Effects of Suvorexant on the Insomnia Severity Index in Patients with Insomnia: Analysis of Pooled Phase-3 Data (P4.292)

Objective: To evaluate the effects of suvorexant on the Insomnia Severity Index (ISI) which assesses sleep problems and their impact on daytime function. Background: Previously-reported Phase-3 results showed that the orexin receptor antagonist suvorexant improves sleep maintenance and onset. Methods: The analysis included pooled-data from two similar randomized, double-blind, placebo-controlled, parallel-group, 3-month trials in elderly (≥65y) and non-elderly (18-64y) insomnia patients. Age-adjusted (non-elderly/elderly) dose-regimes of 40/30mg and 20/15mg were evaluated. Fewer patients were assigned to 20/15mg than 40/30mg or placebo. The ISI, a 7-item patient questionnaire, was administered as an exploratory assessment at Months 1 and 3. Results: 1824 patients were included in the analysis. Compared to placebo, suvorexant improved change-from-baseline in total score at both timepoints (Month 3: 20/15mg = -6.2, 40/30mg = -6.7, placebo = -4.9, p-values <0.001) and the percentage of responders (≥6-point improvement from baseline) at both timepoints (Month 3: 20/15mg = 55.5[percnt], 40/30mg = 54.9[percnt], placebo = 42.2[percnt], p-values <0.001). Scores for individual items of the ISI showed numerical improvement for both suvorexant dose regimes versus placebo at both timepoints; the “impact of insomnia” component (last 3 items) which assesses the impact of insomnia on daytime function/quality-of-life was also improved by both dose regimes. Conclusions: Suvorexant 20/15mg and 40/30 mg improve sleep as assessed by the ISI in patients with insomnia. Improvement in sleep onset/maintenance as well as a reduction of the impact of sleep problems on daytime function contribute to the overall improvement observed in ISI total score. Given that the maximum approved dose is 20mg, the 20/15mg data are the most clinically relevant. Study Support: Merck & Co. Inc., Kenilworth, NJ, USA Disclosure: Dr. Herring has received personal compensation for activities with Merck & Co. Inc., as an employee. Dr. Snyder has received personal compensation for activities for Merck. Dr. Snavely has received personal compensation for activities with Merck & Co., Inc. as an employee. Dr. Lines has received personal compensation for activities with Merck as an employee. Dr. Michelson has received personal compensation for activities with Merck & Co., Inc. as an employee.