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 period. Methods: This was an optional 1-year open-label treatment with ESL for those subjects who completed the double-blind part of Study BIA-2093-301. The starting dose was 800 mg once-daily, for 4 weeks. Thereafter, the ESL dose could be titrated up or down according to therapeutic response. Doses of concomitant AEDs were to be kept stable. Last observation carried forward procedure (LOCF) was used in the efficacy analysis (intent-to-treat population). Results: Three hundred and fourteen patients were enrolled, and 239 (76.1%) completed 1 year. Among the subjects enrolled, 80 (25.5%) subjects were previously on placebo and so received ESL for the first time. The mean daily dose of ESL throughout the 1-year treatment was 877±189 mg (median=800 mg; range=400-1600 mg). Most patients (65%) used two concomitant antiepileptic drugs (AEDs); 34% used 1 concomitant AED. Most commonly used concomitant AEDs were carbamazepine (57% of patients), valproic acid (27%), lamotrigine (26%) and topiramate (14%). Treatment-emergent adverse events (TEAEs) were reported by 51% patients. The most frequent TEAEs were headache (10%), dizziness (10%), diplopia (5%) and nasopharyngitis (5%). TEAEs were mostly (97%) of mild to moderate severity. Eleven (3.5%) patients discontinued due to TEAEs. There were no abnormal results of laboratory tests raising safety concerns. The significant decrease in seizure frequency that was achieved by treatment with 800 mg ESL and 1200 mg ESL during the first 12 weeks in the double-blind part of the study was sustained over the 1-year treatment period. The mean relative change in seizure frequency from baseline decreased during the first 4 weeks of the open-label extension by 31.6% (95% CI: [37.8%, 25.3%]) and continued to decrease to 37.5% in Weeks 5 to 16 to 40.6% in Weeks 41 to 52). The responder rate (≥50% decrease in seizure frequency) was 41% during weeks 1-4; thereafter, ranged between 48% and 53% (Figure 1). Proportion of seizure-free patients per 12 week interval increased over time, from 8.7% (weeks 5-16) to 12.5% (weeks 41-52). The mean (median) number of days with seizures in the baseline period was 8.0 (5.9) and decreased to 5.2 (3.9) during the first 4 weeks of Part II. It continued to decrease over the course of the 52 weeks of treatment to 4.6 (3.0). Conclusions: Adjunctive therapy with ESL proved to be safe and well tolerated, and resulted in a marked and sustained decrease in seizure frequency over a 1-year open-label treatment period. Supported by BIAL- Portela & Co, SA