FIGURE 3.

(A) Estimated AUC_0‐8h,ss for patients in the phase 1 dataset, using a two‐compartmental model (2 Comp model; yellow), the phase 1 regorafenib enterohepatic circulation (EHC) model with fixed standard mealtimes (orange) or with reported mealtime if available and fixed standard times if not (brown), and by using the trapezium method (NCA; grey). Model‐based estimates were derived for reduced datasets with only observations included as indicated in the figure. (B) Estimated AUC_0‐24h,ss based on the EHC model for patients in the phase 1 dataset based on a PK profile at steady state using different assumptions on the mealtimes. In brown are the results using the reported mealtime at the study day, and in orange are the results for fixed mealtimes, with results for the two‐compartment model shown in yellow. In blue are the results when available mealtime was disregarded and the mealtimes were related to the dosing time; the periods between food intake were 0.25 h (dark blue), 0.5 h (blue), or 1 h (light blue). The effect of imputing mealtimes was assessed by using all available data, as well as in sparse sampling settings, as indicated in the figure.

AUC, area under curve; EHC, enterohepatic circulation; NCA, non‐compartmental analysis; PK, pharmacokinetic; ss, steady state