The MeViDa Study: Bioequivalence Study of FDC of Dapagliflozin, Vildagliptin SR and Metformin SR in Healthy Indian Volunteers: A Randomized, Open-Label, Crossover Study

Abstract

Objective: To assess the pharmacokinetics and bioequivalence of Dapagliflozin 10mg + Vildagliptin Sustained Release (SR) 100mg + Metformin SR 1000mg fixed dose combination (FDC) tablets with DAPAMAC V 10 (Dapagliflozin 10mg + Vildagliptin SR 100mg tablets) and Glycomet 1g (Metformin SR 1000 mg tablets) in healthy adult male subjects under fasting conditions. Material and Methods: This was an open-label, balanced, randomized, two-treatment, two-period, two-sequence, single-dose, crossover, oral bioequivalence study. Volunteers were randomized to receive either a test product or a reference product under the fasting condition with a seven-day washout period. The pharmacokinetics parameters evaluated were maximum plasma concentration (Cmax), the area under the curve (AUC) at time t (AUC0-t), and the total area under the curve (AUC0-∞). Adverse events were also assessed as safety endpoints. Results: Twenty-four healthy adult male subjects were randomized, and 24 completed the study. The mean values for Cmax, AUC0-t, and AUC0-∞ were almost identical for test and reference products. The 90% confidence intervals of the ratios of adjusted geometric means for the pharmacokinetic parameters, i.e. Cmax, AUC0-t, and AUC0-∞ of the test product, were within the predefined bioequivalence limits of 80.00 to 125.00%. No adverse events or serious adverse events or deaths were reported during the study. All treatments were well tolerated. Conclusion: The test formulation, Dapagliflozin 10mg + Vildagliptin SR 100mg + Metformin SR 1000mg FDC, were bioequivalent to DAPAMAC V 10 (Dapagliflozin 10mg + Vildagliptin SR 100mg tablets) and Glycomet 1g (Metformin 1000mg SR tablets) in healthy adult male subjects under fasting conditions. Keywords: Bioequivalence, Fixed-Dose Combination, Dapagliflozin, Metformin, Sustained Release, Vildagliptin, AUC, Cmax