FIGURE 4.

Contribution of sex and BMI covariates to the variability of exposure in phase 3 studies determined based on post hoc estimates from the final model and shown as a distribution of the exposure of (A) parent regorafenib AUC at steady state of nominal dosing (160 mg day⁻¹), and (B) protein binding corrected total AUC (parent, M‐2 and M‐5). Horizontal red dots and bars are the median and 90% CI, respectively, of the ratio by dichotomized variable of AUC_0‐24h,ss geometric means. The median and CI were obtained by sampling 10,000 replicate trials based on the individual AUC_0‐24h,ss values with replacement, per group. Individual AUC_0‐24h,ss were derived from the individual clearance estimates using the final PK model. Vertical lines are commonly used bioequivalence boundaries 0.8–1.25.

AUC, area under curve; BMI, body mass index; CI, confidence interval; PK, pharmacokinetic; ss, steady state