Healthy Subjects, Pharmacokinetics of MDV3100
Conditions
Keywords
Phase 1, Mass Balance, MDV3100, Xtandi, Enzalutamide, Metabolism, Excretion
Brief summary
A study to investigate the excretion routes of radio-labelled MDV3100.
Interventions
DRUGMDV3100
Oral
Sponsors
Medivation, Inc.
Astellas Pharma Europe B.V.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Metabolic Profile: Profiling of possible metabolites of MDV3100 in plasma, urine, and feces | Day 1 through Day 78 (14 times) | Identification and possible quantification of metabolites in plasma, and if applicable, in urine and feces |
| 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) | Day 1 through Day 78 (21 times) | Time to attain Cmax (tmax) |
| 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 | Day 1 through Day 78 (21 times) | 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 |
| Assessment of Pharmacokinetic profile of MDV3100 and metabolites in urine | Day 1 through Day 78 (17 times) | 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 |
Secondary
| Measure | Time frame |
|---|---|
| Safety as assessed by recording adverse events, laboratory assessments, vital signs and electrocardiograms (ECGs) | Day 1 through Day 78 |
Countries
Netherlands
Outcome results
None listed