Bioequivalence of Dapagliflozin/Metformin Extended-release Fixed-combination Drug Product and Single-component Dapagliflozin and Metformin Extended-release Tablets in Healthy Russian Subjects |
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Authors: | Yunona Khomitskaya Nadezhda Tikhonova Konstantin Gudkov Svetlana Erofeeva Victoria Holmes Brian Dayton Nigel Davies David W. Boulton Weifeng Tang |
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Affiliation: | 1. AstraZeneca, Moscow, Russian Federation;2. “Bessalar” Clinic LLC, Clinical Trials Center, Moscow, Russian Federation;3. AstraZeneca, Cambridge, United Kingdom;4. Covance Laboratories Inc, Madison, Wisconsin, United States;5. IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden;6. AstraZeneca, Gaithersburg, Maryland, United States |
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Abstract: | PurposeFixed-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 monotherapy tablets currently available for use in the Russian Federation.MethodsHealthy 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 (AUC0–t, Cmax, and Cmax/AUC0–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 × 500 mg]) under standard fed conditions. Safety and tolerability were also assessed.FindingsForty healthy subjects were included (47.5% male; mean age, 30 years; and mean body mass index, 24.2 kg/m2). 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.ImplicationsBioequivalence of dapagliflozin/metformin XR 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. |
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Keywords: | bioequivalence dapagliflozin fixed-combination drug product metformin Russian Federation |
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