Respiratory safety of lemborexant in adult and elderly subjects with moderate‐to‐severe chronic obstructive pulmonary disease

Summary Because some hypnotics worsen respiratory conditions, it was important to determine the respiratory safety of lemborexant, a competitive dual orexin‐receptor antagonist approved to treat adults with insomnia, in subjects with moderate‐to‐severe chronic obstructive pulmonary disease. E2006‐A001‐113 (Study 113; NCT04647383) was a multicentre, multiple‐dose, randomised, double‐blind, placebo‐controlled, two‐period crossover study in adult subjects with moderate or severe chronic obstructive pulmonary disease (per spirometry‐based Global Initiative for Chronic Obstructive Lung Disease GOLD criteria). Subjects ( N = 30) were randomised to two treatment sequences comprising 8‐night treatment periods (washout ≥ 14 days) with lemborexant 10 mg or placebo. Peripheral oxygen saturation (SpO 2 ; primary endpoint), apnea–hypopnea index, objective sleep parameters and sleep architecture measures were assessed after single (Day 1) and multiple (Day 8) doses. There was no significant difference in least‐squares mean SpO 2 after a single dose of lemborexant (91.1%) versus placebo (91.5%). Although a statistically significant difference in SpO 2 was observed after multiple doses (least‐squares mean: lemborexant, 91.3%; placebo, 90.8%) favouring lemborexant, this was not considered clinically meaningful. Apnea–hypopnea index was not significantly different between treatments after single or multiple doses. Total sleep time and total rapid eye movement sleep were significantly greater on Days 1 and 8 with lemborexant versus placebo. Treatment‐emergent adverse events were reported in five (16.7%) subjects when taking lemborexant and four (13.3%) subjects when taking placebo; treatment‐emergent adverse events were mostly mild. Lemborexant was well tolerated and did not adversely impact SpO 2 or apnea–hypopnea index after single and multiple doses relative to placebo in subjects with moderate‐to‐severe chronic obstructive pulmonary disease.