Abstracts

Rationale: Eslicarbazepine acetate (ESL) is a once-daily, oral antiepileptic drug (AED) for focal (partial-onset) seizures. Here, we report an analysis of long-term safety and tolerability data pooled from two open-label extension (OLE) studies of adjunctive treatment with ESL in pediatric patients with focal seizures. Methods: Safety data from patients aged 4−17 years in OLEs of studies 2093-208 and -305 were pooled and analyzed. Studies 208-Part 1 and 305-Part 1 were randomized, double-blind, placebo-controlled studies of adjunctive treatment with ESL in pediatric patients with focal seizures refractory to treatment with 1-2 AEDs; patients could continue into uncontrolled OLEs (up to 5 years total duration). The OLEs evaluated safety and tolerability of ESL (10−30 mg/kg/day; maximum 1200 mg/day). Incidences of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and TEAEs leading to discontinuation were evaluated. Results: The 1-year OLE and post-1-year OLE safety populations (patients aged 4-17 years who received >=1 dose of study drug in Study 208 or 305) comprised 337 and 177 ESL-treated patients, respectively. The overall incidence of TEAEs with ESL was 64.1% during the 1-year OLE and 52.5% during the post-1-year OLE (Table 1). Nasopharyngitis, partial seizures, vomiting, pyrexia, headache, somnolence, and respiratory tract infection were the most frequently reported TEAEs during the 1-year OLE. The overall incidence of SAEs was 8.9% during the 1-year OLE and 10.2% during the post-1-year OLE (Table 2). Partial seizures (1.2%) and pneumonia (1.2%) were the most frequently reported SAEs during the 1-year OLE. The overall incidence of TEAEs leading to discontinuation was 4.2% during the 1-year OLE and 0.6% during the post-1-year OLE (Table 2). Partial seizures (1.5%) was the most frequently reported TEAE leading to discontinuation during the 1-year OLE. Allergic reaction TEAEs were reported in 2.4% of patients during the 1-year OLE and 0.6% of patients during the post-1-year OLE; there were no cases of drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome, or toxic epidermal necrolysis. Hypothyroidism (1-year OLE, 0.9%; post-1-year OLE, 1.1%) and hyponatremia (1-year OLE, 0.3%; post-1-year OLE, 0.6%) were reported infrequently. Conclusions: Overall, long-term treatment with ESL was generally well tolerated in pediatric patients aged 4-17 years with focal seizures. Funding: Studies funded by BIAL; analyses funded by Sunovion Pharmaceuticals Inc.