Abstracts

Rationale: To investigate the efficacy and safety of eslicarbazepine acetate (ESL) as adjunctive therapy in adult patients with ≥4 partial-onset seizures per 4 weeks despite treatment with 1-3 AEDs (other than felbamate and oxcarbazepine). Methods: Data from 1049 patients enrolled in three phase 3 multicentre, double-blind, randomized, placebo-controlled studies were pooled and analyzed. ESL was administered at once daily doses of 400 mg, 800 mg and 1200 mg. The key efficacy endpoints were seizure frequency standardised per 4 weeks (primary analysis in all individual studies), median relative reduction in seizure frequency, and responder rate (≥50% reduction in seizure frequency) in the intent-to-treat population. Standardised seizure frequency per 4 weeks was compared with placebo using an analysis of covariance that modelled seizure frequency as a function of baseline seizure frequency and treatment. Results: Seizure frequency over the 12 week maintenance period was significantly reduced compared to placebo with ESL 800 mg (p<0.0001) and 1200 mg (p<0.0001) (Figure 1). The median relative reduction in seizure frequency was greater with ESL 800 mg (36.4%) and 1200 mg (46.4%) compared to placebo (15%). The responder rate was also significantly higher in the ESL 800 mg (36%, p<0.001) and 1200 mg (44%, p<0.0001) groups than in the placebo group (22%). The most frequently administered concomitant AEDs were carbamazepine (58% of patients), valproic acid (25%) and lamotrigine (21%). Efficacy was maintained in all combinations between ESL and the concomitant AEDs. Adverse events (AEs) occurred mainly during the first weeks of treatment; no difference was found between ESL and placebo in incidence of AEs after 6 weeks of treatment. The majority of AEs were reported by <3% of patients in any treatment group, although AEs tended to increase with increasing dose of ESL. The most common AEs in both placebo and ESL groups were dizziness, somnolence, headache, and nausea. The majority of patients in ESL (84.8%) and placebo (90.3%) treatment groups had AEs of mild or moderate intensity. Hyponatraemia <125 mmol/L was reported in 4 patients (all co-treated with ≥1000 mg carbamazepine/day and all presenting sodium levels <135 mmol/L before starting treatment with ESL): 1 (0.5%) on ESL 400 mg, 2 (0.7%) on 800 mg and 1 (0.4%) on 1200 mg. Hypernatraemia (>