Efficacy and safety of conversion to monotherapy with eslicarbazepine acetate in adults with uncontrolled partial-onset seizures: a randomized historical-control phase III study based in North America.

Abstract

SummaryObjectiveTo assess the efficacy and safety of eslicarbazepine acetate (ESL) as monotherapy in North American patients with partial‐onset seizures (POS).MethodsThis multicenter, randomized, double‐blind “withdrawal to monotherapy” study used historical control data as the comparator. Adults with POS medically uncontrolled by one to two antiepileptic drugs gradually converted to ESL monotherapy. Following an 8‐week baseline period, patients were randomized 2:1 to receive ESL 1,600 mg (n = 128) or 1,200 mg QD (n = 65) for 18 weeks. The primary end point was the proportion of patients meeting predefined exit criteria (signifying worsening seizure control). Treatment was considered effective if the 95% upper confidence limit (UCL) for the Kaplan‐Meier estimated exit rate was lower than the exit rate threshold calculated from the historical control (65.3%).ResultsKaplan‐Meier estimated exit rates were: ESL 1,600 mg, 28.7% (95% CI 21.2–38.1%) and 1,200 mg, 44.4% (32.5–58.3%). The difference between doses was not significant (p = 0.07). For both doses, the 95% UCLs for the exit rate were ˂65.3%; ESL monotherapy was considered superior to the historical control. There was no statistically significant increase in the risk of study exit related to carbamazepine use. Nine (7.6%) and five patients (8.3%) remained seizure‐free during the 10‐week monotherapy period, while taking ESL 1,600 and 1,200 mg, respectively. The reductions in median standardized seizure frequency (seizures per 28 days) between baseline and the 18‐week treatment period were: ESL 1,600 mg, 42% and 1,200 mg, 31%. Treatment‐emergent adverse events (TEAEs) occurring in ≥10% of patients were dizziness, headache, fatigue, somnolence, nausea, and nasopharyngitis. The TEAE most frequently leading to discontinuation was hyponatremia (2.1%).Significance ESL was efficacious and well tolerated as monotherapy in North American patients, and led to a reduction in seizure frequency. Exit rates for ESL 1,600 and 1,200 mg QD were superior to the historical control; the difference in exit rates between doses was not statistically significant.