Abstracts

Rationale: Treatment emergent adverse events (TEAEs) commonly occur during initiation and titration of antiepileptic drug (AED) therapy.¹ Eslicarbazepine acetate (ESL) is a novel once-daily (QD) AED approved in Europe as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization, and has been submitted to the US Food and Drug Administration for review. The purpose of this analysis is to review timing and incidence of AEs with this agent.Methods: We studied subjects (N=790) in the intent-to-treat population from two studies who received at least 1 dose of study medication (ESL 400 mg QD, 800 mg QD, 1200 mg QD or placebo) added to1-3 concomitant AEDs, Using integrated data from two double-blind placebo-controlled trials in which adult subjects . ESL was titrated per protocol and no dose adjustments in any AED were permitted in response to TEAEs. The weekly incidence and time to onset of AEs were calculated for patients completing the titration and maintenance periods (14 weeks). Though similar in overall design, the studies analyzed had different titration schedules and starting doses (Figure 1).Results: The most common TEAEs in the first two weeks of treatment with ESL were dizziness, headache, somnolence, diplopia, and nausea. In each dose group, approximately 30% of all TEAEs occurred during the first week and the incidence declined in later weeks (Figure 2). After 4 weeks of treatment the incidence of new TEAEs appeared similar in the active and placebo treatment groups (Figure 2).Conclusions: In this analysis, there appeared to be a dose related relationship in frequency of TEAEs during the initial 4-weeks of treatment, but time of onset of TEAEs was similar across treatment groups. Based on these results, TEAEs were most likely to begin during the initiation of therapy; thereafter the incidence of new events appeared similar between ESL and placebo. The limitations of this analysis include it was conducted post-hoc without formal statistical testing, and the TEAEs were not evaluated by severity. Studies supported by BIAL-Portela; analysis by Sunovion. Reference: 1. Majkowski J, Neto W, Wapenaar R, Van Oene J. Time course of adverse events in patients with localization-related epilepsy receiving topiramate added to carbamazepine. Epilepsia. 2005;46:648-653.