Sodium and Thyroid Hormone Levels During Phase III Trials of Adjunctive Eslicarbazepine Acetate (ESL), According to Concomitant Antiepileptic Drug (AED) Use (P5.271)

Objective: To evaluate changes in sodium and thyroid hormone levels during treatment with adjunctive ESL, according to concomitant AED use. Background: ESL is a once-daily oral AED for partial-onset (focal) seizures (POS). Reductions in plasma sodium, serum free thyroxine (FT4), and free triiodothyronine (FT3) have been reported in patients taking ESL, and may be influenced by concomitant AED use. Design/Methods: Data from three double-blind, Phase III trials of ESL (BIA-2093-301, -302, and -304) were pooled. After an 8-week baseline, adults with ≥4 POS/month, taking 1–3 AEDs, were randomized equally to placebo (n=426) or ESL (n=1021); 2-week titration, 12-week maintenance. Plasma sodium and serum FT3/FT4 analyses were conducted using the pooled safety population (all patients who received ≥1 dose of study drug), stratified by concomitant AED use (carbamazepine, lamotrigine, valproic acid, and levetiracetam). Minimum post-dose sodium levels ≤125mEq/L, or decreases >10mEq/L, were considered clinically meaningful. Results: Over 70% of 1447 patients were taking ≥2 baseline AEDs. Mean changes in sodium levels were not clinically meaningful (≤1.2mEq/L in each AED subgroup). The proportion of patients with >10mEq/L decreases or minimum post-dose sodium levels ≤125mEq/L was higher with ESL (4.3–7.1% and 0–1.4%, respectively) than placebo (0–1.5% and 0), irrespective of AED use. Larger changes in serum FT3 levels from baseline occurred with ESL (−20.75 to −5.65pg/dL) versus placebo (−1.20 to 3.79pg/dL); reductions with ESL were more marked in patients taking concomitant levetiracetam (−20.75pg/dL) and lamotrigine (−18.72pg/dL), than carbamazepine (−8.50pg/dL) and valproic acid (−5.65pg/dL). Mean changes in serum FT4 levels from baseline were small (≤0.1ng/dL) in all subgroups. Conclusions: Clinically meaningful post-dose sodium levels/reductions were more frequent with ESL than placebo, irrespective of concomitant AED use. Reductions in FT3 were greater with ESL than placebo; greater reductions occurred in the presence of lamotrigine and levetiracetam than carbamazepine and valproic acid. Study Supported by: BIAL and Sunovion Pharmaceuticals Inc. Disclosure: Dr. Trinka has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with UCB, Eisai, Novartis, Gerrot-Lannach, BIAL, Takeda, Biogen, Newbridge, Sunovion. Dr. Bensalem Owen has nothing to disclose. Dr. Grinnell has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employment: Sunovion Pharmaceuticals Inc. Dr. Cantu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employment: Sunovion Pharmaceuticals Inc. Dr. Graca has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employment: BIAL - Portela & Ca, S.A. Dr. Moreira has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with BIAL — Portela & Ca., S.A. Dr. Cheng has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employment: Sunovion Pharmaceuticals Inc. Dr. Blum has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employment: Sunovion Pharmaceuticals Inc.