A 2-part, randomized, double-blind, placebo-controlled, sequential group, dose-escalation study to assess the safety, tolerability and pharmacokinetics of single and multiple ascending oral doses of GLPG2737 in healthy male sub.

GLPG2737 is a new investigational compound that may eventually be used for the
treatment of cystic fibrosis (CF). CF is a genetic disorder that causes the
body to produce unusually thick mucus. The thick mucus results in malfunction
of organs like the lungs, pancreas and liver.

In the human body, the cystic fibrosis transmembrane conductance regulator
(CFTR; this is a protein that can be found on the membrane of cells) plays an
important role in the transport of salt and water in and out of cells. In CF
there are changes (mutations) in the gene (DNA) that is responsible for the
production of CFTR and because of these changes, CFTR does not work correctly
or it is not produced sufficiently. As a result, the transport of salt and
water in and out of cells is disturbed and mucus will become unusually thick.
GLPG2737 is thought to improve CFTR functioning by repairing consequences of
CFTR mutations.

The purpose of the study is to investigate how safe GLPG2737 is and how well
GLPG2737 is tolerated. It will also be investigated how quickly and to what
extent GLPG2737 is absorbed into, distributed in, and eliminated from the body
(this is called pharmacokinetics).

Part1:
Before the study the volunteer will undergo a screening within 21 days before
the day of administration of the study compound (Day 1) during which the
volunteer will be subjected to a number of medical examinations (please refer
to Chapter 7 of the information booklet). Similar examinations will be
performed after the study at the follow-up visit (please refer to Chapter 10 of
the information booklet). The volunteer will be required not to have consumed
any food or drinks (with the exception of water) during the 4 hours prior to
screening visit and the follow-up visit.

The volunteer is expected at the clinical research center on Day -1 at 14:00 h
in the afternoon. The volunteer will be required not to have consumed any food
or drinks (with the exception of water) during the 4 hours prior to arrival in
the clinical research center.

The volunteer will receive GLPG2737 or placebo as an oral suspension in sitting
position. The study compound will be given with a syringe (without needle) due
to the small volume. After intake of the study compound the volunteer is
required to drink 240 milliliters (mL) of water. The study compound will be
administered within 30 minutes after the start of breakfast, which the
volunteer will need to finish entirely within 20 minutes.

Part 2:
Before the study the volunteer will undergo a screening within 21 days before
the day of administration of the study compound (Day 1) during which the
volunteer will be subjected to a number of medical examinations (please refer
to Chapter 7 of the information booklet). Similar examinations will be
performed after the study at the follow-up visit (please refer to Chapter 10 of
the information booklet). The volunteer will be required not to have consumed
any food or drinks (with the exception of water) during the 4 hours prior to
screening visit and the follow-up visit.

The volunteer is expected at the clinical research center on Day -1 at 14:00 h
in the afternoon. The volunteer will be required not to have consumed any food
or drinks during the 4 hours prior to arrival in the clinical research center
(with the exception of water).

On Days 1 to 14, every day the vounteer will receive GLPG2737 or placebo as an
oral suspension in sitting position. The study compound will be given with a
syringe (without needle) due to the small volume. After intake of the study
compound the volunteer is required to drink 240 milliliters (mL) of water. Each
dosing day, the study compound will be administered within 30 minutes after the
start of breakfast, which the volunteer will need to finish entirely within 20
minutes

Part 1:

Group Day
Treatment
How often
A 1 25 milligrams (mg) GLPG2737 or
placebo Once
B 1 TBD, but not exceeding 75 mg GLPG2737 or
placebo Once
C 1 TBD, but not exceeding 150 mg GLPG2737 or placebo
Once
D 1 TBD, but not exceeding 300 mg GLPG2737 or placebo Once
E 1 TBD, but not exceeding 450 mg GLPG2737 or
placebo Once
TBD* 1 TBD1 mg GLPG2737 or
placebo Once
TBD* 1 TBD1 mg GLPG2737 or
placebo Once
TBD* 1 TBD1 mg GLPG2737 or
placebo Once

TBD: to be determined
*: these are additional groups which may possibly be dosed. The dose level of
these groups will be based on results of previous groups in Part 1

Part 2:

Group Days Treatment How often
F 1-14 TBD, but not exceeding 75 milligrams (mg) GLPG2737 or placebo Once
daily
G 1-14 TBD, but not exceeding 150 mg GLPG2737 or placebo Once daily
H 1-14 TBD, but not exceeding 300 mg GLPG2737 or placebo Once daily
TBD1 1-14 TBD mg GLPG2737 or placebo Once daily
TBD1 1-14 TBD mg GLPG2737 or placebo Once daily
TBD1 1-14 TBD mg GLPG2737 or placebo Once daily

TBD: to be determined
1: these are additional groups which may possibly be dosed

All potential drugs cause adverse effects; the extent to which this occurs
differs. As GLPG2737 will be administered to humans for the first time in this
study, adverse effects of GLPG2737 in humans have not been reported to date.

In animal safety studies in rats and dogs, administration of GLPG2737 was shown
to cause effects on the lining of the stomach and redness of the skin
associated with inflammation. These findings were seen at the middle and
highest of 3 doses studied. GLPG2737 administration also modified some
laboratory tests such as cholesterol and liver enzymes. In addition there was a
slight, reduction in the activity of an enzyme (myeloperoxidase) of a type of
white blood cell, the neutrophil, which is involved in the body*s response to
infections. All of the abovementioned effects were reversible.

All these parameters, amongst many others, will be closely monitored during
this clinical study by repeat blood and urine sampling for laboratory
parameters, frequent ECGs and vital signs assessments (blood pressure, pulse
rate and body temperature), frequent physical examinations and continuous
adverse effect monitoring during the course of the study.

The volunteer should be aware that the aforementioned adverse effects and
possibly other, still unknown adverse effects, may occur during the study.
However, with the doses used in this study no serious adverse effects are
expected.