Adjunctive perampanel for refractory partial-onset seizures Randomized phase III study 304
Adjunctive perampanel for refractory partial-onset seizures Randomized phase III study 304
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DOI：
10.1212/wnl.0b013e3182635735
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发表时间：
2012-08-01
期刊：
影响因子：
9.9
通讯作者：
Rogawski, Michael A.
中科院分区：
文献类型：
--
作者：
French, Jacqueline A.;Krauss, Gregory L.;Rogawski, Michael A.
目的：评估每日一次8或12 mg perampanel（一种非竞争性α-氨基-3-羟基-5-甲基-4-异恶唑-丙酸（AMPA）受体拮抗剂）与合并使用的抗癫痫药物（AED）联合治疗耐药性部分性发作癫痫发作的疗效和安全性。方法：这是一项多中心、双盲、安慰剂对照试验（ClinicalTrials.gov标识符：NCT 00699972）。患者（≥ 12岁，尽管使用了1-3种AED但癫痫发作仍持续）被随机（1：1：1）分配至每日一次perampanel 8 mg、12 mg或安慰剂组。基线（6周）后，患者进入19周双盲期：6周滴定（以2 mg/周的增量增加至目标剂量），随后是13周维持期。癫痫发作频率的百分比变化是主要终点; 50%的应答率是欧盟registration.Results的主要终点：388例患者随机和治疗，387提供癫痫发作频率数据。在双盲期内使用该意向治疗人群，安慰剂和perampanel 8 mg和12 mg组癫痫发作频率的中位百分比变化分别为-21.0%、-26.3%和-34.5%（8 mg和12 mg vs安慰剂组分别为p = 0.0261和p = 0.0158）。安慰剂组、perampanel 8 mg组和perampanel 12 mg组在维持治疗期间的50%应答率分别为26.4%、37.6%和36.1%; 8 mg组（p = 0.0760）或12 mg组（p = 0.0914）的这些差异无统计学意义。68例（17.5%）患者停药，包括40例（10.3%）因不良事件停药。最常见的治疗后出现的不良事件是头晕、嗜睡、易激惹、头痛、跌倒和共济失调。结论：本试验证明，每日一次、剂量为8或12 mg的连续perampanel可改善不受控制的部分性癫痫发作患者的癫痫控制。perampanel 8和12 mg剂量安全，耐受性可接受。证据分类：本研究提供了I类证据，证明每日一次8和12 mg剂量的连续性perampanel对不受控制的部分性癫痫发作患者有效。神经病学（R）2012;79：589-596
Objective: To assess efficacy and safety of once-daily 8 or 12 mg perampanel, a noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor antagonist, when added to concomitant antiepileptic drugs (AEDs) in the treatment of drug-resistant partial-onset seizures.Methods: This was a multicenter, double-blind, placebo-controlled trial (ClinicalTrials.gov identifier: NCT00699972). Patients (>= 12 years, with ongoing seizures despite 1-3 AEDs) were randomized (1:1:1) to once-daily perampanel 8 mg, 12 mg, or placebo. Following baseline (6 weeks), patients entered a 19-week double-blind phase: 6-week titration (2 mg/week increments to target dose) followed by a 13-week maintenance period. Percent change in seizure frequency was the primary endpoint; 50% responder rate was the primary endpoint for EU registration.Results: Of 388 patients randomized and treated, 387 provided seizure frequency data. Using this intent-to-treat population over the double-blind phase, the median percent change in seizure frequency was -21.0%, -26.3%, and -34.5% for placebo and perampanel 8 and 12 mg, respectively (p = 0.0261 and p = 0.0158 for 8 and 12 mg vs placebo, respectively). Fifty percent responder rates during the maintenance period were 26.4%, 37.6%, and 36.1%, respectively, for placebo, perampanel 8 mg, and perampanel 12 mg; these differences were not statistically significant for 8 mg (p = 0.0760) or 12 mg (p = 0.0914). Sixty-eight (17.5%) patients discontinued, including 40 (10.3%) for adverse events. Most frequent treatment-emergent adverse events were dizziness, somnolence, irritability, headache, fall, and ataxia.Conclusions: This trial demonstrated that once-daily, adjunctive perampanel at doses of 8 or 12 mg improved seizure control in patients with uncontrolled partial-onset seizures. Doses of perampanel 8 and 12 mg were safe, and tolerability was acceptable.Classification of evidence: This study provides Class I evidence that once-daily 8 and 12 mg doses of adjunctive perampanel are effective in patients with uncontrolled partial-onset seizures. Neurology (R) 2012;79:589-596