Clinical trial NCT01911715: A Study to Explore the Routes of Elimination of MDV3100
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Pharmacokinetics of MDV3100
Keywords: Phase 1
Mass Balance
MDV3100
Xtandi
Enzalutamide
Metabolism
Excretion
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Medivation, Inc.
First posted: 2013-07-30
Enrollment: 6
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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


Eligibility criteria: 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.

Primary outcomes:
measure: Assessment of Pharmacokinetic profile of total radioactivity in plasma and whole blood by Maximum concentration (Cmax)
timeFrame: Day 1 through Day 78 (21 times)
measure: Assessment of Pharmacokinetic profile of total radioactivity in plasma and whole blood by Time to attain Cmax (tmax)
timeFrame: Day 1 through Day 78 (21 times)
measure: Assessment of Pharmacokinetic profile of total radioactivity in plasma and whole blood by Time to reach quantifiable concentrations (tlag)
timeFrame: Day 1 through Day 78 (21 times)
measure: 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)
timeFrame: Day 1 through Day 78 (21 times)
measure: Assessment of Pharmacokinetic profile of total radioactivity in plasma and whole blood by AUC extrapolated to infinity (AUC0-inf)
timeFrame: Day 1 through Day 78 (21 times)
measure: Assessment of Pharmacokinetic profile of total radioactivity in plasma and whole blood by Terminal Disposition Rate Constant (λz)
timeFrame: Day 1 through Day 78 (21 times)
measure: Assessment of Pharmacokinetic profile of total radioactivity in plasma and whole blood by Apparent terminal elimination half life (t1/2)
timeFrame: Day 1 through Day 78 (21 times)
measure: Assessment of Pharmacokinetic profile of total radioactivity in plasma and whole blood by Apparent total body clearance after extra vascular dosing (CL/F)
timeFrame: Day 1 through Day 78 (21 times)
measure: 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)
timeFrame: Day 1 through Day 78 (21 times)
measure: Assessment of Pharmacokinetic profile of total radioactivity in plasma and whole blood by blood-to-plasma ratio (Ratio Cb/p)
timeFrame: Day 1 through Day 78 (21 times)
measure: Assessment of 14C recovery in urine
timeFrame: Day 1 through Day 78 (17 times)
measure: Assessment of 14C recovery in feces
timeFrame: Day 1 through Day 78 (16 times)
measure: Assessment of total 14C recovery (urine and feces combined) within 24 hours
timeFrame: Day 1 through Day 78 (17 times for urine and 16 times for feces)
measure: Assessment of total 14C recovery (urine and feces combined) after Time of last quantifiable concentration (tlast)
timeFrame: Day 1 through Day 78 (17 times for urine and 16 times for feces)
measure: Assessment of Pharmacokinetic profile of MDV3100 and metabolites in plasma
timeFrame: Day 1 through Day 78 (21 times)
measure: Assessment of Pharmacokinetic profile of MDV3100 and metabolites in urine
timeFrame: Day 1 through Day 78 (17 times)
measure: Metabolic Profile: Profiling of possible metabolites of MDV3100 in plasma, urine, and feces
timeFrame: Day 1 through Day 78 (14 times)
Secondary outcomes:
measure: Safety as assessed by recording adverse events, laboratory assessments, vital signs and electrocardiograms (ECGs)
timeFrame: Day 1 through Day 78
Other outcomes:
Locations:
city: Zuidlaren
country: Netherlands
facility: PRA International
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Operation Senior Research Manager
role: STUDY_CHAIR
References:
citation: 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.