Severe Hepatic ImpairmentPhase 1NCT02138162
A Study to Investigate the Effect of Severely Diminished Liver Function on the Metabolism, Safety, and Tolerability of a Single Oral Dose of Enzalutamide in Men
A Phase 1 study testing enzalutamide in people with Severe Hepatic Impairment and Normal Hepatic Function, run by Astellas Pharma Europe B.V. at 1 site in Bulgaria.
Trial summary
The influence of severely diminished liver function on the metabolism, safety, and tolerability of a single oral dose of enzalutamide in a group of 8 men. The results are compared to the data gained from 8 age- and BMI-matched men with normal liver function. Read more about this study
- Who is it for?
- Ages 18 to 69 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Severe Hepatic Impairment, Normal Hepatic Function
- What is being tested?
- enzalutamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteBulgaria
- Study dates
- Aug 2013to Mar 2014
- 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 69 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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 starting at Screening and continue throughout the study period and for 90 days after the final study drug administration.
- Male subject must not donate sperm starting at Screening and throughout the study period and for 90 days after the final study drug administration.
- Subject has a Body Mass Index (BMI) range of 18.5 - 34.0 kg/m2 inclusive. The subject weighs at least 50 kg [at Screening].
- Inclusion Criteria:Subjects with severe hepatic impairment must also meet the following inclusion criteria:
- Subject has a Child-Pugh classification Class C (severe, 10 to 15 points).
- Age- and BMI-matched to subjects with severe liver hepatic impairment.
Who cannot join
- Subject has known or suspected hypersensitivity to enzalutamide, or any components of the formulation used.
- Subject has history of seizure or any condition that may predispose to seizure. Also history of loss of consciousness or transient ischemic attack within 12 months of enrollment (Day 1 visit).
- Subject has used grapefruit (or grapefruit containing products) or marmalade in the week prior to admission to the clinical unit (Day -1), as reported by the subject.
- Subject has any of the liver function tests above the upper limit of normal.
- Exclusion Criteria: Subjects with severe hepatic impairment must also not have any of the following characteristics:
- Subject has fluctuating or rapidly deteriorating hepatic function, as indicated by strongly varying or worsening of clinical and/or laboratory signs of hepatic impairment within the screening period.
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- Subject has surgical porto-systemic shunts, including TIPSS (Trans-jugular intrahepatic portosystemic shunt).
- Subject has presence of severe hepatic encephalopathy (grade > 2).
- Subject has advanced ascites.
- Subject has esophageal variceal bleeding in the medical history (within 6 months before Day -1).
- Subject has thrombocyte level below 40x109 /L and /or hemoglobin below 90 g/L.
- Subject has significant renal dysfunction (creatinine clearance below 50 mL/min, estimated according to the method of Modification of Diet in Renal Disease (MDRD) formula).
- Subject has had previous liver transplantation.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Non-randomized, Open-label, Single-dose Study to Investigate the Pharmacokinetics, Safety and Tolerability of Enzalutamide in Male Subjects With Severe Hepatic Impairment and Normal Hepatic Function
The influence of severely diminished liver function on the metabolism, safety, and tolerability of a single oral dose of enzalutamide in a group of 8 men. The results are compared to the data gained from 8 age- and BMI-matched men with normal liver function.
Read the detailed description
Screening takes place between Day -22 and Day -2, and subjects are admitted to the clinic on Day -1. Each subject receives a single oral dose of enzalutamide on Day 1, under fasted conditions. They are discharged on Day 7; ambulant visits take place until Day 50. An End of Study Visit (ESV) occurs 7-10 days after the last PK sampling or early withdrawal.
Full PK profiles are obtained for enzalutamide, metabolite 1 of enzalutamide (M1) and metabolite 2 of enzalutamide (M2) up to 1176 hours (Day 50) after administration.
Safety assessments are performed throughout the study. For subjects with severe hepatic impairment, additional Child-Pugh classification and laboratory safety tests (including liver function tests) are performed regularly after administration.
