A randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of adjunctive cenobamate in Asian patients with focal seizures

Abstract

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