Abstracts

Rationale: Results from a double-blind, placebo-controlled, dose-response study (YKP3089C017 [C017]) showed that cenobamate (CNB) 100, 200, and 400 mg were effective for the treatment of focal seizures. The effects of different baseline features, including number of concomitant antiepileptic drugs (AEDs), seizure frequency, and epilepsy duration, on the reduction in median percent focal seizure frequency per month during the maintenance phase of the C017 study were assessed post-hoc. Methods: Adults 18-70 years old with uncontrolled focal seizures and who had >=8 focal seizures during the 8-week baseline periods, despite treatment with stable doses of 1-3 antiepileptic drugs (AEDs), were randomized 1:1:1:1: to placebo (PBO) or CBN 100, 200, or 400 mg once daily. The study included a 6-week titration phase and 12-week maintenance phase. Results: In 64 patients who were taking 1 AED at baseline, median percent seizure frequency reductions were 24.1% for PBO and 44.7%, 57.6%, and 86.0% for CNB (100, 200, 400 mg/day, respectively). In 156 patients who were taking 2 AEDs, median percent seizure frequency reductions were 33.3% for PBO and 41.4%, 57.9%, and 57.0% for CNB (100, 200, 400 mg/day respectively). In 177 patients who were taking 3 AEDs, median percent seizure frequency reductions were 26.4% for PBO and 41.5%, 49.3%, and 67.4% for CNB (100, 200, 400 mg/day respectively). When assessed by median baseline seizure frequency per 28 days (9.5), the greatest reduction in median percent seizure frequency for patients with baseline seizure frequency <=9.5 occurred in the 200-mg CNB group (66.5%); the greatest reduction for patients with baseline seizure frequency >9.5 occurred in the 400-mg CNB group (70.7%) (Table). Similar trends were observed when assessed by median duration of epilepsy at baseline (23 years) (Table). Responder rates (response defined as >=50% reduction in seizures) were numerically higher in each CNB group compared with placebo, regardless of median baseline seizure frequency or disease duration (Table). Conclusions: Clinically relevant reductions in seizure frequency occurred with adjunctive CNB regardless of baseline number of AEDs, seizure frequency, and disease duration. The greatest reductions occurred in the 200 and 400 mg CNB groups.  Funding: SK Life Science, Inc.