A NON-RANDOMIZED, OPEN-LABEL, CROSS-OVER, DRUG-DRUG INTERACTION STUDY TO EVALUATE THE EFFECTS OF BIA 28-6156 AT STEADY-STATE ON THE PHARMACOKINETICS OF LEVODOPA/CARBIDOPA AND LEVODOPA/BENSERAZIDE IN HEALTHY SUBJECTS.

BIA 28-6156 is a new compound that may potentially be used for the treatment of
Parkinson*s disease. Parkinson*s disease is a brain disorder with symptoms such
as arm or leg shaking and/or stiffness, and difficulty with walking, balance,
and coordination. It is caused by the death of specific nerve cells in the
brain that are important for controlling movement. There is currently no cure
for Parkinson*s disease, and treatment is aimed at reducing the symptoms.

Some types of Parkinson*s disease may be caused by a reduction in the activity
of the protein beta­glucocerebrosidase. This is due to mutations in the gene,
called GBA1, which is responsible for the production of beta­
glucocerebrosidase. BIA 28­6156 can bind to and activate beta­
glucocerebrosidase and is therefore thought to be helpful in the treatment of
these types of Parkinson*s disease.

In the future, patients may be given both BIA 28-6156 and levodopa-carbidopa or
levodopa-benserazide. It is therefore important to know if these compounds can
influence each other.

This is a medical-scientific research study. The purpose of the study is to
investigate the effect of multiple doses of the study compound BIA 28-6156 on
the pharmacokinetics of the drugs levodopa-carbidopa (Group 1) and
levodopa-benserazide (Group 2) in healthy male and female participants.
Pharmacokinetics is how your body absorbs, breaks down, and removes a drug. We
will also investigate the pharmacokinetics of BIA 28-6156 itself.

We will also investigate how safe the compound BIA 28-6156 is and how well it
is tolerated when healthy participants use it together with levodopa-carbidopa
or together with levodopa-benserazide.

BIA 28-6156 has been administered to humans before. In addition, it has been
extensively tested in the laboratory and on animals. BIA 28-6156 is
investigational and has not been approved for sale in any country.

Group 1: Levodopa-carbidopa is a drug approved in the Netherlands used to treat
the symptoms of Parkinson*s disease such as muscle stiffness, tremors, spasms,
and poor muscle control.

Group 2: Levodopa-benserazide is a drug approved in the Netherlands for the
treatment of Parkinson*s disease.

For the study it is necessary that the volunteer stays in the research center
for 9 days (8 nights). After that stay the volunteer will come back to the
research center once for the follow-up visit.

Day 1 is the first day when the volunteer will receive the study compound. The
volunteer will leave the research center on Day 8 of the study.

On days when the volunteer will receive BIA 28-6156 alone (Day 2 to 6), The
volunteer will be given a standard breakfast that must be finished within 20
minutes. After that they will be given 1 oral capsule of BIA 28-6156 with 240
mL of water. After intake of the study compound, The volunteer has to fast 4
hours until lunch.

Group 1:
On days when the volunteer only receives levodopa-carbidopa (Day 1), the
volunteer will first be given a standard low-protein breakfast, then fast for 2
hours. After that they will be given 1 oral capsule of levodopa-carbidopa
containing 100 mg of levodopa and 25 mg of carbidopa with 240 mL of water.
After intake of levodopa-carbidopa, the volunteer has to fast 4 hours until
lunch.

Group 2:
On days when the volunteer only receives levodopa-benserazide (Day 1), the
volunteer will first be given a standard low-protein breakfast, then fast for 2
hours. After that they will be given 1 oral capsule of levodopa-benserazide
containing 100 mg of levodopa and 25 mg of benserazide with 240 mL of water.
After intake of levodopa-benserazide, the volunteer has to fast 4 hours until
lunch.

On days when BIA 28-6156 is given together with levodopa-benserazide or
levodopa-carbidopa (Day 7), the volunteer will be given a standard low-protein
breakfast, then fast for 2 hours. After that they will be given 1 oral capsule
of BIA 28-6156 and 1 oral tablet levodopa-carbidopa or levodopa-benserazide.
After intake of BIA 28-6156 and levodopa-carbidopa or levodopa-carbidopa they
have to fast 4 hours until lunch.

They will be given a low-protein breakfast on Day 1 and Day 7, because protein
in the diet can reduce the absorption of levodopa-carbidopa by the body.

During fasting the volunteer is allowed to drink water; however water is not
allowed from 2 hours prior to until 1 hour after dosing on Day 1 and 7 (except
for the 240 mL water taken with the dose and fluid given with the breakfast).
There are no fluid restrictions on Days 2-6.

The tablet and capsule should not be chewed. One of the investigators will
inspect the volunteers hands and mouth after the study compound intake. This it
to check if the volunteer has taken the study compound.

Group 1:
• On Day 1: a single dose of 100 mg of levodopa and 25 mg of carbidopa
• On Day 2 to 6: a daily single dose of 60 mg BIA 28-6156
• On Day 7: a single dose of 60 mg BIA 28-6156 and a single dose of 100 mg of
levodopa and 25 mg of carbidopa

Group 2:
• On Day 1: a single dose of 100 mg of levodopa and 25 mg of benserazide
• On Day 2 to 6: a daily single dose of 60 mg BIA 28-6156
• On Day 7: a single dose of 60 mg BIA 28-6156 and a single dose of 100 mg of
levodopa and 25 mg of benserazide

Blood draw
Drawing blood may be painful or cause some bruising. The use of the indwelling
cannula (a tube in a vein in the arm) can sometimes lead to inflammation,
swelling, hardening of the vein, blood clotting, and bleeding in the
environment (bruising) of the puncture site. In some individuals, a blood draw
can sometimes cause pallor, nausea, seating, low heart rate, or drop in blood
pressure with dizziness or fainting.

In total, we will take about 289 milliliters (mL) of blood from screening to
follow-up. This amount does not cause any problems in adults. To compare: a
blood donation involves 500 mL of blood being taken each time at once. If the
investigator thinks it is necessary for the safety of a participant, extra
samples might be taken for possible additional testing. If this happens, the
total amount of blood drawn may be more than the amount indicated above.

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

Fasting
If subjects have to fast for a prolonged time during the study, this may lead
to symptoms such as dizziness, headache, stomach upset, or fainting.

Coronavirus test
Samples for the coronavirus test will be taken from the back of the nose and
throat using swabs. Taking the samples only takes a few seconds, but can cause
discomfort and can give an unpleasant feeling. Taking a sample from the back of
the throat may cause you to gag. When the sample is taken from the back of the
nose, they may experience a stinging sensation and the eyes may become watery.

Eye pressure test
A device blows a brief puff of air onto the eye to measure the eye pressure.
This air puff is not painful, and your eye will not be touched.