A phase 1, open-label study to characterize the absorption, metabolism, and excretion of 14C-JNJ-53718678 after a single oral dose in healthy adult male subjects

JNJ-53718678 is a new investigational compound that may eventually be used for
the treatment of infections with RSV. RSV is a common virus that causes common
colds. However especially in very young children an infection with RSV can
result in lower respiratory tract infections and can cause very serious
pneumonia. Also elderly persons and persons with underlying chronic diseases or
a diminished immunity are at risk of developing serious illness. JNJ-53718678
binds to a specific protein on the surface of the RSV virus and thereby
prevents the virus from entering cells in the body and multiplying inside these
cells. JNJ 53718678 is in development and is not registered as a drug but has
been given to humans before in studies with single and multiple doses. The
highest single dose of JNJ 53718678 given so far was 1000 mg, which is twice
the amount (500 mg) the volunteer will receive in this study.

The purpose of the study is to investigate how quickly and to what extent
JNJ-53718678 is absorbed, distributed, metabolized (broken down) and eliminated
from the body. JNJ-53718678 to be administered will be labeled with 14-Carbon
(14C) and is thus radioactive (also called radiolabeled). In this way
JNJ-53718678 can be traced in blood, urine, feces and duodenual fluid (the
duodenum is the first part of the small intestine). It will also be
investigated to what extent JNJ-53718678 is tolerated.

The study will consist of 1 period during which the volunteer will stay in the
clinical research center in Groningen for minimally 7 days (6 nights) and
maximally 11 days (10 nights).

During the study the volunteer will receive radiolabeled JNJ-53718678 after an
overnight fast (at least 11 hours no eating and drinking) as an oral solution
with 240 milliliters of tap water.

The volunteer will receive a single dose of 500 mg radiolabeled JNJ-53718678 as
an oral solution (50 milliliter).

Gastroscopy, placement of a nasoduodenal tube and duodenal fluid sampling are
safe procedures and complications are rare. Usually these procedures are done
without any problem. During the gastroscopy and placement of the nasoduodenal
tube some people experience pain or gagging, have a feeling that they cannot
breath, or are not able to swallow. Some people have a mildly sore throat for a
day or so after gastroscopy. Nose bleeds and nausea are common after placement
of a nasoduodenal tube. There is a slightly increased risk of developing a lung
infection or pneumonia due to vomiting and aspiration during the procedure. The
risk of this happening increases when the volunteer did not fast long enough.
If, after removal of the nasoduodenal tube, he feels very nauseated or he has
to vomit, the study doctor may treat this with certain medication. In rare
cases the gastroscope or nasoduodenal tube may cause some damage to the gut.
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 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.

All potential drugs cause adverse effects; the extent to which this occurs
differs. Up to February 2016, a total of 154 subjects have participated in
studies with JNJ-53718678: 120 received at least one dose as single doses up to
1000 mg or multiple doses up to a total daily dose of 500 mg for up to 13 days.
During these studies JNJ-53718678 was generally safe and well tolerated. Based
upon the limited available clinical data, no known safety risks associated with
JNJ 53718678 have been identified. The most frequently observed adverse effects
in man are: headache, diarrhea, a bitter taste, nosebleed, tiredness, abdominal
complaints and hot flushes. Other important adverse effects that were observed
once are: inflammation of the gastrointestinal tract (gastroenteritis) and
changes in the ECG. The volunteer should be aware that the aforementioned
adverse effects and possibly other, still unknown adverse effects, may occur
during the study. However, with the dose used in this study no serious adverse
effects are expected.

In this study radiolabeled JNJ-53718678 will be used. The amount of
radioactivity in this dose will be approximately 3.07 MBq (MBq = megaBecquerel,
this is a unit to express the amount of radioactivity in the study compound).
The average environmental background radiation burden in The Netherlands is
approximately 2 mSv per year (mSv = milliSievert, this unit indicates the
burden on the human body; thus the effect on the human body of the amount of
radioactivity administered). The additional radiation burden in this study due
to the administration of approximately 3.07 MBq radiolabeled JNJ-53718678 is
calculated to be 0.07 mSv. This is approximately 3.5% of the average annual
radiation burden.

Procedures: pain, minor bleeding, bruising, possible infection