Pharmacokinetics of MDV3100Phase 1NCT01911728
Drug-drug Interaction Study With MDV3100 and a Cocktail of Substrates
A Phase 1 study testing MDV3100, Pioglitazone and Warfarin in people with Pharmacokinetics of MDV3100 and Castration Resistant Prostate Cancer (CRPC), run by Astellas Pharma Europe B.V. at 2 sites in South Africa.
Trial summary
A drug-drug interaction study to investigate the potential pharmacokinetic interaction between MDV3100 and a cocktail of substrates for pioglitazone (CYP2C8 substrate), S-warfarin (CYP2C9 substrate), omeprazole (CYP2C19 substrate), and midazolam (CYP3A4 substrate). Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Pharmacokinetics of MDV3100, Castration Resistant Prostate Cancer (CRPC)
- What is being tested?
- MDV3100, Pioglitazone and Warfarin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 2 sitesSouth Africa
- Study dates
- 25 Jul 2011to 21 Feb 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 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features;
- Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or orchiectomy (i.e., medical or surgical castration);
- Progressive disease by prostate specific antigen (PSA) or imaging whether or not after chemotherapy in the setting of medical or surgical castration. Disease progression for study entry is defined as one or more of the following 3 criteria:
- PSA progression defined by a minimum of 3 rising PSA levels with an interval of ≥1 week between each determination. The PSA value during the pre investigational period should be ≥2 μg/L (2 ng/mL);
- Soft tissue disease progression defined by the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) for soft tissue disease (see Appendix A);
- Bone disease progression defined by two or more new lesions on bone scan.
Who cannot join
- Confirmed CYP2C8, CYP2C9, or CYP2C19 poor metabolizer status based on genotyping analysis;
- Absolute neutrophil count < 1,500/μL, platelet count < 100,000/μL, and hemoglobin < 5.6 mmol/L (9 g/dL) during the screening period (NOTE: patients may not have received any growth factors or blood transfusions within 7 days prior to the hematologic laboratory values obtained during the screening period);
- Total bilirubin > 1.5 times, or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 times the upper limit of normal during the screening period;
- Creatinine > 177 μmol/L (2 mg/dL) during the screening period;
- Albumin < 30 g/L (3.0 g/dL) during the screening period;
- Treatment with androgen receptor antagonists (bicalutamide, flutamide, nilutamide), 5 α reductase inhibitors (finasteride, dutasteride), estrogens, or chemotherapy within 4 weeks prior to enrollment (Day 1 visit) or plans to initiate treatment with any of these treatments during the study;
Show all 9Show fewer
- Use of herbal products that may decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of prednisone/prednisolone per day within 4 weeks prior to enrollment (Day 1 visit) or plans to initiate treatment with any of these treatments during the study;
- Structurally unstable bone lesions suggesting impending fracture;
- History of seizure, including any febrile seizure, loss of consciousness, or transient ischemia attack within 12 months prior to enrollment (Day 1 visit), or any condition that may pre-dispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization)
Trial locations and contacts
2 sites in 1 country.
About this study
Official title: A Phase I Open-label Study to Evaluate the Effect of Multiple Doses of MDV3100 (ASP9785) on the Pharmacokinetics of Substrates for CYP2C8, CYP2C9, CYP2C19, and CYP3A4 in Patients With Castration-resistant Prostate Cancer
A drug-drug interaction study to investigate the potential pharmacokinetic interaction between MDV3100 and a cocktail of substrates for pioglitazone (CYP2C8 substrate), S-warfarin (CYP2C9 substrate), omeprazole (CYP2C19 substrate), and midazolam (CYP3A4 substrate).
