PDF(Pubmed)
Abstract：
ELEVATE (Study 410; NCT03288129) is the first prospective, multicenter, open-label, Phase IV study of perampanel as monotherapy or first adjunctive therapy in patients aged ≥ 4 years with focal-onset seizures or generalized tonic-clonic seizures in the United States. The study included Screening, Titration (≤ 13 weeks), Maintenance (39 weeks), and Follow-up (4 weeks) Periods. During Titration, perampanel was initiated at 2 mg/day and up-titrated to 4 mg/day at Week 3. Depending on response and tolerability, optional up-titrations to a maximum of 12 mg/day occurred. The primary endpoint was retention rate; additional endpoints included seizure-freedom rate, 50% responder rate, and incidence of treatment-emergent adverse events (TEAEs). At baseline, 10 (18.5%) patients were assigned to the monotherapy group and 44 (81.5%) patients to the first adjunctive therapy group. However, due to the addition of an anti-seizure medication along with perampanel on the first day of treatment, one patient was excluded from the monotherapy subgroup analyses. The mean perampanel exposure duration was 39.8 weeks and 32 (59.3%) patients completed the study. Retention rate at 12 months (or study completion) was 63.0% (monotherapy, 77.8%; first adjunctive therapy, 59.1%). Seizure-freedom rate during the Maintenance Period was 32.7% (monotherapy, 44.4%; first adjunctive therapy, 29.5%) and the 50% responder rate was 78.7% (monotherapy, 85.7%; first adjunctive therapy, 76.9%). TEAEs and serious TEAEs were reported by 88.9% (n = 48/54) and 7.4% (n = 4/54) of patients, respectively. Overall, the efficacy and safety of perampanel as monotherapy or first adjunctive therapy support the use of perampanel as early-line treatment for epilepsy.
摘要：
ELEVATE（研究410；NCT03288129）是第一个前瞻性的，多中心，开放标签，美国≥4岁局灶性发作性癫痫发作或全身性强直阵挛性癫痫发作患者的潘帕奈作为单药或首次辅助治疗的IV期研究。这项研究包括筛查，滴定（≤13周），维护（39周），和随访（4周）期间。在滴定期间,以2mg/天的剂量开始,并在第3周向上滴定至4mg/天。根据反应和耐受性，可选择的向上滴定至最大12mg/天。主要终点是保留率；其他终点包括无癫痫发作率，50%的反应率，以及因治疗引起的不良事件（TEAE）的发生率。在基线,10例（18.5%）患者被分配到单药治疗组，44例（81.5%）患者被分配到第一辅助治疗组。然而,由于在治疗的第一天增加了抗癫痫药物和perampanel，1例患者被排除在单药治疗亚组分析之外.平均perampanel暴露持续时间为39.8周，32例（59.3％）患者完成了研究。12个月(或研究完成)时的保留率为63.0%(单药治疗，77.8%；首次辅助治疗，59.1%）。维持期癫痫发作自由度为32.7%(单药治疗，44.4%；首次辅助治疗，29.5%)，50%的应答率为78.7%(单药治疗，85.7%；首次辅助治疗，76.9%）。88.9%（n=48/54）和7.4%（n=4/54）的患者报告了TEAE和严重TEAE，分别。总的来说,perampanel作为单药治疗或首次辅助治疗的有效性和安全性支持使用perampanel作为癫痫的早期一线治疗.
