Abstracts

Rationale: Eslicarbazepine acetate (ESL) is a novel once-daily voltage-gated sodium channel (VGSC) blocker chemically related to carbamazepine. Differences in ESL metabolism explain a reduced potential for hepatic enzyme induction. Carbamazepine is a potent inducer of P450 enzymes, which has been associated with increases in total cholesterol (TC) and various lipid fractions, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and serum triglycerides (TRIG).^1-6 To gain an understanding of the nature and risks of increases in TC and other lipid fractions when using ESL as an adjunctive antiepileptic drug (AED), lipid parameter values were analyzed in subjects taking ESL compared with placebo as adjunct therapy to 1-3 concomitant AEDs (oxcarbazepine was not allowed) in the pooled data of 3 Phase III studies. Methods: The safety population (N=1049) was defined as all subjects who received at least 1 dose of study medication (400 mg, 800 mg or 1200 mg of ESL or placebo). The incidence of sponsor-defined potentially clinically significant (PCS) values was analyzed by treatment group. PCS values were defined as >300 mg/dL for TC; >160 mg/dL for LDL-C; <30 mg/dL for HDL-C; and >2.5 x ULN for TRIG. TC related adverse events (AEs) and mean changes from baseline were also calculated for each treatment group. Results: PCS incidences for each treatment group are summarized in Table 1 below. Mean changes from baseline to end of the double-blind period for each treatment group are shown in Figure 1. The incidence of TC related AEs in the ESL treatment groups was similar to placebo. Conclusions: In this pooled analysis of 3 Phase III studies, no consistent pattern of PCS values was observed for TC, LDL-C, HDL-C, or TRIG across the treatment groups. No clinically significant mean changes from baseline were observed. The incidence of AEs related to serum lipids was similar between the ESL and placebo treatment groups. 1.Bramswig S, et al. Lipoprotein(a) concentrations increases during treatment with carbamazepine. Epilepsia. 2003;44:457-460. 2.Nikolaos T, et al. The effect of long-term antiepileptic treatment on serum cholesterol (TC, HDL, LDL) and triglyceride levels in adult epileptic patients on monotherapy. Med Sci Monit. 2004;10:MT50-MT52. 3.Calandre EP, et al. Serum lipids, lipoproteins and apolipoproteins A and B in epileptic patients treated with valproic acid, carbamazepine or phenobarbital. Acta Neurol Scand. 1991;83:250-253. 4.Eiris JM, et al. Effects of long-term treatment with anti-epileptic drugs on serum levels in children with epilepsy. Neurology. 1995;45:1155-1157. 5.Verrotti A, et al. Changes in serum lipids and lipoproteins in epileptic children treated with anticonvulsants. J Paediatr Child Health. 1997;33:242-245. 6.Sonmez FM, et al. Effect of antiepileptic drugs on plasma lipids, lipoprotein (a), and liver enzymes. J Child Neurol. 2006;21:70-74.