- Being tested
- MDV3100, Pioglitazone, Warfarin, Omeprazole, Midazolam
- Keywords
- Drug-Drug Interaction, Phase 1, MDV3100, Xtandi, Enzalutamide
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
PioglitazoneDrug
Oral
WarfarinDrug
Oral
OmeprazoleDrug
Oral
MidazolamDrug
Oral
| Study group | Role | What they receive |
|---|---|---|
| Multiple doses of MDV3100 | Experimental | Multiple doses of MDV3100 and a single dose of pioglitazone and a single dose of cocktail containing -warfarin, omeprazole and midazolam Receives: Drug: MDV3100; Drug: Pioglitazone; Drug: Warfarin; Drug: Omeprazole; Drug: Midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of the pharmacokinetic profile of pioglitazone (CYP2C8 substrate) in combination with MDV3100 PTM and MDV3100
(Maximum concentration (observed))Cmax, (Area Under Curve from the time of dosing to the last measurable concentration)AUC0-t, (AUC extrapolated to infinity)AUC0-inf
Measured: Day 1 through Day 72 (75 times)
Assessment of the pharmacokinetic profile of S-warfarin (CYP2C9 substrate) in combination with MDV3100 PTM and MDV3100
(Maximum concentration (observed))Cmax, (Area Under Curve from the time of dosing to the last measurable concentration)AUC0-t, (AUC extrapolated to infinity)AUC0-inf
Measured: Day 1 through Day 72 (75 times)
Assessment of the pharmacokinetic profile of omeprazole (CYP2C19 substrate) in combination with MDV3100 PTM and MDV3100
(Maximum concentration (observed))Cmax, (Area Under Curve from the time of dosing to the last measurable concentration)AUC0-t, (AUC extrapolated to infinity)AUC0-inf
Measured: Day 1 through Day 72 (75 times)
Assessment of the pharmacokinetic profile of midazolam (CYP3A4 substrate) in combination with MDV3100 PTM and MDV3100
(Maximum concentration (observed))Cmax, (Area Under Curve from the time of dosing to the last measurable concentration)AUC0-t, (AUC extrapolated to infinity)AUC0-inf
Measured: Day 1 through Day 72 (75 times)
Secondary outcomes (2)
Assessment of the pharmacokinetic profile of substrates pioglitazone (CYP2C8 substrate), S-warfarin (CYP2C9 substrate), omeprazole (CYP2C19 substrate), and midazolam (CYP3A4 substrate) in combination with MDV3100 PTM and MDV3100
(Time to attain Cmax)tmax (Apparent terminal elimination half-life)t1/2, (Apparent total body clearance after extravascular dosing)CL/F, (Apparent volume of distribution during the terminal phase after extravascular dosing)Vz/F, Cmax, AUC0-t, AUC0-inf, (Pre-dose plasma concentration)C0h, (Minimum concentration (observed))Cmin, (AUC between two consecutive doses at steady-state)AUCtau, (Peak-trough ratio)PTR
Measured: Day 1 through Day 72 (75 times)
Monitoring of safety and tolerability through assessment of vital signs, Electrocardiogram (ECG) and clinical safety laboratory and, adverse events
Measured: Day 1 through Day 97
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2013 (estimated)
- Study start25 Jul 2011
- Primary completion21 Feb 2012
- Study completion21 Feb 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 14 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
- NCT01911728
- Sponsor's protocol ID
- 9785-CL-0007
- Other IDs
- 2011-000163-26
- Status last verified
- Jun 2017
- First submitted
- 26 Jul 2013
- Last updated
- 26 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Gibbons JA, de Vries M, Krauwinkel W, Ohtsu Y, Noukens J, van der Walt JS, Mol R, Mordenti J, Ouatas T. Pharmacokinetic Drug Interaction Studies with Enzalutamide. Clin Pharmacokinet. 2015 Oct;54(10):1057-69. doi: 10.1007/s40262-015-0283-1.
PubMed 25929560
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Open-label Study to Evaluate the Effect of Multiple Doses of MDV3100 (ASP9785) on the Pharmacokinetics of Substrates for CYP2C8, CYP2C9, CYP2C19, and CYP3A4 in Patients With Castration-resistant Prostate Cancer
- ClinicalTrials.gov ID
- NCT01911728
- Acronym / sponsor ID
- 9785-CL-0007
- Keywords
- Drug-Drug Interaction, Phase 1, MDV3100, Xtandi, Enzalutamide
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Astellas Pharma Europe B.V.Industry (pharma, biotech, devices)
- Collaborators
- Medivation, Inc.
- Study start
- 25 Jul 2011 (actual)
- Primary completion
- 21 Feb 2012 (actual)
- Study completion
- 21 Feb 2012 (actual)
- First posted
- 30 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.
