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

Abstract Purpose Fixed- combination drugproducts (FCDPs) combining dapagliflozinand metforminextended 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 bioequivalenceof dapagliflozin/ metforminXR FCDP versus the co-administration of the individual monotherapy 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 crossover study, conducted in a single Russian center. Pharmacokinetic parameters (AUC 0–t , C max , and C max /AUC 0–t ) were used to assess bioequivalenceof dapagliflozin/ metforminXR (10/1000 mg) FCDP to the individual component tablets ( dapagliflozin[10 mg] plus metforminXR [2 × 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 ). Dapagliflozinand metforminXR in the FCDP were bioequivalentto 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% bioequivalencelimits. Both FCDP and the individual component formulations were well tolerated, with no serious adverse events. Implications Bioequivalenceof dapagliflozin/ metforminXR FCDP and the individual components was established without any new safety concerns, presenting a safe alternative for patients currently receiving regimens including each component individually. ClinicalTrials.gov identifier: NCT02722239.