Objective:

Background:

PGTC seizures are the most serious generalized seizure type due to increased risk for seizure-related injury and sudden unexpected death in epilepsy (SUDEP). Cenobamate is an antiseizure medication (ASM) approved in the US, Canada, and Europe for the treatment of focal seizures in adult patients at doses of 100-400 mg/day. Preclinical animal models suggest that cenobamate may exhibit a broad spectrum of antiseizure activity. In human clinical trials, cenobamate demonstrated substantial reductions in the frequency of focal to bilateral tonic-clonic seizures.

Design/Methods:

Study C025 is phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Eligible patients (target N=170) are ≥12 years old with a clinical diagnosis of PGTC seizures (with or without other generalized seizure subtypes) in the setting of idiopathic generalized epilepsy (IGE). Diagnosis will be confirmed by the Epilepsy Study Consortium based on clinical description, EEGs, and radiological tests prior to randomization. Baseline PGTC seizure frequency must be at least 1.67 per 28 days while taking a stable regimen of 1-3 ASMs. The 22-week double-blind treatment period will include a 10-week titration phase and a 12-week maintenance phase. Subjects will be randomized 1:1 to cenobamate titrated to 200 mg/day or matching placebo. The primary efficacy endpoint is the median percent change in 28-day PGTC seizure frequency during the double-blind treatment period compared to baseline. Secondary endpoints will assess seizure freedom as well as the effect of cenobamate on other generalized seizure types.

Results:

The study is ongoing and is currently enrolling subjects ≥12 years of age.

Conclusions:

Study C025 will be the first adequate and well-controlled trial that assesses the effect of cenobamate on PGTC seizures. These results will provide evidence about the broad-spectrum potential of cenobamate.