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

Healthy Subjects Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02138799
• Other study ID #: 9785-CL-0405
• Secondary ID: 2012-004841-34
• Status: Completed
• Phase: Phase 1
• First received: May 13, 2014
• Last updated: October 14, 2014
• Start date: July 2013
• Est. completion date: September 2013

Study information

• Verified date: October 2014
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Drug-Drug Interaction (DDI)
• Healthy Subjects
• Pharmacokinetics of Enzalutamide

Intervention

Drug:
• enzalutamide
oral
• rifampin
oral

Locations

Country	Name	City	State
Germany	Parexel International GmbH	Berlin

Sponsors (2)

Lead Sponsor	Collaborator
Astellas Pharma Europe B.V.	Medivation, Inc.

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)		Days 1 to 50 (29 times)	No
Primary	PK of enzalutamide and the sum of enzalutamide + M2 in plasma measured by AUC extrapolated to infinity (AUCinf)		Days 1 to 50 (29 times)	No
Secondary	PK of enzalutamide, M2, M1 and the sum of enzalutamide + M2 in plasma	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)	Days 8 to 57 (49 times)	No
Secondary	PK of rifampin in plasma	Cmax, tmax, AUC for the defined interval between doses (AUCtau), minimum concentration (Cmin)	Days 6 to 21 (20 times)	No
Secondary	Safety and tolerability of enzalutamide, alone or in the presence of rifampin	vital signs, incidence of adverse events (AE), laboratory assessments, physical examination, electrocardiogram (ECG)	Screening (Day -28 to -7) to End of Study Visit (ESV) (>34 times)	No

External Links

•   Link to Results on JAPIC - enter 140632 in the JapicCTI-RNo. field