Abstracts

Rationale: To investigate the safety and maintenance of the therapeutic effect of eslicarbazepine acetate (ESL) as adjunctive therapy in adult patients with partial-onset seizures over a 1-year open-label extension period of Study BIA-2093-303. Methods: This was an optional 1-year open-label treatment with ESL for those subjects who completed the double-blind part of the study. The starting dose was 800 mg once-daily, for 4 weeks. Thereafter, the ESL dose could be titrated up or down according to clinical response. Doses of concomitant AEDs were to be kept stable. Last observation carried forward (LOCF) was used in the efficacy analysis on the intent-to-treat population. Results: One hundred and ninety four patients were enrolled, and 150 (78.5%) completed 1 year of treatment. Among the 44 (21.5%) who prematurely discontinued, 9 (4.6%) patients discontinued due to treatment-emergent adverse events (TEAEs). The mean daily dose of ESL throughout the 1-year treatment was 917±179 mg (median=800 mg; range: 400-1500 mg). Most patients (72%) used two concomitant antiepileptic drugs (AEDs); 24% used 1 concomitant AED. The most commonly used concomitant AEDs were carbamazepine (56% of patients), valproic acid (32%), levetiracetam (20%), topiramate (17%), phenytoin (16%), and lamotrigine (12%). TEAEs were reported by 58% patients. TEAEs occurring in more than 3 patients were dizziness (17%), somnolence (10%), headache (9%), vomiting (6%), influenza (5%), nausea (4%), blurred vision (4%), diarrhoea (3%), urinary tract infection (3%), anxiety (2%), diplopia (2%), and pyrexia (2%). TEAEs were of mild to moderate severity in 87% of patients reporting TEAEs. There were no abnormal results of laboratory tests to raise safety concerns. In relation to baseline of the double-blind part of the study, median relative reduction of seizure frequency was 48% during the first 4 weeks and ranged between 54% and 58% per 12 week interval from week 5 to week 52 (intent-to-treat population). The responder rate (≥50% decrease in seizure frequency) was 45.5% during weeks 1-4; thereafter, ranged between 53% and 56% per 12 week interval (Figure 1). The proportion of seizure-free patients per 12 week interval increased over time, from 6% (weeks 5-16) to 18% (weeks 41-52). Conclusions: Adjunctive therapy with ESL proved to be safe and well tolerated, and over 50% of patients had a marked and sustained decrease in seizure frequency over a 1-year open-label treatment period. Supported by BIAL- Portela & Co, SA