Dauvilliers Yves, Roth Thomas, Bogan Richard, Thorpy Michael J, Morse Anne Marie, Roy Asim, Gudeman Jennifer
Sleep-Wake Disorders Center, Department of Neurology, Gui-de-Chauliac Hospital, Institute for Neurosciences of Montpellier INM, INSERM, University of Montpellier, Montpellier, France.
Sleep Disorders and Research Center, Henry Ford Health System, Detroit, MI, USA.
Sleep Med. 2024 Dec;124:209-216. doi: 10.1016/j.sleep.2024.09.024. Epub 2024 Sep 17.
OBJECTIVE/BACKGROUND: Extended-release, once-nightly sodium oxybate (ON-SXB) significantly improved narcolepsy symptoms in participants in the phase 3, randomized, double-blind, placebo-controlled REST-ON trial. This post hoc analysis of REST-ON data evaluated ON-SXB efficacy in participants with or without concomitant alerting agent use.
PATIENTS/METHODS: Participants with narcolepsy aged >16 years were randomized 1:1 to ON-SXB (week 1: 4.5 g, weeks 2-3: 6 g, weeks 4-8: 7.5 g, weeks 9-13: 9 g) or placebo. Primary endpoints in this post hoc analysis included change from baseline in mean sleep latency on the Maintenance of Wakefulness Test (MWT), Clinical Global Impression-Improvement (CGI-I) rating, and number of weekly cataplexy episodes. The secondary endpoints were change from baseline in the Epworth Sleepiness Scale (ESS) score and in objective and subjective disrupted nighttime sleep parameters. Post hoc analyses assessed participants with and without alerting agent use across 6-, 7.5-, and 9-g doses.
In the modified intent-to-treat population, 119 (63 %) were (ON-SXB, n = 66; placebo, n = 53) and 71 (37 %) were not (ON-SXB, n = 31; placebo, n = 40) taking alerting agents. Regardless of alerting agent use, treatment with ON-SXB resulted in significant improvements vs placebo (all doses, P < 0.05) for MWT, CGI-I, and number of weekly cataplexy episodes. Significant improvements in ESS (all doses, P < 0.05) with ON-SXB vs placebo were observed in the alerting agent use cohort. Directional improvements in ESS were reported with all doses in the no alerting agent use group.
Regardless of concomitant alerting agent use, ON-SXB improved daytime and nighttime narcolepsy symptoms vs placebo.
目的/背景：在3期随机双盲安慰剂对照REST-ON试验中，缓释型每晚一次服用的羟丁酸钠（ON-SXB）显著改善了发作性睡病患者的症状。这项对REST-ON数据的事后分析评估了ON-SXB在使用或未使用伴随警觉药物的参与者中的疗效。
患者/方法：年龄大于16岁的发作性睡病患者按1:1随机分组，分别接受ON-SXB（第1周：4.5克，第2 - 3周：6克，第4 - 8周：7.5克，第9 - 13周：9克）或安慰剂治疗。本次事后分析的主要终点包括清醒维持测试（MWT）中平均睡眠潜伏期相对于基线的变化、临床总体印象改善（CGI-I）评分以及每周猝倒发作次数。次要终点是爱泼沃斯思睡量表（ESS）评分相对于基线的变化以及客观和主观夜间睡眠紊乱参数的变化。事后分析评估了6克、7.5克和9克剂量下使用和未使用警觉药物的参与者。
在改良意向性治疗人群中，119名（63%）（ON-SXB组，n = 66；安慰剂组，n = 53）正在服用警觉药物，71名（37%）（ON-SXB组，n = 31；安慰剂组，n = 40）未服用警觉药物。无论是否使用警觉药物，与安慰剂相比，ON-SXB治疗在MWT、CGI-I和每周猝倒发作次数方面均有显著改善（所有剂量，P < 0.05）。在使用警觉药物的队列中，与安慰剂相比，ON-SXB在ESS方面有显著改善（所有剂量，P < 0.05）。在未使用警觉药物的组中，所有剂量的ESS均有方向性改善。
无论是否同时使用警觉药物，与安慰剂相比，ON-SXB均能改善发作性睡病的白天和夜间症状。
