{"title":"日本失眠症患者服用 Daridorexant:一项第 3 期随机、双盲、安慰剂对照研究。","authors":"","doi":"10.1016/j.sleep.2024.07.037","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p>This Phase 3 double-blind, placebo-controlled study evaluated the efficacy and safety of daridorexant in Japanese patients with insomnia disorder.</p></div><div><h3>Patients/methods</h3><p>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).</p></div><div><h3>Results</h3><p>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.</p></div><div><h3>Conclusions</h3><p>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.</p></div>","PeriodicalId":21874,"journal":{"name":"Sleep medicine","volume":null,"pages":null},"PeriodicalIF":3.8000,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Daridorexant in Japanese patients with insomnia disorder: A phase 3, randomized, double-blind, placebo-controlled study\",\"authors\":\"\",\"doi\":\"10.1016/j.sleep.2024.07.037\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><p>This Phase 3 double-blind, placebo-controlled study evaluated the efficacy and safety of daridorexant in Japanese patients with insomnia disorder.</p></div><div><h3>Patients/methods</h3><p>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).</p></div><div><h3>Results</h3><p>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.</p></div><div><h3>Conclusions</h3><p>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.</p></div>\",\"PeriodicalId\":21874,\"journal\":{\"name\":\"Sleep medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2024-08-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Sleep medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1389945724003551\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Sleep medicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1389945724003551","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Daridorexant in Japanese patients with insomnia disorder: A phase 3, randomized, double-blind, placebo-controlled study
Objective
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).
Results
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.
Conclusions
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.
期刊介绍:
Sleep Medicine aims to be a journal no one involved in clinical sleep medicine can do without.
A journal primarily focussing on the human aspects of sleep, integrating the various disciplines that are involved in sleep medicine: neurology, clinical neurophysiology, internal medicine (particularly pulmonology and cardiology), psychology, psychiatry, sleep technology, pediatrics, neurosurgery, otorhinolaryngology, and dentistry.
The journal publishes the following types of articles: Reviews (also intended as a way to bridge the gap between basic sleep research and clinical relevance); Original Research Articles; Full-length articles; Brief communications; Controversies; Case reports; Letters to the Editor; Journal search and commentaries; Book reviews; Meeting announcements; Listing of relevant organisations plus web sites.