Effect of daridorexant on nighttime wakefulness and next-morning sleepiness: assessing the transition from night to day in insomnia disorder

Abstract

Objective/background: Reducing wakefulness throughout the night without next-day residual effects are essential characteristics for drugs for chronic insomnia disorder. In Phase 3 trials, daridorexant significantly reduced polysomnography-determined wake after sleep onset (WASO) versus placebo, and rates of daytime somnolence were similar to placebo. This analysis examines the effect of daridorexant on WASO in each 2-h quarter (Q) of the night (8-h recording), and on next-morning sleepiness, daytime alertness and ability to function (assessed daily using visual analog scales [VAS]), and the correlation between these night and day assessments.

Patients/methods: Data from 930 patients with insomnia disorder randomized to daridorexant 50 mg (n = 310), 25 mg (n = 310) or placebo (n = 310) for 3 months were analyzed.

Results: At Month 1, daridorexant 25 mg and 50 mg significantly decreased WASO versus placebo in Q2 (least-square mean difference [LSMD] 25 mg: -4.7 min p < 0.0001; 50 mg: -7.1 min p < 0.0001), Q3 (LSMD 25 mg: -3.3 min p = 0.0086; 50 mg: -7.2 min p < 0.0001) and Q4 (LSMD 25 mg: -4.3 min p = 0.0055; 50 mg -8.5 min p < 0.0001). Results were similar at Month 3. VAS scores for next-morning sleepiness, daytime alertness and ability to function improved from Day 1 in all groups and continued to improve over time, with treatment numerically ranked as daridorexant 50 mg > 25 mg > placebo. No significant correlations were found between WASO (overall and at any quarter) and the three VAS scores.

Conclusion: Daridorexant reduces wakefulness throughout the entire night while independently decreasing morning sleepiness and improving daytime functioning and alertness.

Trial registration: ClinicalTrials.gov NCT03545191.

Keywords: Daridorexant; Daytime functioning; Insomnia; Quarter of night; Residual effect; Wake after sleep onset.