Epilepsia · 2025
A randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of adjunctive cenobamate in Asian patients with focal seizures.
СтатьяРандомизированное исследованиеМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Lee Sang Kun, Yu Peimin, Choe Eunyeong, Ferrari Louis, Heo Kyoung, Hong Seung Bong, Hong Zhen, Iida Koji, Jeon Yong Heui, Jung Jiwon, Kamin Marc, Kawai Kensuke, Kim Ji Hyun, Kim Myung Won, Liu Xiaorong, Park Jungshin, Rosenfeld William E, Yamamoto Takamichi, Zhou Dong, Zhu Suiqiang, Misra Sunita N
Аннотация
OBJECTIVES: This randomized, double-blind, placebo-controlled study (NCT04557085), conducted in China, Japan, and the Republic of Korea, evaluated the efficacy and safety of adjunctive cenobamate in patients with uncontrolled focal seizures.
METHODS: Adults 18-70 years of age with ≥8 seizures (focal aware motor, focal impaired awareness, or focal to bilateral tonic-clonic) during an 8-week baseline, despite treatment with 1-3 antiseizure medications (ASMs), were randomized 1:1:1:1 to placebo or cenobamate 100, 200, or 400 mg/day. The study included an 18-week titration phase and a 6-week maintenance phase. The primary efficacy analysis was a hierarchical step-down comparison of the percent change from baseline in 28-day seizure frequency vs placebo during the maintenance phase for cenobamate 200, then 400, and then 100 mg/day.
RESULTS: Among 519 patients randomized, 446 received ≥1 dose of study drug and had ≥1 efficacy measure during the maintenance phase (placebo, n = 117; 100 mg/day, n = 113; 200 mg/day, n = 113; and 400 mg/day, n = 103). Median percent change in seizure frequency during the maintenance phase was -25.9% for placebo vs -42.6%, -78.3%, and -100% for cenobamate 100, 200, and 400 mg/day, respectively (all p's < .001). During the 12-week period encompassing the last 6 weeks of titration and the 6-week maintenance phase (secondary outcome), the median percent change in seizure frequency was -20.1% for placebo vs -42.6%, -77.1%, and -89.2% for cenobamate 100, 200, and 400 mg/day, respectively. Seizure-free rates during the maintenance phase were 2.6% of patients for placebo vs 12.4%, 30.1%, and 52.4% for cenobamate 100, 200, and 400 mg/day, respectively, and during the 12-week period were 0.8% for placebo vs 8.5%, 19.7%, and 30.6% for the cenobamate groups. The most common treatment-emergent adverse events in cenobamate patients (≥20%) were dose-related dizziness and somnolence.
SIGNIFICANCE: Cenobamate 100, 200, and 400 mg/day reduced focal seizures in Asian patients in a dose-related fashion and was generally well tolerated.
METHODS: Adults 18-70 years of age with ≥8 seizures (focal aware motor, focal impaired awareness, or focal to bilateral tonic-clonic) during an 8-week baseline, despite treatment with 1-3 antiseizure medications (ASMs), were randomized 1:1:1:1 to placebo or cenobamate 100, 200, or 400 mg/day. The study included an 18-week titration phase and a 6-week maintenance phase. The primary efficacy analysis was a hierarchical step-down comparison of the percent change from baseline in 28-day seizure frequency vs placebo during the maintenance phase for cenobamate 200, then 400, and then 100 mg/day.
RESULTS: Among 519 patients randomized, 446 received ≥1 dose of study drug and had ≥1 efficacy measure during the maintenance phase (placebo, n = 117; 100 mg/day, n = 113; 200 mg/day, n = 113; and 400 mg/day, n = 103). Median percent change in seizure frequency during the maintenance phase was -25.9% for placebo vs -42.6%, -78.3%, and -100% for cenobamate 100, 200, and 400 mg/day, respectively (all p's < .001). During the 12-week period encompassing the last 6 weeks of titration and the 6-week maintenance phase (secondary outcome), the median percent change in seizure frequency was -20.1% for placebo vs -42.6%, -77.1%, and -89.2% for cenobamate 100, 200, and 400 mg/day, respectively. Seizure-free rates during the maintenance phase were 2.6% of patients for placebo vs 12.4%, 30.1%, and 52.4% for cenobamate 100, 200, and 400 mg/day, respectively, and during the 12-week period were 0.8% for placebo vs 8.5%, 19.7%, and 30.6% for the cenobamate groups. The most common treatment-emergent adverse events in cenobamate patients (≥20%) were dose-related dizziness and somnolence.
SIGNIFICANCE: Cenobamate 100, 200, and 400 mg/day reduced focal seizures in Asian patients in a dose-related fashion and was generally well tolerated.