Abstracts

Rationale: Eslicarbazepine acetate (ESL) is a novel voltage-gated sodium channel blocker. In two double-blind, adjunct Phase III studies of ESL in subjects with partial-onset seizures, levetiracetam (LEV) was identified as one of the most commonly used concomitant antiepileptic drugs in the study population. To gain an understanding of the efficacy, as well as the nature and risk of Treatment-Emergent Adverse Events (TEAEs) associated with the use of ESL in combination with LEV, a sub-analysis by baseline LEV use was conducted for the double-blind portion of these studies (2093-301 and 2093-302). Methods: For the efficacy analysis we studied randomized subjects (N=790) who received at least 1 dose of study medication (400 mg, 800 mg, or 1200 mg of ESL or placebo), and who had at least 1 post-baseline seizure frequency assessment during the double-blind portion of these studies. The primary efficacy variable was standardized seizure frequency per 4 weeks over the maintenance period, defined as the total number of seizures reported in the diary during the maintenance period divided by the duration of the period, standardized to 28 days. It was evaluated using analysis of covariance (ANCOVA) that modeled standardized seizure frequency as a function of baseline seizure frequency and treatment. For the safety analysis we studied all (N=797) subjects who received at least 1 dose of study medication during the double-blind portion of these studies. The Investigator recorded AEs at each visit from Visit 1 and throughout the study (including at early discontinuation and at the post study visit). A TEAE was defined as an event that occurred on or after the date of first dose, or the date of randomization if the date of the first dose was missing or incomplete. Results: Of the 790 subjects included in the efficacy analysis, 96 (12.1%) used concomitant LEV. The LS mean difference from placebo in standardized seizure frequency in LEV subjects was 2.9 (p=0.13), 3.2 (p=0.08), and 2.7 (p=0.14) for the 400-, 800-, and 1200-mg ESL groups, compared to 0.6 (p=0.68), 2.0 (p=0.0008), and 2.2 (p=0.0002), respectively in 694 subjects without LEV use. In the safety analysis of 797 subjects, 98 (12.3%) had LEV use. The most common TEAEs seen in the sub-groups with and without LEV use are listed in Table 1. Conclusions: In this exploratory analysis, the change from baseline in seizure frequency was numerically similar between subjects taking eslicarbazepine acetate concomitantly with LEV and subjects not taking LEV. The small number of subjects taking eslicarbazepine acetate concomitantly with LEV limited the power of this sub-group analysis.