Elsevier

Respiratory Medicine

Volume 109, Issue 3, March 2015, Pages 416-426
Respiratory Medicine

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

https://doi.org/10.1016/j.rmed.2014.12.010Get rights and content
Under an Elsevier user license
open archive

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 <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.

Keywords

Suvorexant
MK-4305
Orexin
Respiration
Chronic obstructive pulmonary disease
Randomized trial

Cited by (0)

1

Current affiliation is Amgen.

2

Current affiliation is Takeda.

3

Current affiliation is Medivation, Inc.