Ben-Menachem Elinor, Biton Victor, Jatuzis Dalius, Abou-Khalil Bassel, Doty Pamela, Rudd G David
Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.
Epilepsia. 2007 Jul;48(7):1308-17. doi: 10.1111/j.1528-1167.2007.01188.x.
To evaluate the efficacy and safety of lacosamide when added to 1 or 2 antiepileptic drugs (AEDs) in adults with uncontrolled partial-onset seizures, and assess plasma concentrations of concomitant AEDs to determine any potential for drug interactions.
During this multicenter, double-blind, placebo-controlled trial, patients were randomized to placebo or lacosamide 200, 400, or 600 mg/day after an 8-week baseline period. Lacosamide was titrated in weekly increments of 100 mg/day over 6 weeks and maintained for 12 weeks. Results were analyzed on an intention-to-treat basis.
Four hundred eighteen patients were randomized and received trial medication; 312 completed the trial. The median percent reduction in seizure frequency per 28 days was 10%, 26%, 39%, and 40% in the placebo, lacosamide 200, 400, and 600 mg/day treatment groups, respectively. The median percent reduction in seizure frequency over placebo was significant for lacosamide 400 mg/day (p=0.0023) and 600 mg/day (p=0.0084). The 50% responder rates were 22%, 33%, 41%, and 38% for placebo, lacosamide 200, 400, and 600 mg/day, respectively. The 50% responder rate over placebo was significant for lacosamide 400 mg/day (p=0.0038) and 600 mg/day (p=0.0141). Adverse events that appeared dose-related included dizziness, nausea, fatigue, ataxia, vision abnormal, diplopia, and nystagmus. Lacosamide did not affect mean plasma concentrations of concomitantly administered AEDs.
In this trial, adjunctive lacosamide significantly reduced seizure frequency in patients with uncontrolled partial-onset seizures. Along with favorable pharmacokinetic and tolerability profiles, these results support further development of lacosamide as an AED.
评估在联用1种或2种抗癫痫药物（AEDs）治疗的成人部分性发作未得到控制的患者中添加拉考酰胺的疗效和安全性，并评估联用AEDs的血浆浓度以确定是否存在药物相互作用的可能性。
在这项多中心、双盲、安慰剂对照试验中，患者在8周的基线期后被随机分为接受安慰剂或每日200、400或600毫克拉考酰胺治疗组。拉考酰胺在6周内每周递增100毫克/天进行滴定，并维持12周。结果采用意向性分析。
418例患者被随机分组并接受试验药物治疗；312例完成试验。安慰剂组、每日200、400和600毫克拉考酰胺治疗组每28天癫痫发作频率的中位数降低百分比分别为10%、26%、39%和40%。与安慰剂相比，每日400毫克（p = 0.0023）和600毫克（p = 0.0084）拉考酰胺组癫痫发作频率的中位数降低百分比具有显著性差异。安慰剂组、每日200、400和600毫克拉考酰胺组的50%缓解率分别为22%、33%、41%和38%。与安慰剂相比，每日400毫克（p = 0.0038）和600毫克（p = 0.0141）拉考酰胺组的50%缓解率具有显著性差异。出现的与剂量相关的不良事件包括头晕、恶心、疲劳、共济失调、视力异常、复视和眼球震颤。拉考酰胺不影响联用AEDs的平均血浆浓度。
在本试验中，添加拉考酰胺可显著降低部分性发作未得到控制患者的癫痫发作频率。鉴于其良好的药代动力学和耐受性，这些结果支持拉考酰胺作为一种抗癫痫药物进一步研发。
