Ignacio Conde-Carmona1, Sandra García-Medina2, Juan M Jiménez-Vargas2, Alberto Martínez-Muñoz2, Sung-Hack Lee3. 1. Específicos Stendhal SA de CV, Mexico City, Mexico. Electronic address: Ignacio.conde@stendhalpharma.com. 2. Clinical Pharmacology Unit, Faculty of Medicine, Autonomous National University of Mexico, Mexico City, Mexico. 3. Drug Metabolism and Pharmacokinetics, LG Chem, Ltd, Life Sciences R&D, Diabetes Center, Seoul, Republic of Korea.
Abstract
PURPOSE: The aim of this study was to assess the pharmacokinetic interactions between a newly developed dipeptidyl peptidase (DPP)-4 inhibitor, gemigliptin, and metformin in healthy Mexican male volunteers, and the differences in the pharmacokinetic profile of gemigliptin between Korean and Mexican healthy volunteers. METHODS: This was a multiple-dose, randomized, open-label, 3-way, 3-period crossover study. Subjects were randomized to 1 of 3 treatment sequences and received gemigliptin 50mg once a day, metformin1000mg BID, or both drugs during a 7-day treatment period, and underwent sampling for pharmacokinetic analysis and tolerability assessments. Point estimates and 90% CIs of Cmax,ss and AUCτ,ss least squares mean (LSM) ratios of the concurrent administration of gemigliptin + metformin to the administration of monotherapy with either drug were obtained, and the pharmacokinetic profile of gemigliptin observed was compared with that in healthy Korean volunteers studied during the initial development of gemigliptin. FINDINGS: The coadministration of gemigliptin + metformin did not affect the pharmacokinetic characteristics of gemigliptin (LSM ratio [90% CI] for Cmax,ss and AUCτ,ss: 0.98 [0.87-1.10] and 0.94 [0.91-0.98], respectively) or metformin (LSM ratio [90% CI] for Cmax,ss and AUCτ,ss: 0.97 [0.88-1.08] and 1.02 [0.93-1.12], respectively) when administered as monotherapy and was well tolerated. In contrast with Korean healthy volunteers, Mexican subjects showed a modestly higher gemigliptin exposure (LSM ratio [90% CI] for AUCτ,ss: 1.22 [1.14-1.31]). IMPLICATIONS: The results of this study support, in ethnically different populations, the absence of drug-drug interactions between gemigliptin and metformin previously shown in Korean healthy volunteers. Considering the flat effect-concentration curve and wide therapeutic range of gemigliptin, the pharmacokinetic profile of gemigliptin observed in healthy Mexican and Korean subjects suggests that gemigliptin use in Mexican patients may be associated with outcomes, in terms of efficacy and tolerability, similar to those observed in the Korean population. ClinicalTrials.gov identifier: NCT03310749.
RCT Entities:
PURPOSE: The aim of this study was to assess the pharmacokinetic interactions between a newly developed dipeptidyl peptidase (DPP)-4 inhibitor, gemigliptin, and metformin in healthy Mexican male volunteers, and the differences in the pharmacokinetic profile of gemigliptin between Korean and Mexican healthy volunteers. METHODS: This was a multiple-dose, randomized, open-label, 3-way, 3-period crossover study. Subjects were randomized to 1 of 3 treatment sequences and received gemigliptin 50mg once a day, metformin1000mg BID, or both drugs during a 7-day treatment period, and underwent sampling for pharmacokinetic analysis and tolerability assessments. Point estimates and 90% CIs of Cmax,ss and AUCτ,ss least squares mean (LSM) ratios of the concurrent administration of gemigliptin + metformin to the administration of monotherapy with either drug were obtained, and the pharmacokinetic profile of gemigliptin observed was compared with that in healthy Korean volunteers studied during the initial development of gemigliptin. FINDINGS: The coadministration of gemigliptin + metformin did not affect the pharmacokinetic characteristics of gemigliptin (LSM ratio [90% CI] for Cmax,ss and AUCτ,ss: 0.98 [0.87-1.10] and 0.94 [0.91-0.98], respectively) or metformin (LSM ratio [90% CI] for Cmax,ss and AUCτ,ss: 0.97 [0.88-1.08] and 1.02 [0.93-1.12], respectively) when administered as monotherapy and was well tolerated. In contrast with Korean healthy volunteers, Mexican subjects showed a modestly higher gemigliptin exposure (LSM ratio [90% CI] for AUCτ,ss: 1.22 [1.14-1.31]). IMPLICATIONS: The results of this study support, in ethnically different populations, the absence of drug-drug interactions between gemigliptin and metformin previously shown in Korean healthy volunteers. Considering the flat effect-concentration curve and wide therapeutic range of gemigliptin, the pharmacokinetic profile of gemigliptin observed in healthy Mexican and Korean subjects suggests that gemigliptin use in Mexican patients may be associated with outcomes, in terms of efficacy and tolerability, similar to those observed in the Korean population. ClinicalTrials.gov identifier: NCT03310749.