Oxcarbazepine final market image tablet formulation bioequivalence study after single administration and at steady state in healthy subjects.

A final market image (FMI) tablet formulation of oxcarbazepine was compared with the marketed formulation (current market formulation (CMF)) and with the clinical trial formulation (CTF) tablet used during clinical efficacy and safety studies. The goal of the study was to compare the bioavailability after single doses and at steady state of the FMI versus CMF and CTF as well. Additionally, the effect of food was evaluated on the final market formulation. The study was an open-label, single-center, 4-way crossover trial. Each treatment period consisted of a single dose of 600 mg OXC on Day 1. From Day 4 up to including Day 7, 600 mg b.i.d. were administered. A final dose of 600 mg was administered in the morning on Day 8. Blood samples were taken on Day 1 before and on Day 7 (predose) and on Day 8 (morning dose). Plasma concentrations of MHD (the main metabolite of OXC) were determined by using a validated HPLC assay. FMI as test formulation was compared with the CMF and CTF as reference formulations. FMI under fed conditions was also compared with FMI under fasting conditions. These comparisons were made using data following single-dose administration and steady state conditions. Plasma AUC for single dose or AUC(0-12h) for steady state, and plasma Cmax, log-transformed (natural base), were used for the assessment of bioequivalence. The 90% confidence interval (CI) approach was used for testing bioequivalence. Bioequivalence was accepted if the CI was contained within the region (0.8, 1.25). At steady state under fed conditions, tested formulation (FMI) was bioequivalent to CTF and with the reference marketed formulation (CMF) with regard to AUC and Cmax. After single dose under fed conditions, FMI and CTF were bioequivalent with regard to AUC and Cmax, and FMI and CMF were equivalent with regard to AUC but not Cmax. Food had no effect on the bioavailability of the FMI. These results clearly support the switch from the current market formulation (CMF) to the final market image tablet in the countries where Trileptal is or was already registered.

RCT Entities:   Population Interventions Outcomes