title: Effects of the orexin receptor antagonist suvorexant on respiration during sleep in healthy subjects.
abstract: Suvorexant is an orexin receptor antagonist for treating insomnia. The maximum approved dose in the United States and Japan is 20 mg. We evaluated suvorexant effects on respiration during sleep in a randomized, double-blind, 3-period crossover study of healthy adult men (n = 8) and women (n = 4) ≤ 50 years old who received single-dose suvorexant 40 mg, 150 mg, and placebo. Respiration during sleep was measured by oxygen saturation (SpO2 , primary end point) and the Apnea Hypopnea Index (AHI). The study was powered to detect a reduction greater than 5% in SpO2 . There was no effect of suvorexant on mean SpO2 during sleep. The mean (90%CI) treatment differences versus placebo were -0.3 (-1.2-0.6) for 40 mg and 0.0 (-0.9-0.9) for 150 mg. There were no dose-related trends in individual SpO2 values. Mean SpO2 was >96% for all treatments during total sleep time and during both non-REM and REM sleep. There was no effect of either suvorexant dose on AHI. The mean (90%CI) treatment differences versus placebo were 0.8 (-0.7-2.3) for 40 mg and -0.2 (-1.7-1.3) for 150 mg. Suvorexant was generally well tolerated; there were no serious adverse experiences or discontinuations. These data from healthy subjects suggest that suvorexant lacks clinically important respiratory effects during sleep at doses greater than the maximum recommended dose for treating insomnia.
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Naoto
authors.initials: N
authors.lastname: Uemura
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: McCrea
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.affiliation: Clinilabs, New York, NY, USA.
authors.forename: Mardik
authors.initials: M
authors.lastname: Donikyan
authors.affiliation: Clinilabs, New York, NY, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Zammit
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Louridas
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Marsilio
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Lines
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Troyer
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: John
authors.initials: J
authors.lastname: Wagner
mesh_terms: D000328:Adult; D001381:Azepines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D000068796:Orexin Receptor Antagonists / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D010092:Oximetry; D010100:Oxygen / Q000378:metabolism; D017286:Polysomnography; D012119:Respiration / Q000187:drug effects*; D000068776:Sleep Aids, Pharmaceutical / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D014230:Triazoles / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D001381:Azepines; D000068796:Orexin Receptor Antagonists; D000068776:Sleep Aids, Pharmaceutical; D014230:Triazoles; C551624:suvorexant; D010100:Oxygen
keywords: MK-4305; healthy subjects; orexin; randomized trial; respiration; suvorexant