Abstracts

Rationale: The USA prescribing information for eslicarbazepine acetate (ESL) states that decreases in serum thyroid hormones have been observed with ESL use. Therefore, in this analysis we evaluate the effect of ESL treatment on indices of thyroid function across all Phase III clinical trials of ESL. ESL is a once-daily oral antiepileptic drug (AED) approved as adjunctive treatment for partial-onset seizures (POS) in the USA, Europe, and Canada, and as monotherapy for POS in the USA. Methods: Adverse event data and blood samples were collected during clinic visits in Phase III studies of ESL in patients with treatment-refractory POS. Serum concentrations of triiodothyronine (T3) and thyroxine (T4) were measured at baseline and end of study/early termination in the following trials: three 14-week double-blind adjunctive ESL trials (2093-301, -302, -304) and the uncontrolled open-label extensions (OLEs) of studies 301 and 302; two dose-blind 18-week conversion-to-monotherapy trials (093-045, -046) and the associated OLE (093-050). OLEs allowed flexible dosing of ESL and introduction of other AEDs. Results: There were 1812 patients in the analysis population for the controlled studies (adjunctive: ESL, n = 1021 and placebo, n = 426; monotherapy: ESL, n = 365); 913 continued into the uncontrolled OLEs (adjunctive: n = 639; monotherapy: n = 274). Thyroid dysfunction-related treatment emergent adverse events (TEAEs) were reported for a small proportion of patients (Table 1), of which only one led to treatment discontinuation (ESL 1200 mg group, controlled adjunctive ESL trials), and there were no reports of serious TEAEs related to thyroid dysfunction. Decreases in free T3 and T4 from baseline, and potentially clinically relevant changes in indices of thyroid function (free T3 < 0.2 ng/dL; free T3 >