An Open-Label Study to Investigate the Absorption, Metabolism, and Excretion of [14C]-JNJ-67856633, a MALT1 inhibitor, After a Single Oral Dose in Healthy Male Participants

JNJ-67856633 is a new compound that may potentially be used for the treatment
of B cell non Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL).
Lymphomas are blood cancers in the lymph nodes. Leukemia is a group of blood
cancers that usually begin in the bone marrow and result in high numbers of
abnormal blood cells. JNJ-67856633 blocks an enzyme (MALT1) that plays a role
in the regulation of the growth and maturation of B cells, the type of white
blood cells that become cancerous in the above conditions.

In this study we will investigate how quickly and to what extent the new
compound JNJ-67856633 is absorbed, transported, and eliminated from the body.
JNJ-67856633 is radioactively labelled with carbon-14 (14C).

We also investigate how safe JNJ-67856633 is and how well it is tolerated when
it is used by healthy participants.

Part A:
The study will take a maximum of 10 weeks from the screening until the
follow-up visit.
For the study it is necessary that the volunteer stays in the research center
for 1 period of 16 days (15 nights).
The volunteer will be given a single dose [14C]-JNJ-67856633 as 3 oral capsules
with 240 milliliters (mL) of (tap) water.

Part B:
The study will take a maximum of 10 weeks from the screening until the
follow-up visit.
For the study it is necessary that the volunteer stays in the research center
for 1 period of 16 days (15 nights).
The volunteer will be given a single dose [14C]-JNJ-67856633 as 3 oral capsules
with 240 milliliters (mL) of (tap) water.
On Day 1, a nasoduodenal tube will be inserted approximately 2 hours before
administration of the study compound to collect bile.

Screening | Arrival | In-house stay | Departure |
Visits*
Day -21 up to Day -2 Day -1 Day -1 up to Day 15 | Day 15 | Day 22 Day 29
Day 36 Day 43
* These visits are only needed if the volunteer did not excrete enough
radioactivity yet.

Possible side effects:
All medicinal products have known or unforeseeable side effects. There may be
risks, discomforts, side effects to using JNJ-67856633.

The potential risks based on an ongoing study in healthy participants are
outlined below:
As of 6 May 2021, interim safety data are available for 70 healthy participants
from this study. They have been administered a single dose of 100 mg (40
participants) and a single dose of 300 mg (30 participants) of JNJ­-67856633.
Only 4 drug-related side effects were reported. One participant who received
the single dose of 100 mg reported dizziness of mild severity. Two participants
who received the single dose of 300 mg reported headaches, one of mild and one
of moderate severity. One participant who received the single dose of 300 mg
reported diarrhea of mild severity.

There were no clinically significant observations for laboratory safety, vital
signs and ECGs.

Side effects that occurred in at least 10% of the patients during chronic
dosing with JNJ-67856633 are outlined below:
• hyperbilirubinemia (high level of bilirubin in the blood)
• neutropenia (Low numbers of white blood cells)
• anaemia (Low numbers of red blood cells)
• thrombocytopenia (Low numbers of platelets)
• diarrhoea
• fatigue (Feeling tired)
• creatinine increase
• abdominal pain
• nausea
• peripheral oedema
• constipation
• headache
• dyspnoe (difficulty breathing)

Possible discomforts:
ECG.
There is generally no risk with having an ECG. The sticky patches may pull the
volunteers skin or cause redness or itching.

Blood draw.
Taking blood may (rarely) cause pain, bleeding, bruising or infection at the
place where the needle goes into the skin. Similarly, the volunteer may feel
dizzy or even faint during the procedure. The study staff who take the blood
will do all they can to keep these discomforts and risks to a minimum. The
amount of blood drawn during the study will be less than 500 milliliters. This
is less than the amount of blood that people give during a normal blood
donation (which is about 500 milliliters). Sometimes a blood test may need to
be repeated.

Exposure to radiation.
This study involves using radioactive markers. The additional amount of
radiation the volunteer will be exposed to in this study is 0.24 mSv. We call
this radiation exposure. To compare: the background radiation in the
Netherlands is ~2.5 mSv per year. Background radiation is the radiation to
which you are exposed every day. Sources of background radiation are for
example soil, food, and some building materials. There is always radiation from
space as well (cosmic radiation). The total radioactivity can be compared
with that of about 2/5 of a mammogram testing (approximately 0.7 mSv), 1/20 of
a chest CT scan (approximately 5.8 mSv), or approximately 1.5 months of natural
background radiation exposure. A flight from Frankfurt to New York and back
results in an average effective dose of about 0.1 mSv. If you participate in
scientific research involving exposure to radiation more often, you should
discuss with the responsible doctor whether participation at this moment would
be safe/advisable.

Duodenal sampling (Part B)
For the bile sampling the tube will be placed through the volunteers nose: this
may be painful and cause discomfort. Local anesthesia will be used.

Coronavirus test
Samples for the coronavirus test will be taken from the back of the volunteer
his 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 volunteers throat may cause him to gag. When the sample is
taken from the back of the volunteers nose, he may experience a stinging
sensation and his eyes may become watery.