200 mg itraconazole once daily on the PK of a single oral dose of 160 mg Pioglitazone; 9785-CL-0007 To determine the effect of multiple once daily administration of drug cocktail of MDV3100 (160mg; four 40 mg S-warfarin, capsules) on the PK of a single dose of omeprazole pioglitazone (CYP2C8 substrate), S- and midazolam warfarin (CYP2C9 substrate), omeprazole (CYP2C19 substrate) and midazolam (CYP3A4 substrate) in patients with CRPC. Population Healthy Study report To assess the extent of drug-drug PK analyses subjects 9785-PK-0002 interaction of gemfibrozil and itraconazole on single dose MDV3100 PK, using data from study Target Study report To develop a population PK model of population 9785-PK-0001 MDV3100, and population PK-PD models for its effect on antigen (PSA) concentration (a biomarker for prostate cancer progression) and spontaneously reported fatigue (the most frequently reported adverse event), using data from Study S-3100-1-01. Study report To investigate potential factors that icon2147020 may increases in plasma concentrations of MDV3100 metabolite M1 (also referred to as MDCP0001) in CRPC patients in Study CRPC2. Study report To document the relationship(s) of icon2147016 MDV3100 and its active metabolite M2 (also referred to as MDPC0002) steady‐state pre‐dose plasma concentrations (Cmin) with study efficacy and safety outcomes in Study CRPC2. Both healthy Study report To a population PK model of and target icon2147014 MDV3100 after oral administration of population MDV3100 liquid-filled capsules in healthy male subjects and in patients with CRPC, including cofactors that contribute to inter-individual
200 mg itraconazole once daily on the PK of a single oral dose of 160 mg Pioglitazone; drug cocktail of S-warfarin, omeprazole and midazolam 9785-CL-0007 To determine the effect of multiple once daily administration of MDV3100 (160mg; four 40 mg capsules) on the PK of a single dose of pioglitazone (CYP2C8 substrate), (CYP2C9 substrate), omeprazole (CYP2C19 substrate) and midazolam (CYP3A4 substrate) in patients with CRPC. Population PK analyses Healthy subjects Study report 9785-PK-0002 To assess the extent of drug-drug interaction of gemfibrozil and itraconazole on single dose MDV3100 PK, using data from study Target population Study report 9785-PK-0001 To develop a population PK model of MDV3100, and population PK-PD models for its effect on antigen (PSA) concentration (a biomarker for prostate cancer progression) and spontaneously reported fatigue (the most frequently reported adverse event), using data from Study S-3100-1-01. Study report icon2147020 To investigate potential factors that may increases in plasma concentrations of MDV3100 metabolite M1 (also referred to as MDCP0001) in CRPC patients in Study CRPC2. Study report icon2147016 To document the relationship(s) of MDV3100 and its active metabolite M2 (also referred to as MDPC0002) steady‐state pre‐dose plasma concentrations (Cmin) with study efficacy and safety outcomes in Study CRPC2. Both healthy and target population Study report icon2147014 To a population PK model of MDV3100 after oral administration of MDV3100 liquid-filled capsules in healthy male subjects and in patients with CRPC, including cofactors that contribute to inter-individual warfarin S-
auspar-enzalutamide-141124-cer.docx