Efficacy and Safety of Adjunctive Cenobamate for the Treatment of Primary Generalized Tonic-clonic Seizures in Adults and Adolescents
Evelyn Shih1, Michal Bar2, Mark Farkas3, Pavel Klein4, David Vossler5, Sunita Misra1
1SK Life Science, Inc., 2Department of Clinical Neurosciences, University of Ostrava, 3Pediatric Center, Semmelweis University, 4Mid-Atlantic Epilepsy and Sleep Center, 5University of Washington School of Medicine
Objective:
To assess the efficacy and safety of adjunctive cenobamate for the treatment of primary generalized tonic-clonic (PGTC) seizures in patients ≥12 years old.
Background:
Cenobamate is an antiseizure medication (ASM) indicated for treating focal seizures in adults.
Design/Methods:
This phase 3, multicenter, double-blind trial (YKP3089C025; NCT03678753) randomized patients with PGTC seizures 1:1 to cenobamate 200 mg/day or matching placebo administered as an oral tablet in adults (≥18 years) or weight-based equivalent pediatric oral suspension in adolescents (≥12 to <18 years). Patients must have had ≥5 PGTC seizures during the 12-week baseline period (≥1.67 seizures/28 days) despite treatment with 1-3 ASMs. Cenobamate dosing started at 12.5 mg/day (or weight-based equivalent) and was titrated to 150 mg/day (or weight-based equivalent) over 10 weeks. Cenobamate was dosed at 200 mg/day (or weight-based equivalent; minimum 150 mg/day) during the 12-week maintenance phase. Primary efficacy outcomes were median percent change from baseline in 28-day PGTC seizure frequency during the double-blind period and ≥50% responder rates during the maintenance phase. Safety was also assessed.
Results:
Among 169 patients randomized (n=135 adults, n=34 adolescents), 168 (placebo, n=83; cenobamate, n=85) were included in the analysis. Median percent reduction from baseline in seizure frequency/28 days during the double-blind period was 71.9% for cenobamate (vs 39.6% placebo, P=0.003). Among the 161 patients (placebo, n=78; cenobamate, n=83) analyzed during the maintenance-phase, the ≥50% responder rate was 71.1% for cenobamate (vs 51.3% placebo, P=0.01); 43.4% of cenobamate-treated patients were seizure-free (vs 20.5% placebo, P=0.002). Treatment-emergent adverse events occurred in 53.0% (44/83) of placebo-treated patients and 60.0% (51/85) of cenobamate-treated patients (most commonly somnolence [16.5%] and fatigue [10.6%] for cenobamate). No treatment-related serious adverse events, deaths, or cases of drug reaction with eosinophilia and systemic symptoms (DRESS) were reported.
Conclusions:
Adjunctive cenobamate 200 mg/day demonstrated efficacy and safety in treating PGTC seizures in patients ≥12 years old.
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