Bioequivalence of Eslicarbazepine Acetate from Two Different Sources of its Active Product Ingredient in Healthy Subjects

Abstract

Purpose To compare the bioavailability (BA) and pharmacokinetic (PK) properties and to demonstrate the bioequivalence (BE) between two active product ingredient (API) sources of eslicarbazepine acetate (ESL) in healthy volunteers. Design, subjects and methods Forty healthy male and female subjects aged 18-40 years were randomized to treatment with 400 or 800 mg ESL marketed (MF) formulation [current active pharmaceutical ingredient (API) source] and 400 or 800 mg ESL to-be-marketed (TBM) formulation (new API source) under a gender-balanced, two-period, two-sequence crossover open-label study design. Subjects were assigned to receive either 400 or 800 mg ESL dose strengths, and each was randomly administered on two occasions-either a single oral tablet of MF or a single oral tablet of TBM-separated by a washout period of at least 7 days. Formulations were to be considered bioequivalent if, for both 400 or 800 mg ESL dosage strengths, the test (TBM)/reference (MF) geometric mean ratios (GMR) and 90 % confidence intervals (90 % CI) of the area under the plasma concentration-time curve (AUC) and peak plasma concentration (C max ) were within the predetermined range of 80-125 %. Results Test/reference GMR (90 % CI) for the C max and AUC was respectively 100 % (94-109 %) and 96 % (94-98 %) following 400 mg ESL and 100 % (95-105 %) and 100 % (97-103 %) following 800 mg ESL. Conclusion Oral tablet formulations of either 400 or 800 mg ESL from the new API source were found to be bioequivalent to the corresponding marketed Zebinix Ò formulation according to the regulatory definition of bioequivalence.

Modeling and simulations to support dose selection for eslicarbazepine acetate therapy in pediatric patients with partial-onset seizures

“…Nevertheless, C max at the highest approved adult ESL maintenance dose (1600 mg) was considered in setting the upper limit of the targeted exposure range. The proposed doses for subjects aged 4–17 years apply to those taking ESL as an intact tablet, as a crushed tablet, or as an oral suspension, as previous clinical investigations have demonstrated the bioequivalence of these formulations [ 24 – 26 ].…”