Efficacy and safety of perampanel as early add-on therapy in Chinese patients with focal-onset seizures: a multicenter, open-label, single-arm study

Lehong Gao; Qiang Lu; Zan Wang; Wei Yue; Guoping Wang; Xiaoqiu Shao; Yi Guo; Yonghong Yi; Zhen Hong; Yuwu Jiang; Bo Xiao; Guiyun Cui; Feng Gao; Jiasheng Hu; Jianmin Liang; Meiyun Zhang; Yuping Wang

doi:10.3389/fneur.2023.1236046

Efficacy and safety of perampanel as early add-on therapy in Chinese patients with focal-onset seizures: a multicenter, open-label, single-arm study

Front Neurol. 2023 Aug 30:14:1236046. doi: 10.3389/fneur.2023.1236046. eCollection 2023.

Authors

Lehong Gao¹, Qiang Lu², Zan Wang³, Wei Yue⁴, Guoping Wang⁵, Xiaoqiu Shao⁶, Yi Guo⁷, Yonghong Yi⁸, Zhen Hong⁹, Yuwu Jiang¹⁰, Bo Xiao¹¹, Guiyun Cui¹², Feng Gao¹³, Jiasheng Hu¹⁴, Jianmin Liang¹⁵, Meiyun Zhang¹⁶, Yuping Wang^{1

17

18

19}

Affiliations

¹ Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
² Department of Neurology, Peking Union Medical College Hospital, Beijing, China.
³ Department of Neurology, The First Hospital of Jilin University, Changchun, China.
⁴ Department of Neurology, Tianjin Huanhu Hospital, Tianjin, China.
⁵ Division of Life Sciences and Medicine, Department of Neurology, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China.
⁶ Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
⁷ Department of Neurology, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, China.
⁸ Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Department of Neurology, Institute of Neuroscience, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
⁹ Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
¹⁰ Department of Pediatrics and Pediatric Epilepsy Center, Peking University First Hospital, Beijing, China.
¹¹ Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
¹² Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
¹³ Department of Neurology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
¹⁴ Department of Neurology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
¹⁵ Department of Pediatric Neurology, The First Hospital of Jilin University, Changchun, China.
¹⁶ Department of Neurology, Tianjin Union Medical Center, Tianjin, China.
¹⁷ Beijing Key Laboratory of Neuromodulation, Beijing, China.
¹⁸ Center of Epilepsy, Institute of Sleep and Consciousness Disorders, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China.
¹⁹ Neuromedical Technology Innovation Center of Hebei Province, Hebei Hospital of Xuanwu Hospital, Capital Medical University, Shijiazhuang, China.

Abstract

Background: No interventional study has been conducted in China to assess efficacy and safety of perampanel in treating Chinese patients with epilepsy, nor has there been any study on perampanel early add-on therapy in China. This interventional study aimed to assess efficacy and safety of perampanel as an early add-on treatment of focal-onset seizures (FOS) with or without focal-to-bilateral tonic-clonic seizures (FBTCS) in Chinese patients.

Methods: In this multicenter, open-label, single-arm, phase 4 interventional study, Chinese patients ≥ 12 years old with FOS with or without FBTCS who failed anti-seizure medication (ASM) monotherapy from 15 hospitals in China were enrolled and treated with perampanel add-on therapy (8-week titration followed by 24-week maintenance). The primary endpoint was 50% responder rate. Secondary endpoints included seizure-freedom rate and changes in seizure frequency from baseline. Treatment-emergent adverse events (TEAEs) and drug-related TEAEs were recorded.

Results: The full analysis set included 150 patients. The mean maintenance perampanel dose was 5.9 ± 1.5 mg/day and the 8-month retention rate was 72%. The 50% responder rate and seizure-freedom rate for all patients during maintenance were 67.9 and 30.5%, respectively. Patients with FBTCS had higher 50% responder rate (96.0%) and seizure-freedom rate (76.0%) during maintenance. Patients on concomitant sodium valproate had a significantly higher seizure-freedom rate than those on concomitant oxcarbazepine. Eight-six (55.1%) patients experienced treatment-related TEAEs, and the most common TEAEs were dizziness (36.5%), hypersomnia (11.5%), headache (3.9%), somnolence (3.2%), and irritability (3.2%). Withdrawal due to TEAEs occurred to 14.7% of the patients.

Conclusion: Perampanel early add-on was effective and safe in treating Chinese patients≥12 years old with FOS with or without FBTCS.Clinical trial registrationwww.chictr.org.cn, Identifier ChiCTR2000039510.

Keywords: 50% responder rate; Chinese patients; focal-onset seizures; perampanel; perampanel early add-on; seizure-freedom rate; seizure-freedom rate perampanel.