Graduate student Seoul National Univ Hosp Seoul, Seoul-t'ukpyolsi, Republic of Korea
Statement of Purpose: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with increasing prevalence worldwide. Empagliflozin and metformin are oral antidiabetic drugs which are commonly used together for the treatment of T2DM. CKD-375 is a newly developed fixed-dose combination of empagliflozin 5 mg and metformin 1000 mg, which changed the solvate of empagliflozin to empagliflozin L-proline. The aim of this study was to compare the pharmacokinetics (PKs), safety, and tolerability of two fixed-dose combination for empagliflozin and metformin.
Description of Methods & Materials: A randomized, open-label, single dose, two-period, two-treatment, crossover study was conducted in healthy subjects. Subjects were randomly assigned into two sequence groups, and received a single oral dose of reference drug (Jardiance Duo) or test drug (CKD-375) at each period. The PK parameters were calculated using a non-compartmental method. The geometric mean ratios (GMRs) and its 90% confidence intervals (CI) of the plasma maximum concentration (Cmax) and area under concentration-time curve from time zero to the last quantifiable concentration (AUClast) were calculated. Safety and tolerability were evaluated throughout the study by assessing vital signs, physical examination, electrocardiogram, clinical laboratory test and monitoring adverse events.
Data & Results: A total of 28 healthy Korean adult subjects were randomized and 27 subjects were included in the PK analysis. Test drug showed similar PK characteristics to reference drug, showing Cmax and AUClast of empagliflozin and metformin were within bioequivalence criteria. For empagliflozin, the GMRs (90% CI) of test to reference drug for Cmax and AUClast were 1.0304 (0.9855-1.0774) and 1.0265 (0.9969-1.0571), respectively. For metformin, the corresponding values forCmax and AUClast were 0.9898 (0.9204-1.0645), 0.9966 (0.9388-1.0580), respectively. Both drugs were well tolerated.
Interpretation, Conclusion or Significance: A newly developed fixed-dose combination of empagliflozin L-proline and metformin showed similar PK characteristics to reference drug, and both were well tolerated in healthy subjects.
