Pfizer Global Research and Development, Groton, Connecticut.
Pfizer, New York, New York.
Epilepsia. 2020 Apr;61(4):617-626. doi: 10.1111/epi.16466. Epub 2020 Mar 18.
To evaluate the efficacy and safety of pregabalin as adjunctive treatment for children (aged 1 month-<4 years) with focal onset seizures (FOS) using video-electroencephalography (V-EEG).
This randomized, placebo-controlled, international study included V-EEG seizure monitoring (48-72 hours) at baseline and over the last 3 days of 14-day (5-day dose escalation; 9-day fixed dose) double-blind pregabalin treatment (7 or 14 mg/kg/d in three divided doses). This was followed by a double-blind 1-week taper. The primary efficacy endpoint was log-transformed seizure rate (log [24-hour seizure rate + 1]) for all FOS recorded during the double-blind V-EEG monitoring, evaluated in subjects who took ≥1 dose of study medication, experienced ≥1 baseline seizure(s), and had a treatment phase V-EEG. Safety and tolerability were assessed by adverse events (AEs), clinical laboratory data, physical/neurological examinations, vital signs, and electrocardiograms.
Overall, 175 patients were randomized (mean age = 28.2 months; 59% male, 69% white, 30% Asian) in a 2:1:2 ratio to pregabalin 7 or 14 mg/kg/d (n = 71 or n = 34, respectively), or placebo (n = 70). Pregabalin 14 mg/kg/d (n = 28) resulted in a statistically significant 35% reduction of log (24-hour seizure rate + 1) versus placebo (n = 53; P = .022), an effect that was not observed with pregabalin 7 mg/kg/d (n = 59; P = .461). The most frequently reported treatment-emergent AEs for pregabalin 7 mg/kg/d, 14 mg/kg/d, and placebo, respectively, were somnolence (11.3%, 17.6%, and 5.7%) and upper respiratory tract infection (7.0%, 11.8%, and 11.4%). All AEs were mild to moderate in severity.
Pregabalin 14 mg/kg/d (but not 7 mg/kg/d) significantly reduced seizure rate in children with FOS, when assessed using V-EEG, compared with placebo. Both pregabalin dosages were generally safe and well tolerated in children 1 month to <4 years of age with FOS. Safety and tolerability were consistent with the known profile of pregabalin in older children with epilepsy.
评估普瑞巴林作为辅助治疗儿童（1 个月至<4 岁）局灶性发作性癫痫（FOS）的疗效和安全性，使用视频脑电图（V-EEG）。
这项随机、安慰剂对照、国际性研究包括基线和 14 天（5 天剂量递增；9 天固定剂量）双盲普瑞巴林治疗的最后 3 天的 V-EEG 癫痫监测（48-72 小时）（7 或 14 mg/kg/d，分 3 次服用）。随后进行双盲 1 周的减量。主要疗效终点是在双盲 V-EEG 监测期间记录的所有 FOS 的对数转换发作率（log[24 小时发作率+1]），在接受至少 1 剂研究药物、经历至少 1 次基线发作和具有治疗阶段 V-EEG 的受试者中进行评估。安全性和耐受性通过不良事件（AE）、临床实验室数据、体格/神经检查、生命体征和心电图来评估。
总体而言，175 名患者按 2:1:2 的比例随机分组（平均年龄=28.2 个月；59%为男性，69%为白人，30%为亚洲人），分别接受普瑞巴林 7 或 14 mg/kg/d（n=71 或 n=34）或安慰剂（n=70）治疗。与安慰剂（n=53）相比，普瑞巴林 14 mg/kg/d（n=28）导致 log（24 小时发作率+1）的统计学显著降低 35%（P=0.022），而普瑞巴林 7 mg/kg/d（n=59；P=0.461）则没有观察到这种效果。普瑞巴林 7 mg/kg/d、14 mg/kg/d 和安慰剂治疗的最常报告的治疗后出现的 AE 分别为嗜睡（11.3%、17.6%和 5.7%）和上呼吸道感染（7.0%、11.8%和 11.4%）。所有 AE 的严重程度均为轻度至中度。
与安慰剂相比，使用 V-EEG 评估时，普瑞巴林 14 mg/kg/d（而非 7 mg/kg/d）显著降低了 FOS 患儿的癫痫发作率。普瑞巴林在 1 个月至<4 岁 FOS 儿童中，两种剂量均通常安全且耐受良好。安全性和耐受性与在年龄较大的癫痫儿童中普瑞巴林的已知特征一致。
