Subjects
Healthy Korean male volunteers aged between 19 and 45 years with body
mass index (BMI) between 18.0 and 27.0 kg/m2 were
eligible for inclusion in the study. Volunteers with fasting plasma
glucose (FPG) < 70 mg/dL or > 125 mg/dL,
aspartate aminotransferase (AST) or alanine aminotransferase (ALT)
> 60 IU/mL, creatinine clearance (MDRD equation)
< 80 mL/min, corrected QT interval (Bazett correction)
> 450 ms, known allergy or hypersensitivity to components
of investigational drug (evogliptin, pioglitazone) were excluded. Other
major reasons for exclusion were the followings; clinically significant
abnormalities in medical history, vital sign measurements, physical
examination, clinical laboratory tests (hematology, biochemistry,
urinalysis), 12-lead electrocardiogram. According to results from
previous studies, the largest intra-subject variability of selected
pharmacokinetic parameters (Cmax,
AUCτ,ss) of evogliptin, pioglitazone and their major
metabolites were assumed to be 29%[8,
16]. Sample size of 30 was required to
detect 20% difference in those pharmacokinetic parameters with a power
of 80% and significance level of 0.05. Actual sample size of 36 was
determined considering drop-out. Study protocol was approved by
Institutional Review Board (IRB) of Seoul National University Hospital
(ClinicalTrials.gov identifier: NCT02753803, IRB number: 1604-135-757)
and the Ministry of Food and Drug Safety, Republic of Korea. All
volunteers provided written informed consent prior to study procedure.