Eslicarbazepine acetate as adjunctive therapy in patients with uncontrolled partial-onset seizures: Results of a phase III, double-blind, randomized, placebo-controlled trial

ObjectiveTo evaluate the efficacy and safety of adjunctive eslicarbazepine acetate (ESL) in patients with refractory partial-onset seizures. MethodsThis randomized, placebo-controlled, double-blind, parallel-group, phase III study was conducted at 173 centers in 19 countries, including the United States and Canada. Eligible patients were aged 16years and had uncontrolled partial-onset seizures despite treatment with 1-2 antiepileptic drugs (AEDs). After an 8-week baseline period, patients were randomized to once-daily placebo (n=226), ESL 800mg (n=216), or ESL 1,200mg (n=211). Following a 2-week titration period, patients received ESL 800 or 1,200mg once-daily for 12weeks. Seizure data were captured and documented using event-entry or daily entry diaries. ResultsStandardized seizure frequency (SSF) during the maintenance period (primary end point) was reduced with ESL 1,200mg (p=0.004), and there was a trend toward improvement with ESL 800mg (p=0.06), compared with placebo. When data for titration and maintenance periods were combined, ESL 800mg (p=0.001) and 1,200mg (p<0.001) both reduced SSF. There were no statistically significant interactions between treatment response and geographical region (p=0.38) or diary version (p=0.76). Responder rate (50% reduction in SSF) was significantly higher with ESL 1,200mg (42.6%, p<0.001) but not ESL 800mg (30.5%, p=0.07) than placebo (23.1%). Incidence of treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation increased with ESL dose. The most common TEAEs were dizziness, somnolence, nausea, headache, and diplopia. SignificanceAdjunctive ESL 1,200mg once-daily was more efficacious than placebo in adult patients with refractory partial-onset seizures. The once-daily 800mg dose showed a marginal effect on SSF, but did not reach statistical significance. Both doses were well tolerated. Efficacy assessment was not affected by diary format used.