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

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<0.0001), 31.4 minutes (38.0, 24.9; p<0.0001), 19.2 minutes (25.7, 12.6; p<0.0001), and 10.4 minutes (17.0, 3.9; p=0.0018), respectively. Mean total sleep time (TST) was significantly increased with each almorexant dose (mean increases versus placebo ranged 55.1-14.3 minutes; p<0.0001 for each dose). Latency to persistent sleep (LPS) was statistically significantly reduced only with almorexant 200 mg versus placebo (mean [95% CI] treatment effect 10.2 minutes, [15.4, 5.0]; p=0.0001). 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.