Bioequivalence of Dapagliflozin/Metformin Extended-release Fixed-combination Drug Product and Single-component Dapagliflozin and Metformin Extended-release Tablets in Healthy Russian Subjects

Purpose: Fixed-combination drug products (FCDPs) combining dapagliflozin and metformin extended release (XR) may provide patients with type 2 diabetes mellitus with an alternative antihyperglycemic treatment, which could improve adherence by reducing tablet burden. This study evaluated the bioequivalence of dapagliflozin/metformin XR FCDP versus the co-administration of the individual mono therapy tablets currently available for use in the Russian Federation. Methods: Healthy subjects aged 18 to 45 years were enrolled in this randomized, open-label, 2-period cross-over study, conducted in a single Russian center. Pharmacokinetic parameters (AUC(0-t), C-max, and C-max/AUC(0-t),) were used to assess bioequivalence of dapagliflozin/metformin XR (10/1000 mg) FCDP to the individual component tablets (dapagliflozin [10 mg] plus metformin XR [2 x 500 mg]) under standard fed conditions. Safety and tolerability were also assessed. Findings: Forty healthy subjects were included (47.5% male; mean age, 30 years; and mean body mass index, 24.2 kg/m(2)). Dapagliflozin and metformin XR in the FCDP were bioequivalent to the individual component tablets marketed in the Russian Federation, with the 90% CIs of the geometric least-squares mean ratios for all key pharmacokinetic parameters being contained within the 80% to 125% bioequivalence limits. Both FCDP and the individual component formulations were well tolerated, with no serious adverse events. (C) 2018 Elsevier HS Journals, Inc. All rights reserved.