title: Effects of suvorexant, an orexin receptor antagonist, on breathing during sleep in patients with chronic obstructive pulmonary disease.
abstract: OBJECTIVE
  There is a general concern that hypnotic medications in patients with respiratory disorders have the potential to decrease respiratory effort and blunt the arousal response to hypoxemia which may lead to sleep breathing disorders. We investigated whether suvorexant, an orexin receptor antagonist approved for treatment of insomnia at a maximum daily dose of 20 mg in the US, causes sleep breathing disorders in patients with chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  This was a randomized, double-blind, placebo-controlled, 2-period, cross-over, study performed in 9 sleep laboratories/clinical research units in the United States. The participants were 25 COPD patients aged 39-72 y with mild-to-moderate airflow limitation based on GOLD spirometry criteria. In each period, patients received suvorexant (40 mg in <65 y-olds; 30 mg in ≥65 y-olds) or placebo for four consecutive nights. Respiratory function during sleep was measured by oxygen saturation using pulse oximetry (SpO2, primary endpoint) and Apnea Hypopnea Index (AHI, secondary endpoint). The study was powered to rule out a difference between treatments of -2 percentage points in SpO2 on Day 4.
  
  
  RESULTS
  There was no treatment effect following single and multiple doses of suvorexant on mean SpO2 during total sleep time (Day 1: suvorexant = 93.14%, placebo = 93.24%, difference = -0.10 [90% CI: -0.50, 0.31]; Day 4: suvorexant = 93.38%, placebo = 92.99%, difference = 0.39 [90% CI: -0.12, 0.91]). There was no clinically meaningful increase in mean AHI by suvorexant compared with placebo on Day 1 (difference = 0.72 [90% CI: -0.60, 2.04]) or Day 4 (difference = 2.05 [90% CI: 0.33, 3.77]).
  
  
  CONCLUSIONS
  These data do not suggest an overt respiratory depressant effect with 30-40 mg daily doses of suvorexant, up to twice the maximum recommended dose for treating insomnia in the US, in patients with mild-to-moderate COPD. Trial registration Clinicaltrials.gov identifier: NCT01293006.
authors: Merck & Co., Inc., Whitehouse Station, NJ, USA.
authors: Hong
authors: H
authors: Sun
authors: Merck & Co., Inc., Whitehouse Station, NJ, USA.
authors: John
authors: J
authors: Palcza
authors: NeuroTrials Research, Atlanta, GA, USA.
authors: Russell
authors: R
authors: Rosenberg
authors: Yale School of Medicine, New Haven, CT, USA.
authors: Meir
authors: M
authors: Kryger
authors: Merck & Co., Inc., Whitehouse Station, NJ, USA.
authors: Tara
authors: T
authors: Siringhaus
authors: Merck & Co., Inc., Whitehouse Station, NJ, USA.
authors: Janice
authors: J
authors: Rowe
authors: Merck & Co., Inc., Whitehouse Station, NJ, USA. Electronic address: chris_lines@merck.com.
authors: Christopher
authors: C
authors: Lines
authors: Merck & Co., Inc., Whitehouse Station, NJ, USA.
authors: John A
authors: JA
authors: Wagner
authors: Merck & Co., Inc., Whitehouse Station, NJ, USA.
authors: Matthew D
authors: MD
authors: Troyer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001381:Azepines / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000068796:Orexin Receptor Antagonists / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D012119:Respiration / Q000187:drug effects*; D012720:Severity of Illness Index; D012890:Sleep / Q000187:drug effects*; D000068776:Sleep Aids, Pharmaceutical / Q000627:therapeutic use*; D013147:Spirometry; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D014481:United States
chemical_list: D001381:Azepines; D000068796:Orexin Receptor Antagonists; D000068776:Sleep Aids, Pharmaceutical; D014230:Triazoles; C551624:suvorexant
keywords: Chronic obstructive pulmonary disease; MK-4305; Orexin; Randomized trial; Respiration; Suvorexant