Bioequivalence assessment between two formulations of a film-coated fixed-dose combination of metformin and vildagliptin (850/50mg) in healthy Tunisian subjects under fed conditions

Abstract In Tunisia, bioequivalence studies have been required for generic drug approval since 2008. This study aimed to assess the bioequivalence of vildagliptin and metformin fixed-dose combination (FDC) 850/50 mg for a tested (Bi-Galvine) versus the approved reference products (Galvumet). A randomized, two-way, two-period, single oral dose, open-label, crossover, bioequivalence study with a washout period of 7 days to compare metformin/vildagliptin film-coated tablets in 18 healthy Tunisian subjects aged between 18 and 50 years under fed conditions was conducted at the National Center Chalbi Belkahia of Pharmacovigilance. During each period, 20 blood samples were collected from each subject at pre-dosing (0.00) and between 0.25 and 24.00 h after dosing. The bioequivalence between the test (T) and reference (R) products required 90% confidence intervals (CIs) for the geometric least square (LS) mean T/R ratio to be within 80–125% for the pharmacokinetic parameters, maximum plasma concentration (C max ), and Area Under the Curve from zero to 24 h (AUC 0–24 h ). The 90% CIs of the geometric means of the T/R ratios for C max and AUC 0–24 h for metformin were 92.01–102.66% and 93.55–101.80%, respectively; the corresponding results for vildagliptin were 96.03–107.09% and 94.46–101.92%, respectively. Other parameters, such as AUC 0-∞ , time to maximum concentration (T max ), and terminal half-life (t 1/2 ), were comparable between the test and reference products. Adverse events (AEs), mainly hypoglycemia and loose stools events, were reported without relevant differences between the test and reference products. AEs were generally mild and transient. No severe or serious AEs occurred. The new generic drug product of metformin/vildagliptin FDC 850/50 mg demonstrated bioequivalence to the approved product and is therefore expected to provide similar therapeutic effects.