A Randomized, Double-Blind, Placebo-Controlled, Crossover Study of XP13512/GSK1838262 in the Treatment of Patients With Primary Restless Legs Syndrome
A Randomized, Double-Blind, Placebo-Controlled, Crossover Study of XP13512/GSK1838262 in the Treatment of Patients With Primary Restless Legs Syndrome
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DOI：
10.1093/sleep/32.2.159
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发表时间：
2009-02-01
期刊：
影响因子：
5.6
通讯作者：
Barrett, Ronald W.
中科院分区：
文献类型：
--
作者：
Kushida, Clete A.;Walters, Arthur S.;Barrett, Ronald W.
研究目的：评估XP 13512/GSK 1838262的疗效和耐受性，XP 13512/GSK 1838262是一种用于治疗中重度原发性不宁腿综合征（RLS）的研究性非多巴胺能药物。设计：随机、双盲、安慰剂对照、交叉试验。设置：9个美国临床中心。患者：38例初治RLS受试者（平均值+/- SD年龄50.1 +/- 13.2岁）。XP 13512 1800 mg/天，随后安慰剂或安慰剂随后XP 13512 1800 mg/天，持续14天，治疗期间之间有7天洗脱期。测量和结果：主要终点为第14天国际RLS研究组评定量表（IRLS）总评分较基线的平均变化，采用方差分析进行分析，序列、阶段和治疗作为固定效应，序列内受试者作为随机效应。与安慰剂相比，XP 13512显著降低了第14天的IRLS总评分（平均值+/- SD：XP 13512 - 12.1 +/- 6.5，安慰剂-1.9 +/- 6.3; P < 0.0001）。多导睡眠图数据显示，与安慰剂相比，XP 13512在第14天显著改善了睡眠结构（相对于基线睡眠时间[分钟]的平均+/- SD变化：第1阶段：XP 13512 -9.8 +/- 23.9，安慰剂0.4 +/- 23.2;校正P < 0.0054，标称P < 0.0001;第3/4阶段（慢波睡眠）：XP 13512 22.8 +/- 40.8，安慰剂1.4 +/- 34.3;校正P = 0.0092，标称P = 0.0002）。最常报告的不良事件是嗜睡（XP 13512 30.6%，安慰剂2.8%）和头晕（XP 13512 27.8%，安慰剂5.6%）。结论：XP 13512 1800 mg/天显著减轻RLS症状，改善睡眠，并且在治疗14天的中重度原发性RLS受试者中通常耐受良好。
Study Objective: To evaluate the efficacy and tolerability of XP13512/GSK1838262, an investigational nondopaminergic agent for the treatment of moderate-to-severe primary restless legs syndrome (RLS).Design: Randomized, double-blind, placebo-controlled, crossover trial.Setting: Nine US clinical sites.Patients: Thirty-eight treatment-naive subjects with RLS (mean +/- SD age 50.1 +/- 13.2 years).Interventions: XP13512 1800 mg/day followed by placebo or placebo followed by XP13512 1800 mg/day for 14 days, with a 7-day washout between treatment periods.Measurements and Results: The primary endpoint was mean change from baseline International RLS Study Group rating scale (IRLS) total score on Day 14, analyzed using analysis of variance with sequence, period, and treatment as fixed effects and subjects within sequence as a random effect. XP13512 significantly reduced IRLS total score on Day 14 compared with placebo (mean +/- SD: XP13512 - 12.1 +/- 6.5, placebo -1.9 +/- 6.3; P < 0.0001). Polysomnographic data showed that XP13512 significantly improved sleep architecture on Day 14 compared with placebo (mean +/- SD change from baseline sleep time [minutes]: stage 1: XP13512-9.8 +/- 23.9, placebo 0.4 +/- 23.2; adjusted P < 0.0054, nominal P < 0.0001; stage 3/4 (slow-wave sleep): XP13512 22.8 +/- 40.8, placebo 1.4 +/- 34.3; adjusted P = 0.0092, nominal P = 0.0002). The most frequently reported adverse events were somnolence (XP13512 30.6%, placebo 2.8%) and dizziness (XP13512 27.8%, placebo 5.6%).Conclusions: XP13512 1800 mg/day significantly reduced RLS symptoms, improved sleep, and was generally well tolerated in subjects with moderate-to-severe primary RLS across 14 days of treatment.