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-2093-302. 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 (intent-to-treat population). Results: Three hundred and twenty five patients were enrolled, and 223 (68.6%) completed 1 year of treatment. Among the 102 (31.4%) who prematurely discontinued, 37 (11.4%) patients discontinued due to treatment-emergent adverse events (TEAEs). The mean daily dose of ESL throughout the 1-year treatment was 890±192 mg (median=800 mg). Most patients (82%) used two or more concomitant antiepileptic drugs (AEDs), and 18% used 1 concomitant AED. The most commonly used concomitant AEDs were carbamazepine (by 58% of patients), valproic acid (22%), lamotrigine (22%), levetiracetam (17%) and clobazam (17%). TEAEs were reported by 83% patients. TEAEs occurring in at least 5.0% of patients were dizziness (27%), headache (16%), somnolence (12%), decreased diastolic blood pressure (9%), abnormal coordination (9%), diplopia (9%), vomiting (7%), nausea (7%), nasopharyngitis (6%), diarrhea (6%), back pain (5%), blurred vision (5%), and influenza (5%). TEAEs were of mild to moderate severity in 82% of patients who reported TEAEs. There were no abnormal results of laboratory tests raising safety concerns. In relation to baseline of the double-blind part of the study, seizure frequency decreased (median) by 32% during the first 4 weeks and by 38% in weeks 5-16 to 39% in weeks 41-52. The responder rate (≥50% decrease in seizure frequency) was 37% during weeks 1-4; thereafter, ranged between 38% and 42% per 12 week interval (Figure 1). Proportion of seizure-free patients per 12 week interval increased over time, from 5% (weeks 5-16) to 11% (weeks 41-52). Conclusions: ESL was safe and well tolerated as adjunctive therapy in patients refractory to treatment with standard AED therapy, and markedly and sustainedly decreased seizure frequency over a 1-year open-label treatment. Supported by BIAL - Portela & Co, SA