Trial record 3 of 79 for:    Enzalutamide

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

This study has been completed.
Sponsor:
Collaborator:
Medivation, Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe B.V. )
ClinicalTrials.gov Identifier:
NCT02138799
First received: May 13, 2014
Last updated: October 14, 2014
Last verified: October 2014
  Purpose

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 Intervention Phase
Drug-Drug Interaction (DDI)
Healthy Subjects
Pharmacokinetics of Enzalutamide
Drug: enzalutamide
Drug: rifampin
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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)


Enrollment: 28
Study Start Date: July 2013
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02138799

Locations
Germany
Parexel International GmbH
Berlin, Germany, 14050
Sponsors and Collaborators
Astellas Pharma Europe B.V.
Medivation, Inc.
Investigators
Study Director: Central Contact Astellas Pharma Europe B.V.
  More Information

Additional Information:
No publications provided

Responsible Party: Astellas Pharma Inc ( Astellas Pharma Europe B.V. )
ClinicalTrials.gov Identifier: NCT02138799     History of Changes
Other Study ID Numbers: 9785-CL-0405, 2012-004841-34
Study First Received: May 13, 2014
Last Updated: October 14, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Astellas Pharma Inc:
Phase I
Pharmacokinetics
Safety
Drug-drug interactions
Enzalutamide
Rifampin
CYP3A4
CYP2D8
Enzyme induction

Additional relevant MeSH terms:
Rifampin
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antitubercular
Antitubercular Agents
Enzyme Inhibitors
Leprostatic Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014