Porter R J, Partiot A, Sachdeo R, Nohria V, Alves W M
University of Pennsylvania, Philadelphia, PA, USA.
Neurology. 2007 Apr 10;68(15):1197-204. doi: 10.1212/01.wnl.0000259034.45049.00.
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.
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.
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.
Adjunctive therapy with retigabine is well tolerated and reduces the frequency of partial-onset seizures in a dose-dependent manner.
评估瑞替加滨每日600、900和1200毫克，分三次服用作为部分性发作癫痫患者辅助治疗的疗效和安全性。
进行了一项多中心、随机、双盲、安慰剂对照试验。在8周的基线期后，患者被随机分配到16周的双盲治疗期（8周强制滴定和8周维持期），随后逐渐减量或进入开放标签扩展研究。主要疗效指标是每月癫痫发作频率相对于基线的变化百分比，并在各治疗组之间进行比较。次要疗效比较包括癫痫发作频率降低≥50%的患者比例（应答率）、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）、体格和神经系统检查以及临床实验室评估。疗效分析在意向性治疗人群中进行。
399例随机分组的患者中，279例（69.9%）完成了双盲治疗期。每月总的部分性癫痫发作频率相对于基线的中位变化百分比，600毫克/天组为-23%，900毫克/天组为-29%，1200毫克/天组为-35%，而安慰剂组为-13%（所有治疗组之间的总体差异p<0.001）。瑞替加滨的应答率，600毫克/天组为23%，900毫克/天组为32%（p=0.021），1200毫克/天组为33%（p=0.016），而安慰剂组为16%。最常见的治疗中出现的不良事件为嗜睡、头晕、意识模糊、言语障碍、眩晕、震颤、失忆、思维异常、步态异常、感觉异常和复视。
瑞替加滨辅助治疗耐受性良好，并以剂量依赖的方式降低部分性发作癫痫的发作频率。
