Efficacy of Eslicarbazepine Acetate by Type of Concomitantly Used AEDs: An Exploratory Integrated Analysis of Two Phase III Studies (P06.105)

Abstract

Objective: It is not known if the efficacy of adjunct eslicarbazepine acetate (ESL) varies based on concomitant antiepileptic drug (con-AED). Background Eslicarbazepine acetate (ESL) is a novel voltage-gated sodium channel blocker not approved for use in the United States. Two double-blind, placebo-controlled Phase III studies evaluated ESL once-daily (QD) as adjunct therapy in patients with partial-onset seizures. Design/Methods: We studied subjects (N=790) in the intent-to-treat population 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, and had at least 1 post-dose seizure assessment in the two studies. An exploratory analysis on the impact of con-AEDs on efficacy was conducted for the double-blind portion of these studies. Log-transformed standardized seizure frequency per 4 weeks over the 12-week maintenance period was analyzed using ANCOVA model with fixed effects for treatment, study, baseline standardized seizure frequency and number of con-AEDs, and interaction of treatment with the 4 most commonly used con-AEDs. Results: The most commonly used con-AEDs were carbamazepine (58.7%), lamotrigine (23.5%), valproic acid (23.5%), and topiramate (16.7%). ESL 800 and 1200 mg QD significantly reduced seizure frequency compared to placebo. There was no significant interaction between type of con-AED and treatment effect. Conclusions: Adjunct treatment with ESL 800 and 1200 mg QD had a consistent effect in reducing seizure frequency compared to placebo independent of type of con-AEDs. The limitation of these analyses was that patients may have been on more than a single con-AED and the impact of these combinations could not be assessed. Supported by: BIAL-Portela & Ca, SA. Data analysis and editorial support provided by Sunovion Pharmaceuticals, Inc., Marlborough, MA. Disclosure: Dr. Versavel has received personal compensation for activities with Sunovion Pharmaceuticals Inc. as an employee. Dr. Cheng has received personal compensation for activities with Sunovion Pharmaceuticals, Inc. Dr. Blum has received personal compensation for activities with Sunovion Pharmaceuticals Inc as an emplyee. Dr. Blum holds stock and/or stock options in GlaxoSmithKline, which sponosred research in which Dr. Blum was involved as an investigator. Ms. Zummo has received personal compensation for activities with Sunovion Pharmaceuticals Inc. Dr. Nunes has received personal compensation for activities with BIAL as an employee. Dr. Soares da Silva has received personal compensaiton for activities with Bial-Portela & Co., S.A. as an employee.