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

ABSTRACT

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 400mg (studies 301, 302), 800mg, or 1200mg QD. The primary endpoint was standardized seizure frequency (SSF; per 4weeks); 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 800mg (p=0.0001) and 1200mg (p<0.0001) but not 400mg (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 800mg QD, regardless of titration regimen and maintenance dose. SAE incidence was <10%; there were 3 deaths (placebo, n=2; ESL 800mg, n=1). CONCLUSIONS: ESL (800 and 1200mg QD) was effective and well tolerated as adjunctive therapy for adults with refractory POS.