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
Sunita Misra1, Louis Ferrari1, Zhen Hong2, Kensuke Kawai3, Sang Kun Lee4, William Rosenfeld5, Peimin Yu2
1SK Life Science, Inc., 2Fudan University, 3Jichi Medical University, 4Seoul National University Hospital, 5Comprehensive Epilepsy Care Center for Children and Adults
Objective:
This randomized, controlled, double-blind, multinational study (NCT04557085) evaluated efficacy and safety of adjunctive cenobamate in Asian patients with uncontrolled focal seizures.
Background:
Cenobamate, an antiseizure medication (ASM) approved in the US, Europe, and other countries for the treatment of focal seizures in adults, has shown good efficacy in focal seizures.
Design/Methods:
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 placebo or adjunctive cenobamate 100, 200, or 400 mg once daily. The study included an 18-week titration phase and 6-week maintenance phase and used the currently approved cenobamate titration schedule. The primary 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 maintenance phase efficacy measure).
Results:
Among 519 patients randomized (mean age 35.7 years), 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 28-day seizure frequency from baseline were -25.9% for placebo vs -42.6%, -78.3%, and
-100% for cenobamate 100, 200, and 400 mg, respectively (P<0.001 each). 100% responder rates during the 12-week treatment period, combining the last 6 weeks of titration and the 6-week maintenance phase, were 0.8% (1/122) for placebo vs 8.5% (10/118) for the 100-mg (P=0.005), 19.7% (23/117) for 200-mg (P<0.001), and 30.6% (37/121) for 400-mg (P<0.001) groups. The most common treatment-emergent adverse events (≥20%) were dizziness and somnolence in cenobamate-treated patients.
Conclusions:
This study supports the efficacy and safety profile of cenobamate using the approved titration regimen in a multinational Asian population. Adjunctive cenobamate 100, 200, and 400 mg significantly reduced focal seizure frequency vs placebo and was generally well tolerated.
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