A Phase 1, Open Label Study to Characterize the Absorption, Metabolism, and Excretion of 14C JNJ 67953964 After a Single Dose in Healthy Adult Male Participants

This study will evaluate the routes of excretion and explore metabolic pathways
for aticaprant after a single dose of aticaprant in healthy adult male
participants.

The aim of this study is to investigate how quickly and to what extent
aticaprant is absorbed, transported, and eliminated from the body (this is
called pharmacokinetics). For this study, aticaprant is radioactively labelled
with carbon-14 (14C). In this way aticaprant can be traced in blood, urine, and
feces and for Part B bile (liquid from the duodenum [the first part of the
small intestine]). The bile will be collected via a nasoduodenal tube (a tube
inserted through your nose). The radioactivity is not harmful to your health.

We also investigate how safe aticaprant is and how well it is tolerated when it
is used by healthy male participants.

We also look at the effect of your genetic information on your body*s response
to aticaprant (this is called pharmacogenetics). This part of the study is
mandatory.

Aticaprant has been used by humans before in previous drug studies. In
addition, it has been extensively tested in the laboratory and on animals.

Screening -> Day -28 to Day -2

Stay - Arrival -> Day -1
Stay - In-house stay -> Day -1 until Day 15-19*
Stay - Departure -> Day 15-19*

Visits** - 24-hour visit -> Day 25
Visits** - 24-hour visit -> Day 32

Follow-up -> Within 7 days after the last urine/feces collection

* The length of the stay depends on the amount of radioactivity that has left
the body.
** The visits on Day 25 and 32 are only needed if they did not meet de
predetermined criteria at the previous collection moment.


As a capsule by mouth with water.

14C-radioactively labeled aticaprant once

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 364 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 at once each time. 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).

Meals/Fasting
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.

Part B Only:
Duodenal sampling
During a period of 5 hours after intake of the study compound on Day 1 they
will have samples of the fluid (bile) in the duodenum collected via the
nasoduodenal tube. An experienced gastroenterologist (a doctor specialized in
diseases of the stomach and intestines) will place this nasoduodenal tube
before the study compound intake. This will take place in the Martini Hospital
in Groningen. A nasoduodenal tube is placed through the nose with the aid of a
nasal gastroscope. A gastroscope is an instrument to look inside the body and
consists of a thin flexible tube that contains a video camera and a lamp. The
camera produces images of the inside of the gullet (esophagus), stomach and
intestines. These images can be viewed on a television screen. A slim model
gastroscope will be used that usually is used for children.

One of the nostrils will be numbed by applying xylocaine gel in the nostril.
Subsequently the throat will be numbed using a spray that contains 10%
xylocaine. In addition xylocaine gel will be applied on the tip of the
gastroscope.

They will be asked to lie down on the left side with your head on a pillow. The
gastroenterologist introduces the gastroscope through the nose into the back of
the throat. They may be asked to swallow to help the gastroscope move easier.
For most people this is the most uncomfortable stage of the procedure. There
will be enough room left to breathe through the mouth and nose. The gastroscope
is gradually advanced further through the esophagus and stomach until it
reaches the duodenum. Through the gastroscope a thin wire is introduced. This
is called a guide wire. The nasoduodenal tube is then introduced gradually over
the guide wire, through the nose, throat, esophagus and stomach until it
reaches the duodenum. Thereafter a sample will be taken from the fluid in the
intestine to check if the tube is in the right place. This sample is taken from
the nasoduodenal tube using a syringe. The nasoduodenal tube will be fixed to
the nose and possibly also behind the ear using plasters.

During a stabilization period of approximately 15 minutes after placement of
the tube it is monitored whether they tolerate the tube well. If this is not
the case, the nasoduodenal tube will be removed immediately. Also, if at any
moment thereafter they do not tolerate the nasoduodenal tube well anymore, the
tube will be removed.

After the nasoduodenal tube has been placed, they will be escorted back to the
PRA clinical research center by an employee of PRA.

Five (5) hours after intake of the study compound the nasoduodenal tube will be
removed by the responsible doctor, this will occur at the research center.
Removal of the nasoduodenal probe will give a short lasting unpleasant feeling,
and often an unpleasant aftertaste.

Gastroscopy, placement of a nasoduodenal tube and duodenal fluid sampling are
safe procedures and serious complications are rare. Usually these procedures
are done without any problem. Nose bleeds and nausea are common after placement
of a nasoduodenal tube. If, after removal of the nasoduodenal tube, they feel
very nauseated or they have to vomit, the responsible doctor may treat this
with certain medication.

Pain experience is different for everyone and many people find the insertion of
the endoscope unpleasant because they have to gag. Sometimes people experience
shortness of breath, which is because there is a tube in their throat. It is
important that they follow the instructions of the doctor and the assistant.
They will indicate that they can keep breathing through the nose. There is
enough room in the throat to breathe.

So they don't have to worry that they can't get any air. In most cases, the
throat is numbed before the doctor inserts the endoscope. It is therefore
usually not really painful. Some people have a mildly sore throat for a day or
so after gastroscopy

To minimize pain and discomfort, a gastroscope used in young children, in
combination with local anesthesia is chosen as method for placement of the nose
tube.

Serious complications occur rarely. On average, per 1000 gastroscopies 1 or 2
times a complication occurs:
• There is a slightly increased risk of developing a lung infection or
pneumonia due to vomiting and aspiration . The risk of this happening increases
if they did not fast for long enough before the procedure.
• In rare cases the gastroscope or nasoduodenal tube may cause some damage to
the wall of the gastrointestinal tract. This may cause bleeding, infection and
very rarely a small puncture (perforation).
• A small number of people can have a heart attack or a stroke during or soon
after a gastroscopy but these tend to be older people who are already in poor
health.

To numb the throat, xylocaine (lidocaine) will be used. The following side
effects are described: hypersensitivity reactions (1 to 10 in 1000 users),
severe allergic reactions (with hypotension, paleness, anxiety, weak and fast
pulse, clammy skin, and decreased consciousness as a result of a sudden
vasodilation [anaphylactic shock]), loss of voice, hoarseness, sore throat,
local irritation on the place of application (incidence cannot be assessed
based on the current data).