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

ObjectiveTo 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 1,600mg (n=128) or 1,200mg QD (n=65) for 18weeks. 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 1,600mg, 28.7% (95% CI 21.2-38.1%) and 1,200mg, 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 1,200mg, respectively. The reductions in median standardized seizure frequency (seizures per 28days) between baseline and the 18-week treatment period were: ESL 1,600mg, 42% and 1,200mg, 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%). SignificanceESL 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 1,200mg QD were superior to the historical control; the difference in exit rates between doses was not statistically significant.