- Conditions
- Severe Hepatic Impairment, Normal Hepatic Function
- Being tested
- enzalutamide
- Keywords
- Phase 1, Pharmacokinetics, Safety, Severe hepatic impairment, Enzalutamide
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
| Study group | Role | What they receive |
|---|---|---|
| 1:Single dose of enzalutamide in hepatically impaired subjects | Experimental | Single dose of enzalutamide Receives: Drug: enzalutamide |
| 2:Single dose of enzalutamide in healthy subjects | Experimental | Single dose of enzalutamide Receives: Drug: enzalutamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics (PK) of enzalutamide after a single oral dose
area under the plasma concentration - time curve (AUC) extrapolated to infinity (AUC0-inf)
Measured: Days 1-6, 8, 12, 15, 19, 22, 26, 29, 36, 43, 50
PK of enzalutamide after a single oral dose
maximum concentration (observed) (Cmax)
Measured: Days 1-6, 8, 12, 15, 19, 22, 26, 29, 36, 43, 50
PK of enzalutamide plus N-desmethyl enzalutamide (M2) after a single oral dose
area under the plasma concentration - time curve (AUC) extrapolated to infinity (AUC0-inf)
Measured: Days 1-6, 8, 12, 15, 19, 22, 26, 29, 36, 43, 50
PK of enzalutamide plus N-desmethyl enzalutamide (M2) after a single oral dose
maximum concentration (observed) (Cmax)
Measured: Days 1-6, 8, 12, 15, 19, 22, 26, 29, 36, 43, 50
Secondary outcomes (2)
PK of enzalutamide, M1, M2 and the sum of enzalutamide plus N-desmethyl enzalutamide (M2)
Cmax and AUC0-inf (M1, M2 only), time to attain Cmax (tmax), AUC up to last quantifiable concentration (AUC0-last), apparent terminal elimination half life (t1/2), apparent volume of distribution during the terminal phase after extra vascular dosing (Vz/F), apparent total body clearance after extra vascular dosing (CL/F) (parent compound only), Metabolite-to-Parent Ratio (MPR), percent extrapolated for AUC0-inf (%AUC)
Measured: Days 1-6, 8, 12, 15, 19, 22, 26, 29, 36, 43, 50
Additional pharmacokinetic variables for enzalutamide, and, as appropriate, for M1 and M2, based upon unbound plasma concentrations
Unbound Cmax (Cmax,u), unbound AUC0-inf (AUC0-inf,u), and unbound AUC0-last (AUC0-last,u). Unbound CL/F (CLu/F) and unbound Vz/F (Vz,u/F) (parent only)
Measured: Days 1-6, 8, 12, 15, 19, 22, 26, 29, 36, 43, 50
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2014 (estimated)
- Study startAug 2013
- Primary completionMar 2014
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe Hepatic ImpairmentStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 16 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
- Medical Monitor, Study director, Astellas Pharma Europe B.V.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02138162
- Sponsor's protocol ID
- 9785-CL-0404
- Other IDs
- 2012-004858-29
- Status last verified
- May 2014
- First submitted
- 12 May 2014
- Last updated
- 14 May 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Non-randomized, Open-label, Single-dose Study to Investigate the Pharmacokinetics, Safety and Tolerability of Enzalutamide in Male Subjects With Severe Hepatic Impairment and Normal Hepatic Function
- ClinicalTrials.gov ID
- NCT02138162
- Acronym / sponsor ID
- 9785-CL-0404
- Conditions
- Severe Hepatic Impairment, Normal Hepatic Function
- Keywords
- Phase 1, Pharmacokinetics, Safety, Severe hepatic impairment, Enzalutamide
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Astellas Pharma Europe B.V.Industry (pharma, biotech, devices)
- Collaborators
- Medivation, Inc.
- Study start
- Aug 2013
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 14 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.
The influence of severely diminished liver function on the metabolism, safety, and tolerability of a single oral dose of enzalutamide in a group of 8 men. The results are compared to the data gained from 8 age- and BMI-matched men with normal liver function.
