Abstract
PURPOSE: This study was performed to compare the pharmacokinetics of two fixed-dose combination (FDC) formulations of teneligliptin combined with modified-release metformin in healthy Korean subjects under fasting and fed conditions. PATIENTS AND METHODS: The study was a single-center, open-label, single-dose, 2-way, 2-period, crossover trial. A total of 72 eligible subjects (40 subjects in the fasting state study and 32 subjects in the fed study) were enrolled in the study and were randomized to treatment. After the administration of a single FDC tablet of the investigational products, blood samples were collected at specific time intervals from 0 to 96 hours. The plasma concentrations of teneligliptin and metformin were measured by ultra performance liquid chromatography-tandem mass spectrometry (UPLC‒MS/MS). Pharmacokinetic parameters were calculated, and 90% confidence intervals (CIs) of the geometric mean ratios (test/reference) of the parameters were obtained through analysis of variance of the logarithmically transformed data. RESULTS: The corresponding 90% CIs of area under the plasma concentration-time curve from time zero to the time of last measurable concentration (AUC(t)) and maximum plasma drug concentration (C(max)) for the test/reference geometric mean ratio (GMR) of teneligliptin were 94.81-101.32% and 86.03-97.63%, respectively, under fasting conditions. The corresponding 90% CIs of AUC(t) and C(max) for the test/reference GMR of metformin were 95.01-108.36% and 94.69-108.40%, respectively, under the fasting state and 98.82-107.56% and 97.25-106.99%, respectively, after feeding. All adverse events were of mild intensity, and the subjects recovered spontaneously without sequelae. CONCLUSION: The test FDC drug is equivalent to the reference FDC drug in subjects under fasting and fed conditions within the Korean regulatory bioequivalence criteria. Both formulations were safe and well tolerated, and there were no differences in the safety profiles between the two single FDC formulation drugs. TRIAL REGISTRATION NO: Clinicaltrials.gov. KCT0007757, KCT0007759.