Analysis of Indices of Thyroid Function with Short- and Long-term Use of Eslicarbazepine Acetate as Adjunctive and Monotherapy (P3.245)

Objective: To evaluate the effect of eslicarbazepine acetate (ESL) treatment on indices of thyroid function. Background: ESL is a once-daily oral antiepileptic drug (AED) for the treatment of partial-onset seizures (POS). The USA prescribing information for ESL states that decreases in serum thyroid hormones have been observed with ESL use. Design/Methods: Treatment-emergent adverse event (TEAE) 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 ESL dosing and introduction of other AEDs. Results: Of 1812 patients in the analysis population of the controlled studies (adjunctive ESL, 1021; placebo, 426; ESL monotherapy, 365), 913 continued into OLEs (adjunctive ESL, 639; ESL monotherapy, 274). Thyroid dysfunction-related TEAEs were reported for 0–1.5% of the ESL group and 0–0.7% of the placebo group; no serious TEAEs and only one TEAE leading to treatment discontinuation (controlled trial, 1200 mg adjunctive ESL) were reported. Decreases in T3 and T4, and potentially clinically relevant changes in indices of thyroid function occurred in some patients. Conclusions: Decreases in serum free T3 and T4 between baseline and end of study/early termination were reported for some patients taking ESL, but were not associated with other results suggestive of hypothyroidism. Thyroid dysfunction-related TEAEs were reported for some patients. Patients with abnormal thyroid function test results should be clinically evaluated. Study Supported by: Sunovion Pharmaceuticals Inc. Disclosure: Dr. Alexopoulos has received personal compensation for activities with Eisai and Neuropace as a speaker and/or advisory board member. Dr. Gidal has received personal compensation for activities with UCB, Eisai, and Sunovion for speaking engagements. Dr. Gidal has received personal compensation from UCB, Eisai, Sunovion, Upsher-Smith, Lundbeck LLC, and SK-Bioscience as a consultant. Dr. Ben-Menachem has received personal compensation for activities with Bial, Eisai, UCB Pharma, and Abbott as a consultant and/or advisory board member. Dr. Ben-Menachem has received research support from Bial, Eisai, and UCB Pharma. Dr. Biraben has received personal compensation for activities with Eisai. Dr. Biraben has received research support from Eisai. Employee of BIAL - Portela & Ca, S.A.. Dr. Moreira has received personal compensation for activities with BIAL as an employee. Dr. Rocha has received personal compensation for activities with Bial - Portela & Ca as an employee. Dr. Rocha has received research support from Eisai, Marinus, Pfizer, Sunovion, and UCB Dr. Cheng has received personal compensation for activities with Sunovian Pharmaceuticals, Inc. as an employee. Dr. Grinnell has received personal compensation for activities with Sunovion Pharmaceuticals as an employee. Employee of Sunovion Pharmaceuticals Inc..