Evaluation of the pharmacokinetics of the DPP-4 inhibitor gemigliptin when coadministered with rosuvastatin or irbesartan to healthy subjects

Abstract

Objective:

Gemigliptin is a selective DPP4 inhibitor used to treat type 2 diabetes. The objective of this study was to evaluate the pharmacokinetics (PKs) of gemigliptin, rosuvastatin, and irbesartan monotherapies and combination therapies.

Research design and methods:

Randomized, open-label, three-treatment, six-sequence, three-period, crossover studies were performed on healthy male volunteers. The three treatments were: 50 mg gemigliptin alone; 20 mg rosuvastatin (part A) or 300 mg irbesartan alone (part B); and rosuvastatin or irbesartan with concomitant gemigliptin. Each drug was administered as part of once daily, 7 day, repeated dosing regimens with a 14 day washout period.

Clinical trial registration:

NCT01823133 (part A) and NCT01825850 (part B).

Main outcome measures:

The primary PK parameters – C_max and AUC_τ – were compared to the geometric mean ratios (GMRs) and 90% confidence intervals (90% CIs) that were determined for the combination therapies and monotherapies.

Results:

A total of 60 participants were administered the study drugs, and 52 participants (27 participants in part A; 25 participants in part B) were analyzed as part of the PK dataset. In part A, the GMRs (gemigliptin + rosuvastatin/gemigliptin) of the C_max and AUC_τ values of gemigliptin were 0.955 (90% CI = 0.874–1.044) and 1.023 (90% CI = 0.991–1.057), and those of rosuvastatin were 1.012 (90% CI = 0.946–1.084) and 1.086 (90% CI = 1.032–1.142), respectively. In part B, the GMRs of the C_max and AUC_τ values of gemigliptin were 1.046 (90% CI = 0.964–1.134) and 1.035 (90% CI = 1.005–1.065), and those of irbesartan were 0.966 (90% CI = 0.897–1.040) and 1.050 (90% CI = 0.993–1.111), respectively. The limitations of this study include its relatively short treatment period and small sample size, as only healthy participants were included.

Conclusions:

Gemigliptin does not affect the PK properties of rosuvastatin or irbesartan; also, rosuvastatin and irbesartan do not affect the PKs of gemigliptin.

Keywords: :

• Drug interactions
• Irbesartan
• LC15-0444
• Pharmacokinetics
• Rosuvastatin

Transparency

Declaration of funding

This study was funded by LG Life Science Ltd, Seoul, Republic of Korea, which is the manufacturer of gemigliptin. This study was also supported by a grant from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI07C0001).

Declaration of financial/other relationships

H.Y.C., H.-S.L., Y.H.K., H.S.J., M.J.K., S.H.L., and K.-S.B. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article. J.H.J., Y.K.L., and H.J.K. have disclosed that they are employees of LG Life Sciences Ltd.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors thank the subjects and staff who participated at the Clinical Trial Center, Asan Medical Center, Republic of Korea.

Notes

¹Crestor is a registered trade name of AstraZeneca Korea, Seoul, Republic of Korea

²Aprovel is a registered trade name of Handok Pharmaceuticals Co. Ltd, Seoul, Republic of Korea