Data Supplement
Files in this Data Supplement:
- Supplemental Data -
Supplemental Table 1 - Kinetic parameters of sonidegib metabolism in HLM
Supplemental Table 2 - Input parameters for sonidegib using the ADAM model for healthy volunteers
Supplemental Table 3 - Calculation of fmCYP3A4 based upon metabolites excreted in the human ADME study (data from Table 2 of Zollinger et al., 2014)
Supplemental Table 4 - Predicted 'Top Down' or HLM Clearance predicted PK parameters of sonidegib (800 mg dose) in healthy volunteers
Supplemental Table 5 - PBPK model input parameters for ketoconazole (KTZ)
Supplemental Table 6 - PBPK model input parameters for rifampin (RIF)
Supplemental Table 7 - PBPK model input parameters for erythromycin (ERY)
Supplemental Table 8 - PBPK model input parameters for efavirenz (EFV)a
Supplemental Table 9 - Observed and simulated (1st order absorption or ADAM model) clinical PK parameters of sonidegib in the presence and absence of the strong CYP3A perpetrators, KTZ and RIF, in healthy subjects
Supplemental Table 10 - Observed and simulated (1st order absorption model or ADAM) clinical PK parameters of a single dose of sonidegib in healthy subjects
Supplemental Figure 1 - The chemical structure of sonidegib
Supplemental Figure 2 - The impact of sonidegib fugut on Fg and DDI magnitude
Supplemental Figure 3 - A comparison of simulated mean concentration-time profiles of sonidegib between cancer patients (black line) and healthy volunteers (grey line) dosed with a single 200 mg (A) or 800 mg (B) sonidegib dose
Supplemental Figure 4 - Metabolite profile and kinetics of sonidegib in HLM
Supplemental Figure 5 - Levels of the CYP3A biomarkers, 4-beta-HC (A) or 6-beta-CR (B) with a single dose of sonidegib on day 5 or multiple doses of KTZ or RIF on days 1-14