Impact of Lemborexant Versus Placebo and Zolpidem on REM Sleep Duration by Quarter-of-the-Night Intervals in Older Adults with Insomnia Disorder

Document Type

Conference Proceeding

Publication Date

12-1-2022

Publication Title

Sleep Med

Keywords

lemborexant, placebo, zolpidem, zolpidem tartrate, aged, conference abstract, controlled study, double blind procedure, drug therapy, female, human, insomnia, major clinical study, male, night, randomized controlled trial, REM sleep, REM sleep latency, sleep time

Abstract

Introduction: Lemborexant (LEM) is a dual orexin receptor antagonist approved in multiple countries, including the United States, Japan, Canada and Australia for the treatment of adults with insomnia. The effects of LEM on sleep architecture in adults ≥55y with insomnia disorder were assessed in Study E2006-G000-304 (Study 304; SUNRISE-1; NCT02783729). These post hoc analyses examined the acute effect of LEM on REM pressure, as assessed by changes from baseline in REM latency and in REM sleep duration in 2-hour quarter-of-the-night (QoN) intervals. Materials and Methods: Study 304 was a 1 month, randomized, double-blind, placebo (PBO)- and active-controlled (zolpidem tartrate extended-release 6.25mg [ZOL]) study of LEM (5mg, LEM5; 10mg, LEM10). Subjects received PBO (n=208), ZOL (n=263), LEM5 (n=266), or LEM10 (n=269). Paired polysomnographic assessments were conducted at baseline, the first 2 (N1/2), and the last 2 (N29/30) nights of treatment; mean values from the paired assessments are reported. Results: Baseline REM latency (minutes) was similar across treatments (98.4-101.4). On N1/2, significant mean (SD) decreases from baseline in REM latency were observed for LEM5 (−42.6 [53.9]) and LEM10 (−49.6[52.9]) vs PBO (−6.9[54.5]) and vs ZOL (0.2[54.2]) (all P<0.0001). On N29/30, REM latency was also significantly decreased from baseline with LEM5 (−30.7[55.7]) and LEM10 (−37.7[56.2]) vs PBO (−7.7[62.3]) and vs ZOL (−4.0[56.4]) (all P<0.0001). No difference was observed for ZOL vs PBO at either N1/2 or N29/30. Within each QoN, baseline REM sleep duration (minutes) was similar across treatments. On N1/2, mean REM (minutes) across quarters ranged from 16.5-23.8 for LEM5, 19.7-26.1 for LEM10, 10.3-21.6 for PBO, and 8.5-22.8 for ZOL. On N29/30, mean REM values were 14.4-22.4 for LEM5, 16.9-24.1 for LEM10, 9.2-21.5 for PBO, and 8.3-22.3 for ZOL. In each QoN during N1/2, REM sleep duration (minutes) significantly increased from baseline with LEM10 vs PBO (all P<0.0001) and vs ZOL (all P<0.001). With LEM5 during N1/2, REM sleep significantly increased from baseline vs PBO during Q1, Q3, and Q4 (all P<0.05) and vs ZOL in Q1 and Q2 (both P<0.01). With ZOL, REM was significantly decreased vs PBO during Q1 (P<0.05) and significantly increased vs PBO during Q3 (P<0.05). On N29/30, REM sleep (minutes) significantly increased from baseline with LEM10 vs PBO in each QoN (all P<0.05) and vs ZOL in Q1, Q3, and Q4 (all P<0.05). With LEM5, REM sleep significantly increased from baseline vs PBO and vs ZOL in Q1 (both P<0.0001). No significant differences were observed for ZOL vs PBO in any QoN on N29/30. In each QoN, the increases in REM sleep were significantly greater on N1/2 than N29/30 with LEM5 (all P<0.05) and LEM10 (all P<0.0001). Conclusion: LEM, but not ZOL, acutely increases REM pressure as evidenced by REM latency and REM duration per QoN. In each QoN, increases in REM sleep were greater with LEM5 and LEM10 than with ZOL or PBO. Decreases in REM latency and increases in REM sleep per QoN with LEM were greater during N1/2 than N29/30. Acknowledgements: Supported by Eisai Inc.

Volume

100

Issue

S1

First Page

S123

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