-individual variability in suvorexant respiratory effects.
  
  
  CONCLUSIONS
  Suvorexant 40 mg, twice the 20 mg maximum recommended dose for treating insomnia in the USA and Japan, does not appear to have clinically important respiratory effects during sleep in patients with mild to moderate OSA as assessed by mean AHI and SpO2. Due to inter- and intra-individual variability in respiratory effects, suvorexant should be used with caution in patients with compromised respiratory function, and at the lowest effective dose.
  
  
  BACKGROUND
  clinicaltrials.gov, NCT01300455.
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: John
authors.initials: J
authors.lastname: Palcza
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Deborah
authors.initials: D
authors.lastname: Card
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Adrianna
authors.initials: A
authors.lastname: Gipson
authors.affiliation: NeuroTrials Research, Atlanta, GA.
authors.forename: Russell
authors.initials: R
authors.lastname: Rosenberg
authors.affiliation: Yale School of Medicine, New Haven, CT.
authors.forename: Meir
authors.initials: M
authors.lastname: Kryger
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Christopher
authors.initials: C
authors.lastname: Lines
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: John A
authors.initials: JA
authors.lastname: Wagner
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Troyer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001381:Azepines / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000068796:Orexin Receptor Antagonists / Q000494:pharmacology*; D017286:Polysomnography; D012119:Respiration / Q000187:drug effects*; D012890:Sleep; D020181:Sleep Apnea, Obstructive / Q000150:complications*; D007319:Sleep Initiation and Maintenance Disorders / Q000150:complications* / Q000188:drug therapy*; D014230:Triazoles / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D001381:Azepines; D000068796:Orexin Receptor Antagonists; D014230:Triazoles; C551624:suvorexant
keywords: MK-4305; obstructive sleep apnea; orexin; randomized trial; respiration; suvorexant