Abstracts

Rationale: Eslicarbazepine acetate (ESL) is a novel once-daily voltage-gated sodium channel (VGSC) blocker. A QTc study of ESL in healthy volunteers (Study 2093-116)¹ had previously been conducted to evaluate the potential effect of ESL on cardiac repolarization, and demonstrated no effect of ESL on QTc. To further evaluate the effects of ESL on ECG parameters in patients, 12 lead electrocardiograms (ECGs) were evaluated at screening, study baseline, and Week 14 of treatment during Part I of the 3 Phase III studies of ESL as adjunct treatment to 1-3 other AEDs (OXC was not allowed) in subjects with partial epilepsy at doses between 400 and 1200 mg. Methods: ECGs were over-read by a central vendor. A cardiologist over-read each ECG manually using handheld Vernier calipers on the original ECG paper tracing. Over-reads were attempted on 5532 ECGs. The ECG parameters analyzed included ventricular heart rate, QT interval, PR interval, QRS duration, RR interval, and QTc intervals corrected by Bazett (QTc-B) and Fridericia (QTc-F). The incidence of sponsor-defined potentially clinically significant (PCS) values was analyzed by treatment group, and mean changes from baseline were also calculated for each treatment group. Results: Of the 5532 ECGs, 82% (n=4541) were successfully over-read. Mean changes from baseline to Treatment week 14 for each ECG parameter were small, similar to those observed in the placebo group, and not clinically relevant in all treatment groups (Table 1). The placebo and ESL groups had similar incidences for each postdose ECG abnormality. The placebo and ESL groups had similar incidences for each PCS ECG abnormality (Table 2). The incidence of each PCS abnormality did not exceed 1% in any treatment group. No subject in the active treatment groups had a QTc interval (QTc-B or QTc-F) that exceeded 500 ms. Conclusions: In this pooled analysis of 3 Phase III studies, no clinically relevant ECG abnormalities were observed in association with ESL treatment. There was no relevant trend toward changes in heart rate or prolongation of ECG intervals. No clinically significant prolongations of the QTc intervals were seen in any subject despite “real-use” conditions with use of concomitant medications, including 1 to 3 AEDs. These findings are consistent with the results of the earlier ESL QTc study.^{1 1}1.Almeida L, et al. A randomized, double-blind, placebo- and moxifloxacin-controlled, 4 period crossover trial to evaluate the effect of eslicarbazepine acetate on cardiac repolorization in healthy subjects. Poster presented at the European Congress on Epileptology. September 21-25, 2008; Berlin, Germany. Epilepsia. 2008;50 (Suppl 4): 104 (abstract T210).