OBJECTIVE To evaluate long-term safety and tolerability of adjunctive brivaracetam (BRV) in children with epilepsy. METHODS This was an interim analysis (cut-off March 15, 2017) of pooled data from two open-label, single-arm, multicentre trials. N01263 (NCT00422422) was a 3-week trial of BRV 0.8-4 mg/kg/day in patients (1 month-<16 years) with epilepsy. Patients who completed this trial could continue into a long-term follow-up trial (N01266, NCT01364597) which also directly enrolled patients (4-<17 years) with focal seizures. After dose-escalation, patients received BRV 1-5 mg/kg/day (maximum 200 mg/day) during long-term evaluation. Data are reported for patients aged 4 to <16 years with focal seizures. RESULTS The safety set comprised 149 patients: 34 from the initial trial (26 entered long-term trial) and 115 directly enrolled into the long-term trial. At the cut-off, 90 patients were receiving BRV (total exposure: 299.4 patient-years). Treatment-emergent adverse events (TEAEs) were reported by 140/149 (94.0%) patients, most commonly (≥20%) nasopharyngitis (24.8%), pharyngitis (22.1%), convulsion (21.5%), and pyrexia (20.1%). TEAEs considered drug-related by the investigator were reported by 56/149 (37.6%) patients, most commonly somnolence (6.0%). Two patients died; neither death was considered related to BRV. Mean changes from baseline in child behaviour rating scales were small; most patients remained in their baseline category. CONCLUSION In this pooled analysis of two open-label trials including long-term data, adjunctive BRV was generally well tolerated in children aged 4 to <16 years with focal seizures. These findings supported approval of BRV as a new therapy option for children aged ≥4 years with focal seizures.

中文翻译：

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局灶性癫痫儿童辅助性布立西坦的安全性和耐受性：两项开放标签试验汇总数据的中期分析

目的 评估辅助性布立西坦 (BRV) 在儿童癫痫中的长期安全性和耐受性。方法 这是一项中期分析（截止日期为 2017 年 3 月 15 日）来自两项开放标签、单臂、多中心试验的汇总数据。N01263 (NCT00422422) 是一项为期 3 周的试验，在癫痫患者（1 个月 - <16 岁）中使用 BRV 0.8-4 mg/kg/天。完成该试验的患者可以继续进行长期随访试验（N01266，NCT01364597），该试验也直接招募了局灶性癫痫患者（4-<17 岁）。剂量递增后，患者在长期评估期间接受 BRV 1-5 毫克/公斤/天（最大 200 毫克/天）。报告了 4 至 <16 岁局灶性癫痫患者的数据。结果 安全组包括 149 名患者：初试34人（26人进入长期试验），115人直接进入长期试验。截止时，90 名患者正在接受 BRV（总暴露量：299.4 患者年）。140/149 (94.0%) 名患者报告了治疗中出现的不良事件 (TEAE)，最常见的是 (≥20%) 鼻咽炎 (24.8%)、咽炎 (22.1%)、抽搐 (21.5%) 和发热 (20.1%) ）。56/149 (37.6%) 患者报告了研究者认为与药物相关的 TEAE，最常见的是嗜睡 (6.0%)。两名患者死亡；两种死亡都被认为与 BRV 无关。儿童行为评定量表与基线的平均变化很小；大多数患者仍处于基线类别。结论 在这项对包括长期数据在内的两项开放标签试验的汇总分析中，辅助 BRV 在 4 至 < 局灶性癫痫发作 16 年。这些发现支持批准 BRV 作为 4 岁以上儿童局灶性癫痫的新治疗选择。