Pharmacokinetic Equivalence of the High Dose Strength Fixed-Dose Combination Tablet of Gemigliptin/Metformin Sustained Release (SR) and Individual Component Gemigliptin and Metformin XR Tablets in Healthy Subjects

Abstract

Background: In type 2 diabetes mellitus therapy, fixed-dose combination (FDC) can offer not only benefits in glucose control via the combined use of agents, but also increase patient compliance. The aim of this study was to assess the pharmacokinetic equivalence of the high dose of the FDC tablet (gemigliptin/metformin sustained release [SR] 50/1,000 mg) and a corresponding co-administered dose of individual tablets.

Methods: This study was randomized, open-label, single dose, two treatments, two-period, crossover study, which included 24 healthy subjects. Subjects received the FDC or individual tablets of gemigliptin (50 mg) and metformin XR (1,000 mg) in each period. Geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of the FDC tablet and co-administration of individual tablet for both gemigliptin and metformin were calculated.

Results: The GMRs (FDC tablets/co-administration; 90% CIs) for Cmax and AUClast of gemigliptin were 1.079 (0.986-1.180) and 1.047 (1.014-1.080), respectively. For metformin, the GMRs for Cmax, and AUClast were 1.038 (0.995-1.083) and 1.041 (0.997-1.088), respectively. The 90% CIs for GMRs of Cmax and AUClast for gemigliptin and metformin fell entirely within bounds of 0.800-1.250. Both administration of FDC tablet and co-administration of individual tablets were well tolerated.

Conclusion: FDC tablet exhibited pharmacokinetic equivalence and comparable safety and tolerability to co-administration of corresponding doses of gemigliptin and metformin XR as individual tablets. Trial registry at ClinicalTrials.gov, NCT02056600.

Keywords: FDC; Gemigliptin/Metformin-SR; Pharmacokinetic Equivalence; Pharmacokinetics.

Conflict of interest statement

Disclosure: The authors have no potential conflicts of interest to disclose.

Figures

Fig. 1. Mean plasma concentration-time profile of gemigliptin and metformin following administration of a single dose of FDC tablet (gemigliptin/metformin SR 50/1,000 mg) and co-administration of gemigliptin 50 mg+metformin XR 1,000 mg. Plasma concentrations of gemigliptin are plotted on a (A) linear or (B) log scale and those of metformin are plotted on a (C) linear or (D) log scale. The error bars indicate standard deviations.

FDC = fixed-dose combination, SR = sustained release.

Fig. 2. Systemic exposure comparison between FDC tablet and co-administration of separate tablets. Cmax values (A) and AUClast values (B) of gemigliptin and Cmax values (C) and AUClast values (D) of metformin are presented as gray points and box-and-whisker plots. Each box shows the 25th, 50th (median) and 75th percentiles of individual values.

FDC = fixed-dose combination, Cmax = maximum plasma concentration, AUClast = area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration.