Number, Duration, and Distribution of Wake Bouts in Patients with Insomnia Disorder: Effect of Daridorexant and Zolpidem.

Abstract

Daridorexant, a dual orexin receptor antagonist approved in early 2022, reduces wake after sleep onset without reducing the number of awakenings in patients with insomnia. The objective of this post hoc analysis was to explore the effect of daridorexant on the number, duration, and distribution of night-time wake bouts, and their correlation with daytime functioning. Adults with insomnia disorder were randomized 1:1:1:1:1:1 to placebo, zolpidem 10mg, or daridorexant 5, 10, 25, or 50mg in a phase II dose-finding study, and 1:1:1 to placebo or daridorexant 25 or 50mg in a pivotal phase III study. We analyzed polysomnography data for daridorexant 25 and 50mg, zolpidem 10mg, and placebo groups. Polysomnography was conducted at baseline, then on Days 1/2, 15/16, and 28/29 in the phase II study, and Months 1 and 3 in the phase III study. The number, duration, and distribution of wake bouts (≥ 0.5min) were assessed. Data from 1111 patients (phase II study: daridorexant 50mg [n = 61], zolpidem 10mg [n = 60], placebo [n = 60]; phase III study: daridorexant 25mg [n = 310], daridorexant 50mg [n = 310], placebo [n = 310]) were analyzed. Long wake bouts were defined as > 6min. Compared with placebo, daridorexant 50mg reduced overall wake time (p < 0.05; all time points, both studies), the odds of experiencing long wake bouts (p < 0.001; Months 1 and 3, phase III study), and the cumulative duration of long wake bouts (p < 0.01; all time points, both studies). Reductions in long wake bouts were sustained through the second half of the night and correlated with improvements in daytime functioning. An increase in the cumulative duration of short wake bouts was observed with daridorexant 50mg (p < 0.01 vs placebo, Months 1 and 3, phase III study); this was uncorrelated with daytime functioning. Daridorexant reduced the number and duration of longer wake bouts throughout the night compared with placebo, corresponding with improved daytime functioning. Clinicaltrials.gov NCT02839200 (registered July 20, 2016), NCT03545191 (registered June 4, 2018).