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

MDV3100 is a new investigational compound that may eventually be used for the
treatment of prostate cancer. MDV3100 is not registered as a drug but has been
given to humans before.

Primary objective:
- To evaluate the pharmacokinetics, metabolism, and excretion of MDV3100 in
plasma, urine, and feces after a single oral 160 mg (100 µCi) dose of
14C-MDV3100.

Secondary objective:
- To evaluate safety and tolerability of a single oral 160 mg (100 µCi) dose of
14C-MDV3100.

Design:
This will be an open-label ADME study in 6 healthy male subjects receiving a
single-dose study of 14C labeled studymedication (3,7 MBq; 0,99 mSv).

Procedures and assessments:
screening and follow up:
Screening consists of bestaat uit een medical history, physical exam, blood -
urine analysis, (i.e. . alcohol, drugs, HBsAG, anti-HIV, anti-HCV), vital sigs,
and an ECG. At entry a abbrevaiated physical exam will be performed, ECG and
blood - urine analysis, (i.e. . alcohol, drugs, HBsAG, anti-HIV, anti-HCV),

observation period:
1 period in the clinic -17 h -240 h post dose , followed by minimal 5 short
periods (Day 13-15, 20-22, 27-29, 34-36 and 48-50) of 3 days each (2 nights),
with possible extention till Day 78 if the criteria have not been met (total
extretion radioactivity *90%) on Day 50. If the release criteria have not been
met on Day 50, the volunteer will be asked o come to the clinci for 2
additional periods (day 62-64 and 76-78).

Bloodsampling:
-Blood sampling for determination of plasma concentrations of MDV3100 and its
metabolites MDPC0001 and MDPC0002 and of 14C radioactivity in plasma and whole
blood will take place at pre dose and at 30min, 1h, 1h 30min, 2h, 3h, 4h, 6h,
8h, and 12h (Day 1), 24h (Day 2), 48h (Day 3), 72h (Day 4), 96h (Day 5), 168h
(Day 8), 240h (Day 11), 312h (Day 14), 480h (Day 21), 648h (Day 28), 816h (Day
35) and 1152h (Day 49) post-dose.
-Blood sampling for metabolic profiling will take place at pre dose and at 2h,
6h and 12h (Day 1), 24h (Day 2), 48h (Day 3), 96h (Day 5), 168h (Day 8), 240h
(Day 11), 312h (Day 14), 480h (Day 21), 648h (Day 28), 816h (Day 35) and 1152h
(Day 49) post-dose.
- genotyping 1x on Day 1 (only period 1), post dose.
-Hematocrit will be measured at pre-dose and at 24h (Day 2), 48h (Day 3), 72h
(Day 4), 96h (Day 5), 168h (Day 8) and 240h (Day 11) post-dose. No separate
sample should be taken for hematocrit measurement: 1 mL of the blood sample for
total radioactivity will be used.

Urine sampling:
- Urine sampling for determination of concentrations of MDV3100 and its
metabolites MDPC0001 and MDPC0002 and of 14C radioactivity will take place at
pre dose and collection intervals at 0-12, 12-24, 24-48, 48-72, 72-96, 96-120,
120-144, 144-168, 168-192, 192-216 and 216-240 hours post-dose and for 24 hours
on Day 14 (312 336 hours), Day 21 (480-504 hours), Day 28 (648-672 hours), Day
35 (816-840 hours) and Day 49 (1152-1176 hours) post-dose.
- urine, sampling for metabolic profiling will take place at pre dose and at
2h, 6h and 12h (Day 1), 24h (Day 2), 48h (Day 3), 96h (Day 5), 168h (Day 8),
240h (Day 11), 312h (Day 14), 480h (Day 21), 648h (Day 28), 816h (Day 35) and
1152h (Day 49) post-dose.

Feces sampling:
-Feces sampling for determination of 14C radioactivity will take place at pre
dose and in intervals at 0-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168,
168-192, 192-216 and 216-240 hours post-dose and for 24 hours on Day 14
(312-336 hours), Day 21 (480-504 hours), Day 28 (648-672 hours), Day 35
(816-840 hours) and Day 49 (1152 1176 hours) post-dose.- feces sampling for
metabolic profiling will take place at pre dose and at 2h, 6h and 12h (Day 1),
24h (Day 2), 48h (Day 3), 96h (Day 5), 168h (Day 8), 240h (Day 11), 312h (Day
14), 480h (Day 21), 648h (Day 28), 816h (Day 35) and 1152h (Day 49) post-dose.
Veiligheidsmaatregelen:
Bijwerkingen tijdens de hele studie. Klinisch chemisch lab op dag 11 en 35, ECG
en vitale functies vóór dosering en 1 maal daags op dagen 2-10, 13-15, 20-22,
27-19, 34-36, 48-50 na dosering.

Bioanalysis:
-Analyse of the studymedication in plasma, urine and feces using validated
methods by PRA,
-analysis of total radioactivity in whole blood, plasma, urine and faeces using
validated methods by PRA
-metabolite and genotyping profile using validated methods by PRA

active substance MDV3100 and [14C]- MDV3100

Procedures: pain, licht bleeding, bruses, possible infection.

In an earlier study with 60 healthy volunteers receiving a single dose of 160
mg given twice (one in fed and one in fasted condition) the most important
adverse events reported were: headache, diarrhea, pharyngitis and skin
laceration. All events were of mild intensity and resolved prior to the end of
the study (clinical conduct part). The occurrence of known or other effects
cannot be excluded. All potential drugs cause adverse events to some extent.
Therefore you should take into account that some risks are still unknown at
this moment.