Abstracts

Rationale: Eslicarbazepine acetate (ESL) is approved by EMA and FDA as adjunctive therapy for the treatment of partial-onset seizures (POS). Given the efficacy of ESL in controlling POS as adjunctive therapy, and the demonstrated safety, ESL may represent an alternative as a first-line therapy in monotherapy. This phase-III, randomized, double-blind, active-controlled, non-inferiority study aims to demonstrate the efficacy and safety of ESL once-daily as monotherapy treatment for newly diagnosed adults with POS in comparison to controlled-release carbamazepine (CBZ-CR) twice-daily (BID).Methods: Patients (≥18 years) newly diagnosed with ≥2 unprovoked seizures in the past year and ≥1 in the last 3-months before enrolment were randomized in a 1:1 ratio to receive either ESL QD or CBZ-CR BID in a 3-step dose level study design (Figure 1). After 1-week Titration Period (TP), during which subjects received either ESL 400mg QD or CBZ-CR 200mg QD, the first target dose level (Dose-level A) of ESL 800mg QD or CBZ-CR 200mg BID was established and maintained through a 26-week Evaluation Period (EP). Subjects who experienced a seizure during the EP increased to Dose-level B, reached by a 1-week TP to ESL 1200mg QD or CBZ-CR 300mg BID before the target of ESL 1200mg QD or CBZ-CR 400mg BID (maintained through a 26-week EP). Subjects who had another seizure during EP at Dose-level B increased to Dose-level C, reached by a 1-week TP to ESL 1600mg QD or CBZ-CR 500mg BID before the target of ESL 1600mg QD or CBZ-CR 600mg BID (maintained through a 26-week EP). Subjects who remain seizure free during the 26-week EP at any dose level continue through a Maintenance Period and a subsequent Extension Phase. The primary endpoint is seizure freedom in the 26-week EP at the last received dose level. The sample size was calculated to achieve a ≥90% power to establish non-inferiority compared to CBZ-CR, using a -12% margin. Secondary endpoints include tolerability, QOLIE-31, sedation and clinical laboratory assessments.Results: The study is currently ongoing with an expected completion by mid-2015. Overall, from the 984 patients screened 815 were randomized. As of May 2015, 591 (72.5%) patients are at Dose-level A (ESL 800mg QD or CBZ-CR 200mg BID), 130 (16%) at Dose-level B (ESL 1200mg QD or CBZ-CR 400mg BID) and 94 (11.5%) patients at Dose-level C (ESL 1600mg QD or CBZ-CR 600mg BID).Conclusions: This study will focus in demonstrating ESL non-inferiority versus a gold standard (CBZ-CR) as a monotherapy treatment. Sponsored by BIAL-Portela & Cª S.A.