Investigate the impact of lemborexant (LEM), a competitive dual orexin receptor antagonist approved in multiple countries for the treatment of adults with insomnia, on the Insomnia Severity Index (ISI) and Fatigue Severity Scale (FSS), and on correlation between the 2 measures.

An effective insomnia treatment should both improve sleep and reduce daytime impairments and fatigue in patients reporting these symptoms. Study E2006-G000-303 (Study 303; NCT02952820) showed LEM provided significant benefit versus placebo (PBO) on patient-reported sleep outcomes based on the ISI and on fatigue assessed by FSS.

Study 303 was a 12mo, randomized, double-blind PBO-controlled (first 6mo) phase 3 study in subjects (age ≥18y) with insomnia disorder and baseline (BL) ISI Total Score (TS) ≥15. There was no fatigue criterion for study eligibility. Subjects were randomized to PBO or LEM 5mg (LEM5) or 10mg (LEM10) for 6mo. ISI and FSS were administered at BL and Months 1, 3, and 6. Mean changes from BL in ISI daytime functioning score (ISI-DFS; items 4-7) and FSS-TS were assessed.

Mean (SD) ISI-DFS and FSS-TS at BL were similar between groups (PBO, n=318; LEM5, n=316; LEM10, n=315). At 6mo, mean (SD) ISI-DFS decreased (improved) from BL (PBO, −4.3 [3.66]; LEM5, −6.0 [3.76] and LEM10, −5.7 [4.00], both P<0.0001 versus PBO) and mean FSS-TS decreased (improved) (PBO, −6.3 [12.07]; LEM5, −10.1 [13.56], P=0.0134 versus PBO; LEM10, −8.9 [14.91], P=0.0128 versus PBO) for both LEM groups. Pearson analysis showed a positive correlation over time between reductions in ISI-DFS and FSS-TS (correlation: PBO, 0.513; LEM5, 0.553; LEM10, 0.539; all P<0.0001). Most adverse events were mild/moderate in severity.

Compared with PBO, in these post-hoc analyses, LEM significantly improved daytime functioning and fatigue in subjects with insomnia, and improvements in both measures were correlated.