Evaluation of Carisbamate for the Treatment of Migraine in a Randomized, Double-Blind Trial
Evaluation of Carisbamate for the Treatment of Migraine in a Randomized, Double-Blind Trial
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DOI：
10.1111/j.1526-4610.2008.01326.x
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发表时间：
2009-02-01
期刊：
影响因子：
5
通讯作者：
Novak, Gerald P.
中科院分区：
文献类型：
--
作者：
Cady, Roger K.;Mathew, Ninan;Novak, Gerald P.
本研究探讨了100 mg/d、300 mg/d或600 mg/d剂量的Carisbamate预防偏头痛的剂量-反应关系。Carisbamate（[S]-2-O-carbamoyl-1-o-chlorophenyl-ethanol; RWJ 333369）是一种新的化学实体，正在研究其作为部分发作癫痫的连续治疗的有效性。由于一些抗癫痫药物对偏头痛也有效，例如托吡酯和丙戊酸钠，我们测试了卡立氨酯预防偏头痛的作用。这是一项双盲、安慰剂对照试验，持续时间约22周。主要疗效变量是使用48小时规则的平均每月偏头痛频率从基线到双盲期的百分比降低。患者以1：1：1：1的比例随机接受卡立氨酯100、300或600 mg/天或安慰剂治疗。在前瞻性4周基线期内对偏头痛发作进行计数，随后是2周滴定期、12周维持期、1周药物减量期和3周观察期。患者有明确的偏头痛病史，有或无先兆，至少1年，3个月内每月偏头痛发作3-12次，患者（n = 323）主要为女性（85%）和白色（89%），平均年龄41岁。任何Carisbamate组和安慰剂组之间均无统计学显著差异（P >= .6）从基线到终点的平均每月偏头痛频率的中位数（范围）百分比降低（与安慰剂相比的P值）：37%（-250%，100%; P = .7）CRS 100 mg/天; 27%（-100%，100%; P = .8）CRS 300 mg/天; 35%（-87%，100%; P = .6）CRS 600 mg/天。次要疗效指标（有效率、使用24小时规则的平均每月偏头痛频率减少百分比以及平均每月偏头痛天数减少百分比）的结果是一致的（P >= .075）。安慰剂组和卡立巴酯组因不良事件停药的患者比例相似（各13%）。在接受Carisbamate治疗的患者中，最常见的（发生在>= 5%的患者中）治疗后出现的不良事件是疲劳（17%）和鼻咽炎（13%）。疲劳似乎与剂量有关。在这项包括适当人群的对照良好的研究中，Carisbamate在预防偏头痛方面并不比安慰剂更有效。然而，在高达600 mg/天的剂量下，卡立氨酯单药治疗耐受性良好。
This study explored the dose-response relationship of carisbamate administered at doses of 100 mg per day, 300 mg per day, or 600 mg per day, in the prevention of migraine.Carisbamate ([S]-2-O-carbamoyl-1-o-chlorophenyl-ethanol; RWJ 333369) is a new chemical entity being studied for efficacy as adjunctive therapy in partial onset epilepsy. Because some antiepileptic drugs are also efficacious in migraine, for example, topiramate and valproate sodium, we tested carisbamate in migraine prophylaxis.This was a double-blind, placebo-controlled trial, approximately 22-week duration. The primary efficacy variable was the percent reduction from baseline through the double-blind phase in average monthly migraine frequency using a 48-hour rule. Patients were randomized 1 : 1 : 1 : 1 to treatment with carisbamate 100, 300, or 600 mg per day, or placebo. Migraine attacks were counted during a prospective 4-week baseline period, which was followed by a 2-week titration period, a 12-week maintenance period, a 1-week medication reduction period, and a 3-week observation period. Patients had an established history of migraine, with or without aura, for at least 1 year and a 3-month history of 3-12 migraine attacks per month.Patients (n = 323) were predominantly women (85%) and white (89%); mean age was 41 years. There were no statistically significant differences between any of the carisbamate groups and placebo (P >= .6) for the median (range) percentage reduction from baseline to end point in average monthly migraine frequency (P value vs placebo): 37% (-250%, 100%) for placebo; 33% (-210%, 100%; P = .7) CRS 100 mg/day; 27% (-100%, 100%; P = .8) CRS 300 mg/day; and 35% (-87%, 100%; P = .6) CRS 600 mg/day. Results for secondary efficacy measures (responder rate, percent reduction in average monthly migraine frequency using the 24-hour rule, and percent reduction in average monthly migraine days) were consistent (P >= .075). The proportion of patients discontinuing because of adverse events was similar for placebo and carisbamate-treated patients (13% each). The most common (occurring in >= 5% of patients) treatment-emergent adverse events in patients treated with carisbamate were fatigue (17%) and nasopharyngitis (13%). Fatigue appeared to be dose related.Carisbamate was not more efficacious in migraine prophylaxis than placebo in this well-controlled study that included a suitable population. However, carisbamate monotherapy was well tolerated at doses up to 600 mg per day.