J Korean Med Sci.  2018 Oct;33(41):e258. 10.3346/jkms.2018.33.e258.

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

• Cho YS
• Lee SH
• Lim HS
• Bae KS

• KMID: 2421399
• DOI: http://doi.org/10.3346/jkms.2018.33.e258

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.

Keyword

Gemigliptin/Metformin-SR; FDC; Pharmacokinetic Equivalence; Pharmacokinetics

MeSH Terms

Cross-Over Studies
Diabetes Mellitus, Type 2
Glucose
Healthy Volunteers*
Metformin*
Patient Compliance
Pharmacokinetics
Plasma
Tablets*
Glucose
Metformin
Tablets