Randomized, multicenter, dose-ranging trial of retigabine for partial-onset seizures
Randomized, multicenter, dose-ranging trial of retigabine for partial-onset seizures
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DOI：
10.1212/01.wnl.0000259034.45049.00
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发表时间：
2007-04-10
期刊：
影响因子：
9.9
通讯作者：
Alves, W. M.
中科院分区：
文献类型：
--
作者：
Porter, R. J.;Partiot, A.;Alves, W. M.
目的：评估瑞替加滨 600、900 和 1,200 mg/天（每日 3 次）作为辅助治疗对部分性癫痫发作患者的疗效和安全性。方法：进行了一项多中心、随机、双盲、安慰剂对照试验。 8 周基线期后，患者被随机分配至 16 周双盲治疗期（8 周强制滴定和 8 周维持），然后逐渐减量或进入开放标签扩展研究。主要疗效是每月癫痫发作频率相对于基线的百分比变化，并在治疗组之间进行比较。次要疗效比较包括癫痫发作频率（应答率）降低≥50%的患者比例、新癫痫发作类型的出现以及医生对整体临床改善的评估。安全性/耐受性评估包括不良事件（AE）、身体和神经系统检查以及临床实验室评估。对意向治疗人群进行了疗效分析。结果：在 399 名随机患者中，279 名（69.9%）完成了双盲治疗期。每月总部分性癫痫发作频率相对于基线的中位百分比变化在 600 mg/天时为 -23%，在 900 mg/天时为 -29%，在 1,200 mg/天时为 -35%，而安慰剂组为 -13%（所有治疗组的总体差异 p < 0.001）。瑞替加滨 600 毫克/天的反应率为 23%，900 毫克/天为 32%（p = 0.021），1,200 毫克/天为 33%（p = 0.016），而安慰剂为 16%。最常见的治疗中出现的 AE 是嗜睡、头晕、精神错乱、语言障碍、眩晕、震颤、健忘症、思维异常、步态异常、感觉异常和复视。结论：瑞替加滨辅助治疗耐受性良好，并以剂量依赖性方式降低部分性癫痫发作的频率。
Objective: To evaluate the efficacy and safety of retigabine 600, 900, and 1,200 mg/day administered three times daily as adjunctive therapy in patients with partial-onset seizures. Methods: A multicenter, randomized, double-blind, placebo-controlled trial was performed. After an 8-week baseline phase, patients were randomized to a 16-week double-blind treatment period (8-week forced titration and 8-week maintenance) followed by either tapering or entry into an open-label extension study. Primary efficacy was the percentage change from baseline in monthly seizure frequency and compared across treatment arms. Secondary efficacy comparisons included the proportion of patients experiencing >= 50% reduction in seizure frequency (responder rate), emergence of new seizure types, and physician assessment of global clinical improvement. Safety/tolerability assessments included adverse events (AEs), physical and neurologic examinations, and clinical laboratory evaluations. Efficacy analyses were performed on the intent-to-treat population. Results: Of the 399 randomized patients, 279 (69.9%) completed the double-blind treatment period. The median percent change in monthly total partial seizure frequency from baseline was -23% for 600 mg/day, -29% for 900 mg/day, and -35% for 1,200 mg/day vs -13% for placebo (p < 0.001 for overall difference across all treatment arms). Responder rates for retigabine were 23% for 600 mg/day, 32% for 900 mg/day (p = 0.021), and 33% for 1,200 mg/day (p = 0.016), vs 16% for placebo. The most common treatment-emergent AEs were somnolence, dizziness, confusion, speech disorder, vertigo, tremor, amnesia, abnormal thinking, abnormal gait, paresthesia, and diplopia. Conclusion: Adjunctive therapy with retigabine is well tolerated and reduces the frequency of partial-onset seizures in a dose-dependent manner.