Consultants in Epilepsy and Neurology, PLLC, Boise, Idaho, U.S.A.
Epilepsia. 2014 Jul;55(7):1088-98. doi: 10.1111/epi.12681. Epub 2014 Jun 10.
To evaluate the efficacy and safety of conversion to lacosamide 400 mg/day monotherapy in adults with focal epilepsy.
This historical-controlled, double-blind study (NCT00520741) enrolled patients aged 16-70 years on stable doses of 1-2 antiepileptic drugs (AEDs) and experiencing 2-40 partial-onset seizures per 28 days during the 8-week prospective Baseline. Patients were randomized to lacosamide 400 or 300 mg/day (3:1 ratio), starting at 200 mg/day and titrated over 3 weeks to randomized dose. Patients then withdrew background AEDs over 6 weeks and entered a 10-week Monotherapy Phase. The primary assessment was the Kaplan-Meier-predicted percentage of patients on 400 mg/day in the full analysis set (FAS) meeting ≥ 1 predefined seizure-related exit criterion by day 112, compared with the historical-control threshold (65.3%).
Four hundred twenty-five patients were enrolled and were eligible for safety analyses (400 mg/day, n = 319; 300 mg/day, n = 106). A total of 271 (63.8%) of 425 patients completed the Lacosamide Maintenance Phase (combined AED Withdrawal and Monotherapy Phases). Among 284 patients in the 400 mg/day group in the FAS, 82 (28.9%) met ≥ 1 exit criterion; the Kaplan-Meier-predicted exit percentage at day 112 for 400 mg/day (30.0%; 95% confidence interval [CI] 24.6-35.5%) was lower than the historical control. When exit events, withdrawal due to treatment-emergent adverse events (TEAEs), and withdrawal due to lack of efficacy were summed (n = 90), the predicted exit percentage (32.3%; 95% CI 26.8-37.8%) was also lower than the historical control. Most patients receiving 400 mg/day reported some improvement on the Clinical Global Impression of Change (75.4%) and Patient Global Impression of Change (74.3%). Overall, the most common (>10%) TEAEs were dizziness (24.0%), headache (14.4%), nausea (13.4%), convulsion (11.5%), somnolence (10.4%), and fatigue (10.1%); most (74.1%) were mild-to-moderate in intensity. Seventy-two patients (16.9%) discontinued due to TEAEs. Seventeen patients (4%, all receiving 400 mg/day) experienced serious AEs.
Lacosamide 400 mg/day monotherapy was effective, with a favorable safety profile in patients with focal epilepsy.
评估转换为左乙拉西坦 400mg/日单药治疗成人局灶性癫痫的疗效和安全性。
这是一项历史对照、双盲研究（NCT00520741），纳入了年龄在 16-70 岁之间、正在服用 1-2 种抗癫痫药物（AEDs）且在 8 周前瞻性基线期内每 28 天经历 2-40 次部分发作的患者。患者随机分为左乙拉西坦 400mg 或 300mg/日（3:1 比例），起始剂量为 200mg/日，3 周内滴定至随机剂量。然后，患者在 6 周内逐渐停用背景 AEDs，并进入 10 周的单药治疗期。主要评估是在全分析集（FAS）中，接受 400mg/日治疗的患者在第 112 天达到≥1 项预先设定的与癫痫发作相关的退出标准的 Kaplan-Meier 预测百分比，与历史对照阈值（65.3%）相比。
共纳入 425 例患者进行安全性分析（400mg/日组，n=319；300mg/日组，n=106）。共有 271 例（63.8%）425 例患者完成了左乙拉西坦维持期（联合 AED 停药和单药治疗期）。在 400mg/日组的 284 例 FAS 患者中，82 例（28.9%）达到≥1 项退出标准；400mg/日组第 112 天的 Kaplan-Meier 预测退出率为 30.0%（95%CI 24.6-35.5%），低于历史对照。当退出事件、因治疗引起的不良事件（TEAE）停药和因疗效不佳而停药（n=90）相加时，预测的退出率（32.3%，95%CI 26.8-37.8%）也低于历史对照。大多数接受 400mg/日治疗的患者在临床总体印象变化量表（75.4%）和患者总体印象变化量表（74.3%）上报告了一些改善。总体而言，最常见（>10%）的不良事件为头晕（24.0%）、头痛（14.4%）、恶心（13.4%）、抽搐（11.5%）、嗜睡（10.4%）和疲劳（10.1%）；大多数（74.1%）为轻至中度。72 例（16.9%）因不良事件停药。17 例（4%，均接受 400mg/日治疗）发生严重不良事件。
左乙拉西坦 400mg/日单药治疗对局灶性癫痫患者有效，安全性良好。
