Early Response Rates with Adjunctive Cenobamate in Uncontrolled Focal Seizures: A Randomized, Double-blind, Placebo-controlled, Multicenter Study in a Multinational Asian Population
Abstract number :
1.404
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2024
Submission ID :
1013
Source :
www.aesnet.org
Presentation date :
12/7/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Pranoti Pradhan, MD, MPH – SK Life Science, Inc.
Louis Ferrari, RPh, MBA – SK Life Science, Inc.
Zhen Hong, MD – Fudan University
Sang Kun Lee, MD, PhD – Seoul National University Hospital
Sunita N Misra, MD, PhD – SK Life Science, Inc.
Peimin Yu, MD – Fudan University
William E Rosenfeld, MD – Comprehensive Epilepsy Care Center for Children and Adults
Kensuke Kawai, MD – Jichi Medical University
Rationale: Results from a multicenter, randomized, double-blind, placebo-controlled, dose-response study (YKP3089C035 [C035]) showed that adjunctive cenobamate 100, 200, and 400 mg/day significantly reduced seizure frequency compared to placebo in a multinational Asian population. Here we report changes in seizure frequency during 2-week intervals of the early titration phase.
Methods: Adults aged 18-70 years with ≥8 focal seizures (focal aware motor, focal impaired aware, or focal to bilateral tonic clonic) during an 8-week baseline period, despite treatment with 1-3 antiseizure medications, 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 uptitrated at 2-week intervals. The study consisted of an 18-week titration phase and a 6-week maintenance phase and used the currently approved cenobamate titration schedule. Changes in seizure frequency at 2-week intervals during the first 8 weeks of titration were assessed for all cenobamate dose groups combined 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: Among 519 patients randomized (mean age 35.7 years), 516 received ≥1 dose of study drug and 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 (Figure 1). During Weeks 1-2, 3-4, 5-6, and 7-8, the ≥50% responder rate in the MITT-M population was 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 (Figure 2). Treatment-emergent adverse events (TEAEs) occurred in 66.2% (86/130) of placebo-treated patients and 78.9% (101/128), 85.4% (111/130), and 96.1% (123/128) of patients in the 100-, 200-, and 400-mg groups, respectively. The most common TEAEs (≥20%) were dizziness and somnolence in the cenobamate dose groups.
Anti-seizure Medications