Yves Dauvilliers, Thomas Roth, Richard Bogan, Michael J Thorpy, Anne Marie Morse, Asim Roy, Jordan Dubow, Jennifer Gudeman
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Assessments included mean sleep latency on Maintenance of Wakefulness Test (MWT) and Clinical Global Impression-Improvement (CGI-I) rating (coprimary endpoints) and sleep stage shifts, nocturnal arousals, and patient-reported sleep quality, refreshing nature of sleep, and Epworth Sleepiness Scale (ESS) score (secondary endpoints) separately in NT1 and NT2 subgroups.</p><p><strong>Results: </strong>The modified intent-to-treat population comprised 190 participants (NT1, n = 145; NT2, n = 45). Significant improvements were demonstrated with ON-SXB vs placebo in sleep latency for NT1 (all doses, p < .001) and NT2 (6 and 9 g, p < .05) subgroups. Greater proportions of participants in both subgroups had CGI-I ratings of much/very much improved with ON-SXB vs placebo. Sleep stage shifts and sleep quality significantly improved in both subgroups (all doses vs placebo, p < .001). 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引用次数: 0
摘要
研究目的:3期REST-ON试验的事后分析评估了每晚一次的缓释氧酸钠(ON-SXB;FT218)与安慰剂对1型(NT1)和2型(NT2)发作性睡病患者白天嗜睡和夜间睡眠中断的影响。方法:参与者按发作性睡病类型分层,按1:1随机分配ON-SXB (4.5 g,第1周;6克,2-3周;7.5 g,第4-8周;9克(第9-13周)或安慰剂。评估包括NT1和NT2亚组中清醒维持测试(MWT)和临床总体印象改善(gi - i)评分的平均睡眠潜伏期(主要终点)和睡眠阶段变化、夜间觉醒、患者报告的睡眠质量、睡眠的清新性和Epworth嗜睡量表(ESS)评分(次要终点)。结果:修正意向治疗人群包括190名参与者(NT1, n = 145;NT2, n = 45)。与安慰剂相比,ON-SXB在NT1(所有剂量,p < 0.001)和NT2(6和9 g, p < 0.05)亚组的睡眠潜伏期有显著改善。与安慰剂相比,两个亚组中更大比例的参与者使用ON-SXB的CGI-I评分得到了很大/非常大的改善。两个亚组的睡眠阶段变化和睡眠质量都有显著改善(所有剂量与安慰剂相比,p < 0.001)。与安慰剂相比,所有ON-SXB剂量在NT1的睡眠清新性(p < 0.001)、夜间唤醒(p < 0.05)和ESS评分(p≤0.001)方面均有显著改善,而NT2则有方向性改善。结论:单一ON-SXB睡前剂量对NT1和NT2患者的日间嗜睡和DNS有临床意义的改善,对有限NT2亚组的作用较小。
Efficacy of once-nightly sodium oxybate (FT218) in narcolepsy type 1 and type 2: post hoc analysis from the Phase 3 REST-ON Trial.
Study objectives: Post hoc analyses from the phase 3 REST-ON trial evaluated efficacy of extended-release once-nightly sodium oxybate (ON-SXB; FT218) vs placebo for daytime sleepiness and disrupted nighttime sleep in narcolepsy type 1 (NT1) and 2 (NT2).
Methods: Participants were stratified by narcolepsy type and randomized 1:1 to ON-SXB (4.5 g, week 1; 6 g, weeks 2-3; 7.5 g, weeks 4-8; and 9 g, weeks 9-13) or placebo. Assessments included mean sleep latency on Maintenance of Wakefulness Test (MWT) and Clinical Global Impression-Improvement (CGI-I) rating (coprimary endpoints) and sleep stage shifts, nocturnal arousals, and patient-reported sleep quality, refreshing nature of sleep, and Epworth Sleepiness Scale (ESS) score (secondary endpoints) separately in NT1 and NT2 subgroups.
Results: The modified intent-to-treat population comprised 190 participants (NT1, n = 145; NT2, n = 45). Significant improvements were demonstrated with ON-SXB vs placebo in sleep latency for NT1 (all doses, p < .001) and NT2 (6 and 9 g, p < .05) subgroups. Greater proportions of participants in both subgroups had CGI-I ratings of much/very much improved with ON-SXB vs placebo. Sleep stage shifts and sleep quality significantly improved in both subgroups (all doses vs placebo, p < .001). Significant improvements with all ON-SXB doses vs placebo in refreshing nature of sleep (p < .001), nocturnal arousals (p < .05), and ESS scores (p ≤ .001) were reported for NT1 with directional improvements for NT2.
Conclusions: Clinically meaningful improvements of a single ON-SXB bedtime dose were shown for daytime sleepiness and DNS in NT1 and NT2, with less power for the limited NT2 subgroup.
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