Effect of Lemborexant on Early Morning Awakening in Elderly Subjects with Severe Problems with Waking Too Early (S6.010)

Abstract

<h3>Objective:</h3> Evaluate treatment with lemborexant (LEM) in subjects age ≥65y reporting “problems waking up too early” on the Insomnia Severity Index (ISI) Item-3 as assessed by wake after sleep onset in the second half of the night (WASO2H). <h3>Background:</h3> LEM is a competitive dual orexin receptor antagonist approved in several countries for the treatment of adults with insomnia. In Study 304 (NCT02783729), LEM improved sleep onset and sleep maintenance as measured by WASO2H. <h3>Design/Methods:</h3> Study 304 was a 1-month, placebo (PBO)-controlled and active-comparator (zolpidem extended-release 6.25mg [ZOL]) study of LEM 5mg (LEM5) and 10mg (LEM10). Subjects whose baseline ISI Item-3 scores were ≥3 (severe/very severe) and were age ≥65y were included in this post-hoc analysis. WASO2H was measured at Nights 1/2 (NT1/2) and 29/30 (NT29/30) using polysomnography and averaged across consecutive nights. <h3>Results:</h3> “Early morning awakening” treatment groups were LEM5 (n=68), LEM10 (n=53), ZOL (n=60) and PBO (n=48). Baseline WASO2H (minutes) mean (SD) ranged from 83.7–91.1 (30.9–41.0) across treatment groups. In these subjects, by NT1/2, WASO2H mean (SD) change from baseline improved significantly with LEM5 (−42.4[37.1]) and LEM10 (−45.2[31.4]) versus both ZOL (−22.3[36.7]) and PBO (−9.5[31.4]; all P&lt;0.001). Improvements were maintained through NT29/30: LEM5 (−33.4[38.9]), LEM10 (−34.4[31.7]), ZOL (−18.46[32.5]), and PBO (−10.4 [32.5]) (LEM5 and LEM10: P&lt;0.05 versus ZOL and P&lt;0.001 versus PBO). ISI Item-3 decreased (improved) from 4 (“very severe”) at baseline to 0 (“no problem”) or 1 (“mild problem”) at NT29/30 in a greater percentage of subjects receiving LEM (LEM5, 56%; LEM10, 50%) versus ZOL (25%) or PBO (33%). <h3>Conclusions:</h3> Treatment with LEM provided significant improvement in WASO2H compared with ZOL and PBO at both NT1/2 and NT29/30 in subjects aged ≥65y with severe/very severe problems waking too early. Improvements reported for ISI Item-3 for LEM-treated subjects support this benefit. <b>Disclosure:</b> 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. Dr. Zee has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Aventis. Dr. Zee has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Harmony Biosciences. Dr. Zee has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Jazz Pharmaceuticals Inc.. Dr. Zee has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai. The institution of Dr. Zee has received research support from National Institutes of Health. The institution of Dr. Zee has received research support from Vanda. Dr. Zee has received intellectual property interests from a discovery or technology relating to health care. Dr. Zee has received intellectual property interests from a discovery or technology relating to health care. Dr. Zee has received publishing royalties from a publication relating to health care. Dinesh Kumar has received personal compensation for serving as an employee of Eisai. Dr. Pappadopulos has received personal compensation for serving as an employee of Eisai Inc.