A Study to Explore the Routes of Elimination of MDV3100

Study Overview
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Brief Summary
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A study to investigate the excretion routes of radio-labelled MDV3100.

Official Title
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A Phase I Open-label Study to Investigate the Mass Balance and Biotransformation of a Single Oral 160 mg (100 µCi) Dose of 14C-MDV3100 (ASP9785) in Healthy Male Subjects

Conditions
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Healthy Subjects, Pharmacokinetics of MDV3100

Intervention / Treatment
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* Drug: MDV3100


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body Mass Index within 18.5 to 30.0kg/m2 Regular defecation pattern (minimum once per 2 days). Subject must be non-fertile, i.e., surgically sterilized or must practice an adequate contraceptive method to prevent pregnancies as defined in the protocol. Exclusion Criteria: Known or suspected hypersensitivity to MDV3100, or any components of the formulation used. Any of the liver function tests above the upper limit of normal. A retest to confirm the result may be performed once. 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 measurements at the pre-study visit as follows: Pulse <40 or >90 bpm; mean systolic blood pressure >140 mmHg ; mean diastolic blood pressure >90 mmHg (blood pressure measurements taken in triplicate after subject has been resting in supine position for 5 min; pulse will be measured automatically). A QTc interval of > 430 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). Use of any prescribed or OTC (over-the-counter) drugs (including vitamins, natural and herbal remedies, e.g. St. John's wort) in the 2 weeks prior to admission to the Clinical Unit, except for occasional use of paracetamol (up to 3 g/day). Regular use of any inducer of metabolism (e.g., barbiturates, rifampin) in the 3 months prior to admission to the Clinical Unit. Positive serology test for HBsAg, anti HAV (IgM), anti-HCV or anti-HIV 1+2. Exposure to radiation for diagnostic reasons (except dental X-rays and plain X-rays of thorax and bony skeleton (excluding spinal column)), during work or during participation in a clinical study in the previous year.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Oral MDV3100 dose<br> | Drug: MDV3100<br>* Oral<br>* Other names: enzalutamide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of Pharmacokinetic profile of total radioactivity in plasma and whole blood by Maximum concentration (Cmax) |  | Day 1 through Day 78 (21 times) | 
| Assessment of Pharmacokinetic profile of total radioactivity in plasma and whole blood by Time to attain Cmax (tmax) | Time to attain Cmax (tmax) | Day 1 through Day 78 (21 times) | 
| Assessment of Pharmacokinetic profile of total radioactivity in plasma and whole blood by Time to reach quantifiable concentrations (tlag) |  | Day 1 through Day 78 (21 times) | 
| Assessment of Pharmacokinetic profile of total radioactivity in plasma and whole blood by AUC from the time of dosing to the last measurable concentration (AUC0-t) |  | Day 1 through Day 78 (21 times) | 
| Assessment of Pharmacokinetic profile of total radioactivity in plasma and whole blood by AUC extrapolated to infinity (AUC0-inf) |  | Day 1 through Day 78 (21 times) | 
| Assessment of Pharmacokinetic profile of total radioactivity in plasma and whole blood by Terminal Disposition Rate Constant (λz) |  | Day 1 through Day 78 (21 times) | 
| Assessment of Pharmacokinetic profile of total radioactivity in plasma and whole blood by Apparent terminal elimination half life (t1/2) |  | Day 1 through Day 78 (21 times) | 
| Assessment of Pharmacokinetic profile of total radioactivity in plasma and whole blood by Apparent total body clearance after extra vascular dosing (CL/F) |  | Day 1 through Day 78 (21 times) | 
| Assessment of Pharmacokinetic profile of total radioactivity in plasma and whole blood by Apparent volume of distribution during the terminal phase after extra vascular dosing (Vz/F) |  | Day 1 through Day 78 (21 times) | 
| Assessment of Pharmacokinetic profile of total radioactivity in plasma and whole blood by blood-to-plasma ratio (Ratio Cb/p) |  | Day 1 through Day 78 (21 times) | 
| Assessment of 14C recovery in urine |  | Day 1 through Day 78 (17 times) | 
| Assessment of 14C recovery in feces |  | Day 1 through Day 78 (16 times) | 
| Assessment of total 14C recovery (urine and feces combined) within 24 hours |  | Day 1 through Day 78 (17 times for urine and 16 times for feces) | 
| Assessment of total 14C recovery (urine and feces combined) after Time of last quantifiable concentration (tlast) |  | Day 1 through Day 78 (17 times for urine and 16 times for feces) | 
| Assessment of Pharmacokinetic profile of MDV3100 and metabolites in plasma | PK of MDV3100, MDPC0001, and MDPC0002 in plasma based on validated LC-MS/MS methods: In plasma: Cmax, tmax, tlag, AUC0-t, AUC0-inf, λz, t1/2, CL/F (parent only), and Vz/F (parent only) The ratios of AUCMDV3100/AUC14C , AUCMDPC0001/AUCMDV3100 and AUCMDPC0001/AUC14C (and the same for MDPC0002) will be calculated | Day 1 through Day 78 (21 times) | 
| Assessment of Pharmacokinetic profile of MDV3100 and metabolites in urine | PK of MDV3100, MDPC0001, and MDPC0002 in urine based on validated LC-MS/MS methods: In urine: Cumulative amount excreted in urine from time zero to the last measurable concentration after dosing (Ae0-t), Renal clearance (CLR), Percent of dose excreted in urine from time zero to the last measurable concentration after dosing (Ae0-t%), Cumulative amount excreted in urine from time zero extrapolated to infinity (Ae0-inf), Percent of dose excreted in urine from time zero extrapolated to infinity (Ae0-inf%) The ratios of AUCMDV3100/AUC14C , AUCMDPC0001/AUCMDV3100 and AUCMDPC0001/AUC14C (and the same for MDPC0002) will be calculated | Day 1 through Day 78 (17 times) | 
| Metabolic Profile: Profiling of possible metabolites of MDV3100 in plasma, urine, and feces | Identification and possible quantification of metabolites in plasma, and if applicable, in urine and feces | Day 1 through Day 78 (14 times) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety as assessed by recording adverse events, laboratory assessments, vital signs and electrocardiograms (ECGs) |  | Day 1 through Day 78 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, Mass Balance, MDV3100, Xtandi, Enzalutamide, Metabolism, Excretion