PLASMA CONCENTRATION, EXCRETION AND MASS BALANCE OF ORALLY ADMINISTERED 14C-FYX-051 IN HEALTHY MALE SUBJECTS

The drug to be given, FYX-051 is a new, investigational compound that may
eventually be used for the treatment of gout. Gout can present itself in a
number of ways, although the most common is a recurrent attack of acute
inflammation of joints. Gout is caused by abnormal high levels of uric acid in
the blood. In order to prevent reoccurrence of gout, patients are treated with
a drug that controls uric acid concentrations in the blood. The drugs that are
currently used for clinical treatment are known to cause serious side effects,
such as liver problems. Others are safe, however they can be difficult to use
and less effective.
FYX-051 is a new type of drug that has a two-fold working mechanism: it
inhibits two different enzymes involved in the production of uric acid.
FYX-051 is expected to cause less side effects and is a more potent drug than
the drugs that are currently used.

The purpose of the study is to investigate how quickly and to what extent
FYX-051 is absorbed, distributed, metabolized (converted) and eliminated from
the body. The compound to be administered will be labeled with 14-Carbon (14C)
and is thus radioactive. This enables the investigator to trace the compound in
blood, exhaled air, urine and feces. The safety of the compound will also be
evaluated.

Design:
This is a Phase I, 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 80 mg FYX-051 containing 3.7 MBq
(0.6 mSv) of 14C FYX-051.

Procedures and assessments
Screening and end-of-study visit:
clinical laboratory (including clinical chemistry, haematology and urinalysis),
physical examination, vital signs (including supine systolic and diastolic
blood pressure and pulse rate), 12 lead electrocardiogram (ECG).
Screening: demographics, body weight and height, medical history, drug and
alcohol screen, HBsAg, anti HCV and anti HIV 1/2
Admission: physical examination, drug and alcohol screen, adverse events (AEs).

Blood sampling:
for total radioactivity in plasma and whole blood: pre-dose and 0.25, 0.5, 1,
2, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 h post-dose and each 24 h in case
of prolonged in-house stay
for hematocrit measurement in whole blood: pre-dose, 0.5, 24 and 48 h post-dose
for FYX-051 and its metabolites in plasma : pre-dose and 0.25, 0.5, 1, 2, 4, 8,
12, 24, 48, 72, 96, 120, 144 and 168 h post-dose (The time points of 48 h
post-dose would not be analyzed for FYX-051 and metabolites when the total
radioactivities in these points are quite low.) .
Metabolic profiling in plasma: 1, 4, 8 and 24 h post-dose

Urine sampling:
for total radioactivity, FYX-051 and its metabolites, and metabolite profiling:
pre-dose and 0-6, 6-12 and 12-24 h post-dose and then every 24 h interval until
criteria are met (The time points of after 48 h post-dose would not be
analyzed for FYX-051 and metabolites when the total radioactivities in these
points are quite low.).

Feces sampling:
for total radioactivity, FYX-051 and its metabolites, and metabolite profiling:
pre-dose and then every 24 h interval after drug administration until criteria
are met (The time points of after 48 h post-dose would not be analyzed for
FYX-051 and metabolites when the total radioactivities in these points are
quite low.).

Expired air sampling:
for total radioactivity: pre-dose (baseline) and 0.5, 4, 12, 24, 48, 72 and 96
h post-dose

Safety assessments:
AEs: throughout the study; 12-lead ECG: pre-dose and at 2, 8 and 24 h post-dose
and end-of-study visit; vital signs: pre dose and at 2, 4, 8 and 12 h post-dose
and once daily on Days 2-8; physical examination on Day -1 (pre-dose), Day 1
post-dose and on Day 5.

Bioanalysis:
analysis of plasma, feces and urine samples for FYX-051 and its metabolites
using radio-HPLC method by Sekisui Medical;
analysis of total radioactivity in whole blood, plasma, urine, feces and
expired air using a validated method by PRA
metabolic profiling by Sekisui Medical
quick counts by PRA

Active compound: 14C enriched FYX-051, 80 mg FYX-051, 3,7 MBq (0,6 mSv) as an
oral suspension (2 mg/ml)

Procedures: pain, light bleeding, heamatoma, possibly an infection,
The following adverse effects were reported during previous studies: nausea,
feeling hot and diarrhea.