Dauvilliers Yves, Braunstein Guy, Zammit Gary, Olivieri Antonio, Luyet Pierre-Philippe
National Reference Centre for Orphan Diseases, Narcolepsy-Rare Hypersomnias, Sleep Unit, Department of Neurology, CHU Montpellier, Institute for Neurosciences of Montpellier INM, Univ Montpellier, INSERM, Montpellier, France.
Idorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, 4123, Allschwil, Switzerland.
Sleep Med. 2025 Jul;131:106523. doi: 10.1016/j.sleep.2025.106523. Epub 2025 Apr 17.
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.
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.
目的/背景：整夜减少清醒时间且无次日残留效应是慢性失眠障碍药物的重要特性。在3期试验中，与安慰剂相比，达立多雷生显著减少了多导睡眠图测定的睡眠起始后清醒时间（WASO），且日间嗜睡发生率与安慰剂相似。本分析考察了达立多雷生对夜间每2小时时段（8小时记录）的WASO的影响，以及对次晨嗜睡、日间警觉性和功能能力（每日使用视觉模拟量表[VAS]评估）的影响，以及这些夜间和日间评估之间的相关性。
患者/方法：分析了930例失眠障碍患者的数据，这些患者被随机分配接受50mg达立多雷生（n = 310）、25mg达立多雷生（n = 310）或安慰剂（n = 310）治疗3个月。
在第1个月时，25mg和50mg达立多雷生在第2时段（最小二乘均值差[LSMD] 25mg：-4.7分钟，p < 0.0001；50mg：-7.1分钟，p < 0.0001）、第3时段（LSMD 25mg：-3.3分钟，p = 0.0086；50mg：-7.2分钟，p < 0.0001）和第4时段（LSMD 25mg：-4.3分钟，p = 0.0055；50mg -8.5分钟，p < 0.0001）与安慰剂相比显著降低了WASO。第3个月时结果相似。所有组次晨嗜睡、日间警觉性和功能能力的VAS评分从第1天开始改善，并随时间持续改善，治疗效果按数值排序为50mg达立多雷生>25mg达立多雷生>安慰剂。在WASO（总体及任何时段）与三个VAS评分之间未发现显著相关性。
达立多雷生可减少整夜的清醒时间，同时独立减轻早晨嗜睡并改善日间功能和警觉性。
