A single-center, open-label, single oral dose study to investigate the absorption, distribution, metabolism, and excretion (ADME) and pharmacokinetics of EMA401 after a single dose of [14C]EMA401 in healthy male subjects

EMA401 is a new investigational compound that may eventually be used for the
treatment of peripheral neuropathic pain (also called neuralgia). Peripheral
neuropathic pain is a long lasting type of pain that may occur after damage to
the brain, spinal cord or peripheral nerves (the word *peripheral* refers to
the long nerves reaching out to the arms and legs). This pain is characterized
by abnormal pain sensations including burning, stabbing or piercing pains.

In previous studies, EMA401 has shown to decrease the pain intensity in
patients with shingles pain (nerve pain caused by a herpes zoster virus
infection) and in patients with pain due to chemotherapy. EMA401 is in
development and is not registered as a drug but has been given to humans before

The purpose of the study is to investigate how quickly and to what extent
EMA401 is absorbed, distributed, metabolized (broken down) and eliminated from
the body (this is called pharmacokinetics). EMA401 will be labeled with
14-Carbon (14C) and is thus radioactive (also called radiolabeled). In this way
EMA401 can be traced in blood, urine and feces. It will also be investigated to
what extent EMA401 is tolerated. In addition, the influence of genetic factors
on the pharmacokinetics of EMA401 may be explored.

The actual study will consist of 1 period during which the volunteer will stay
in the clinical research center in Groningen (location Martiniziekenhuis) for 9
to 15 days (8 to 14 nights).

During the study the volunteer will receive radiolabeled EMA401 after an
overnight fast (at least 10 hours no eating and drinking) as a capsule,
together with a minimum of 240 milliliters and a maximum of 480 milliliters of
water.

The volunteer will receive a single dose of 100 mg radiolabeled EMA401 as an
oral capsule.

All potential drugs cause adverse effects; the extent to which this occurs
differs. In previous clinical studies, approximately 316 people have been
treated with EMA401. EMA401 has been administered to healthy volunteers as a
single dose of up to 2000 mg or as twice daily doses of up to 1600 mg/day for 7
days. Possible side effects that were observed in previous studies include
allergic skin rashes, elevation in liver enzymes (liver abnormalities), and a
decreased level of white blood cells (neutropenia). Although there is some
basis of suspicion that these side effects may be associated with EMA401, such
an association has not been confirmed. Mild to moderate nausea and diarrhea
were the most frequent side effects, which were mostly seen in doses higher
than will be tested in this study.

For the current study the possible side effects of EMA401 include: nausea,
upper respiratory tract infections, headache, dizziness and pre syncope (state
of lightheadedness, muscle weakness, and feeling faint). However, you should be
aware that the aforementioned adverse effects and possibly other, still unknown
adverse effects, may occur during the study. With the dose used in this study
no serious adverse effects are expected.

In this study radiolabeled EMA401 will be used. The amount of radioactivity in
this dose will be approximately 3.7 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 = miliSievert, 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 3.7 MBq radiolabeled EMA401 is calculated to be
0.17 mSv. This is approximately 8.5% of the average annual radiation burden.