醋酸艾司利卡西平转换为单药治疗对成人部分性发作控制不佳患者的疗效和安全性：一项历史对照III期研究。
Efficacy and safety of conversion to monotherapy with eslicarbazepine acetate in adults with uncontrolled partial-onset seizures: a historical-control phase III study.
作者信息
Jacobson Mercedes P, Pazdera Ladislav, Bhatia Perminder, Grinnell Todd, Cheng Hailong, Blum David
机构信息
Department of Neurology, Temple University School of Medicine, Philadelphia, PA, USA.
CTC Rychnov nad Kněznou s.r.o, Rychnov nad Kneznou, Czech Republic.
出版信息
BMC Neurol. 2015 Mar 28;15:46. doi: 10.1186/s12883-015-0305-5.
BACKGROUND
Eslicarbazepine acetate (ESL, Aptiom®) is a once-daily (QD) anticonvulsant, approved as adjunctive treatment of partial-onset seizures (POS). It is extensively converted after oral administration to eslicarbazepine, and is believed to exert its effect through inhibition of voltage-gated sodium channels. The possible role of ESL as monotherapy to treat POS has not yet been established.
METHODS
This study was an 18-week, multicenter, randomized double-blind trial of gradual conversion to ESL monotherapy in adults with POS not well controlled by 1-2 antiepileptic drugs (AEDs), using historical data as the control. The study comprised an 8-week baseline period, a 2-week titration period, a 6-week AED conversion period, a 10-week monotherapy period, and either a 1-week taper period or optional entry to an open-label extension study. The primary endpoint compared the Kaplan-Meier (KM)-estimated 112-day exit rate with a threshold value calculated from the historical controls.
RESULTS
There were 172 randomized patients; 154 (90%) entered the AED conversion period and 121 (70%) completed the study. The KM-estimated exit rates [confidence interval (CI)] were 15.6% [8.1-28.7%] for ESL 1200 mg, and 12.8% [7.5-21.5%] for ESL 1600 mg. The upper limits of the 95% CI KM-estimates were below the pre-specified threshold for historical control of 65.3%, indicating that ESL was efficacious in reducing seizure-related exits, compared with historical control. During the 18-week double-blind treatment period, median reductions in standardized seizure frequency occurred with ESL 1200 mg (36.1%) and ESL 1600 mg (47.5%). The responder rates (a 50% or greater reduction in seizure frequency from baseline) during the 18-week double-blind period and the monotherapy period, respectively, were 35.2% and 38.9% for ESL 1200 mg, and 46.0% and 46.0% for ESL 1600 mg. The overall adverse event profile was consistent with the known safety profile of ESL.
CONCLUSIONS
These findings indicate that ESL monotherapy (1200 and 1600 mg QD) was efficacious and well tolerated in this study.
TRIAL REGISTRATION
NCT01091662 ; EudraCT No. 2010-018684-42.
背景
醋酸艾司利卡西平（ESL，商品名Aptiom®）是一种每日一次（QD）的抗惊厥药物，被批准作为部分性发作（POS）的辅助治疗药物。口服给药后，它会广泛转化为艾司利卡西平，据信其通过抑制电压门控钠通道发挥作用。ESL作为POS单药治疗的潜在作用尚未确定。
方法
本研究是一项为期18周的多中心随机双盲试验，针对1 - 2种抗癫痫药物（AEDs）未能良好控制的POS成年患者，逐步转换为ESL单药治疗，以历史数据作为对照。该研究包括一个8周的基线期、一个2周的滴定期、一个6周的AED转换期、一个10周的单药治疗期，以及一个1周的减量期或可选择进入开放标签扩展研究。主要终点是将Kaplan - Meier（KM）估计的第112天退出率与根据历史对照计算的阈值进行比较。
结果
共有172例随机分组患者；154例（90%）进入AED转换期，121例（70%）完成研究。ESL 1200 mg组的KM估计退出率[置信区间（CI）]为15.6%[8.1 - 28.7%]，ESL 1600 mg组为12.8%[7.5 - 21.5%]。95%CI KM估计值的上限低于历史对照预先设定的65.3%的阈值，表明与历史对照相比，ESL在减少与癫痫发作相关的退出方面有效。在18周的双盲治疗期内，ESL 1200 mg组（36.1%）和ESL 1600 mg组（47.5%）的标准化癫痫发作频率中位数有所降低。在18周双盲期和单药治疗期，ESL 1200 mg组的缓解率（癫痫发作频率较基线降低50%或更多）分别为35.2%和38.9%，ESL 1600 mg组分别为46.0%和46.0%。总体不良事件谱与ESL已知的安全性谱一致。
结论
这些发现表明，在本研究中ESL单药治疗（1200和1600 mg QD）有效且耐受性良好。
试验注册
NCT01091662；EudraCT编号2010 - 018684 - 42。
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