Study Objectives To assess the efficacy and safety of FT218, a novel once-nightly formulation of sodium oxybate (ON-SXB), in patients with narcolepsy in the phase 3 REST-ON trial. Methods Narcolepsy patients aged ≥16 years were randomized 1:1 to uptitration of ON-SXB (4.5, 6, 7.5, and 9 g) or placebo. Three coprimary endpoints were change from baseline in mean sleep latency on the Maintenance of Wakefulness Test, Clinical Global Impression-Improvement rating, and weekly cataplexy attacks at 9, 7.5, and 6 g. Secondary endpoints included change from baseline on the Epworth Sleepiness Scale. Safety included adverse drug reactions and clinical laboratory assessments. Results In total, 222 patients were randomized; 212 received ≥1 dose of ON-SXB (n = 107) or placebo (n = 105). For the three coprimary endpoints and Epworth Sleepiness Scale, all three doses of ON-SXB demonstrated clinically meaningful, statistically significant improvement versus placebo (all p < 0.001). For ON-SXB 9 g versus placebo, increase in mean sleep latency was 10.8 versus 4.7 min (Least squares mean difference, LSMD [95% CI], 6.13 [3.52 to 8.75]), 72.0% versus 31.6% were rated much/very much improved on Clinical Global Impression-Improvement (OR [95% CI], 5.56 [2.76 to 11.23]), change in mean weekly number of cataplexy attacks was –11.5 versus –4.9 (LSMD [95% CI], –6.65 [–9.32 to –3.98]), and change in Epworth Sleepiness Scale was –6.5 and –2.7 (LSMD [95% CI], –6.52 [–5.47 to –2.26]). Common adverse reactions included nausea, vomiting, headache, dizziness, and enuresis. Conclusions ON-SXB significantly improved narcolepsy symptoms; its safety profile was consistent with SXB. ON-SXB conferred efficacy with a clearly beneficial single nighttime dose. Clinical Trial Registration ClinicalTrials.gov: NCT02720744, https://clinicaltrials.gov/ct2/show/NCT02720744.

中文翻译：

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在一项针对发作性睡病患者的 3 期随机临床试验中，每晚一次的羟丁酸钠 (FT218) 证明症状有所改善


研究目的 在 3 期 REST-ON 试验中评估 FT218（一种每晚一次的新型羟丁酸钠制剂 (ON-SXB)）对发作性睡病患者的疗效和安全性。方法 年龄≥16 岁的发作性睡病患者以 1:1 的比例随机接受 ON-SXB（4.5、6、7.5 和 9 g）或安慰剂的增量治疗。三个共同主要终点是维持清醒测试的平均睡眠潜伏期相对于基线的变化、临床总体印象改善评级以及每周 9、7.5 和 6 g 的猝倒发作。次要终点包括 Epworth 嗜睡量表相对于基线的变化。安全性包括药物不良反应和临床实验室评估。结果 总共 222 名患者被随机分组​​； 212 人接受了 ≥1 剂 ON-SXB (n = 107) 或安慰剂 (n = 105)。对于三个共同主要终点和 Epworth 嗜睡量表，与安慰剂相比，所有三种剂量的 ON-SXB 均表现出临床意义、统计学上显着的改善（所有 p < 0.001）。与安慰剂相比，ON-SXB 9 g 的平均睡眠潜伏期增加了 10.8 分钟与 4.7 分钟（最小二乘平均差，LSMD [95% CI]，6.13 [3.52 至 8.75]），72.0% 与 31.6% 被评为“非常”/“非常”临床整体印象改善（OR [95% CI]，5.56 [2.76 至 11.23]）有很大改善，平均每周猝倒发作次数的变化为 –11.5 与 –4.9（LSMD [95% CI]，–6.65 [– 9.32 至 –3.98]），Epworth 嗜睡量表的变化为 –6.5 和 –2.7（LSMD [95% CI]，–6.52 [–5.47 至 –2.26]）。常见的不良反应包括恶心、呕吐、头痛、头晕和遗尿。结论 ON-SXB 显着改善发作性睡病症状；其安全性与 SXB 一致。 ON-SXB 具有明显有益的单次夜间剂量的功效。临床试验注册临床试验。政府：NCT02720744，https://clinicaltrials.gov/ct2/show/NCT02720744。