Adjunctive eslicarbazepine acetate: A pooled analysis of three phase III trials

Objective To assess the safety and efficacy of once-daily (QD) adjunctive eslicarbazepine acetate (ESL). Methods This post-hoc pooled analysis of three randomized, placebo-controlled trials (2093-301, -302, -304) involved adults with refractory partial-onset seizures (POS) receiving 1–3 antiepileptic drugs (AEDs). All studies included 8-week baseline, 2-week titration, and 12-week maintenance periods. Patients were randomized equally to placebo, ESL 400 mg (studies 301, 302), 800 mg, or 1200 mg QD. The primary endpoint was standardized seizure frequency (SSF; per 4 weeks); secondary endpoints included responder rates (maintenance period), and incidence of treatment-emergent adverse events (TEAEs), TEAEs leading to discontinuation, serious AEs (SAEs), and deaths. Results The safety and efficacy analysis populations totaled 1447 and 1410 patients, respectively. SSF was significantly reduced versus placebo with ESL 800 mg (p = 0.0001) and 1200 mg (p < 0.0001) but not 400 mg (p = 0.81). There were no significant interactions between treatment effect and age, gender, race/ethnicity, geographic region, epilepsy duration, or concomitant AED use. Incidences of TEAEs and TEAEs leading to discontinuation increased with ESL dose. Incidences of the most frequent TEAEs were lower for patients who initiated dosing at 400 versus 800 mg QD, regardless of titration regimen and maintenance dose. SAE incidence was < 10%; there were 3 deaths (placebo, n = 2; ESL 800 mg, n = 1). Conclusions ESL (800 and 1200 mg QD) was effective and well tolerated as adjunctive therapy for adults with refractory POS.