Abstracts

Rationale: Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED) for partial-onset (focal) seizures (POS). Reductions from baseline in sodium, free thyroxine (T4) and free triiodothyronine (T3) have previously been reported in some patients taking ESL. Concomitant use of certain AEDs could influence ESL-induced changes in sodium and thyroid hormone levels. This exploratory post-hoc analysis of data pooled from three Phase III trials compares changes in sodium and thyroid hormone levels during treatment with adjunctive ESL, between patients taking, or not taking, specific concomitant AEDs. Methods: Plasma sodium and serum thyroid hormone (free T3 and T4) levels were assessed during three double-blind, Phase III studies of adjunctive ESL (BIA-2093-301, -302 and -304). After an 8-week baseline period, adults with =4 POS/month, taking 1–3 AEDs were randomized equally to receive placebo or ESL 400 mg (studies 301/302 only), 800 mg or 1200 mg QD (2-week titration; 12-week maintenance). Patients continued to receive stable doses of AEDs during the studies. This analysis evaluates sodium, free T3, and free T4 levels according to concomitant use of carbamazepine (CBZ), lamotrigine (LTG), valproic acid (VPA), and levetiracetam (LEV) (the most frequently used AEDs during the trials). Results: The pooled safety population (all patients who received =1 dose of study drug) comprised 1447 patients (ESL, n = 1021; placebo, n = 426); >70% of patients were taking =2 baseline AEDs. Mean changes in sodium level between baseline and end of study were =1.2 mEq/L in all patient subgroups (i.e., in patients taking ESL or placebo +/-CBZ, LTG, VPA and LEV), and so were not clinically meaningful (decreases >10 mEq/L within 12 weeks are generally considered to be clinically meaningful). The proportions of patients with >10 mEq/L decrease in sodium between baseline and end of study were higher for ESL than for placebo, irrespective of baseline AED use, as were the proportions with minimum post-dose sodium levels =125 mEq/L (Table 1). Larger reductions in free T3 between baseline and end of study were apparent for ESL than for placebo, irrespective of concomitant AED use; the magnitude of the reductions differed slightly with specific AEDs (Table 2). Reductions in free T4 levels between baseline and end of study were small (=0.1 ng/dL) in all patient subgroups. Conclusions: Clinically meaningful post-dose sodium levels (=125 mEq/L) and decreases in sodium levels (>10 mEq/L) between baseline and end of study were more frequent in patients taking ESL than in those taking placebo, irrespective of concomitant AED use. ESL use was also associated with larger reductions in free T3 levels between baseline and end of study, compared with placebo. Decreases in free T3 were observed irrespective of concomitant AED use; however, these decreases appeared to be greater in the presence of LTG and LEV and smaller in the presence of CBZ and VPA than in the absence of these AEDs. Funding: Studies sponsored by Sunovion Pharmaceuticals Inc.