Résumé
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.
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.
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.
Daridorexant reduces wakefulness throughout the entire night while independently decreasing morning sleepiness and improving daytime functioning and alertness.
•This was an analysis of Phase 3 data in patients with chronic insomnia disorder.•Daridorexant reduced wakefulness throughout the night including the last 2 h.•Upon awakening, daridorexant decreased next-morning sleepiness.•These are two essential characteristics for chronic insomnia disorder drugs.