Relationship Between Daytime Functioning and Fatigue Over 6 Months in Lemborexant-Treated Subjects with Insomnia Disorder

Abstract: Introduction: Study E2006-G000-303 (Study 303; NCT02952820) showed lemborexant (LEM) provided significant benefit vs placebo (PBO) on patient-reported sleep and fatigue severity, based on the Insomnia Severity Index (ISI) and Fatigue Severity Scale (FSS), respectively. We investigated the impact of LEM on scores, and whether improvements in each were correlated. Methods: 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 at 1, 3, and 6mo. Mean changes from BL in ISI daytime functioning score (DFS; Items 4-7) and FSS-TS were assessed. Results: Mean (SD) ISI DFS and FSS-TS were similar between groups at BL (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]; LEM10, −5.7 [4.00], both P