0371 Lemborexant Treatment for Insomnia in Phase 3: Impact on Disease Severity. (12th April 2019) - Roth, Tom
Abstract: Introduction: The effectiveness of treatments for insomnia in clinical trials is generally based on polysomnographic and patient assessments of sleep onset and/or sleep maintenance relative to placebo. Ideally, treatment success should lead to decreases in disease severity, measurable by the Insomnia Severity Index (ISI). In two Phase 3 studies, lemborexant (LEM 5 and 10mg) showed statistically significant benefits in sleep diary-based sleep onset latency and sleep maintenance variables versus placebo. Results from a pooled analysis of these studies of LEM from one month of nightly use are presented here. Methods: SUNRISE-1 was a 1-month blinded, placebo- and active-controlled (zolpidem extended release [ZOL]; not reported here), parallel-group study in 1006 female and male subjects with insomnia disorder age ≥55y, with baseline ISI total score (TS) ≥13 after placebo run-in. Subjects were randomized to placebo, ZOL, LEM 5mg (LEM5) or LEM 10mg (LEM10). SUNRISE-2 was a 12-month placebo-controlled (first 6 months), blinded, parallel-group study in 959 female and male subjects with insomnia disorder age ≥18y, with baseline TS ≥15 after placebo run-in. In both studies, ISI was administered at baseline and Month 1. An analysis of covariance model, with baseline TS as covariate, and region, study, and age group as factors was used for change from baseline and Cochran-Mantel-Haenszel test stratified by study, region and age group for responder rate analyses. Results: Mean baseline TS was 19.2 (placebo), 19.3 (LEM5), and 19.0 (LEM10). Mean TS decreased at Month 1 relative to baseline for all treatment groups. Decreases were significantly larger for LEM5 and LEM10 versus placebo (P<0.0001). The percentage whose TS decreased by ≥7 points was 33.6% (placebo) versus 47.3% (LEM5) and 47.8% (LEM10). The percentage whose TS was <10 points at Month 1 (clinical insomnia threshold) was 20.3% (placebo) versus 33.0% (LEM5) and 33.4% (LEM10). These differences versus placebo were statistically significant (P<0.0001). Conclusion: Treatment with LEM significantly decreased the severity of insomnia symptoms. Approximately 1/3 of those in the LEM groups experienced declines in ISI below the threshold for clinically important insomnia. Support (If Any): Eisai Inc., Purdue Pharma L.P.