Detailed description
Screening takes place between Day -22 and Day -2, and subjects are admitted to the clinic on Day -1. Each subject receives a single oral dose of enzalutamide on Day 1, under fasted conditions. They are discharged on Day 7; ambulant visits take place until Day 50. An End of Study Visit (ESV) occurs 7-10 days after the last PK sampling or early withdrawal.
Full PK profiles are obtained for enzalutamide, metabolite 1 of enzalutamide (M1) and metabolite 2 of enzalutamide (M2) up to 1176 hours (Day 50) after administration.
Safety assessments are performed throughout the study. For subjects with severe hepatic impairment, additional Child-Pugh classification and laboratory safety tests (including liver function tests) are performed regularly after administration.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1:Single dose of enzalutamide in hepatically impaired subjects | Experimental | Drug: enzalutamideSingle dose of enzalutamide |
| 2:Single dose of enzalutamide in healthy subjects | Experimental | Drug: enzalutamideSingle dose of enzalutamide |
Who may qualify
- Ages
- 18 to 69 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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 starting at Screening and continue throughout the study period and for 90 days after the final study drug administration.
- Male subject must not donate sperm starting at Screening and throughout the study period and for 90 days after the final study drug administration.
- Subject has a Body Mass Index (BMI) range of 18.5 - 34.0 kg/m2 inclusive. The subject weighs at least 50 kg [at Screening].
- Inclusion Criteria:Subjects with severe hepatic impairment must also meet the following inclusion criteria:
- Subject has a Child-Pugh classification Class C (severe, 10 to 15 points).
Key exclusion criteria (13 listed)
- Subject has known or suspected hypersensitivity to enzalutamide, or any components of the formulation used.
- Subject has history of seizure or any condition that may predispose to seizure. Also history of loss of consciousness or transient ischemic attack within 12 months of enrollment (Day 1 visit).
- Subject has used grapefruit (or grapefruit containing products) or marmalade in the week prior to admission to the clinical unit (Day -1), as reported by the subject.
- Subject has any of the liver function tests above the upper limit of normal.
- Exclusion Criteria: Subjects with severe hepatic impairment must also not have any of the following characteristics:
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 in hepatically impaired subjects, 2:Single dose of enzalutamide in healthy subjects |
Primary outcome
Pharmacokinetics (PK) of enzalutamide after a single oral dose
Time frame: Days 1-6, 8, 12, 15, 19, 22, 26, 29, 36, 43, 50
area under the plasma concentration - time curve (AUC) extrapolated to infinity (AUC0-inf)
PK of enzalutamide after a single oral dose
Time frame: Days 1-6, 8, 12, 15, 19, 22, 26, 29, 36, 43, 50
maximum concentration (observed) (Cmax)
PK of enzalutamide plus N-desmethyl enzalutamide (M2) after a single oral dose
Time frame: Days 1-6, 8, 12, 15, 19, 22, 26, 29, 36, 43, 50
area under the plasma concentration - time curve (AUC) extrapolated to infinity (AUC0-inf)
PK of enzalutamide plus N-desmethyl enzalutamide (M2) after a single oral dose
Time frame: Days 1-6, 8, 12, 15, 19, 22, 26, 29, 36, 43, 50
maximum concentration (observed) (Cmax)
2 secondary outcomes
PK of enzalutamide, M1, M2 and the sum of enzalutamide plus N-desmethyl enzalutamide (M2)
Time frame: Days 1-6, 8, 12, 15, 19, 22, 26, 29, 36, 43, 50
Additional pharmacokinetic variables for enzalutamide, and, as appropriate, for M1 and M2, based upon unbound plasma concentrations
Time frame: Days 1-6, 8, 12, 15, 19, 22, 26, 29, 36, 43, 50
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 14 May 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.
Medical Monitor 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 in people with Severe Hepatic Impairment and Normal Hepatic Function, run by Astellas Pharma Europe B.V. at 1 site in Bulgaria.
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 6 inclusion and 13 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 14 May 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 Bulgaria. 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?
Pharmacokinetics (PK) of enzalutamide after a single oral dose (time frame: Days 1-6, 8, 12, 15, 19, 22, 26, 29, 36, 43, 50). The study lists 4 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 14 May 2014.