Assessing Early Efficacy After Initiation of Once-Nightly Sodium Oxybate (ON-SXB; FT218) in Participants with Narcolepsy Type 1 or 2: A Post Hoc Analysis from the Phase 3 REST-ON Trial.

IF 7.4 2区医学 Q1 CLINICAL NEUROLOGY

CNS drugs Pub Date : 2025-03-01 Epub Date: 2025-03-20 DOI:10.1007/s40263-024-01143-7

Lois Krahn, Asim Roy, John W Winkelman, Anne Marie Morse, Jennifer Gudeman

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引用次数: 0

Abstract

Background: Once-nightly sodium oxybate (LUMRYZ™; ON-SXB; FT218) significantly improved narcolepsy symptoms in the phase 3 REST-ON trial. The objective of this post hoc analysis was to investigate the early efficacy of ON-SXB at weeks 1 (4.5-g dose) and 2 (6-g dose).

Methods: In REST-ON, participants (≥ 16 years) with narcolepsy type 1 or 2 were randomized 1:1 to ON-SXB (4.5 g, 1 week; 6 g, 2 weeks; 7.5 g, 5 weeks; 9 g, 5 weeks) or placebo. Protocol-prespecified efficacy assessments were conducted at weeks 3 (6-g dose), 8 (7.5-g dose), and 13 (9-g dose). A post hoc analysis was conducted to assess the early efficacy of ON-SXB, defined as efficacy at weeks 1 (4.5-g dose) and 2 (6-g dose) on Epworth Sleepiness Scale (ESS) score, visual analog scale (VAS) sleep quality, and VAS refreshing nature of sleep. Least squares mean differences (LSMD) in change from baseline to weeks 1 and 2, 95% confidence intervals (CIs), and P values were calculated using mixed-effects models for repeated measures.

Results: In the modified intent-to-treat population (n = 190; ON-SXB, n = 97; placebo, n = 93), baseline ESS scores were 16.6 and 17.5, sleep quality scores were 53.8 and 55.9, and refreshing nature of sleep scores were 46.5 and 49.9 with ON-SXB and placebo, respectively. At week 1 (4.5 g), numerical improvement in ESS score (LSMD [95% CI], - 0.7 [- 1.6 to 0.2]) and significant improvements in sleep quality (3.6 [1.1-6.1]; P < 0.01) and refreshing nature of sleep (3.2 [0.5-5.9]; P < 0.05) were observed with ON-SXB versus placebo. At week 2 (6 g), significant improvements with ON-SXB versus placebo were observed for ESS score (- 1.3 [- 2.4 to - 0.2]; P < 0.02), sleep quality (7.0 [3.8-10.1]; P < 0.001), and refreshing nature of sleep (5.8 [2.3-9.4]; P = 0.001).

Conclusions: ON-SXB improved daytime sleepiness, sleep quality, and refreshing nature of sleep, with observable benefits beginning in the first week of treatment. These data may help clinicians set expectations with patients.

Clinical trial id: NCT02720744.

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每晚一次氧酸钠（ON-SXB）治疗的早期疗效评估FT218)在1型或2型发作性睡病患者中的应用：来自3期REST-ON试验的事后分析

背景：每晚一次的氧化钠(LUMRYZ™；ON-SXB;在3期REST-ON试验中，FT218显著改善了发作性睡病症状。这项事后分析的目的是研究ON-SXB在第1周（4.5 g剂量）和第2周（6 g剂量）的早期疗效。方法：在REST-ON试验中，患有1型或2型发作性睡病的参与者（≥16岁）以1:1的比例随机分配到ON-SXB组(4.5 g， 1周；6 g， 2周；7.5 g， 5周；9 g， 5周)或安慰剂。在第3周（6-g剂量）、第8周（7.5-g剂量）和第13周（9-g剂量）进行方案预先指定的疗效评估。通过事后分析评估on - sxb的早期疗效，定义为第1周（4.5 g剂量）和第2周（6 g剂量）对Epworth嗜睡量表（ESS）评分、视觉模拟量表（VAS）睡眠质量和VAS睡眠清爽性的疗效。使用重复测量的混合效应模型计算从基线到第1周和第2周变化的最小二乘平均差异（LSMD）、95%置信区间（ci）和P值。结果：在修改意向治疗人群中(n = 190；ON-SXB, n = 97；n = 93)， ON-SXB组和安慰剂组的ESS基线评分分别为16.6和17.5分，睡眠质量评分分别为53.8和55.9分，睡眠清新性评分分别为46.5和49.9分。在第1周（4.5 g）， ESS评分数值改善（LSMD [95% CI], - 0.7[- 1.6至0.2]），睡眠质量显著改善(3.6 [1.1-6.1]；P < 0.01)和睡眠清爽性(3.2 [0.5 ~ 5.9]；P < 0.05)。在第2周（6 g），与安慰剂相比，ON-SXB显著改善了ESS评分(- 1.3[- 2.4至- 0.2]；P < 0.02)，睡眠质量(7.0 [3.8-10.1]；P < 0.001)，睡眠清爽性(5.8 [2.3-9.4]；P = 0.001)。结论：ON-SXB改善了白天嗜睡、睡眠质量和睡眠清爽性，从治疗第一周开始就有明显的益处。这些数据可以帮助临床医生对患者设定期望。临床试验编号：NCT02720744。

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来源期刊

CNS drugs 医学-精神病学

CiteScore

12.00

自引率

3.30%

发文量

审稿时长

6-12 weeks

期刊介绍： CNS Drugs promotes rational pharmacotherapy within the disciplines of clinical psychiatry and neurology. The Journal includes: - Overviews of contentious or emerging issues. - Comprehensive narrative reviews that provide an authoritative source of information on pharmacological approaches to managing neurological and psychiatric illnesses. - Systematic reviews that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement. - Adis Drug Reviews of the properties and place in therapy of both newer and established drugs in neurology and psychiatry. - Original research articles reporting the results of well-designed studies with a strong link to clinical practice, such as clinical pharmacodynamic and pharmacokinetic studies, clinical trials, meta-analyses, outcomes research, and pharmacoeconomic and pharmacoepidemiological studies. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in CNS Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.