Effects of lemborexant on sleep quality and its association with morning alertness: Post hoc analysis of two phase 3 trials.

Study objectives: This analysis was conducted to determine whether lemborexant (LEM) treatment affects ratings of patient-reported sleep quality and to identify subjective and objective parameters associated with improved subjective sleep quality. Methods: This was a post hoc analysis of two global phase 3 trials (Study 303: 12-month, randomized, double-blind, placebo-controlled trial; Study 304: 1-month, randomized, double-blind, placebo-controlled, active-comparator trial) of LEM for patients with insomnia. A 9-point Likert scale (higher numbers indicating better quality) was used to assess subjective sleep quality (sQual). Subjective and objective sleep parameters were assessed by electronic sleep diaries and polysomnography, respectively. Spearman's rank correlation analysis and stepwise regression analysis were performed to explore the associations between sleep parameters and sQual. Results: The analyses included 949 patients from Study 303 and 743 patients from Study 304. LEM showed significantly larger increases from baseline in sQual than placebo in both studies (least square mean change: placebo 0.89, LEM5 1.17 (p < 0.05), LEM10 1.21 (p < 0.05) at Month 6 in Study 303, and placebo 0.93, LEM5 1.46 (p < 0.001), LEM10 1.35 (p < 0.05) at Month 1 in Study 304). Of subjective sleep parameters, changes in morning alertness showed the strongest association with changes in sQual. The changes in subjective total sleep time and wake after sleep onset were moderately correlated with sQual positively and negatively, respectively. These findings were further confirmed using stepwise regression analyses. Conclusions: LEM improved ratings of sQual more than placebo. To improve self-reported sleep quality, lemborexant treatment should focus on improving morning alertness. Clinical trial registration: Study 303 (ClinicalTrials.gov NCT02952820): Long-term Study of Lemborexant in Insomnia Disorder (SUNRISE 2). https://clinicaltrials.gov/study/NCT02952820, Study 304 (ClinicalTrials.gov NCT02783729): Study of the Efficacy and Safety of Lemborexant in Subjects 55 Years and Older with Insomnia Disorder (SUNRISE 1). https://clinicaltrials.gov/study/NCT02783729.