A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Adjunctive Cenobamate in Asian Patients with Focal Seizures, with Optional Open-label Extension
Abstract number :
1.4
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2024
Submission ID :
1010
Source :
www.aesnet.org
Presentation date :
12/7/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Sunita N Misra, MD, PhD – SK Life Science, Inc.
Louis Ferrari, RPh, MBA – SK Life Science, Inc.
Zhen Hong, MD – Fudan University
Kensuke Kawai, MD – Jichi Medical University
Sang Kun Lee, MD, PhD – Seoul National University Hospital
William E Rosenfeld, MD – Comprehensive Epilepsy Care Center for Children and Adults
Peimin Yu, MD – Fudan University
Rationale: Cenobamate, an antiseizure medication (ASM) approved in the US, Canada, and Europe for the treatment of focal seizures in adults, has good efficacy in focal seizures. This randomized, controlled study (YKP3089C035) evaluated the efficacy and safety of adjunctive cenobamate in Asian patients with uncontrolled focal seizures.
Methods: This was a randomized, double-blind, placebo-controlled, multicenter study with optional open-label extension conducted in multiple Asian countries. Adults 18-70 years old with ≥8 focal seizures during an 8-week baseline period, 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. The study included an 18-week titration phase and a 6-week maintenance phase and used the currently approved cenobamate titration schedule. The primary efficacy outcome was median percent change from baseline in 28-day seizure frequency for all focal aware motor, focal impaired aware, or focal to bilateral tonic-clonic seizures in the modified intent-to-treat maintenance phase population (MITT-M, ≥1 dose of study drug and ≥1 efficacy measure during maintenance phase). Secondary efficacy outcomes included change in seizure frequency and responder rates (≥50%, ≥75%, ≥90%, and 100% reduction from baseline) during the 12-week treatment period, combining the last 6 weeks of the titration phase and the 6-week 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; 100 mg, n=113; 200 mg, n=113; and 400 mg, n=103). Median percent changes in seizure frequency per 28 days from baseline in the MITT-M population were -25.9% for placebo vs -42.6%, -78.3%, and -100% for cenobamate 100, 200, and 400 mg, respectively (P< 0.001 each) (Figure 1). Median percent changes in seizure frequency per 28 days from baseline during the 12-week treatment period were -20.1% for placebo vs -42.6%, -77.1%, and -89.2% for cenobamate 100, 200, and 400 mg, respectively (P< 0.001 each). The ≥50% responder rates during the 12-week treatment period were 27.9% (34/122) for placebo vs 44.9% (53/118) for the 100-mg (
Anti-seizure Medications