A phase 1 study to evaluate the absorption, metabolism and excretion of BCX7353 following administration of a single, oral dose of [14C]-radiolabeled BCX7353 to healthy male subjects.

BCX7353 is a new compound that may eventually be used for the treatment of
hereditary angioedema. Hereditary angioedema is a rare genetic disorder that
causes episodes of swelling that may affect the face, extremities, genitals,
gastrointestinal tract and upper airways. BCX7353 blocks a step in a series of
reactions leading to the activation of bradykinin, a small enzyme (a peptide)
involved in controlling the blood pressure by widening the blood vessels.
Bradykinin is thought to play an important role in the episodes of swelling.

The purpose of this study is to investigate how quickly and to what extent
BCX7353 is absorbed, metabolized (changed or broken down by the body) and
eliminated from the body (this is called pharmacokinetics). For this study
BCX7353 will be labelled with 14 Carbon (14C) and is thus radioactive. In this
way BCX7353 can be traced in blood, urine, feces, and exhaled air.

It will also be investigated how safe the new compound BCX7353 is when it is
administered to healthy subjects.

BCX7353 has been administered to healthy volunteers and patients suffering from
hereditary angioedema in 7 studies. Of these studies 2 were completed and the
results are known, 2 have been completed but no results are known yet and 3 are
still ongoing.

BCX7353 is a new compound that may eventually be used for the treatment of
hereditary angioedema. Hereditary angioedema is a rare genetic disorder that
causes episodes of swelling that may affect the face, extremities, genitals,
gastrointestinal tract and upper airways. BCX7353 blocks a step in a series of
reactions leading to the activation of bradykinin, a small enzyme (a peptide)
involved in controlling the blood pressure by widening the blood vessels.
Bradykinin is thought to play an important role in the episodes of swelling.

The actual study will consist of 1 period during which the volunteers will
stay in the research center in Groningen Martini Hospital for 16 to 22 days (15
to 21 nights). This may be followed by 1 to 4 24-hour visits to the research
center.

Day 1 is the day of administration of the study compound. They are expected at
the research center in the afternoon prior to the day of administration of the
study compound. They will leave the research center between Day 15 and 21 of
the study, depending on the amount of radioactivity excreted in the urine and
feces. Twenty-four hour visits, which may also be required depending on the
amount of radioactivity excreted, are planned on Days 28-29, 35 36, 42-43 and
Day 49-50.

The participation in the entire study, from the pre-study screening until the
last visit, will depend on the amount of radioactivity left in the urine and
feces at the end of the study (Day 21). The amount of radioactivity in urine
and feces will be measured daily from Day 1. If, from Day 15 onwards, the
radioactivity levels in urine and feces are below the pre-defined levels, the
volunteers will be allowed to leave the research center upon completion of the
discharge assessments.

If the amount of radioactivity in the urine and/or feces are not below the
pre-defined levels on Day 21, they will return to the research center for
24-hour collection of urine and feces. For these collection intervals, they are
expected in the research center at 10 AM of Day 28, 35, 42 and Day 49, and
they can leave after the 24 hour collection interval (Day 29, 36, 43 and Day
50). After each 24-hour period you will be contacted to inform the volunteer
whether they will be required to return for another 24-hour period.

Not applicable.

Pain, minor bleedings, bruises, possibly an infection.