A phase 1, randomized, placebo-controlled, double-blind, single center, multiple-dose, parallel trial evaluating the impact of apraglutide on gastric emptying of liquids in healthy subjects

Apraglutide is an investigational medication. This means that it has not been
approved by the regulatory authorities for prescription or over-the-counter
use. Apraglutide is currently being developed for the treatment of patients
with short bowel syndrome and graft-versus-host disease. Short bowel syndrome
is where the bowel is not able to absorb nutrients normally. Graft-versus-host
disease is where patients suffer from swelling in different organs following
bone marrow or stem cell transplants. Patients with these conditions may also
suffer from imbalances of some gastrointestinal hormones (hormones in the
digestive system), which can cause complications such as accelerated
gastrointestinal motility (movement of food through the digestive system). It
is important to find out if and how apraglutide affects gastric emptying of the
stomach as it may be helpful in these patients. Apraglutide can be tested by
measuring how another medication, paracetamol (also known as acetaminophen),
is taken into the blood and passed out from the body in healthy subjects. The
levels of paracetamol will then show if apraglutide has any effect on gastric
emptying.

In this trial they will receive liquid paracetamol with a liquid meal. They
will also receive either apraglutide or a placebo.

The purpose of this study is to see if the study compound, apraglutide, has any
effect on the gastric emptying of liquids in healthy subjects. Gastric emptying
is the normal way in which food passes through the body, when the contents of
the stomach are moved into the small intestines. This study wants to find out
if apraglutide may speed up or delay the gastric emptying of the stomach. The
study will also look at how safe and how tolerable apraglutide is in healthy
subjects.

Apraglutide has been administered to humans before. In addition, it has been
extensively tested in the laboratory and on animals. Up to the start of this
study, 130 subjects (74 healthy subjects and 56 patients) received at least one
dose of apraglutide.

In total volunteers will come 4 times to the research center:
• once for the screening.
• 2 periods where they stay in the research center. The first one will last 3
days (2 nights) and the second one will last 4 days (3 nights).
• a follow-up visit on Day 22 (±2 days, i.e., between Day 20 and Day 24).

For the first period, they will be admitted on Day -1 (the day before any
compound is given). The next day (Day 1), after an overnight fast (i.e.,
nothing to eat or drink, except water) of at least 8 hours, they will be given
a single liquid dose of paracetamol followed by a liquid meal. The liquid meal
ensures all subjects have exactly the same amount of calories. After drinking
the paracetamol dose and liquid meal, they will fast for a further 4 hours.
Several blood samples will be taken over the next 14 hours to measure how much
paracetamol is in the blood over this time. On Day 2, after a light breakfast,
they will receive the first dose of study compound (apraglutide or placebo) and
will be allowed to go home later that day. Assessments will be carried out
throughout their stay in the research center to check that the study compound
is safe.

For the second period, they will be admitted on Day 8 of the study. On Day 9,
following a light breakfast, they will receive their second dose of study
compound (apraglutide or placebo). On Day 10, after an overnight fast of at
least 8 hours, they will be given a single liquid dose of paracetamol followed
by a liquid meal. After drinking the paracetamol and liquid meal, they will
fast for a further 4 hours. Several blood samples will be taken over the next
14 hours to measure how much paracetamol is in the blood over this time. They
will be allowed to go home the following morning on Day 11.

They will be given apraglutide or placebo as an injection under the skin
(subcutaneous) of the abdomen. It will be given 30 minutes after breakfast.

Whether they will receive apraglutide or placebo will be determined by chance.
Per 3 subjects, 2 subjects will receive apraglutide and 1 subject will receive
placebo.

Volunteers will receive an injection of apraglutide two times: once on Day 2
and once on Day 9. The dose that will be given each time is 5 milligram (mg).

Paracetamol will be given twice: once on Day 1 and once on Day 10. Each dose is
1000 mg.

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, sweating, low heart rate, or drop in blood
pressure with dizziness or fainting.

In total, we will take 198 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 subject, 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).

Meals/Fasting
Some side effects are possible after consuming a liquid meal. These side
effects are generally mild:
- Constipation
- Nausea
- Diarrhea or vomiting

As with anything that people consume, hypersensitivity or allergic reactions
are also possible.

If they 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 them 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.

When visiting the research center they may be exposed to viruses, including
COVID-19. The study staff will advise them on steps to take to minimize your
risk, which may include using had gel, hand washing, and maintaining social
distancing when possible.

Injections
Injection site reactions have been reported with similar medicines. That is why
they will be monitored every day for skin irritations during their stay in the
research center and again at the follow-up visit. When injecting the study
compound under the skin, this may cause discomfort, bruising, bleeding or
swelling where the needle goes in. There is also a very small risk for
infection where the needle goes in. It will regularly be checked if they
develop any symptoms at the place where the needle goes in.