Long-term safety of adjunctive cenobamate in patients with uncontrolled focal seizures: Open-label extension of a randomized clinical study

Epilepsia. 2021 Sep;62(9):2142-2150. doi: 10.1111/epi.17007. Epub 2021 Jul 13.


Objective: This study was undertaken to examine long-term (up to 7.8 years) retention rate, safety, and tolerability of the antiseizure medication (ASM) cenobamate as adjunctive treatment in the open-label extension (OLE) of study YKP3089C013 (C013; ClinicalTrials.gov: NCT01397968).

Methods: Patients who completed the 12-week, multicenter, multinational, double-blind, randomized, placebo-controlled C013 study, which examined adjunctive cenobamate treatment of adults with uncontrolled focal seizures, were eligible to enroll in the OLE. During the OLE, dose adjustments of cenobamate and concomitant ASMs were allowed. Safety assessments included frequency of treatment-emergent adverse events (TEAEs) and serious TEAEs, TEAE severity, and TEAEs leading to discontinuation. Probability of patient continuation in the OLE was examined using a Kaplan-Meier analysis.

Results: One hundred forty-nine patients entered the OLE (median duration of cenobamate treatment = 6.25 years). As of the data cutoff, 57% of patients (85/149) remained in the OLE (median treatment duration = 6.8 years, range = 6.4-7.8 years). The median modal daily cenobamate dose was 200 mg (range = 50-400 mg). The probability of treatment continuation at 1-6 years of cenobamate treatment was 73%, 67%, 63%, 61%, 60%, and 59%, respectively. Among patients who continued at 1 year (n = 107), the probability of continuing at Years 2-5 was 92%, 87%, 83%, and 82%. The most common discontinuation reasons were patient withdrawal (19.5%, 29/149), adverse event (10.1%, 15/149), and lack of efficacy (5.4%, 8/149). TEAEs leading to discontinuation in 1% or more of patients were fatigue (1.3%, 2/149), ataxia (1.3%, 2/149), and memory impairment or amnesia (1.3%, 2/149). Dizziness (32.9%, 49/149), headache (26.8%, 40/149), and somnolence (21.5%, 32/149) were the most frequently reported TEAEs and were primarily mild or moderate in severity.

Significance: Long-term retention in the C013 OLE study demonstrated sustained safety and tolerability of adjunctive cenobamate treatment up to 7.8 years in adults with treatment-resistant focal seizures taking one to three ASMs.

Keywords: epilepsy; focal seizures; long-term; retention; safety.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticonvulsants / adverse effects
  • Carbamates / therapeutic use
  • Chlorophenols
  • Double-Blind Method
  • Drug Therapy, Combination
  • Humans
  • Seizures* / drug therapy
  • Tetrazoles
  • Treatment Outcome


  • Anticonvulsants
  • Carbamates
  • Chlorophenols
  • Tetrazoles
  • Cenobamate

Associated data

  • ClinicalTrials.gov/NCT01397968