PHARMACOKINETICS AND METABOLISM OF 14C-LABELED GRC 4039 SODIUM FOLLOWING A SINGLE ORAL ADMINISTRATION IN HEALTHY MALE VOLUNTEERS

GRC 4039 is a new investigational compound that may eventually be used for the
treatment of chronic inflammatory disorders. GRC 4039 is not registered as a
drug but has been given to humans before.

Primary:
To assess the pharmacokinetic (PK) characteristics of total radioactivity in
plasma and urine after a single oral dose of 14C-GRC 4039 sodium
To assess the PK characteristics of parent GRC 4039 and metabolite GRC 4037 in
plasma and urine after a single oral dose of 14C-GRC 4039 sodium
To determine the recovery of total radioactivity in urine and faeces after a
single oral dose of 14C-GRC 4039 sodium
To characterize and identify the metabolites found in plasma, urine and faeces
after a single dose of 14C-GRC 4039 sodium
To compare the plasma exposures (area under the concentration-time curve [AUC])
of parent GRC 4039 and metabolite GRC 4037
To assess the partitioning of total radioactivity between plasma and red blood
cells, based on total radioactivity in whole blood and plasma.

Secondary:
To assess the safety and tolerability of a single dose of 14C GRC 4039 sodium

This study is a Phase 1, open-label, non-randomised, single centre, absorption,
distribution, metabolism and excretion (ADME) study in 6 healthy male subjects
who will all receive a single oral dose of 30 mg GRC 4039 sodium containing
approximately 100 *Ci of 14C-GRC 4039 sodium under fasting conditions.

Procedures and assessments
Several timepoints during the study (Screening, Follow up and/or throughout the
study): Demographics, medical history, informed consent, previous and
concomitant medication, physical examination (including height and body weight
and calculation of body mass index [BMI]), vital signs (body temperature,
respiratory rate, supine blood pressure and pulse), 12-lead electrocardiogram
(ECG), clinical laboratory (including clinical chemistry, haematology and
urinalysis), faecal occult blood, drug, alcohol and cotinine screen, HBsAg,
anti HAV, anti HCV and anti-HIV 1/2, *how do you feel?* enquiry and adverse
event (AE) evaluations

Blood sampling: Plasma samples for radioanalysis, metabolite profiling and
parent GRC 4039 and GRC 4037 analysis will be collected throughout the study.

Urine sampling: Urine samples for radioanalysis, parent GRC 4039 and GRC 4037
analysis, and metabolite profiling will be collected throughout the study.

Faeces sampling: Faecal samples for radioanalysis and metabolite profiling will
be collected throughout the study.

A single oral dose of 30 mg GRC 4039 sodium, containing appromxiately 3.7 MBq
radiocarbon on Day 1.

The possible adverse effects of the investigational procedures (e.g. the use of
the indwelling canula) are described in section 9 of the information booklet.
In previous studies in healthy volunteers, with single doses up to 50 mg and
multiple doses ranging from 6 mg up to 8 mg, the most important adverse events
reported were: diarrhea, headache, abdominal pain, nausea, tiredness and
stomach cramps. Two male volunteers reported itching skin irritation (rash).
With the doses used in this study no serious adverse effects are expected. The
occurrence of known or other effects cannot be excluded. All potential drugs
cause adverse events to some extent.

In this study radio labeled GRC 4039 will be used. The amount of radioactivity
in this dose will be 3.7 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 3.7 MBq 14C-labeled GRC 4039 is calculated to be 0.85 mSv.
This is approximately 42.5 % of the average annual radiation burden.

Registration af adverse effects: During the entire investigation all adverse
effect you report will be documented.

Blood draw, indwelling canula:During this study less then 500 ml of blood will
be drawn. It is anticipated that on Day -1 an indwelling cannula will be
inserted for most of the blood sampling on Day 1 and 2. On the other days
during this study, blood will be drawn by direct puncture of the vein.

Collection of urine and feces: Urine and feces will be collected until the day
of discharge (thus until Day 8 - 14). In addition, when the radioactivity level
is above the pre-defined levels, collection of urine and feces may have to be
continued at home. Before arrival in the clinical research centre, one feces
sample should be collected at home to serve as a blank.

Heart trace (ECG*s): ECG*s will be made on Day 1 and 2.