Drug-Drug Interaction (DDI)Phase 1NCT02138799
A Study to Evaluate How a Drug That Alters Liver Enzymes (Rifampin) Affects the Metabolism of Enzalutamide in Men
A Phase 1 study testing enzalutamide and rifampin in people with Drug-Drug Interaction (DDI) and Healthy Subjects, run by Astellas Pharma Europe B.V. at 1 site in Germany.
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. Read more about this study
- Who is it for?
- Ages 18 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Drug-Drug Interaction (DDI), Healthy Subjects, Pharmacokinetics of Enzalutamide
- What is being tested?
- enzalutamide and rifampin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteGermany
- Study dates
- Jul 2013to Sep 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Being tested
- enzalutamide, rifampin
- Keywords
- Phase I, Pharmacokinetics, Safety, Drug-drug interactions, Enzalutamide, Rifampin, CYP3A4, CYP2D8, Enzyme induction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
enzalutamideDrug
Also called ASP9785,, MDV3100,, Xtandi
oral
rifampinDrug
oral
| Study group | Role | What they receive |
|---|---|---|
| 1: single dose of enzalutamide | Experimental | Not described Receives: Drug: enzalutamide |
| 2: multiple doses of rifampin and single dose of enzalutamide | Experimental | Not described Receives: Drug: enzalutamide; Drug: rifampin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Days 1 to 50 (29 times)
PK of enzalutamide and the sum of enzalutamide + M2 in plasma measured by AUC extrapolated to infinity (AUCinf)
Measured: Days 1 to 50 (29 times)
Secondary outcomes (3)
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)
Measured: Days 8 to 57 (49 times)
PK of rifampin in plasma
Cmax, tmax, AUC for the defined interval between doses (AUCtau), minimum concentration (Cmin)
Measured: Days 6 to 21 (20 times)
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)
Measured: Screening (Day -28 to -7) to End of Study Visit (ESV) (>34 times)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2014 (estimated)
- Study startJul 2013
- Primary completionSep 2013
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Drug-Drug Interaction (DDI)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma Europe B.V.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Medivation, Inc.
- Responsible party
- Sponsor
- Investigators
- Central Contact, Study director, Astellas Pharma Europe B.V.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02138799
- Sponsor's protocol ID
- 9785-CL-0405
- Other IDs
- 2012-004841-34
- Status last verified
- Oct 2014
- First submitted
- 13 May 2014
- Last updated
- 15 Oct 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02138799
- Acronym / sponsor ID
- 9785-CL-0405
- Keywords
- Phase I, Pharmacokinetics, Safety, Drug-drug interactions, Enzalutamide, Rifampin, CYP3A4, CYP2D8
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Astellas Pharma Europe B.V.Industry (pharma, biotech, devices)
- Collaborators
- Medivation, Inc.
- Study start
- Jul 2013
- Primary completion
- Sep 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 15 May 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1: single dose of enzalutamide | Experimental | Drug: enzalutamide |
| 2: multiple doses of rifampin and single dose of enzalutamide | Experimental | Drug: enzalutamide, Drug: rifampin |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| enzalutamideAlso: ASP9785,, MDV3100,, Xtandioral | Drug | 1: single dose of enzalutamide, 2: multiple doses of rifampin and single dose of enzalutamide |
| rifampinoral | Drug | 2: multiple doses of rifampin and single dose of enzalutamide |
Primary outcome
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)
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)
3 secondary outcomes
PK of enzalutamide, M2, M1 and the sum of enzalutamide + M2 in plasma
Time frame: Days 8 to 57 (49 times)
PK of rifampin in plasma
Time frame: Days 6 to 21 (20 times)
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Central Contact study director
Astellas Pharma Europe B.V.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing enzalutamide and rifampin in people with Drug-Drug Interaction (DDI) and Healthy Subjects, run by Astellas Pharma Europe B.V. at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2014.