0351 Differential Effect of Lemborexant and Zolpidem on Wake Across the Night in Patients with Insomnia Disorder

Abstract

Abstract Introduction Insomnia can involve difficulty with falling and/or staying asleep; older adults tend to report more sleep maintenance issues. While zolpidem tartrate extended-release 6.25mg (ZOL) is indicated to treat sleep onset and maintenance, data indicate that ZOL may be less effective in the last 2 hours of the night. It is important to understand the differences between ZOL and lemborexant (LEM), a dual-orexin-receptor-antagonist with the same indication. In Study 304 (E2006-G000-304; NCT02783729), LEM treatment significantly improved objective sleep maintenance (wake after sleep onset [WASO] and WASO in the second half of the night) assessed by polysomnography (PSG) over 1 month compared with placebo (PBO) and ZOL in older adults with insomnia disorder. This post-hoc analysis assessed the effect of LEM and ZOL on wake at each hour (H) of an 8-h sleep period. Methods Study 304 was a randomized, double-blind, PBO- and active-controlled, parallel-group study in adults ≥55y. Subjects (n=1006) received PBO, LEM 5mg (LEM5) or 10mg (LEM10), or ZOL for 1 month. Wake (minutes) was assessed hourly from paired PSGs during single-blind PBO run-in and post-randomization at nights (NT) 1/2 and NT29/30. Change from baseline (CfB) for H1-8 was analyzed using pooled t-tests. Results Between-group baseline wake was similar. On NT1/2 and NT29/30, CfB for LEM10 was significantly greater (less wake) than PBO for all hours except H4 NT29/30. On NT1/2 and NT29/30, CfB for LEM5 was significantly greater than PBO for all hours except H4 NT1/2 and NT29/30 and H8 NT1/2. On NT1/2 and NT29/30, CfB for LEM5 and LEM10 were significantly greater than ZOL during H1,2,7, and 8. CfB for ZOL was not significantly different than PBO except for H2-6 NT1/2 and H3,5,6 NT29/30; CfB for PBO was significantly greater (better) than ZOL during H1 NT29/30. Conclusion LEM improves total sleep time by decreasing wake time throughout the night after sleep onset compared to PBO, and at the beginning/end of the night compared to ZOL. These findings support that ZOL may be less effective in maintaining sleep during the last 2 hours of the night compared with LEM in older subjects, especially those with sleep maintenance difficulties. Support (if any) Eisai Inc.