Pharmacokinetics of MDV3100Phase 1NCT01901133
Hepatic Impairment Study With MDV3100 in Subjects With Mild and Moderate Hepatic Impairment Compared to a Healthy Control Group
A Phase 1 study testing MDV3100 in people with Pharmacokinetics of MDV3100 and Healthy Subjects, run by Astellas Pharma Europe B.V. at 1 site in Moldova.
Trial summary
This study will assess the influence of hepatic impairment on the pharmacokinetics, safety and tolerability of a single dose of MDV3100 in male subjects. The study will consist of two treatment arms. 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
- Pharmacokinetics of MDV3100, Healthy Subjects, Kidney Diseases
- What is being tested?
- MDV3100
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteMoldova
- Study dates
- Oct 2011to Jan 2012
- 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
- All subjects must meet all of the following inclusion criteria:
- Subject must be non-fertile, i.e., surgically sterilized or must practice an adequate contraceptive method to prevent pregnancies
- Body Mass Index (BMI) of at least 18.5 and no greater than 34.0 kg/m2.
- Subjects with mild or moderate hepatic impairment must also meet the following inclusion criteria:
- Child-Pugh classification Class A (mild, 5 or 6 points) or Class B (moderate, 7 to 9 points) liver function impairment.
Who cannot join
- All subjects must not have any of the following characteristics:
- Known or suspected hypersensitivity to MDV3100 or any components of the formulation used.
- 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).
- Any clinically significant history of asthma, eczema, any other allergic condition or previous severe hypersensitivity to any drug (excluding non-active hay fever).
- Abnormal pulse and/or blood pressure (BP) measurements at the pre-study visit as follows: Pulse <40 or >90 bpm; mean systolic BP >160 mmHg; mean diastolic BP >100 mmHg (BP measurements taken in triplicate after subject has been resting in supine position for 5 min; pulse will be measured
- A QTcF interval of >450 ms after repeated measurements (consistently after duplicate measurements), a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease, or a family history of Long QT Syndrome (LQTS).
Show all 24Show fewer
- Significant renal dysfunction (creatinine clearance below 60 mL/min, estimated according to the method of modification of diet in renal disease (MDRD) formula).
- Regular use of any inducer of metabolism (e.g. barbiturates, rifampin) in the 3 months prior to admission to the Clinical Unit.
- Participation in any clinical study within 3 months or participation in more than 3 clinical studies within 12 months, prior to the expected date of enrolment into the study, provided that the clinical study did not entail a biological compound with a long terminal half life.
- For subjects with normal hepatic function:
- Regular use of any prescribed or OTC (over-the-counter) drugs, which includes vitamins, natural and herbal remedies (e.g. St John's wort) and food supplements in the 4 weeks prior to admission to the Clinical Unit and use of any drugs in the 2 weeks prior to admission to the Clinical Unit, except for occasional use of paracetamol (up to 3 g/day).
- Positive serology test for HBsAg, anti HAV (IgM), anti-HCV, anti-HIV-1 or anti-HIV-2.
- For subjects with mild or moderate hepatic impairment:
- 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. (e.g. advanced ascites, infection of ascites, fever, active gastrointestinal bleeding).
- Change in dose regimen of medically required medication within the last two weeks before pre-study examination (allowed co-medication in patients), and/or the use of unallowed co-medication in the 3 weeks prior to admission to the clinical unit (not allowed: any known hepatic enzyme altering agents or compounds known to restrict metabolism).
- Presence of a hepatocellular carcinoma, or an acute liver disease caused by an infection or drug toxicity.
- Severe portal hypertension or surgical porto-systemic shunts, including TIPSS (Transjugular intrahepatic portosystemic shunt).
- Biliary obstruction or other cause of hepatic impairment not related to parenchymal disorder and/or disease of the liver.
- Signs of significant hepatic encephalopathy (Hepatic encephalopathy score >2).
- Severe ascites and/or pleural effusion
- Esophageal variceal bleeding in the medical history.
- Thrombocyte level below 40x109/L and /or hemoglobin below 90 g/L.
- Previous liver transplantation.
