Comparison of the Pharmacokinetics, Safety, and Tolerability of Two Empagliflozin Formulations in Healthy Korean Subjects

Xu Jiang; Sungyeun Bae; Deok Yong Yoon; Shin Jung Park; Jaeseong Oh; Joo-Youn Cho; Kyung-Sang Yu

doi:10.2147/DDDT.S409368

Comparison of the Pharmacokinetics, Safety, and Tolerability of Two Empagliflozin Formulations in Healthy Korean Subjects

Drug Des Devel Ther. 2023 Jul 24:17:2137-2145. doi: 10.2147/DDDT.S409368. eCollection 2023.

Authors

Xu Jiang¹, Sungyeun Bae¹, Deok Yong Yoon², Shin Jung Park³, Jaeseong Oh¹, Joo-Youn Cho^{1

4}, Kyung-Sang Yu^{1

4}

Affiliations

¹ Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
² Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, FL, USA.
³ Department of Pharmaceutical Research Laboratory, Chong Kun Dang Research Institute, Chong Kun Dang Pharmaceutical Corporation, Yongin, Republic of Korea.
⁴ Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.

Abstract

Purpose: Empagliflozin is a sodium-glucose cotransporter 2 inhibitor that is commonly used for the treatment of type 2 diabetes mellitus. As cocrystal formulation can improve the chemical properties of drugs, CKD-370 was newly developed as a cocrystal formulation of empagliflozin with solvate L-proline. This study aimed to compare the pharmacokinetics, safety, and tolerability of these two empagliflozin formulations in healthy Korean subjects.

Methods: A randomized, open-label, two-sequence, two-period crossover study was conducted on healthy Korean participants. The subjects received a single oral 25 mg dose of either test (CKD-370) or reference treatment (Jardiance^®) tablet at each period. Plasma empagliflozin concentrations were determined using liquid chromatography with tandem mass spectrometry. Pharmacokinetic (PK) parameters were analyzed using non-compartmental methods. The primary PK parameters included the maximum concentration (C_max) and the area under the concentration-time curve from 0 to last (AUC_last). The safety of both formulations was monitored and evaluated.

Results: A total of 28 healthy Korean adult subjects were randomized, and 27 subjects were included in the PK analysis. The mean ± standard deviation values of the primary PK parameters, C_max and AUC_last after administration of the test treatment, were 442.02 ± 103.37 μg/L and 3131.08 ± 529.30 μg·h/L, respectively, and those after administration of the reference treatment were 436.29 ± 118.74 μg/L and 3006.88 ± 514.21 μg·h/L, respectively. The geometric mean ratio and its 90% confidence interval of test to reference treatment for C_max and AUC_last were 1.0221 (0.9527-1.0967) and 1.0411 (1.0153-1.0677), respectively, which were within the commonly accepted bioequivalence criteria of 0.80 to 1.25. Both treatments were well-tolerated.

Conclusion: The two formulations of empagliflozin showed similar PK characteristics and were generally well tolerated in healthy subjects.

Keywords: CKD-370; L-proline; T2DM; biosimilar; cocrystal.

Publication types

Randomized Controlled Trial

MeSH terms

Administration, Oral
Adult
Area Under Curve
Cross-Over Studies
Diabetes Mellitus, Type 2* / drug therapy
Healthy Volunteers
Humans
Renal Insufficiency, Chronic*
Republic of Korea
Tablets
Therapeutic Equivalency

Substances

empagliflozin
Tablets

Grants and funding

This study was sponsored by a research grant from Chong Kun Dang Pharmaceutical Corporation, South Korea. The funders had no role in data collection and analysis or preparation of the manuscript.