A drug-drug interaction study to investigate the potential pharmacokinetic interaction between MDV3100 and a cocktail of substrates for pioglitazone (CYP2C8 substrate), S-warfarin (CYP2C9 substrate), omeprazole (CYP2C19 substrate), and midazolam (CYP3A4 substrate).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Multiple doses of MDV3100 | Experimental | Drug: MDV3100, Drug: Pioglitazone, Drug: Warfarin, Drug: Omeprazole, Drug: MidazolamMultiple doses of MDV3100 and a single dose of pioglitazone and a single dose of cocktail containing -warfarin, omeprazole and midazolam |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features;
- Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or orchiectomy (i.e., medical or surgical castration);
- Progressive disease by prostate specific antigen (PSA) or imaging whether or not after chemotherapy in the setting of medical or surgical castration. Disease progression for study entry is defined as one or more of the following 3 criteria:
Key exclusion criteria (9 listed)
- Confirmed CYP2C8, CYP2C9, or CYP2C19 poor metabolizer status based on genotyping analysis;
- Absolute neutrophil count < 1,500/μL, platelet count < 100,000/μL, and hemoglobin < 5.6 mmol/L (9 g/dL) during the screening period (NOTE: patients may not have received any growth factors or blood transfusions within 7 days prior to the hematologic laboratory values obtained during the screening period);
- Total bilirubin > 1.5 times, or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 times the upper limit of normal during the screening period;
- Creatinine > 177 μmol/L (2 mg/dL) during the screening period;
- Albumin < 30 g/L (3.0 g/dL) during the screening period;
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 | Multiple doses of MDV3100 |
| PioglitazoneOral | Drug | Multiple doses of MDV3100 |
| WarfarinOral | Drug | Multiple doses of MDV3100 |
| OmeprazoleOral | Drug | Multiple doses of MDV3100 |
| MidazolamOral | Drug | Multiple doses of MDV3100 |
Primary outcome
Assessment of the pharmacokinetic profile of pioglitazone (CYP2C8 substrate) in combination with MDV3100 PTM and MDV3100
Time frame: Day 1 through Day 72 (75 times)
(Maximum concentration (observed))Cmax, (Area Under Curve from the time of dosing to the last measurable concentration)AUC0-t, (AUC extrapolated to infinity)AUC0-inf
Assessment of the pharmacokinetic profile of S-warfarin (CYP2C9 substrate) in combination with MDV3100 PTM and MDV3100
Time frame: Day 1 through Day 72 (75 times)
(Maximum concentration (observed))Cmax, (Area Under Curve from the time of dosing to the last measurable concentration)AUC0-t, (AUC extrapolated to infinity)AUC0-inf
Assessment of the pharmacokinetic profile of omeprazole (CYP2C19 substrate) in combination with MDV3100 PTM and MDV3100
Time frame: Day 1 through Day 72 (75 times)
(Maximum concentration (observed))Cmax, (Area Under Curve from the time of dosing to the last measurable concentration)AUC0-t, (AUC extrapolated to infinity)AUC0-inf
Assessment of the pharmacokinetic profile of midazolam (CYP3A4 substrate) in combination with MDV3100 PTM and MDV3100
Time frame: Day 1 through Day 72 (75 times)
(Maximum concentration (observed))Cmax, (Area Under Curve from the time of dosing to the last measurable concentration)AUC0-t, (AUC extrapolated to infinity)AUC0-inf
2 secondary outcomes
Assessment of the pharmacokinetic profile of substrates pioglitazone (CYP2C8 substrate), S-warfarin (CYP2C9 substrate), omeprazole (CYP2C19 substrate), and midazolam (CYP3A4 substrate) in combination with MDV3100 PTM and MDV3100
Time frame: Day 1 through Day 72 (75 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 97
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 26 Jun 2017.
- Derived from this study: PubMed 25929560Gibbons JA, de Vries M, Krauwinkel W, Ohtsu Y, Noukens J, van der Walt JS, Mol R, Mordenti J, Ouatas T. Pharmacokinetic Drug Interaction Studies with Enzalutamide. Clin Pharmacokinet. 2015 Oct;54(10):1057-69. doi: 10.1007/s40262-015-0283-1.
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.
2 sites 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, Pioglitazone and Warfarin in people with Pharmacokinetics of MDV3100 and Castration Resistant Prostate Cancer (CRPC), run by Astellas Pharma Europe B.V. at 2 sites in South Africa.
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 9 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 26 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in South Africa. 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 the pharmacokinetic profile of pioglitazone (CYP2C8 substrate) in combination with MDV3100 PTM and MDV3100 (time frame: Day 1 through Day 72 (75 times)). 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?
On the ClinicalTrials.gov record for NCT01911728, 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 26 Jun 2017.