Sample size and statistical analysis
Sample size was determined based on the intrasubject variability of Cmax,ss and AUCτ,ss of evogliptin and glimepiride from previous studies in healthy subjects. The sample size of 32 was calculated in order to detect 20% differences in PK parameters ensuring a statistical power of 80%, with a significance level of 5% under the assumptions that the maximum of intra-subject coefficient of variation for PK parameters of evogliptin or glimepiride was 33%. Considering possible dropouts, 36 subjects were chosen as the final sample size.
To evaluate the PK interactions between evogliptin and glimepiride, the geometric mean ratios (GMRs) and 90% confidence intervals (90% CIs) for the Cmax,ss and AUCτ,ss of the combination therapy to the monotherapy (EVO+GLI/GLI or EVO+GLI/EVO) were calculated from the analyses of variance (ANOVA) model, with sequence, period and treatment as fixed effects.