Effect of the novel dual orexin receptor antagonist daridorexant on night‐time respiratory function and sleep in patients with moderate chronic obstructive pulmonary disease

Abstract

In patients with chronic obstructive pulmonary disease (COPD), sleep is often fragmented while, conversely, the use of sleep medications is of concern in these patients due to potential impairment of nocturnal breathing. This randomised, double‐blind, placebo‐controlled, two‐period crossover study was conducted to evaluate the effect of the new dual orexin receptor antagonist daridorexant on night‐time respiratory function and sleep in patients with moderate COPD. In each period, the highest Phase‐III dose of 50 mg daridorexant or placebo was administered once daily in the evening for 5 consecutive days. The primary endpoint was peripheral oxygen saturation (SpO2) during total sleep time (TST) after last dosing. Night‐time respiratory function and sleep were further evaluated based on the apnea–hypopnea index (AHI), sleep duration, and objective sleep parameters. Pharmacokinetics, safety, and tolerability were also assessed. Primary endpoint analysis revealed no significant mean treatment difference (i.e. daridorexant – placebo) for SpO2 during TST as it was 0.18% (90% confidence interval: −0.21 to 0.57). There was also no difference from placebo for SpO2 during non‐rapid eye movement (REM) and REM sleep at Night 5 and after first dosing. The AHI was slightly increased compared to placebo, but not to a clinically meaningful extent. In addition, daridorexant improved objective sleep parameters (i.e. prolonged TST, increased sleep efficiency, and decreased wake after sleep onset), reached expected plasma concentrations, and was safe and well tolerated. In conclusion, single and multiple doses of 50 mg daridorexant do not impair night‐time respiratory function and improves sleep in patients with moderate COPD.