An open label, single oral dose study to investigate the pharamcokinetics - absorption, distribution, metabolism, and elimination - of 75 mg of 14C-labeled BCT197 in healthy male volunteers.

BCT197 is a new investigational compound that may eventually be used for the
treatment of chronic obstructive pulmonary disease (COPD). BCT197 blocks an
enzyme (p38 mitogen-activated protein kinase (MAPK), which is known to play a
role in the inflammatory reaction causing the obstruction of the airways in
COPD. BCT197 is not registered as a drug but has been given to humans before.

Primary Objectives

To quantify BCT197, and to identify and quantify its metabolites in plasma,
urine, and feces.
To determine the pharmacokinetics of total 14C-radioactivity in blood and
plasma, and of any important metabolites in plasma and excreta.
To determine the rate and routes of excretion and the mass balance by total
radioactivity in urine and feces.
To elucidate the key biotransformation pathways and clearance mechanisms of
BCT197 in humans.

Secondary Objectives

To assess the safety and tolerability of a single 75 mg oral dose of
14C-radiolabeled BCT197 in healthy male volunteers.

This will be a single center, open-label, single arm study in healthy male
subjects. Subjects will receive a single oral 14C-radiolabeled dose of 75 mg
BCT197 (1.85 MBq, 50 µCi) as three 25 mg capsules after an overnight fast of at
least 10 hours. The whole-body radiation dose will be <1 mSv (DMPK
RCBCT197A2205a).

The study will consist of 2 cohorts of 2 subjects. Each cohort will follow:

Screening visit may occur between Day -28 and Day -2
*Baseline visit on Day -1
A single dose treatment on Day 1
216 hours in-house observation period Days 1-10
Optional sample collections and assessments at Day 14 and Day 21
Study completion Visit Day 25
Optional visits on Day 14 and/or Day 21 will be deemed necessary if blood,
excreta or skin sampling does not allow reliable assessment of PK parameters
for determination of radioactivity during the elimination phase.
Baseline safety evaluation results must be available prior to dosing.

a single oral 14C-radiolabeled dose of 75 mg BCT197 (1.85 MBq, 50 µCi) as three
25 mg capsules after an overnight fast of at least 10 hours

The most important adverse event reported was mild skin rash. Possible side
effects identified from the mechanism of action but not observed in humans yet
are: Gastrointestinal (GI) toxicity including elevated Liver enzymes, and
Central Nervous System (CNS) symptoms such as dizziness and lightheadedness

In this study radio labeled BCT197 will be used. The amount of radioactivity in
this dose will be 1.85 MBq (MBq = megaBecquerel, this is a unit to express the
amount of radioactivity in the study drug). The average environmental
background radiation burden in The Netherlands is approximately 2 mSv per year
(mSv = miliSievert, this is the unit which indicates the burden on the human
body; thus the effect on the human body of the amount of radioactivity
administered). The additional radiation burden in this study due to the
administration of 1.85 MBq 14C-labeled BCT197 is calculated to be 0.86 mSv.
This is approximately 45 % of the average annual radiation burden.

Registration of adverse effects: During the entire investigation all adverse
effects will be documented.

Blood draw, indwelling canula: During this study approximately 500 ml of blood
will be drawn. It is anticipated that on Day -
1 an indwelling canula will be inserted for most of the blood sampling on Day
1. On the other days during this study,
blood will be drawn by direct puncture of the vein.

Collection of urine: A pre-dose urine sample of approximately 250 ml will be
collected at anytime before administration of
BCT197 on either Day -1 or Day 1. Further 24-hour urine samples of
approximately 250 ml will be collected on Day 1 until Day 9 and optionally on
day 14 and 21.

Collection of feces: One stool sample will be collected at any time before
administration of BCT197 (within 48 hours prior
to dosing). Further all feces will be collected completely on Day 1 until Day 9
and optionally on day 14 and 21.

Collection of vomitus: If a participant vomits within 24 hours following CBT197
dosing, the vomitus will be collected and
analyzed to confirm the level of radioactivity.

Collection of skin biopsies: On day 2,3,5,7,9 and optionally day 14 and 21 a
single skin biopsy will be taken.

Heart trace (ECG*s): ECG*s will be made during screening visit, pre-dose and
during end of study visit.

Blood sample for DNA tests: On Day -1 a blood sample will be taken for possible
DNA tests.