Abstract

Objective: To assess the bioequivalence of vildagliptin/metformin fixeddose 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 openlabel, randomized, single-center, singledose, 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 ~ 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.

Author Details

Authors

• Sachiko Mita¹
• Shripad D. Chitnis²
• Kenneth Kulmatycki²
• Atish Salunke³
• Yan-Ling He²
• Wei Zhou⁴
• Hikoe Suzuki¹

Departments

• ¹ Novartis Pharma K.K., Tokyo, Japan;
• ² Novartis Institutes for BioMedical Research, Cambridge, MA, USA,
• ³ Novartis Healthcare Private Limited, Hyderabad, India, and
• ⁴ Novartis Institute for BioMedical Research, East Hanover, NJ, USA

Address

Sachiko Nozaki (Mita)
Novartis Pharma K.K.
23-1, Toranomon 1-chome, Minato-ku, Tokyo 105-6333, Japan
Email: [email protected]

Citation