Effects of Food on the Pharmacokinetics of Gemigliptin/metformin Sustained-Release 50/1,000 Mg (25/500 Mg × 2 Tablets) Fixeddose Combination Tablet in Healthy Male Volunteers

Objectives: For patient convenience, a gemigliptin/metformin sustained-release fixed-dose combination (FDC) tablet was developed. This study was conducted to investigate the effects of food on the pharmacokinetic (PK) profile of the FDC tablets. Materials and methods: This was an open-label, randomized, single dose, 2-period, 2-sequence crossover study in 24 healthy male volunteers. The FDC tablets (25/500 mg x 2 tablets) were administered in high-fat fed and fasted states on separate occasions, and each subject was randomly allocated to each sequence with a 7-day washout period. PK blood samplings were conducted from pre-dose to 48 hours after dosing. Tolerability assessments were performed throughout the study. Results: Nine adverse events (AEs) of mild intensity were reported from 8 subjects after study drug administration, and the AE frequency was similar between treatments. No serious AEs were reported. The PK parameters of gemigliptin and metformin were compared between fasting and fed states. For gemigliptin, the geometric mean ratios (GMRs) (fed : fasted state) of the C-max and AUC(last) were 0.886 (90% confidence interval (CI) 0.781 - 1.006) and 1.021 (90% CI 0.949 - 1.099), respectively. For metformin, the GMRs of the C-max and AUC(last) were 0.811 (90% CI 0.712 - 0.923) and 1.144 (90% CI 1.013 - 1.291), respectively. A prolonged t(max) for metformin was observed. These results are similar to the effects of food on each component. Conclusion: The FDC tablet may have a similar PK profile as that of individual drugs and is generally tolerable when administered with food. These results indicate that the FDC tablet can be administered in the same dosing regimen as each component, especially that of metformin sustained-release.