Auvin Stéphane, Arzimanoglou Alexis, Beller Cynthia, Floricel Florin, Daniels Tony, Bozorg Ali
Université Paris-Cité, INSERM NeuroDiderot, Paris, France.
Pediatric Neurology Department, APHP, Robert Debré University Hospital, ERN EpiCARE member, Paris, France.
Epilepsia. 2023 Nov;64(11):2947-2957. doi: 10.1111/epi.17741. Epub 2023 Aug 23.
To evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of lacosamide (LCM) (up to 12 mg/kg/day or 600 mg/day) as adjunctive therapy in pediatric patients with epilepsy syndromes associated with generalized seizures.
Phase 2, multicenter, open-label exploratory trial (SP0966; NCT01969851; 2012-001446-18) of oral LCM for epilepsy syndromes associated with generalized seizures in pediatric patients ≥1 month to <18 years of age taking one to three concomitant antiseizure medications. The trial comprised a 6-week prospective baseline period, 6-week flexible titration period, and 12-week maintenance period.
Fifty-five patients (mean age: 9.2 years; 56.4% male) took at least one dose of LCM and had at least one post-baseline efficacy-related assessment. The median treatment duration was 127.0 days. There were no clinically significant mean or median changes or worsening from baseline to end of the titration period in the count of generalized spike-wave discharges per interpretable hour on 24-h ambulatory electroencephalogram recordings, or from baseline to the maintenance period in mean and median days with any generalized or focal to bilateral tonic-clonic seizures per 28 days. Treatment-emergent adverse events (TEAEs) were reported by 49 patients (89.1%), and three patients (5.5%) discontinued due to TEAEs. The median change and median percentage change in days with any generalized or focal to bilateral tonic-clonic seizures per 28 days from baseline to the maintenance period were both 0. Trends toward improvement (decrease) were observed in median change and median percentage change in days with each individual seizure type (absence, myoclonic, clonic, tonic, tonic-clonic, atonic, and focal to bilateral tonic-clonic) per 28 days.
Safety findings were consistent with the known safety profile of LCM and were as expected for the pediatric population. There was no worsening of generalized seizures with LCM. Limitations include the inability to correlate spike and wave data with clinical outcomes, and the lack of similar studies against which the results can be compared.
评估拉考沙胺（LCM）（剂量高达12mg/kg/天或600mg/天）作为辅助治疗药物，用于治疗伴有全身性发作的癫痫综合征患儿的安全性、耐受性、药代动力学及初步疗效。
一项2期、多中心、开放标签的探索性试验（SP0966；NCT01969851；2012-001446-18），研究口服LCM用于年龄≥1个月至<18岁、正在服用1至3种抗癫痫药物的伴有全身性发作的癫痫综合征患儿。该试验包括一个为期6周的前瞻性基线期、一个为期6周的灵活滴定期和一个为期12周的维持期。
55例患者（平均年龄：9.2岁；56.4%为男性）服用了至少一剂LCM，并至少进行了一次基线后疗效相关评估。中位治疗持续时间为127.0天。在24小时动态脑电图记录中，每可解释小时的全身性棘波放电次数，从基线期到滴定期结束，或从基线期到维持期，每28天发生的任何全身性或局灶性至双侧强直阵挛性发作的平均天数和中位天数，均未出现具有临床意义的均值或中位数变化或恶化。49例患者（89.1%）报告了治疗中出现的不良事件（TEAE），3例患者（5.5%）因TEAE停药。从基线期到维持期，每28天发生的任何全身性或局灶性至双侧强直阵挛性发作天数的中位变化和中位百分比变化均为0。每28天各发作类型（失神发作、肌阵挛发作、阵挛发作、强直发作、强直阵挛发作、失张力发作和局灶性至双侧强直阵挛发作）天数的中位变化和中位百分比变化均呈现改善（减少）趋势。
安全性研究结果与LCM已知的安全性特征一致，符合儿科人群的预期情况。LCM治疗未使全身性发作恶化。局限性包括无法将棘波和慢波数据与临床结果相关联，以及缺乏可与本研究结果进行比较的类似研究。
