A Phase I, open-label, drug-drug interaction study between multiple oral doses of GLPG1972 and a single dose of midazolam in healthy male subjects.

GLPG1972 is a new investigational compound that may eventually be used for the
treatment of osteoarthritis.

GLPG1972 is a potent inhibitor of human ADAMTS-5. ADAMTS-5 is an enzyme
(protein) which is present in many tissues in the body, mainly in uterus,
placenta and cartilage. ADAMTS-5 is responsible for the destruction of the
cartilage which could lead to osteoarthritis. Blocking ADAMTS-5 could result in
an inhibition of the cartilage destruction which may be a treatment for
osteoarthritis.

GLPG1972 is not yet registered as a drug but has been given to humans before.

The other compound that will be given in this study is midazolam which is an
approved drug and already available in the market under several dosages and
formulations. Midazolam is a short acting sedative used prior to invasive
diagnostic or surgical procedures.

The purpose of the study is to investigate the effect of GLPG1972 on the
absorption, distribution and elimination (this is called pharmacokinetics) of
midazolam. It will also be investigated how safe GLPG1972 is and how well
GLPG1972 is tolerated.

This study will be performed in 18 healthy male volunteers.

The actual study will consist of 1 period during which the volunteers will stay
in the clinical research center in Groningen (location UMCG Hospital) for 14
days (13 nights): from the afternoon of Day -1 to the morning of Day 13. They
are expected at the clinical research center at 14:00 h in the afternoon prior
to the first day of administration of the study compound. They 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). They will leave the
clinical research center on Day 13.

The post-study visit will take place 7 - 10 days after the last administration
of the study compound on Day 12. The appointment for the post-study visit will
be made with the volunteers during the study. The participation to the entire
study, from the pre-study screening until the post study visit, will be a
maximum of 43 days.

During the study they will receive GLPG1972 as oral tablets with 240
milliliters of tap water at 30 minutes after a breakfast. On Days 1 and 12,
before administration of the study compound they will receive a breakfast. They
are not allowed to eat for at least 10 hours before consumption of this
breakfast. During fasting they are allowed to drink water with the exception of
2 hours prior to until 2 hours after administration of the study compound. At
30 minutes after the breakfast they will receive midazolam alone on Day 1 or
with GLPG1972 on Day 12. On Day 12, they will receive midazolam immediately
after GLPG1972 intake. They are not allowed to eat for at least 4 hours after
administration of the study compound. Then the volunteers will receive a lunch.

One of the investigators will inspect the hands and mouth after study compound
intake.

Treatment 1: a single dose of 2 mg midazolam on Day 1 (Day 1 is the first day
of administration of the study compound)
Treatment 2: a single dose of 300 mg GLPG1972 once daily for 10 days (from Day
2 to Day 11)
Treatment 3: a single dose of 300 mg GLPG1972 will be given together with a
single dose of 2 mg midazolam on Day 12

Pain, minor bleeding, bruising, possibly an infection due to blood sampling