Early Response Rates With Adjunctive Cenobamate in Uncontrolled Focal Seizures: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study in a Multinational Asian Population
Pranoti Pradhan1, Louis Ferrari1, Zhen Hong2, Sang Kun Lee3, Sunita Misra4, Peimin Yu2, William Rosenfeld5, Kensuke Kawai6
1SK Life Science, Inc., 2Fudan University, 3Seoul National University Hospital, 4SK Life Science, 5Comprehensive Epilepsy Care Center for Children and Adults, 6Jichi Medical University
Objective:
To report changes in seizure frequency during 2-week intervals of the early titration phase of a multicenter, randomized, double-blind, placebo-controlled, dose-response study (NCT04557085) of adjunctive cenobamate for the treatment of focal seizures in a multinational Asian population.
Background:
Cenobamate is an antiseizure medication (ASM) approved in the US, Canada, and Europe for the treatment of focal seizures in adults. Cenobamate demonstrated efficacy in treating focal seizures in previous controlled studies in adults.
Design/Methods:
Patients 18-70 years with uncontrolled focal seizures despite treatment with 1-3 ASMs were randomized 1:1:1:1 to receive either placebo or adjunctive cenobamate 100, 200, or 400 mg once daily, initiated at 12.5 mg/day and up-titrated at 2-week intervals. Changes in seizure frequency at 2-week intervals during early titration (first 8 weeks) were assessed for cenobamate (combined dose groups) vs placebo in the modified intent-to-treat maintenance population (MITT-M, ≥1 dose and any post-baseline seizure data in the maintenance phase). Safety and tolerability were also assessed.
Results:
519 patients were randomized (mean age 35.7 years); 446 were included in the MITT-M population (placebo, n=117; cenobamate, n=329). During Weeks 1-2, 3-4, 5-6, and 7-8 of titration, cenobamate-treated patients experienced a median reduction from baseline in 28-day seizure frequency of 16.0% (vs 20.0% placebo, P=0.81), 27.2% (vs 22.2% placebo, P=0.42), 42.9% (vs 15.4% placebo, P=0.002), and 55.6% (vs 20.0% placebo, P<0.001) respectively. During Weeks 1-2, 3-4, 5-6, and 7-8, the ≥50% responder rates in the MITT-M population were 26.1% for cenobamate (vs 32.5% placebo, P=0.19), 36.5% (vs 25.6% placebo, P=0.03), 45.3% (vs 34.2% placebo, P=0.04), and 54.4% (vs 29.1% placebo, P<0.001), respectively. The most common TEAEs (≥20%) were dizziness and somnolence in the cenobamate dose groups.
Conclusions:
Statistically significant reductions in focal seizure frequency were observed early during cenobamate titration (at Week 5-6). Adjunctive cenobamate was generally well-tolerated.
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