A Study to Evaluate How a Drug That Alters Liver Enzymes (Rifampin) Affects the Metabolism of Enzalutamide in Men
Drug-Drug Interaction (DDI)
Pharmacokinetics of Enzalutamide
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
|Official Title:||A Phase I, Randomized, Open-label, 2-arm Parallel-design Study to Determine the Effect of Multiple-dose Rifampin on the Pharmacokinetics, Safety and Tolerability of Single-dose Enzalutamide in Healthy Male Subjects|
- PK of enzalutamide and the sum of enzalutamide + M2 in plasma measured by area under the curve (AUC) from time 0 to 336 hours after dosing (AUC0-336h) [ Time Frame: Days 1 to 50 (29 times) ] [ Designated as safety issue: No ]
- PK of enzalutamide and the sum of enzalutamide + M2 in plasma measured by AUC extrapolated to infinity (AUCinf) [ Time Frame: Days 1 to 50 (29 times) ] [ Designated as safety issue: No ]
- PK of enzalutamide, M2, M1 and the sum of enzalutamide + M2 in plasma [ Time Frame: Days 8 to 57 (49 times) ] [ Designated as safety issue: No ]AUC0-336h, AUCinf, Cmax (M2, M1), time to attain Cmax (tmax), terminal elimination half life (t1/2), AUC up to last quantifiable concentration (AUClast), apparent total body clearance after extra vascular dosing (CL/F), apparent volume of distribution during the terminal phase after extra vascular dosing (Vz/F) (parent compound only), Metabolite-to-Parent Ratio (MPR), percent extrapolated for AUCinf (%AUC)
- PK of rifampin in plasma [ Time Frame: Days 6 to 21 (20 times) ] [ Designated as safety issue: No ]Cmax, tmax, AUC for the defined interval between doses (AUCtau), minimum concentration (Cmin)
- Safety and tolerability of enzalutamide, alone or in the presence of rifampin [ Time Frame: Screening (Day -28 to -7) to End of Study Visit (ESV) (>34 times) ] [ Designated as safety issue: No ]vital signs, incidence of adverse events (AE), laboratory assessments, physical examination, electrocardiogram (ECG)
|Study Start Date:||July 2013|
|Study Completion Date:||September 2013|
|Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
|Experimental: 1: single dose of enzalutamide||
|Experimental: 2: multiple doses of rifampin and single dose of enzalutamide||
Other Names:Drug: rifampin
The study consists of 2 randomized treatment arms. In both arms the subjects receive a single oral dose of enzalutamide.
In Arm 1 the subjects are admitted to the clinic on Day -1 where they remain until Day 3. Each subject receives a single oral dose of enzalutamide, administered under fasted conditions on Day 1. Ambulant visits take place from Day 4 to Day 50. Full PK profiles are obtained for enzalutamide, Major Inactive Carboxylic Acid Metabolite (M1) and Active Metabolite N-desmethyl Enzalutamide (M2) from Day 1 up to Day 50 after intake of enzalutamide.
In Arm 2 each subject receives a once-daily dose of rifampin on Days 1 to 21. On Day 8, a single oral dose of enzalutamide is administered under fasted conditions concomitantly with rifampin. Full PK profiles are obtained for enzalutamide, M1 and M2 from Day 8 up to Day 57 after intake of enzalutamide.
An End of Study Visit (ESV) takes place between 7 and 10 days after the last PK sample or early withdrawal.
Safety assessments are performed throughout the study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02138799
|Parexel International GmbH|
|Berlin, Germany, 14050|
|Study Director:||Central Contact||Astellas Pharma Europe B.V.|