Respiratory Safety of Lemborexant in Healthy Subjects: A Single-Dose, Randomized, Double-Blind, Placebo-Controlled, Crossover Study

Plain Language Summary Insomnia is a sleep disorder in which people have trouble falling asleep or staying asleep, or both. People can take prescription medicines to help improve sleep, but these drugs can have side effects including making breathing more difficult during sleep. We looked at a new medicine for insomnia, lemborexant, and with the aim of finding out how it affects breathing during sleep and if there were any side effects. A group of 17 healthy adult and elderly people took a normal or high dose of lemborexant or a placebo that did not contain active medicine. Researchers measured people's breathing while they slept. We found that lemborexant did not change the amount of oxygen in people's blood during sleep, and that lemborexant did not cause people to have shallow breathing or to have brief pauses in their breathing. People who took lemborexant reported few side effects and these were all mild. In this study, lemborexant was well tolerated in healthy adults and elderly people and did not make breathing more difficult during sleep. Background and Objective Lemborexant is a dual orexin receptor antagonist recently approved in the USA, Japan, and Canada for the treatment of adults with insomnia. Because some pharmacotherapy for insomnia causes respiratory depression, this study assessed the effects of lemborexant treatment on respiratory safety parameters. Methods This single-dose, randomized, double-blind, placebo-controlled, three-period crossover study enrolled healthy adult and elderly subjects (n = 17). Subjects were randomized to one of three treatment sequences, each consisting of three treatment periods in which they received a single dose of placebo, lemborexant 10 mg, or lemborexant 25 mg. Each treatment period was separated by a washout period of at least 14 days. Assessments included pharmacodynamic respiratory parameters (peripheral capillary oxygen saturation (SpO(2)) and apnea-hypopnea index (AHI)) and safety. Results There were no significant differences for either dose of lemborexant versus placebo in mean peripheral capillary oxygen saturation (SpO(2); least squares mean (LSM) difference (95% confidence interval (CI)): lemborexant 10 mg, -0.36 (-0.78 to 0.07); lemborexant 25 mg, - 0.29 (- 0.72 to 0.14)) or AHI (LSM difference (95% CI): lemborexant 10 mg, 0.52 (- 1.72 to 2.76); lemborexant 25 mg, - 1.16 (- 3.40 to 1.08)) during sleep. Additionally, significant differences were not observed for the percentage of total sleep during which SpO(2) was < 85% (LSM difference (95% CI): lemborexant 10 mg, 0.004 (- 0.058 to 0.067); lemborexant 25 mg, 0.044 (- 0.018 to 0.107)) or < 80% (LSM difference (95% CI): lemborexant 10 mg, 0.001 (- 0.002 to 0.005); lemborexant 25 mg, 0.002 (-0.001 to 0.006)) for either lemborexant dose versus placebo. There was also no significant difference for lemborexant 10 mg versus placebo, for which SpO(2) was < 90% during total sleep time (LSM difference (95% CI): 0.185 (- 0.034 to 0.405)). Conclusion Overall, lemborexant at recommended doses did not have a negative effect on mean SpO(2) or AHI and was well tolerated in this cohort of healthy subjects.