A single-center, open-label study to evaluate the absorption, distribution, metabolism and excretion (ADME) and pharmacokinetics of LOU064 following a single dose of [14C]LOU064 administered orally or intravenouslyl in healthy male and female subjects at steady-state.

LOU064 is a new compound that may eventually be used for the treatment of
autoimmune and chronic inflammatory diseases. LOU064 inhibits the enzyme
Bruton*s tyrosine kinase which is present in immune cells and is essential for
signaling through various receptors. The effect of LOU064 on Bruton*s tyrosine
kinase is believed to be an attractive way to treat various autoimmune and
chronic inflammatory diseases, including rheumatoid arthritis, multiple
sclerosis, atopic dermatitis and asthma.

The purpose of this study is to investigate how quickly and to what extent
LOU064 is absorbed, broken down, and eliminated from the body. LOU064 will be
labeled with 14 carbon (14C) and is thus radioactive. In this way LOU064 can be
traced in blood, urine, and feces. LOU064 has been administered to humans
before. It has also been previously tested in the laboratory and on animals.

It will also be investigated how safe the new compound LOU064 is and how well
it is tolerated when it is administered to healthy volunteers.

Furthermore, the effect of the genetic information on the body*s response to
LOU064 will be investigated. This part of the study is optional.

Part 2A and 2B:
In Part 1, 5 volunteers received LOU064 as oral capsules twice a day. The
morning administration of Day 2 was with radioactive [14C]LOU064 (as a drink).
The results of Part 1 did not show clearly how LOU064 was absorbed and excreted
by the body. Therefore, in this Part 2, [14C]LOU064 will be administered as an
intravenous injection (solution of the compound administered directly into a
blood vessel). One volunteer will receive a capsule of LOU064 twice a day for 5
days, with radiolabeled [14C]LOU064 as an intravenous injection on Day 2 (Part
2A). The second volunteer will receive LOU064, twice daily, as a capsule for 9
days, with radiolabeled [14C]LOU064 as an intravenous injection on Day 6 (Part
2B).
It will also be investigated how safe the new compound LOU064 is and how well
it is tolerated when it is administered to healthy volunteers.
Furthermore, the effect of your genetic information on the body*s response to
LOU064 will be investigated. This part of the study is optional.

The participation from screening until the follow-up visit will last up to 9
weeks.

The volunteer will receive 9 doses of 100 milligram (mg) of non-radiolabeled
LOU064 as 2 oral capsules (containing 50 mg of non-radiolabeled LOU064 each)
with 240 milliliters (mL) of (tap) water. One of the investigators will inspect
the hands and mouth after each study treatment intake, to check whether the
volunteers have actually taken the study treatment. They will furthermore
receive 1 dose of 100 mg of 14C-labeled LOU064 as an oral solution of 20 mL.
After this they will receive a glass with 240 mL water, that they will also
have to drink. The [14C]LOU064 dose contains 0.074 MBq (2 µCi) radioactivity.
After administration of [14C]LOU064, the vial will be rinsed with water, which
they will also be required to drink. All subjects will receive the same study
treatment.

The study will consist of 1 period during which the volunteer will stay in the
research center for 12 days (11 nights).

Day 1 is the day of the first administration of the study treatment. They are
expected at the research center at 14:00 h in the afternoon prior to the day of
the first administration of the study treatment, so on Day -1. They will leave
the research center on Day 11 of the study. The volunteer will also have to
take into account the 4 additional 24-hour visits for the collection of urine.
feces and blood.

For the additional 24-hour visits, they are expected at the research center at
11:00 h in the morning of Days 15, 19, 23 and/or 27. They will leave the
research center on Days 16, 20, 24 and/or 28, respectively.

During the stay, the urine and feces will be collected and blood will be
sampled each day to measure the amount of radioactivity. Depending on the test
results of the amount of radioactivity left in the blood, urine and/or feces,
24-hour visits can be cancelled.

Part 2A and 2B:
The participation from screening until the follow-up visit will last about 9
weeks (Part 2A) or 10 weeks (Part 2B).
The volunteer will receive 100 milligram (mg) of non-radiolabeled LOU064 twice
daily for 5 days or 9 days. Each non-radiolabeled dose of LOU064 will be
administered as 2 oral capsules (containing 50 mg of non-radiolabeled LOU064
each) with 240 milliliters (mL) of water. One of the investigators will inspect
the hands and mouth after each study treatment intake, to check whether they
have actually taken the study treatment. On Day 2 or Day 6, 1 hour after the
capsules with LOU064, you will receive intravenous injection of 2 mL with 0.1
mg radio-labeled [14C]LOU064. The [14C]LOU064 dose contains 0.074 MBq (2 µCi)
of radioactivity.

Not applicable.

Drawing blood and/or insertion of the indwelling cannula (tube in an arm vein)
may be painful or cause some bruising.

In total, we will take up to 500 mL of blood from the volunteer.

To make a heart tracing, electrodes (small, plastic patches) will be pasted at
specific locations on the arms, chest and legs. Prolonged use of these
electrodes can cause skin irritation (rash and itching).

This study involves using radioactive markers. The additional amount of
radiation the volunteers will be exposed to in this study is 3.2 µSv