Relationship Between Daytime Functioning and Fatigue Over 6 Months in Lemborexant-Treated Subjects with Insomnia Disorder (P4-13.002)

Abstract

<h3>Objective:</h3> 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. <h3>Background:</h3> 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. <h3>Design/Methods:</h3> 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. <h3>Results:</h3> 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&lt;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&lt;0.0001). Most adverse events were mild/moderate in severity. <h3>Conclusions:</h3> 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. <b>Disclosure:</b> Craig Chepke has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Janssen. Craig Chepke has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Otsuka. Craig Chepke has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurocrine. Craig Chepke has received personal compensation in the range of $100,000-$499,999 for serving on a Speakers Bureau for Neurocrine. Craig Chepke has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for AbbVie. Craig Chepke has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Acadia. Craig Chepke has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Otsuka. Craig Chepke has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Takeda. Craig Chepke has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Janssen. Craig Chepke has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Ironshore. Craig Chepke has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Teva. Craig Chepke has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sunovion. Craig Chepke has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Intracellular. Craig Chepke has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Eisai. Craig Chepke has received research support from Acadia. Craig Chepke has received research support from Harmony. Craig Chepke has received research support from Neurocrine. Jane Yardley has received personal compensation for serving as an employee of Eisai Ltd. Kate Pinner has received personal compensation for serving as an employee of Eisai Ltd. Dr. Lundwall has received personal compensation for serving as an employee of Eisai. Margaret Moline has received personal compensation for serving as an employee of EISAI, INC.. Margaret Moline has received intellectual property interests from a discovery or technology relating to health care. Margaret Moline has received personal compensation in the range of $0-$499 for serving as a review, loan repayment program with NIH.