INVESTIGATION OF THE LONG-TERM EFFECTS OF LEMBOREXANT ON OBJECTIVE SLEEP MEASURES USING A MINIATURE ELECTROENCEPHALOGRAM

Abstract Background Lemborexant (LEM), a competitive dual orexin receptor antagonist, has improved both sleep onset and sleep maintenance in subjects with insomnia disorder in two phase 3 studies using polysomnography and/or sleep diaries. Older adults are more susceptible than younger adults to adverse events (somnolence, daytime cognitive and psychomotor impairment, falls, and fractures) commonly associated with prescribed sleep medications. Until now, the long-term efficacy of LEM has only been measured via subjective assessment for 6 months versus placebo and there have been no long-term objective measures in natural sleeping conditions. Aims & Objectives Sleep at home was assessed after 4 and 12 weeks of LEM administration using a small and light sleep electroencephalogram. Methods Subjects with insomnia disorder (DSM-5) were enrolled to receive LEM (5 mg or 10 mg) open- label at bedtime for 12 weeks. At baseline, after 4 weeks, and after 12 weeks, sleep indices (latency to persistent sleep [LPS], wake after sleep onset [WASO], total sleep time [TST], sleep efficiency [SE]) were evaluated. Sleep diaries were also completed throughout the study. The Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and Beck Depression Inventory (BDI) were also assessed at baseline, 4 weeks, and 12 weeks. Written and oral consent was obtained from all subjects in accordance with the approval items of the Nagoya University Clinical Research Review Board. Results A total of 31 subjects (15 male, 16 female, mean age 58.5 years) enrolled in the study, all completed 4-week assessments and 29 completed 12-week assessments. Objective SE (both P<0.05) and all subjective sleeping measures (all P<0.001) were significantly improved at Weeks 4 and 12 of LEM treatment compared with baseline, and objective TST tended to increase at 12 weeks (P=0.05). When baseline values were considered (MANOVA), at 4 weeks objective WASO (P=0.003) and objective TST (P<0.001) significantly improved, and at 12 weeks all objective sleep measures (LPS [P=0.002], WASO [P=0.006], TST [P=0.009], SE [P<0.001]) significantly improved. ESS scores significantly improved (P<0.001) at 4 weeks compared with baseline and PSQI (P=0.012), ESS (P<0.001), and BDI (P=0.003) scores significantly improved at 12 weeks. Somnolence (29.0%, 9 of 31 subjects) was the most commonly reported adverse event (AE). AEs were mostly mild, and no serious AEs were reported. Discussion & Conclusion The findings of this study demonstrated improvement in objective SE with LEM treatment over 12 weeks, supporting the previously reported utility of short-term efficacy of LEM using polysomnography. LEM was well tolerated, and also associated with improvements in subjective sleep parameters, ESS, PSQI and BDI. Support Eisai Co., Ltd.