Abstract
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.