Kurume University, Kurume, Fukuoka, Japan.
Osaka Kaisei Hospital, Osaka, Japan.
Sleep Med. 2024 Oct;122:27-34. doi: 10.1016/j.sleep.2024.07.037. Epub 2024 Aug 2.
This Phase 3 double-blind, placebo-controlled study evaluated the efficacy and safety of daridorexant in Japanese patients with insomnia disorder.
PATIENTS/METHODS: 490 patients with insomnia disorder from 95 sites in Japan were randomized to daridorexant 50 mg (n = 163), 25 mg (n = 163) or placebo (n = 164) for 4 weeks, followed by a 7-day placebo run-out and a 30-day safety follow-up. The primary efficacy endpoints, in hierarchical order, were change from baseline at Week 4 in subjective total sleep time (sTST) and subjective latency to sleep onset (sLSO), for daridorexant 50 mg vs placebo. sTST and sLSO were also evaluated (secondary endpoints) for daridorexant 25 mg vs placebo. Safety endpoints included adverse events and next-morning sleepiness (Visual Analog Scale, VAS).
Daridorexant 50 mg significantly increased sTST and decreased sLSO versus placebo at Week 4 (least-squares mean difference [LSMD]: sTST 20.3 min [95 % CI 11.4, 29.2] p < 0.001; sLSO -10.7 min [-15.8, -5.5] p < 0.001). Daridorexant 25 mg also significantly improved both endpoints versus placebo (LSMD: sTST 9.2 min [0.3, 18.1] p = 0.042; sLSO -7.2 min [-12.3, -2.0] p = 0.006). Overall incidence of adverse events was similar across groups (50 mg: 22 %; 25 mg: 18 %; placebo 23 %); somnolence, the most common event, increased with increasing dose (50 mg: 6.8 %; 25 mg: 3.7 %; placebo 1.8 %). However, daridorexant did not increase VAS next-morning sleepiness. No rebound or withdrawal-related symptoms were observed after treatment discontinuation.
In Japanese patients with insomnia disorder, daridorexant (25 and 50 mg) was well tolerated and significantly improved subjective sleep outcomes, with no evidence of residual effects.
本 3 期双盲、安慰剂对照研究评估了 daridorexant 在日本失眠障碍患者中的疗效和安全性。
患者/方法：来自日本 95 个地点的 490 例失眠障碍患者被随机分配至 daridorexant 50mg（n=163）、25mg（n=163）或安慰剂（n=164）组，治疗 4 周，随后进行 7 天安慰剂洗脱期和 30 天安全性随访。主要疗效终点按等级顺序为：与安慰剂相比，daridorexant 50mg 治疗第 4 周时主观总睡眠时间（sTST）和主观入睡潜伏期（sLSO）的变化。（次要终点）还评估了 daridorexant 25mg 与安慰剂相比时的 sTST 和 sLSO。安全性终点包括不良事件和次日嗜睡（视觉模拟量表，VAS）。
与安慰剂相比，daridorexant 50mg 在第 4 周时显著增加了 sTST 并减少了 sLSO（最小二乘均数差[LSMD]：sTST 20.3min [95%CI 11.4，29.2]，p<0.001；sLSO-10.7min [-15.8，-5.5]，p<0.001）。daridorexant 25mg 与安慰剂相比也显著改善了这两个终点（LSMD：sTST 9.2min [0.3，18.1]，p=0.042；sLSO-7.2min [-12.3，-2.0]，p=0.006）。各组不良反应总发生率相似（50mg：22%；25mg：18%；安慰剂 23%）；最常见的事件是嗜睡，随剂量增加而增加（50mg：6.8%；25mg：3.7%；安慰剂 1.8%）。然而，daridorexant 并未增加 VAS 次日嗜睡。治疗停止后未观察到反弹或停药相关症状。
在日本失眠障碍患者中，daridorexant（25mg 和 50mg）耐受性良好，显著改善了主观睡眠结局，且无残留效应的证据。
