在印度进行的 II 期和 III 期双盲和开放标签扩展研究的事后分析：添加吡仑帕奈辅助治疗局灶性发作或全面强直-阵挛性发作的疗效和安全性。

Efficacy and safety of adjunctive perampanel in patients with focal seizures or generalized tonic-clonic seizures: Post hoc analysis of Phase II and Phase III double-blind and open-label extension studies in India.

机构信息

Janakpuri Super Specialty Hospital Society, Janakpuri, New Delhi, India.

Curie Manavata Cancer Centre, Nashik, India.

出版信息

Epilepsia Open. 2021 Feb 8;6(1):90-101. doi: 10.1002/epi4.12448. eCollection 2021 Mar.

DOI:10.1002/epi4.12448

PMID:33681652

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7918331/

Abstract

OBJECTIVE

This post hoc analysis assessed the efficacy and safety of adjunctive perampanel in patients (aged ≥ 12 years) with focal seizures (FS), with/without focal to bilateral tonic-clonic seizures (FBTCS), or generalized tonic-clonic seizures (GTCS) in India.

METHODS

Centers in India were identified from six double-blind, randomized, Phase II and Phase III studies of adjunctive perampanel (2-12 mg/day) and their open-label extensions (OLEx). Efficacy assessments included median percent change in seizure frequency per 28 days, 50% and 75% responder and seizure-freedom rates. Treatment-emergent adverse events (TEAEs) were monitored.

RESULTS

Overall, 128 patients (placebo, n = 39; perampanel, n = 89) were included in the double-blind Safety Analysis Set and 126 (FS, n = 113 [placebo, n = 32; perampanel, n = 81]; FBTCS, n = 35 [placebo, n = 14; perampanel, n = 21]; GTCS, n = 13 [placebo, n = 6; perampanel, n = 7]) comprised the Full Analysis Set. Median percent reductions in seizure frequency per 28 days for placebo vs perampanel for Indian patients were as follows: 34.8% vs 49.8% (FS; not significant [NS]) and 43.1% vs 60.5% (FBTCS; NS) at 4-12 mg/day, respectively, and -22.4% vs 8.2% (GTCS; NS) at 8 mg/day, respectively. Fifty-percent responder rates were 37.5% vs 55.1% (FS; NS), 42.9% vs 60.0% (FBTCS; NS), and 16.7% vs 42.9% (GTCS; NS), respectively; seizure-freedom rates were 0.0% vs 5.8%, 7.1% vs 10.0%, and 0.0% vs 14.3%, respectively (all NS). Overall, 110 patients entered OLEx studies (FS, n = 99; GTCS, n = 11). Perampanel was efficacious for up to four years for FS and FBTCS and two years for GTCS. Across double-blind and OLEx studies, TEAEs occurred in 58.4% and 83.6% of Indian perampanel-treated patients, respectively; dizziness was most common. Efficacy and safety outcomes were generally similar overall between Indian and non-Indian patients.

SIGNIFICANCE

These data suggest adjunctive perampanel (up to 12 mg/day) may be a suitable anti-seizure medication for patients (aged ≥ 12 years) with FS, with/without FBTCS, or GTCS in India.

摘要

目的

本事后分析评估了在印度接受辅助性吡仑帕奈（剂量为 2-12mg/天）治疗的局灶性发作（FS）、伴或不伴局灶性到双侧强直阵挛发作（FBTCS）或全面强直阵挛发作（GTCS）患者的疗效和安全性。

方法

从六项吡仑帕奈辅助治疗的双盲、随机、Ⅱ期和Ⅲ期研究及开放标签扩展研究（OLEx）中确定了印度的研究中心。疗效评估包括每 28 天的癫痫发作频率的中位数百分比变化、50%和 75%应答率和无癫痫发作率。监测治疗引起的不良事件（TEAEs）。

结果

共有 128 例患者（安慰剂组，n=39；吡仑帕奈组，n=89）纳入双盲安全性分析集，126 例（FS，n=113[安慰剂组，n=32；吡仑帕奈组，n=81]；FBTCS，n=35[安慰剂组，n=14；吡仑帕奈组，n=21]；GTCS，n=13[安慰剂组，n=6；吡仑帕奈组，n=7]）纳入全分析集。印度患者中，安慰剂组和吡仑帕奈组的癫痫发作频率每 28 天的中位数百分比降低分别为：4-12mg/天，分别为 34.8%比 49.8%（FS；无统计学意义[NS]）和 43.1%比 60.5%（FBTCS；NS），8mg/天，分别为-22.4%比 8.2%（GTCS；NS）。50%应答率分别为 37.5%比 55.1%（FS；NS）、42.9%比 60.0%（FBTCS；NS）和 16.7%比 42.9%（GTCS；NS）。无癫痫发作率分别为 0.0%比 5.8%、7.1%比 10.0%和 0.0%比 14.3%（均 NS）。总体而言，有 110 例患者进入 OLEx 研究（FS，n=99；GTCS，n=11）。在 FS 和 FBTCS 中，吡仑帕奈最长治疗时间达 4 年，在 GTCS 中，吡仑帕奈最长治疗时间达 2 年。在双盲和 OLEx 研究中，分别有 58.4%和 83.6%的印度吡仑帕奈治疗患者发生 TEAEs；头晕最常见。双盲和 OLEx 研究中，印度和非印度患者的疗效和安全性结局总体上相似。