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.