(R-8813) 14874 Exploratory analysis of regorafenib Exploratory analysis not fully – exposure and safety data from Study evaluated (PH-37281) 14874 14387+14874 Exploratory analysis of regorafenib Exploratory analysis not fully – exposure and pooled safety data from evaluated (PH-37105) Studies trial and 14874 16392 Exploratory analysis of regorafenib Exploratory analysis, based on pharmacokinetics using modelled parameters (no actual (PH-37027) pharmacokinetic (PBPK) modelling patients with hepatic or renal effect of hepatic and renal impairment impairment) and in virtual – populations, base model not submitted for evaluation. Summary of pharmacokinetics The information in the following summary is derived from conventional pharmacokinetic studies unless otherwise stated. Physicochemical characteristics of the active substance No new data was presented with this submission. Pharmacokinetics in healthy subjects No new data was presented with this submission. Pharmacokinetics in the target population/patients with advanced malignancies Absorption No new data was presented with this submission. As described in the PI: Regorafenib reaches mean peak plasma levels of approximately 2.5 mg/L at approximately to four hours after a single oral dose of 160 mg regorafenib. Bioavailability No new data was presented with this submission. As described in the PI: The mean relative bioavailability of the tablets compared to an oral solution is 69-83%. Distribution No new data was presented with this submission. The population PK analyses used the Volume of distribution at steady state (VSS) of 88.0L as a fixed parameter, as calculated from Study 11650 (previously evaluated by the TGA).
(R-8813) 14874 (PH-37281) Exploratory analysis of regorafenib exposure and safety data from Study 14874 Exploratory analysis – not fully evaluated 14387+14874 (PH-37105) Exploratory analysis of regorafenib exposure and pooled safety data from Studies and 14874 Exploratory analysis – not fully evaluated 16392 (PH-37027) Exploratory analysis of regorafenib pharmacokinetics using pharmacokinetic (PBPK) modelling – effect of hepatic and renal impairment Exploratory analysis, based on modelled parameters (no actual patients with hepatic or renal impairment) and in virtual populations, base model not submitted for evaluation. Summary of pharmacokinetics The information in the following summary is derived from conventional pharmacokinetic studies unless otherwise stated. Physicochemical characteristics of the active substance No new data was presented with this submission. Pharmacokinetics in healthy subjects No new data was presented with this submission. Pharmacokinetics in the target population/patients with advanced malignancies Absorption No new data was presented with this submission. As described in the PI: Regorafenib reaches mean peak plasma levels of approximately 2.5 mg/L at approximately to four hours after a single oral dose of 160 mg regorafenib. Bioavailability No new data was presented with this submission. As described in the PI: The mean relative bioavailability of the tablets compared to an oral solution is 69-83%. Distribution No new data was presented with this submission. The population PK analyses used the Volume of distribution at steady state (VSS) of 88.0L as a fixed parameter, as calculated from Study 11650 (previously evaluated by the TGA). trial