- Positive serology test for, anti HAV (IgM), anti-HIV-1 or anti-HIV-2.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Non-randomized, Open-label, Single-dose Study to Investigate the Pharmacokinetics, Safety and Tolerability of MDV3100 in Male Subjects With Mild or Moderate Hepatic Impairment and Normal Hepatic Function
This study will assess the influence of hepatic impairment on the pharmacokinetics, safety and tolerability of a single dose of MDV3100 in male subjects.
The study will consist of two treatment arms. Arm A will assess the influence of mild hepatic impairment, and Arm B will assess the influence of moderate hepatic impairment. Data obtained from subjects with hepatic impairment will be compared to data from Body Mass Index (BMI) and age-matched subjects with normal hepatic function.
- Being tested
- MDV3100
- Keywords
- Phase 1, MDV3100, Hepatic Impairment, Kidney Diseases, Xtandi, enzalutamide
- Medical subject headings
- Kidney Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MDV3100Drug
Also called Xtandi, enzalutamide
Oral
| Study group | Role | What they receive |
|---|---|---|
| A: Mild hepatic impairment subjects + control | Experimental | Not described Receives: Drug: MDV3100 |
| B: Moderate hepatic impairment subjects + control | Experimental | Not described Receives: Drug: MDV3100 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of pharmacokinetics measured by AUC0-inf following single dose of MDV3100
Area under the plasma concentration - time curve extrapolated to infinity (AUC0-inf) in subjects with mild and moderate hepatic impairment to matched control subjects with normal hepatic function.
Measured: Day 1 through Day 50 (25 times)
Assessment of pharmacokinetics measured by Cmax following single dose of MDV3100
Maximum concentration (observed) (Cmax) in subjects with mild and moderate hepatic impairment to matched control subjects with normal hepatic function.
Measured: Day 1 through Day 50 (25 times)
Secondary outcomes (2)
Composite of pharmacokinetics following single dose of MDV3100
Measured by 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), Cmax, t1/2, AUC0-inf, Unbound maximum concentration (observed) (Cmax,u), Unbound AUC extrapolated to infinity (AUC0-inf,u), Unbound apparent total body clearance after extra vascular dosing (CLu/F), Unbound apparent volume of distribution during the terminal phase after extra vascular dosing (Vz,u/F), Fraction unbound (fu).
Measured: Day 1 through Day 50 (25 times)
Monitoring of safety and tolerability through assessment of vital signs, Electrocardiogram (ECG) and clinical safety laboratory and adverse events
For hepatic impaired subjects, additional Child-Pugh classification will be performed after MDV3100 administration.
Measured: Day 1 through Day 50
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2013 (estimated)
- Study startOct 2011
- Primary completionJan 2012
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pharmacokinetics of MDV3100Studies 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
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 33 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
- Operation Senior Research Manager, Study chair, Astellas Pharma Europe B.V.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01901133
- Sponsor's protocol ID
- 9785-CL-0009
- Status last verified
- Sep 2014
- First submitted
- 18 Jun 2013
- Last updated
- 15 Sep 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Gibbons JA, Ouatas T, Krauwinkel W, Ohtsu Y, van der Walt JS, Beddo V, de Vries M, Mordenti J. Clinical Pharmacokinetic Studies of Enzalutamide. Clin Pharmacokinet. 2015 Oct;54(10):1043-55. doi: 10.1007/s40262-015-0271-5.
PubMed 25917876
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Non-randomized, Open-label, Single-dose Study to Investigate the Pharmacokinetics, Safety and Tolerability of MDV3100 in Male Subjects With Mild or Moderate Hepatic Impairment and Normal Hepatic Function
- ClinicalTrials.gov ID
- NCT01901133
- Acronym / sponsor ID
- 9785-CL-0009
- Keywords
- Phase 1, MDV3100, Hepatic Impairment, Kidney Diseases, Xtandi, enzalutamide
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Astellas Pharma Europe B.V.Industry (pharma, biotech, devices)
- Collaborators
- Medivation, Inc.
