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A Study to Evaluate How a Drug That Alters Liver Enzymes (Rifampin) Affects the Metabolism of Enzalutamide in Men

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02138799
Recruitment Status : Completed
First Posted : May 15, 2014
Last Update Posted : October 15, 2014
Sponsor:
Collaborator:
Medivation, Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe B.V. )

Brief Summary:
This study evaluates how a drug that alters liver enzymes (rifampin) affects the metabolism of enzalutamide in men by measuring concentrations of enzalutamide and its metabolites in plasma.

Condition or disease Intervention/treatment Phase
Drug-Drug Interaction (DDI) Healthy Subjects Pharmacokinetics of Enzalutamide Drug: enzalutamide Drug: rifampin Phase 1

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : July 2013
Actual Primary Completion Date : September 2013
Actual Study Completion Date : September 2013

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 1: single dose of enzalutamide Drug: enzalutamide
oral
Other Names:
  • ASP9785,
  • MDV3100,
  • Xtandi

Experimental: 2: multiple doses of rifampin and single dose of enzalutamide Drug: enzalutamide
oral
Other Names:
  • ASP9785,
  • MDV3100,
  • Xtandi

Drug: rifampin
oral




Primary Outcome Measures :
  1. 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) ]
  2. 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) ]

Secondary Outcome Measures :
  1. PK of enzalutamide, M2, M1 and the sum of enzalutamide + M2 in plasma [ Time Frame: Days 8 to 57 (49 times) ]
    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)

  2. PK of rifampin in plasma [ Time Frame: Days 6 to 21 (20 times) ]
    Cmax, tmax, AUC for the defined interval between doses (AUCtau), minimum concentration (Cmin)

  3. 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) ]
    vital signs, incidence of adverse events (AE), laboratory assessments, physical examination, electrocardiogram (ECG)



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subject has a Body Mass Index (BMI) of at least 18.5 and no greater than 29.9 kg/m2 at screening.
  • Subject must use a condom when having sex with a pregnant woman.
  • Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of two forms of birth control.
  • Male subject must not donate sperm starting at screening and throughout the study period and for 90 days after the final study drug administration.

Exclusion Criteria:

  • Subject has a confirmed CYP2C8 poor metabolizer status based on genotyping analysis.
  • Subject has a history of seizure or any condition that may predispose to seizure. Historically or currently on any convulsive medication or drugs that may lower the seizure threshold. History of any central nervous system (CNS) infections. Also history of transient ischemic attack or cerebrovascular accident with or without head trauma within 12 months of enrollment (Day -1 visit).
  • Subject has any significant blood loss, donated one unit (450 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to clinic admission on Day -1.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02138799


Locations
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Germany
Parexel International GmbH
Berlin, Germany, 14050
Sponsors and Collaborators
Astellas Pharma Europe B.V.
Medivation, Inc.
Investigators
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Study Director: Central Contact Astellas Pharma Europe B.V.
Additional Information:
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Responsible Party: Astellas Pharma Europe B.V.
ClinicalTrials.gov Identifier: NCT02138799    
Other Study ID Numbers: 9785-CL-0405
2012-004841-34 ( EudraCT Number )
First Posted: May 15, 2014    Key Record Dates
Last Update Posted: October 15, 2014
Last Verified: October 2014
Keywords provided by Astellas Pharma Inc ( Astellas Pharma Europe B.V. ):
Phase I
Pharmacokinetics
Safety
Drug-drug interactions
Enzalutamide
Rifampin
CYP3A4
CYP2D8
Enzyme induction
Additional relevant MeSH terms:
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Rifampin
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP2C8 Inducers
Cytochrome P-450 CYP2C19 Inducers
Cytochrome P-450 CYP2C9 Inducers
Cytochrome P-450 CYP3A Inducers