Pfizer Inc, Groton, CT, USA.
Pfizer Inc, New York, NY, USA.
Epilepsia Open. 2021 Jun;6(2):381-393. doi: 10.1002/epi4.12492. Epub 2021 May 16.
Generalized tonic-clonic (GTC) seizures are the most common type of generalized seizure and more common in children than adults. This phase 3 study evaluated the efficacy and safety of pregabalin for GTC seizures in adults and children with epilepsy.
This randomized, double-blind, multicenter study evaluated pregabalin (5 mg/kg/day or 10 mg/kg/day) vs placebo as adjunctive therapy for 10 weeks (following a 2-week dose escalation), in pediatric and adult patients (aged 5-65 years) with GTC seizures. Primary endpoint was change in log-transformed 28-day seizure rate during active treatment. Secondary endpoints included responder rates, defined as proportion of patients with ≥50% reduction in 28-day GTC seizure rate from baseline. Safety was monitored throughout.
Of 219 patients, 75, 72, and 72 were randomized to adjunctive pregabalin 5 mg/kg/day, 10 mg/kg/day, and placebo, respectively. Fifteen, 11, and 6 patients discontinued from the 5 mg/kg/day, 10 mg/kg/day, and placebo arms, respectively, most commonly due to adverse events (AEs; 10.7%, 6.9%, and 5.6%, respectively). A nonsignificant change in log-transformed mean 28-day seizure rate was seen with pregabalin 10 mg/kg/day vs placebo (least-squares [LS] mean difference -0.01 [95% confidence interval (CI) -0.19 to 0.16]; P = .8889) and with pregabalin 5 mg/kg/day vs placebo (LS mean difference 0.02 [CI -0.15 to 0.19]; P = .8121). Similar observations were noted for adults and children. No significant differences were seen for secondary endpoints with pregabalin vs placebo, including responder rate. The most common AEs (≥10%) were dizziness, headache, and somnolence. Most were of mild/moderate intensity. Seven patients had serious AEs, with one death in the placebo arm (sudden unexpected death in epilepsy).
Adjunctive pregabalin treatment did not change GTC seizure rate in adults or children. The safety profile of pregabalin was similar to that known; treatment was well tolerated with few discontinuations due to AEs.
全面性强直-阵挛发作（GTC）是最常见的全面性发作类型，在儿童中比成人更常见。这项 3 期研究评估了普瑞巴林作为附加疗法治疗癫痫儿童和成人 GTC 发作的疗效和安全性。
这项随机、双盲、多中心研究评估了普瑞巴林（5mg/kg/天或 10mg/kg/天）与安慰剂作为附加治疗，为期 10 周（在 2 周剂量递增后），纳入年龄为 5-65 岁的 GTC 发作的儿科和成人患者。主要终点是活跃治疗期间 28 天癫痫发作率的对数值变化。次要终点包括应答率，定义为 28 天 GTC 发作率从基线降低≥50%的患者比例。整个过程中监测安全性。
219 例患者中，分别有 75、72 和 72 例患者随机接受附加普瑞巴林 5mg/kg/天、10mg/kg/天和安慰剂治疗。分别有 15、11 和 6 例患者因不良事件（AE；分别为 10.7%、6.9%和 5.6%）而退出 5mg/kg/天、10mg/kg/天和安慰剂组。普瑞巴林 10mg/kg/天与安慰剂相比，28 天癫痫发作率的对数平均值变化无显著差异（最小二乘[LS]均值差-0.01[95%置信区间（CI）-0.19 至 0.16]；P=0.8889），普瑞巴林 5mg/kg/天与安慰剂相比 LS 均值差为 0.02（CI-0.15 至 0.19]；P=0.8121）。在成人和儿童中也观察到类似的结果。普瑞巴林与安慰剂相比，次要终点（包括应答率）无显著差异。最常见的 AE（≥10%）为头晕、头痛和嗜睡。大多数为轻度/中度。7 例患者发生严重 AE，安慰剂组 1 例死亡（癫痫猝死）。
附加普瑞巴林治疗未改变成人或儿童的 GTC 发作率。普瑞巴林的安全性与已知的安全性相似；治疗耐受性良好，因 AE 停药的病例很少。
