目的:报告来自两个双盲患者的辅助西诺膦酸盐和伴随的抗癫痫药物(ASM)对体重的影响,安慰剂对照,第二阶段研究(YKP3089C013[C013]和YKP3089C017[C017])及其开放标签扩展(OLE),从长期来看,开放标签阶段3安全性研究,YKP3089C021(C021)。
背景:Cenobamate是美国和欧盟批准用于治疗成人局灶性癫痫发作的ASM。一些ASM与体重增加相关(例如,丙戊酸盐,加巴喷丁,普瑞巴林),这会对患者健康产生负面影响。
方法:在每项研究中纳入不受控制的局灶性癫痫发作患者,服用稳定剂量的1-3种ASM。在C013中,将西诺膦酸滴定至200mg/天的目标剂量(最大OLE剂量400mg/天)。在C017中,患者被随机分配至西诺本100、200或400mg/天(最大OLE剂量400mg/天)。在C021中,锡溴酸铵被滴定至200mg/天的目标剂量(最大剂量400mg/天)。事后分析了距基线1年和2年时的中位体重变化。
结果:分析包括来自C013、C017(联合剂量组)的39、206和1054名患者,和C021,分别。从基线开始的平均体重变化范围为1年-0.2至-0.9kg,2年-1.0至+1.0kg。在停用丙戊酸钠1(-13.0kg,C013,n=1)或2年(-24.5千克,C017,n=2)和停用加巴喷丁1(-7.1kg,C017,n=2)或2年(-7.0千克,C017,n=2)。否则,同时接受丙戊酸钠的患者的中位体重相对于基线的变化,加巴喷丁,1年或普瑞巴林的范围为-3.1至2.6kg,2年为-1.6至2.7kg。
结论:在接受1年和2年治疗的患者中,辅助性cenobamate与体重相对于基线的临床显着变化无关。包括那些同时接受丙戊酸盐的人,加巴喷丁,或者普瑞巴林.
OBJECTIVE: To report the effects of adjunctive cenobamate and concomitant antiseizure medications (ASMs) on weight from two double-blind, placebo-controlled, phase 2 studies (YKP3089C013 [C013] and YKP3089C017 [C017]) and their open-label extensions (OLEs) and from a long-term, open-label phase 3 safety study, YKP3089C021 (C021).
BACKGROUND: Cenobamate is an ASM approved in the US and EU for treatment of focal seizures in adults. Some ASMs are associated with weight gain (e.g., valproate, gabapentin, pregabalin), which can negatively affect patient health.
METHODS: Patients with uncontrolled focal seizures taking stable doses of 1-3 ASMs were enrolled in each study. In C013, cenobamate was titrated to a target dose of 200 mg/day (max OLE dose 400 mg/day). In C017, patients were randomized to cenobamate 100, 200, or 400 mg/day (max OLE dose 400 mg/day). In C021, cenobamate was titrated to a target dose of 200 mg/day (max dose 400 mg/day). Median weight changes at 1 and 2 years from baseline were analyzed post hoc.
RESULTS: Analyses included 39, 206, and 1054 patients from C013, C017 (dose groups combined), and C021, respectively. Median weight changes from baseline ranged from -0.2 to -0.9 kg at 1 year and from -1.0 to +1.0 kg at 2 years. Some numerical reductions in weight were noted in patients who discontinued valproate by 1 (-13.0 kg, C013, n=1) or 2 years (-24.5 kg, C017, n=2) and in patients who discontinued gabapentin by 1 (-7.1 kg, C017, n=2) or 2 years (-7.0 kg, C017, n=2). Otherwise, median weight changes from baseline for patients receiving concomitant valproate, gabapentin, or pregabalin ranged from -3.1 to +2.6 kg at 1 year and from -1.6 to +2.7 kg at 2 years.
CONCLUSIONS: Adjunctive cenobamate was not associated with clinically significant changes in weight from baseline in patients treated for 1 and 2 years, including those receiving concomitant valproate, gabapentin, or pregabalin.