在三项双盲、安慰剂对照的III期随机临床试验及一项合并的扩展研究中，吡仑帕奈治疗青少年耐药性部分性癫痫发作的疗效与安全性。
Efficacy and safety of perampanel in adolescent patients with drug-resistant partial seizures in three double-blind, placebo-controlled, phase III randomized clinical studies and a combined extension study.
作者信息
Rosenfeld William, Conry Joan, Lagae Lieven, Rozentals Guntis, Yang Haichen, Fain Randi, Williams Betsy, Kumar Dinesh, Zhu Jin, Laurenza Antonio
机构信息
Comprehensive Epilepsy Care Center for Children and Adults, St Louis, MO, USA.
Children's National Medical Center, Washington, DC, USA.
出版信息
Eur J Paediatr Neurol. 2015 Jul;19(4):435-45. doi: 10.1016/j.ejpn.2015.02.008. Epub 2015 Mar 5.
OBJECTIVE
Assess perampanel's efficacy and safety as adjunctive therapy in adolescents (ages 12-17) with drug-resistant partial seizures.
METHODS
Adolescent patients enrolled in multinational, double-blind, placebo-controlled, phase III core studies (studies 304, 305, or 306) completed 19-week, double-blind phase (6-week titration/13-week maintenance) with once-daily perampanel or placebo. Upon completion, patients were eligible for the extension (study 307), beginning with 16-week, blinded conversion, during which placebo patients switched to perampanel. Patients then entered the open-label treatment.
RESULTS
Of 1480 patients from the core studies, 143 were adolescents. Pooled adolescent data from these core studies demonstrated median percent decreases in seizure frequency for perampanel 8 mg (34.8%) and 12 mg (35.6%) were approximately twice that of placebo (18.0%). Responder rates increased with perampanel 8 mg (40.9%) and 12 mg (45.0%) versus placebo (22.2%). Adolescents receiving concomitant enzyme-inducing antiepileptic drugs (AEDs) had smaller reductions in seizure frequency (8 mg:31.6%; 12 mg:26.8%) than those taking non-inducing AEDs (8 mg:54.6%; 12 mg:52.7%). Relative to pre-perampanel baseline, seizure frequency and responder rates during the extension (Weeks 1-52) improved with perampanel. Most commonly reported adverse events in adolescents during the core studies were dizziness (20.4%), somnolence (15.3%), aggression (8.2%), decreased appetite (6.1%), and rhinitis (5.1%). Dizziness (13.2%), somnolence (11.6%), and aggression (6.6%) most often led to perampanel interruption/dose adjustment during the extension.
SIGNIFICANCE
Data demonstrated adjunctive perampanel treatment in adolescents with drug-resistant partial seizures produced better seizure control versus placebo, sustained seizure frequency improvements, and a generally favorable safety profile. Results were comparable to the overall study population.
CLINICAL TRIAL REGISTRATION
clinicaltrials.gov Identifiers: Study 304: NCT00699972; 305: NCT00699582; 306: NCT00700310; Study 307: NCT00735397.
目的
评估吡仑帕奈作为辅助治疗药物，用于治疗12至17岁耐药性部分性癫痫青少年患者的疗效和安全性。
方法
参与多国、双盲、安慰剂对照III期核心研究（研究304、305或306）的青少年患者，完成了为期19周的双盲阶段（6周滴定期/13周维持期），每日服用一次吡仑帕奈或安慰剂。完成该阶段后，患者有资格进入延长期研究（研究307），首先是为期16周的盲法转换期，在此期间安慰剂组患者换用吡仑帕奈。然后患者进入开放标签治疗阶段。
结果
核心研究中的1480名患者中，143名是青少年。这些核心研究中汇总的青少年数据显示，8毫克（34.8%）和12毫克（35.6%）吡仑帕奈组癫痫发作频率的中位数下降百分比约为安慰剂组（18.0%）的两倍。8毫克（40.9%）和12毫克（45.0%）吡仑帕奈组的缓解率高于安慰剂组（22.2%）。接受酶诱导抗癫痫药物（AED）联合治疗的青少年癫痫发作频率下降幅度（8毫克：31.6%；12毫克：26.8%）小于服用非诱导性AED的青少年（8毫克：54.6%；12毫克：52.7%）。相对于服用吡仑帕奈前的基线水平，延长期（第1至52周）使用吡仑帕奈后癫痫发作频率和缓解率有所改善。核心研究期间青少年最常报告的不良事件为头晕（20.4%）、嗜睡（15.3%）、攻击行为（8.2%）、食欲减退（6.1%）和鼻炎（5.1%）。在延长期，头晕（13.2%）、嗜睡（11.6%）和攻击行为（6.6%）最常导致吡仑帕奈中断治疗/调整剂量。
意义
数据表明，吡仑帕奈辅助治疗耐药性部分性癫痫青少年患者，与安慰剂相比，能更好地控制癫痫发作，持续改善癫痫发作频率，且总体安全性良好。结果与总体研究人群相当。
临床试验注册
clinicaltrials.gov标识符：研究304：NCT00699972；305：NCT00699582；306：NCT00700310；研究307：NCT00735397。
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