Abstracts

Rationale: Eslicarbazepine acetate (ESL) is a once-daily (QD), oral antiepileptic drug (AED) for focal (partial-onset) seizures in patients aged ≥4 years. Epilepsy is a heterogeneous disease; it is therefore important to understand the profile of ESL across epilepsy etiologies. Here we report the safety and efficacy of ESL (800 and 1200 mg) as adjunctive therapy in adults with focal seizures, according to epilepsy etiology at baseline. Methods: This post-hoc analysis evaluated data pooled from three Phase III, randomized, double-blind, placebo-controlled trials (2093-301, -302, -304). After an 8-week baseline period, adults with ≥4 focal seizures/month and taking 1–3 AEDs were randomized equally to receive placebo, ESL 400 mg (Studies 301 and 302 only; not reported here), ESL 800 mg or ESL 1200 mg QD (2-week titration; 12-week maintenance). Standardized seizure frequency (SSF), responder rates (response defined as a ≥50% reduction from baseline in SSF), treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), TEAEs leading to ESL discontinuation, cognitive TEAEs, and psychiatric TEAEs were analyzed according to epilepsy etiology, characterized on the basis of medical history interviews conducted at screening: congenital/hereditary disorders, cranial trauma/injuries, idiopathic, infectious diseases, and other/unknown. Results: Epilepsy etiology categories (safety/efficacy analysis populations) included: other/unknown (n=526/520), idiopathic (n=255/239), cranial trauma/injuries (n=166/164), congenital/hereditary disorders (n=109/106), and infectious diseases (n=105/104). Responder rates were consistently higher with ESL versus placebo across categories (Table 1). Responder rates were higher with ESL 1200 mg versus 800 mg for all etiologies except congenital/hereditary disorders. Patients with infectious disease and cranial trauma/injuries etiologies had the highest responder rates with ESL 1200 mg (58.3% and 46.3%, respectively); patients with congenital/hereditary disorders had the lowest (29.0%). TEAE incidences were higher with ESL than placebo across etiologies (except for ESL 800 mg in patients with epilepsy due to infectious disease), but were generally similar between ESL doses. SAEs occurred in <10% of patients in most groups; incidences did not appear to be dose-dependent and were generally similar between ESL and placebo. Incidences of TEAEs leading to ESL discontinuation were dose-dependent. TEAEs leading to ESL discontinuation and psychiatric TEAEs were most frequent in patients with congenital/hereditary disorders receiving ESL 1200 mg. Conclusions: The efficacy of ESL was generally comparable between patients with different epilepsy etiologies (responder rates: 23–58%). Responder rates were higher with ESL than placebo and were related to dose. Responder rates were highest in patients with epilepsy caused by infectious disease and cranial trauma/injuries, and lowest in those with congenital/hereditary disorders. Incidences of TEAEs leading to ESL discontinuation were dose-dependent. TEAEs leading to ESL discontinuation and psychiatric TEAEs occurred most frequently in patients with congenital/hereditary disorders. Funding: Studies funded by BIAL and Sunovion Pharmaceuticals Inc.; analyses funded by Sunovion Pharmaceuticals Inc.