Abstracts

Rationale: Eslicarbazepine acetate (ESL) and carbamazepine (CBZ) share the same basic mechanism of action - voltage-gated sodium channels blockade - but antiepileptic drugs (AEDs) are usually combined mainly on empirical grounds rather than on basis of different mechanisms of action. Hence, rationale was not to exclude CBZ from concomitant AEDs in 3 pivotal Phase III studies with ESL as adjunct therapy in subjects with partial-onset seizures. To gain an understanding on efficacy and safety of ESL when combined with CBZ, an evaluation was performed in subjects taking ESL/Placebo as add-on to CBZ. Methods: ESL was tested in the 3 pivotal Phase III add-on studies in 1049 adults treated with 1-3 AEDs; subjects were randomized to treatment with once-daily ESL (400mg, 800mg, 1200mg) or placebo for 12 weeks. Of the 1049 subjects, 611 (58%) received CBZ as a concomitant AED. Standardized seizure frequency, responder rate (a decrease in seizure frequency ≥50% relative to baseline) and relative reduction in seizure frequency were evaluated as efficacy variables. Results: The analysis of covariance (ANCOVA) of seizure frequency over the 12-week maintenance period showed similar dose-dependent decrease in seizure frequency in the overall population and in CBZ-treated subjects; difference from placebo was statistically significant for 800mg and 1200mg ESL groups in overall population and subjects treated with CBZ. Similarly, responder rate(Table I) and relative reduction in seizure frequency (Table II) presented similar results for overall population as for subjects treated with CBZ. Both responder rate and relative reduction in seizure frequency were significantly greater in ESL 800mg and 1200mg groups than in placebo group in overall and in CBZ-treated subjects. The incidence of subjects with at least 1 treatment-emergent adverse event (TEAE) was higher for those with concomitant CBZ (placebo: 50.3% with and 39.8% without CBZ, respectively, and total ESL: 70.9% and 54.8%, respectively). In both placebo and total ESL groups, subjects with concomitant CBZ generally had higher incidence of common TEAEs than subjects without CBZ, except for somnolence in the total ESL group, where CBZ subjects had a slightly lower incidence than those without CBZ (12.3% and 14.2%, respectively). For total ESL treated subjects, diplopia, dizziness, and nausea occurred with more than twice the frequency in subjects with concomitant CBZ compared to subjects without CBZ. Placebo treated subjects with concomitant CBZ had more than twice the frequency of nausea and vomiting than subjects without CBZ. Conclusions: In this pooled analysis of 3 Phase III studies, ESL showed to be an effective adjunct therapy to CBZ. Concomitant administration of CBZ increased the incidence of dizziness, diplopia, and nausea. By using ESL in addition to CBZ, it is possible to enhance efficacy without dramatically increasing the level of side effects. There is therefore evidence to support the use of ESL as adjunctive therapy with CBZ. Supported by BIAL- Portela & Co, SA