Bioequivalence And Food Effect Assessment For Vildagliptin/Metformin Fixed-Dose Combination Tablets Relative To Free Combinations Of Vildagliptin And Metformin In Japanese Healthy Subjects

Objective: To assess the bioequivalence of vildagliptin/metformin fixed dose combination (FDC) tablets (50/250 mg and 50/500 mg) to free combinations of vildagliptin and metformin and the effect of food on the pharmacokinetics (PK) of vildagliptin and metformin following administration of 50/500 mg FDC tablets. Methods: Two open label, randomized, single-center, single dose, 2-period crossover studies were conducted in Japanese healthy male volunteers. Participants were administered vildagliptin/metformin FDC tablets (study I: 50/250 mg, study II: 50/500 mg) or their free combinations under fasted condition. Food effect (standard Japanese breakfast: fat, 20 - 30% with similar to 600 kcal in total) was assessed during an additional period in study II (50/500 mg). PK parameters (AUC, C-max, t(max), t(1/2)) were calculated for vildagliptin and metformin. Results: In both studies, vildagliptin/metformin FDC tablets were bioequivalent to their respective free combinations. Administration of FDC tablets after meals had no effect on vildagliptin PK parameters. The rate of absorption of metformin decreased when administered under fed condition, as reflected by a prolonged t(max) (3 hours in fasted state vs. 4 hours in fed state) and decrease in C-max by 26%, however, the extent of absorption (AUC(last)) was similar to that in the fasted state. Conclusions: Vildagliptin/metformin FDC tablets were bioequivalent to their free combinations. Food decreased the C-max of metformin by 26%, while AUC(last) was unchanged, consistent with previous reports. No food effect was observed on the C-max or AUC(last) of vildagliptin. Thus, food had no clinically relevant effects on the PK of metformin or vildagliptin.