CompletedNCT01911728Updated Jun 26, 2017

Drug-drug Interaction Study With MDV3100 and a Cocktail of Substrates

A Phase 1 interventional study of MDV3100 and Pioglitazone in Pharmacokinetics of MDV3100 and Castration Resistant Prostate Cancer (CRPC), sponsored by Astellas Pharma Europe B.V.. Completed at 2 sites in South Africa. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-06-26.

Sponsored by Astellas Pharma Europe B.V. · Phase 1, Interventional, and Treatment

From the registry’s dates

Registered 2 years after the study started (first participant enrolled Jul 2011, registered Jul 2013).

Phase: Phase 1
Study type: Interventional
Enrollment: 14
Allocation: Non-randomized
Ages: 18 Years and older
Sex: Male

Study 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).

Conditions studied

Pharmacokinetics of MDV3100
Castration Resistant Prostate Cancer (CRPC)

Browse trials for

Prostatic Neoplasms 6,370

Keywords

Drug-Drug Interaction
Phase 1
MDV3100
Xtandi
Enzalutamide

In context

Prostatic Neoplasms

6,370 studies on the registry are indexed under Prostatic Neoplasms; 1,397 are open to participants now.

This study's enrollment of 14 is below the median of 58 across 4,821 interventional studies indexed under Prostatic Neoplasms.

Browse Prostatic Neoplasms studies →

Lead sponsor

Astellas Pharma Europe B.V. is the lead sponsor of 93 studies on the registry; none are open to participants now.

Of its 5 completed or terminated interventional studies of FDA-regulated products, 4 (80%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: Male
Accepts healthy volunteers: No

Inclusion criteria

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.

Exclusion criteria

Exclusion Criteria:

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;
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)

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Crossover assignment
Masking: None (open label)
Enrollment: 14 participants (actual)

Study arms

Experimental
Multiple doses of MDV3100
Multiple doses of MDV3100 and a single dose of pioglitazone and a single dose of cocktail containing -warfarin, omeprazole and midazolam
Drug: MDV3100 · Drug: Pioglitazone · Drug: Warfarin · Drug: Omeprazole · Drug: Midazolam

Interventions

DrugMDV3100
Oral
Also known as: Xtandi, enzalutamide
DrugPioglitazone
Oral
DrugWarfarin
Oral
DrugOmeprazole
Oral
DrugMidazolam
Oral

What researchers measure

Primary outcomes

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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Day 1 through Day 72 (75 times)

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 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
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

Study locations

2 sites

Parexel
George, South Africa
Parexel/Qdot Pharma
Port Elizabeth, South Africa

References and documents

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 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jun 26, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01911728
Lead sponsor: Astellas Pharma Europe B.V.
Collaborators: Medivation, Inc.
Responsible party: Sponsor
First posted: Jul 30, 2013
Start date: Jul 25, 2011
Primary completion: Feb 21, 2012
Completion: Feb 21, 2012
Last update: Jun 26, 2017

Study contacts

Operation Senior Research Manager

study chair · Astellas Pharma Europe B.V.

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Jun 2017. You cannot join it, but the record below documents what was studied.

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