Inoue Yushi, Liao Weiping, Wang Xuefeng, Du Xinlu, Tennigkeit Frank, Sasamoto Hiroshi, Osakabe Toru, Hoshii Naoki, Yuen Nancy, Hong Zhen
NHO Shizuoka Institute of Epilepsy and Neurological Disorders, 886 Urushiyama, Aoi-ku, Shizuoka, 420-8688, Japan.
The Second Affiliated Hospital of Guangzhou Medical University, 250 Changgang East Road, Guangzhou, Guangdong, 510260, China.
Epilepsy Res. 2021 Oct;176:106705. doi: 10.1016/j.eplepsyres.2021.106705. Epub 2021 Jun 29.
This Phase III, long-term, open-label extension (OLE) trial (EP0009; NCT01832038) was conducted to evaluate the long-term safety, tolerability, and efficacy of adjunctive lacosamide (100-400 mg/day) in Chinese and Japanese people with epilepsy (PWE) (16-70 years) who had completed a double-blind, randomized, placebo-controlled trial of adjunctive lacosamide (EP0008; NCT01710657). PWE entered the OLE trial on 200 mg/day lacosamide and up to 3 concomitant antiseizure medications. Dose adjustments were permitted to optimize tolerability and seizure reduction. Safety variables were treatment-emergent adverse events (TEAEs) and discontinuations due to TEAEs. Efficacy variables were percent change in focal seizure frequency per 28 days from Baseline of the double-blind trial, ≥50 % and ≥75 % responder rates, seizure-freedom, and proportion of PWE on lacosamide monotherapy. Overall, 473 PWE (74.0 % Chinese and 26.0 % Japanese) were enrolled; 238 (50.3 %) PWE completed the trial and 235 (49.7 %) discontinued, most commonly due to lack of efficacy (81 [17.1 %]), adverse events (55 [11.6 %]), and consent withdrawn (49 [10.4 %]). During the trial, PWE received lacosamide for a median of 1016.0 days (∼3 years), with a total exposure of 1454.8 person-years; 321 (67.9 %) PWE received lacosamide for >24 months, and 246 (52.0 %) for >36 months. The median modal dose of lacosamide was 300 mg/day. Overall, 410/473 (86.7 %) PWE reported TEAEs, 244 (51.6 %) had a TEAE that was considered drug-related, and 49 (10.4 %) discontinued due to a TEAE. The most common TEAEs (≥20 % of PWE) were nasopharyngitis, dizziness, and upper respiratory tract infection. The median reduction in focal seizure frequency per 28 days from Baseline was 57.1 %, and the ≥50 % and ≥75 % responder rates were 57.1 % (269/471) and 29.7 % (140/471), respectively. Among PWE who completed 12, 24, and 36 months of treatment, the 12-, 24-, and 36-month seizure-freedom rates were 3.5 % (13/375), 3.4 % (11/321), and 2.0 % (5/247), respectively. Among PWE exposed to lacosamide for ≥6 months and ≥12 months, the proportions of PWE that maintained continuous monotherapy for ≥6 months and ≥12 months were 5.0 % (21/421) and 5.0 % (19/378), respectively. Overall, lacosamide was well-tolerated as long-term adjunctive therapy in Chinese and Japanese PWE and uncontrolled focal seizures, with improvements in seizure reduction maintained over 36 months of treatment.
这项III期长期开放标签扩展(OLE)试验(EP0009;NCT01832038)旨在评估拉科酰胺(100 - 400毫克/天)作为辅助治疗药物,在中国和日本16至70岁癫痫患者(PWE)中的长期安全性、耐受性和疗效。这些患者已完成拉科酰胺辅助治疗的双盲、随机、安慰剂对照试验(EP0008;NCT01710657)。PWE以200毫克/天的拉科酰胺剂量及最多3种抗癫痫药物伴随治疗进入OLE试验。允许进行剂量调整以优化耐受性并减少癫痫发作。安全性变量为治疗中出现的不良事件(TEAE)以及因TEAE导致的停药情况。疗效变量为双盲试验基线起每28天局灶性癫痫发作频率的变化百分比、≥50%和≥75%的缓解率、无癫痫发作率以及接受拉科酰胺单药治疗的PWE比例。总体而言,共纳入473例PWE(74.0%为中国人,26.0%为日本人);238例(50.3%)PWE完成试验,235例(49.7%)停药,最常见的原因是缺乏疗效(81例[17.1%])、不良事件(55例[11.6%])和撤回同意(49例[10.4%])。试验期间,PWE接受拉科酰胺治疗的中位时间为1016.0天(约3年),总暴露人年数为1454.8;321例(67.9%)PWE接受拉科酰胺治疗超过24个月,246例(52.0%)超过36个月。拉科酰胺的中位模式剂量为300毫克/天。总体而言,410/473(86.7%)例PWE报告了TEAE,244例(51.6%)有被认为与药物相关的TEAE,49例(10.4%)因TEAE停药。最常见的TEAE(≥20%的PWE)为鼻咽炎、头晕和上呼吸道感染。从基线起每28天局灶性癫痫发作频率的中位降低率为57.1%,≥50%和≥75%的缓解率分别为57.1%(269/471)和29.7%(140/471)。在完成12、24和36个月治疗的PWE中,12个月、24个月和36个月的无癫痫发作率分别为3.5%(13/375)、3.4%(11/321)和2.0%(5/247)。在接受拉科酰胺治疗≥6个月和≥12个月的PWE中,维持连续单药治疗≥6个月和≥12个月的PWE比例分别为5.0%(21/421)和5.0%(19/378)。总体而言,拉科酰胺作为中国和日本PWE长期辅助治疗药物以及控制局灶性癫痫发作耐受性良好,在36个月的治疗期间癫痫发作减少情况持续改善。