- Study start
- Oct 2011
- Primary completion
- Jan 2012 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 17 Jul 2013 (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 will assess the influence of hepatic impairment on the pharmacokinetics, safety and tolerability of a single dose of MDV3100 in male subjects.
The study will consist of two treatment arms. Arm A will assess the influence of mild hepatic impairment, and Arm B will assess the influence of moderate hepatic impairment. Data obtained from subjects with hepatic impairment will be compared to data from Body Mass Index (BMI) and age-matched subjects with normal hepatic function.
Study design
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A: Mild hepatic impairment subjects + control | Experimental | Drug: MDV3100 |
| B: Moderate hepatic impairment subjects + control | Experimental | Drug: MDV3100 |
Who may qualify
- Ages
- 18 to 69 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- All subjects must meet all of the following inclusion criteria:
- Subjects with mild or moderate hepatic impairment must also meet the following inclusion criteria:
Key exclusion criteria (24 listed)
- All subjects must not have any of the following characteristics:
- For subjects with normal hepatic function:
- For subjects with mild or moderate hepatic impairment:
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 |
|---|---|---|
| MDV3100Also: Xtandi, enzalutamideOral | Drug | A: Mild hepatic impairment subjects + control, B: Moderate hepatic impairment subjects + control |
Primary outcome
Assessment of pharmacokinetics measured by AUC0-inf following single dose of MDV3100
Time frame: Day 1 through Day 50 (25 times)
Area under the plasma concentration - time curve extrapolated to infinity (AUC0-inf) in subjects with mild and moderate hepatic impairment to matched control subjects with normal hepatic function.
Assessment of pharmacokinetics measured by Cmax following single dose of MDV3100
Time frame: Day 1 through Day 50 (25 times)
Maximum concentration (observed) (Cmax) in subjects with mild and moderate hepatic impairment to matched control subjects with normal hepatic function.
2 secondary outcomes
Composite of pharmacokinetics following single dose of MDV3100
Time frame: Day 1 through Day 50 (25 times)
Monitoring of safety and tolerability through assessment of vital signs, Electrocardiogram (ECG) and clinical safety laboratory and adverse events
Time frame: Day 1 through Day 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 15 Sep 2014.
- Derived from this study: PubMed 25917876Gibbons JA, Ouatas T, Krauwinkel W, Ohtsu Y, van der Walt JS, Beddo V, de Vries M, Mordenti J. Clinical Pharmacokinetic Studies of Enzalutamide. Clin Pharmacokinet. 2015 Oct;54(10):1043-55. doi: 10.1007/s40262-015-0271-5.
Related trials for Pharmacokinetics of MDV3100
RecruitingPhase 3
A Study to Learn How PF-06821497 (Mevrometostat) Works in Men With Metastatic Castration-resistant Prostate Cancer.
Metastatic Castration-Resistant Prostate Cancer
RecruitingPhase 1/2
Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors
Liposarcoma, Prostate Cancer
RecruitingPhase 1
AXT-1003 Combination With Enzalutamide in Participants With mCRPC
mCRPC
RecruitingPhase 1
A Study to Learn How Enzalutamide, Apalutamide and Bicalutamide Affect the Way Fezolinetant is Processed in Men With Prostate Cancer
Prostate Cancer
RecruitingPhase 3
This Study Will Explore Whether a Combination of the Investigational Drug Mevrometostat (PF-06821497) and Enzalutamide Will Work Better Than Taking Enzalutamide Alone in Participants With mCSPC Who Are ARPI naïve.
Metastatic Castration Sensitive Prostate Cancer (mCSPC), Hormone Sensitive Prostate Cancer
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.
Operation Senior Research Manager study chair
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 MDV3100 in people with Pharmacokinetics of MDV3100 and Healthy Subjects, run by Astellas Pharma Europe B.V. at 1 site in Moldova.
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 5 inclusion and 24 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 Sep 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 Moldova. 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?
Assessment of pharmacokinetics measured by AUC0-inf following single dose of MDV3100 (time frame: Day 1 through Day 50 (25 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?
On the ClinicalTrials.gov record for NCT01901133, which also lists 1 linked publication.
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 Sep 2014.