A Study to Explore the Routes of Elimination of MDV3100

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Subjects; Pharmacokinetics of MDV3100
• Intervention / Treatment: Drug: MDV3100

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Zuidlaren, Netherlands, 9471GP
    • PRA International

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Single Oral MDV3100 dose	Drug: MDV3100; Oral; Other Names: Xtandi; enzalutamide

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Astellas Pharma Europe B.V.
• Collaborators: Medivation, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (ACTUAL): July 1, 2011
• Study Completion (ACTUAL): July 1, 2011

Study Registration Dates

• First Submitted: July 26, 2013
• First Submitted That Met QC Criteria: July 26, 2013
• First Posted (ESTIMATE): July 30, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): July 30, 2013
• Last Update Submitted That Met QC Criteria: July 26, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: Phase 1; Xtandi; MDV3100; Enzalutamide; Metabolism; Excretion; Mass Balance
• Other Study ID Numbers: 9785-CL-0001; 2011-000089-37 (EUDRACT_NUMBER)