随机 2 期研究附加用 Cenobamate 治疗未控制局灶性发作患者。
Randomized phase 2 study of adjunctive cenobamate in patients with uncontrolled focal seizures.
机构信息
From the Neuroscience Institute (S.S.C), Banner-University Medical Center, University of Arizona, Phoenix; NYU Langone Comprehensive Epilepsy Center (J.A.F.), New York; NZOZ Vito-Med (J.K.), Gliwice, Poland; Johns Hopkins University School of Medicine (G.L.K.), Baltimore, MD; Adult Comprehensive Epilepsy Center (S.K.L.), Seoul National University Hospital, Republic of Korea; NZOZ Diagnomed Clinical Research (M.M.), Katowice, Poland; Comprehensive Epilepsy Care Center for Children and Adults (W.E.R.), St. Louis, MO; Thomas Jefferson University (M.R.S.), Philadelphia, PA; MedVal Scientific Information Services (S.M.), Princeton, NJ; and SK Life Science, Inc (M.K.), Paramus, NJ.
出版信息
Neurology. 2020 Jun 2;94(22):e2311-e2322. doi: 10.1212/WNL.0000000000009530. Epub 2020 May 14.
OBJECTIVE
To evaluate the efficacy and safety of adjunctive cenobamate 200 mg/d in patients with uncontrolled focal (partial-onset) seizures despite treatment with 1 to 3 antiepileptic drugs.
METHODS
In this multicenter, double-blind, placebo-controlled study, adults 18 to 65 years of age with focal seizures were randomized 1:1 (cenobamate:placebo) after an 8-week baseline period. The 12-week double-blind treatment period consisted of a 6-week titration phase and a 6-week maintenance phase. The primary outcome was percent change in seizure frequency (from baseline) per 28 days during double-blind treatment.
RESULTS
Two hundred twenty-two patients were randomized; 113 received cenobamate and 109 received placebo; and 90.3% and 90.8% of patients, respectively, completed double-blind treatment. Median baseline seizure frequency was 6.5 in 28 days (range 0-237). Compared to placebo, cenobamate conferred a greater median percent seizure reduction (55.6% vs 21.5%; < 0.0001) The responder rate (≥50% reduction in seizure frequency) was 50.4% for cenobamate and 22.2% for placebo ( < 0.0001). Focal seizures with motor component, impaired awareness, and focal to bilateral tonic-clonic seizures were significantly reduced with cenobamate vs placebo. During maintenance, 28.3% of cenobamate-treated and 8.8% of placebo-treated patients were seizure-free. Treatment-emergent adverse events reported in >10% in either group (cenobamate vs placebo) were somnolence (22.1% vs 11.9%), dizziness (22.1% vs 16.5%), headache (12.4% vs 12.8%), nausea (11.5% vs 4.6%), and fatigue (10.6% vs 6.4%).
CONCLUSION
Adjunctive treatment with cenobamate 200 mg/d significantly improved seizure control in adults with uncontrolled focal seizures and was well tolerated.
CLINICALTRIALSGOV IDENTIFIER
NCT01397968.
CLASSIFICATION OF EVIDENCE
This study provides Class I evidence that, for patients with uncontrolled focal seizures, adjunctive cenobamate reduces seizures.
目的
评估辅助用 200 毫克/天的依诺巴比妥治疗 1 至 3 种抗癫痫药物治疗后仍控制不佳的局灶性（部分性发作）癫痫患者的疗效和安全性。
方法
在这项多中心、双盲、安慰剂对照的研究中，18 至 65 岁的局灶性癫痫患者在 8 周基线期后按 1:1（依诺巴比妥：安慰剂）随机分组。12 周的双盲治疗期包括 6 周的滴定期和 6 周的维持期。主要结局是双盲治疗期间每 28 天癫痫发作频率的变化百分比（相对于基线）。
结果
222 例患者被随机分组；113 例接受依诺巴比妥治疗，109 例接受安慰剂治疗；分别有 90.3%和 90.8%的患者完成了双盲治疗。中位基线期癫痫发作频率为 28 天 6.5 次（范围 0-237 次）。与安慰剂相比，依诺巴比妥使癫痫发作频率的中位数降低幅度更大（55.6%比 21.5%；<0.0001），应答率（癫痫发作频率降低≥50%）为 50.4%对 22.2%（<0.0001）。依诺巴比妥治疗组与安慰剂组相比，局灶性伴运动成分、意识障碍和局灶性双侧强直-阵挛性癫痫发作明显减少。在维持期，28.3%的依诺巴比妥治疗患者和 8.8%的安慰剂治疗患者无癫痫发作。在两组中，报告发生率均超过 10%的治疗中出现的不良事件（依诺巴比妥组与安慰剂组）分别为：嗜睡（22.1%比 11.9%）、头晕（22.1%比 16.5%）、头痛（12.4%比 12.8%）、恶心（11.5%比 4.6%）和疲劳（10.6%比 6.4%）。
结论
依诺巴比妥 200 毫克/天的辅助治疗可显著改善局灶性癫痫发作控制不佳的成人癫痫发作，并具有良好的耐受性。
临床试验.gov 标识符：NCT01397968。
证据分类
这项研究提供了 I 级证据，表明对于控制不佳的局灶性癫痫患者，辅助用依诺巴比妥可减少癫痫发作。
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