Dual orexin receptor antagonist, almorexant, in elderly patients with primary insomnia: A randomized, controlled study

Abstract

Objective: Sleep laboratory study to determine the dose-related efficacy and safety of almorexant in elderly patients with primary chronic insomnia. Methods: Patients aged ?65 years with primary insomnia were enrolled into a prospective, randomized, double-blind, placebo-controlled, multicenter dose-finding study with a five-period, five-way Latin square cross-over design. Patients were randomized to one of 10 unique sequences of two-night treatment with oral almorexant 25, 50, 100, or 200 mg capsules, or matching placebo. The primary efficacy endpoint was polysomnography (PSG)-determined mean wake time after sleep onset (WASO). Secondary and exploratory efficacy endpoints were also assessed. Results: 112 patients were randomized (mean [SD] age 72.1 [5.0] years; 69.9% female). Significant, dose-related improvements (reductions) in mean WASO were observed with almorexant. Least-squares mean (95% CI) treatment effects in the almorexant 200, 100, 50, and 25 mg dose groups versus placebo were ?46.5 minutes (?53.0, ?39.9; p < .0001), ?31.4 minutes (?38.0, ?24.9; p < .0001), ?19.2 minutes (?25.7, ?12.6; p < .0001), and ?10.4 minutes (?17.0, ?3.9; p = .0018), respectively. Mean total sleep time was significantly increased with each almorexant dose (mean increases versus placebo ranged 55.1-14.3 minutes; p < .0001 for each dose). Latency to persistent sleep was statistically significantly reduced only with almorexant 200 mg versus placebo (mean [95% CI] treatment effect ?10.2 minutes, [?15.4, ?5.0]; p = .0001). No unexpected safety concerns were identified. Adverse events were similar between all almorexant dose groups and placebo. Conclusions: Two-night oral administration of almorexant was effective and well tolerated in treating primary insomnia in elderly patients.