Effects of suvorexant, an orexin receptor antagonist, on breathing during sleep in patients with chronic obstructive pulmonary disease

Summary Objectives 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). Design 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 2 , 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 SpO 2 on Day 4. Results There was no treatment effect following single and multiple doses of suvorexant on mean SpO 2 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.