Assessment of safety, tolerability and pharmacokinetics of single and multiple ascending oral doses of GLPG2451 and of the combination of GLPG2451 and GLPG2222 in healthy female subjects.

GLPG2451 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 mutations in the gene (DNA) that is responsible for
the production of CFTR and because of these mutations 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. GLPG2451 is thought to improve CFTR functioning by
repairing consequences of CFTR mutations. GLPG2451 is not registered as a drug
and has not been given to humans before.

This study will be performed in about 56 healthy female volunteers. The study
will be performed in 3 parts, Parts 1, 2 and 3.
In Part 2, multiple doses of GLPG2451 or placebo (same formulation but without
the active ingredient GLPG2451) will be administered and about 3 dose levels of
GLPG2451 will be investigated in Part 2. The purpose of Part 2 is to
investigate how safe GLPG2451 is and how wellGLPG2451 is tolerated. Part 2 will
also investigate how quickly and to what extent GLPG2451 is absorbed into,
distributed in, and eliminated from the body (this is called pharmacokinetics).
Part 2 will be performed in about 3 dose groups (Cohorts C, D and E) and each
dose group will
consist of 8 healthy female volunteers. Part 2 will be performed in about 24
healthy female volunteers.

The actual study will consist of 1 treatment period during which the volunteers
will stay in the clinical research center in Groningen for 17 days (16 nights):
from the afternoon of Day -1 (1 day before the first administration of the
study compound) to the morning of Day 16.
The post-study visit will take place 14 days after the last administration of
the study compound on Day 14. The appointment for the post-study visit will be
made with you during the study. The participation to the entire study, from the
screening until the post-study visit, will be approximately 7 weeks.

Cohort C Day 1 to 14 GLPG2451 15 mg (administered as 15 mg once daily or 7.5 mg
twice daily) or placebo
Cohort D Day 1 to 14 GLPG2451 45 mg (administered as 45 mg once daily or 22.5
mg twice daily) or placebo
Cohort E Day 1 to 14 GLPG2451 100 mg (administered as 100 mg once daily or 50
mg twice daily) or placebo

Procedures: pain, minor bleeding, bruising, possible infection.