Daridorexant, a new dual orexin receptor antagonist in elderly subjects with insomnia disorder: a randomized clinical trial

Objective: To assess the dose-response of daridorexant, a new dual orexin receptor antagonist, on wake after sleep onset (WASO).

Methods: Elderly (≥65 years) subjects (n = 58) with insomnia were randomly allocated (Latin square design) to receive five treatments (5, 10, 25, and 50 mg daridorexant and placebo) during five treatment periods, each consisting of two treatment nights followed by a 5–12-day washout period. Main efficacy endpoints were the absolute change from baseline in WASO (primary) and latency to persistent sleep (LPS; secondary) to Days 1&2 (mean of two treatment nights assessed by polysomnography) in each period. Safety and tolerability were also assessed.

Results: Of 58 subjects included, 67% were female and median age was 69 years [range 65–85]). WASO and LPS were dose-dependently reduced from baseline to Days 1&2 following daridorexant administration (multiple comparison procedure-modeling, p<0.0001 and p=0.004, respectively); reductions were statist...