031: Comparison of the Pharmacokinetics, Safety & Tolerability of Two Empagliflozin Formulations in Healthy Korean Subjects

Statement of Purpose: Empagliflozin is a sodium-glucose cotransporter (SGLT)-2 inhibitor that is commonly used for the treatment of type 2 diabetes mellitus (T2DM). CKD-370 is a newly developed formulation of empagliflozin which changed the solvate of empagliflozin to empagliflozin L-proline. The aim of this study was to compare the pharmacokinetics, safety, and tolerability of those two empagliflozin formulations in healthy Korean subjects.

Description of Methods & Materials: A randomized, open-label, two-sequence, two-treatment, two-period crossover study was conducted in healthy Korean subjects. Subjects received a single oral 25 mg dose of either test drug (CKD-370) or reference drug (Jardiance®) tablet at each period. Plasma empagliflozin concentrations were determined by liquid chromatography with tandem mass spectrometry (LC/MS/MS). Pharmacokinetic (PK) parameters were analyzed with non-compartmental methods and the primary PK parameters were maximum concentration (C_max) and area under the concentration-time curve from 0 to last (AUC_last). Safety was monitored and evaluated.

Data & Results: A total of 28 healthy Korean adult subjects were randomized and 27 subjects were included in the PK analysis. The PK characteristics of test drug were similar to the reference drug. The mean ± standard deviation (SD) values of the primary PK parameters C_max and AUC_last after administration of test drug were 442.02 ± 103.37 and 3131.08 ± 529.30 hr·μg/L, respectively and those values after administration of reference drug were 436.29 ± 118.74, and 3006.88 ± 514.21 hr·μg/L, respectively. The geometric mean ratio and its 90% confidence intervals of test to reference drug 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 drugs were well tolerated.

Interpretation, Conclusion or Significance: The two formulations of empagliflozin showed similar PK characteristics and both were generally well tolerated in the healthy subjects.