Pediatric Neurologists of Palm Beach, 12959 Palms West Drive, Suite 120, Loxahatchee, FL, 33470, USA.
UCB Pharma, 8010 Arco Corporate Drive, Raleigh, NC, 27617, USA.
Paediatr Drugs. 2019 Aug;21(4):291-301. doi: 10.1007/s40272-019-00332-y.
This trial evaluated the short-term safety and tolerability, steady-state pharmacokinetics, and preliminary efficacy of brivaracetam oral solution in children aged 1 month to < 16 years with epilepsy.
This was a phase IIa, open-label, single-arm, fixed three-step dose escalation trial of 3-weeks duration (N01263; NCT00422422). Patients were taking one to three concomitant antiepileptic drugs. Brivaracetam oral solution dosage, in two divided daily doses, was increased each week: approximately 0.8, 1.6, and 3.2 mg/kg/day for patients aged ≥ 8 years, and 1.0, 2.0, and 4.0 mg/kg/day for patients aged < 8 years.
Of the 100 patients enrolled, 90 (90.0%) completed the trial. The safety population comprised 99 patients. Treatment-emergent adverse events (TEAEs) considered drug related by the investigator were reported by 32/99 (32.3%) patients, most commonly (≥ 5%) somnolence (7.1%) and decreased appetite (6.1%). TEAEs were reported by 66/99 (66.7%) patients, most commonly (≥ 5%) convulsion, irritability, pyrexia, somnolence, and decreased appetite. In patients with a history of focal seizures with or without secondary generalization and no primary generalized seizures aged 4 to < 16 years (n = 34), drug-related TEAEs and TEAE incidences were 47.1% and 67.6%, respectively. Steady-state trough brivaracetam and brivaracetam metabolite plasma concentrations increased proportionally with dose. The ≥ 50% responder rates (all seizure types) were 21.3% (all patients, n = 80) and 36.4% (patients with focal seizures, aged 4 to < 16 years, n = 22).
This open-label trial in pediatric patients with epilepsy provides preliminary information that short-term, adjunctive brivaracetam treatment is well tolerated and effective. Plasma concentrations of brivaracetam and metabolites increased with increasing dose.
本试验评估了 1 月龄至<16 岁癫痫患儿短期使用溴维曲坦口服溶液的安全性和耐受性、稳态药代动力学和初步疗效。
这是一项为期 3 周的 IIa 期、开放性、单臂、固定三步骤剂量递增试验（N01263；NCT00422422）。患者正在服用一种或三种抗癫痫药物。溴维曲坦口服溶液的剂量，每日分两次服用，每周递增一次：年龄≥8 岁的患者约为 0.8、1.6 和 3.2mg/kg/天，年龄<8 岁的患者为 1.0、2.0 和 4.0mg/kg/天。
在纳入的 100 例患者中，90 例（90.0%）完成了试验。安全性人群包括 99 例患者。研究者认为与药物相关的治疗中出现的不良事件（TEAE）在 32/99（32.3%）例患者中报告，最常见（≥5%）为嗜睡（7.1%）和食欲减退（6.1%）。66/99（66.7%）例患者报告了 TEAEs，最常见（≥5%）为癫痫发作、烦躁不安、发热、嗜睡和食欲减退。在有或无继发全面性发作的局灶性癫痫发作史且无原发性全面性发作的 4 至<16 岁患者（n=34）中，药物相关的 TEAEs 和 TAE 发生率分别为 47.1%和 67.6%。溴维曲坦和溴维曲坦代谢物的稳态谷浓度与剂量成比例增加。所有发作类型的≥50%应答率（所有患者，n=80）和局灶性发作（4 至<16 岁患者，n=22）的应答率分别为 21.3%和 36.4%。
这项针对癫痫儿科患者的开放性试验提供了初步信息，表明短期辅助使用溴维曲坦治疗是耐受良好且有效的。溴维曲坦和代谢物的血浆浓度随剂量增加而增加。
