0481 Impact of Lemborexant on Fatigue Severity in Subjects with Clinically Significant Levels of Fatigue at Baseline

Abstract

Introduction: In Phase 3 SUNRISE‐1 (NCT02783729; E2006‐G000‐304) and SUNRISE‐2 (NCT02952820; E2006‐G000‐303), lemborexant (LEM) provided significant benefit versus placebo on sleep diary‐based sleep onset/maintenance outcomes over 1mo and 6mo, respectively, in subjects with insomnia disorder. The impact of LEM on patient‐reported fatigue, assessed using the Fatigue Severity Scale (FSS), in subjects with clinically significant fatigue (CSF) at baseline was examined for each study. Methods: SUNRISE‐1 was a 1mo, randomized, double‐blind, placebo‐ and active‐controlled, parallel‐group study in female (≥55y) and male (≥65y) subjects (n=1006); subjects received placebo, LEM 5mg (LEM5), LEM 10mg (LEM10) or zolpidem tartrate extended‐release (not reported here). SUNRISE‐2 was a 12mo, randomized, double‐blind study in subjects age ≥18y (n=949). Subjects received placebo, LEM5, or LEM10 for 6mo. Placebo subjects were rerandomized to LEM5 or LEM10 for another 6mo; LEM subjects continued assigned treatment. CSF was defined as FSS total score (FSSts) ≥36. Results: In subjects with baseline CSF, in SUNRISE‐1, baseline FSSts was 46.8, 46.5, and 46.6 in placebo (n=117), LEM5 (n=157), and LEM10 (n=153) groups, respectively, and, in SUNRISE‐2, was 45.7, 46.4, and 45.8 in placebo (n=169), LEM5 (n=181), and LEM10 (n=173) groups, respectively. At 1mo, mean changes from baseline in FSSts were not significantly different vs placebo for LEM5 in both studies, and for LEM10 in SUNRISE‐1. In SUNRISE‐2, LEM10 significantly decreased mean [SD] FSSts from baseline vs placebo at 1mo (LEM10, ‐11.2[13.9] vs placebo, ‐8.7[10.5]; P=0.03). By 6mo in SUNRISE‐2, both LEM5 and LEM10 significantly decreased mean [SD] FSSts from baseline versus placebo (LEM5, ‐15.4[13.8]; LEM10, ‐15.0[14.2] vs placebo, ‐11.2[11.6]; both P<0.05). At 12mo, mean [SD] FSSts improvements were sustained for LEM5 (‐20.4[12.8]) and LEM10 (‐18.1[14.7]). Conclusion: In subjects with CSF, longer treatments (>1mo) may be needed to observe significant FSSts improvements, which were evident at 6mo and sustained at 12mo with continuous LEM treatment.