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).

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.

“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<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<0.05 versus ZOL and P<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%).

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.