A Study to Explore the Routes of Elimination of MDV3100

NCT01911715 | Completed Phase 1

• 2 other identifiers: 9785-CL-00012011-000089-37
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

A study to investigate the excretion routes of radio-labelled MDV3100.

Conditions

Healthy Subjects; Pharmacokinetics of MDV3100

Keywords

Phase 1; Mass Balance; MDV3100; Xtandi; Enzalutamide; Metabolism; Excretion

Outcome Measures

Primary Outcomes (17)

• 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 Outcomes (1)

• Safety as assessed by recording adverse events, laboratory assessments, vital signs and electrocardiograms (ECGs)

  Day 1 through Day 78

Study Arms (1)

Single Oral MDV3100 dose

EXPERIMENTAL

Drug: MDV3100

Interventions

MDV3100 DRUG

Oral

Also known as: Xtandi, enzalutamide

Single Oral MDV3100 dose

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma Europe B.V.: lead
• Medivation, Inc.: collaborator

Study Sites (1)

PRA International

Zuidlaren, 9471GP, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 25917876 DERIVED

MeSH Terms

Interventions

enzalutamide

Study Officials

• Operation Senior Research Manager

  Astellas Pharma Europe B.V.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2013
• First Posted: July 30, 2013
• Study Start: April 1, 2011
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: July 30, 2013

Record last verified: 2013-07

Locations

NL (1)