A Phase I, Open-label, Single Dose Study to Evaluate the Disposition, Metabolism, and Excretion of Radiolabelled [14C]-BIM23B065 Following Subcutaneous Administration in Healthy Male Subjects

BIM23B065 is a new investigational compound that may eventually be used for the
treatment of tumors of the pituitary gland.

The pituitary gland is situated in the middle of the head at the base of the
brain. The pituitary gland secretes a number of hormones which play an
important role in a variety of processes in the body. The gland is about the
size of a chickpea (diameter of approximately 1 centimeter). A pituitary tumor
is a benign or malignant (cancerous) growth that develops in the pituitary
gland. The vast majority of pituitary tumors are benign (in the sense of
'non-cancerous*). This abnormal growth may result in the overproduction of
hormones. One of these hormones is the growth hormone, which, when it is
overproduced, leads to acromegaly (gigantism).

BIM23B065 binds to 2 types of receptors (proteins) present in the pituitary
tumor: the somatostatin receptor 2 and the dopamine receptor 2. It is expected
that this will inhibit the overproduction of hormones.

BIM23B065 is in development and is not registered as a drug but has been given
to healthy volunteers as a single dose first and then as repeated doses.

The purpose of the study is to investigate how quickly and to what extent
BIM23B065 is distributed, metabolized (broken down) and excreted from the body,
and what the main route of excretion from the body is (urine or feces); this is
called pharmacokinetics. BIM23B065 is labeled with 14-Carbon (14C) and is thus
radioactive (also called radiolabeled). In this way BIM23B065 and its
metabolites can be traced in blood, urine and feces. It will also be
investigated to what extent BIM23B065 is safe and tolerated by the human body.

Before the study the volunteer will undergo a pre-study screening within 28
days before the day of administration of the study compound (Day 1) during
which the volunteer will be subjected to a number of medical examinations.
Similar examinations will be performed after the study at the post-study
screening.

The actual study will consist of 1 period during which the volunteer will stay
in the clinical research center for a minimum of 9 days (8 nights) to a maximum
of 16 days (15 nights). Thus, the volunteer will stay from the afternoon of Day
-1 (1 day before administration of the study compound; also called admission)
until at least Day 8. After administration of the study compound on Day 1, all
urine and feces will be collected. The total amount of radioactivity excreted
in urine and feces will be measured daily after administration of the study
compound. From Day 7 onwards, if the radioactivity levels in urine and feces
are below pre-defined levels, the volunteer will be allowed to leave the
clinical research center the next day (from Day 8 onwards). The volunteer will
leave the clinical research center at the latest on Day 15 (around noon). If
the radioactivity levels are still above the pre-defined levels on Day 15,
additional short visits will be scheduled for the 24-hour collection of urine
and/or feces on Days 22-23 and, if necessary based on the radioactivity levels
in urine and feces, on Days 29-30.

Day 1 is the day of administration of study compound. The volunteer is expected
at the clinical research center at 14:00 h in the afternoon prior to the day of
administration of the study compound. The volunteer will be required not to
have consumed any food or drinks during the 4 hours prior to arrival in the
clinical research center (with the exception of water).

On the first day of each potential additional short visit, the volunteer is
expected at the clinical research center at 9:30 h in the morning and you will
leave the clinic the next day in the afternoon after the 24-hour urine and/or
feces collection has been completed. There are no food or fluid restrictions
prior to arrival for these potential additional short visits.

The post-study screening will be planned within 5 to 9 days after the volunteer
left the clinical research center for the last time. The appointment for the
post-study screening will be made with as soon as it is known when the study
will end for the volunteer.

Participation in the entire study, from pre-study screening until the
post-study screening, will be a maximum of 66 days.

The volunteer will receive a single dose of 1.2 mg radiolabeled BIM23B065 as a
subcutaneous injection of 1 milliliter (mL) in the abdominal region. BIM23B065
will be given under fasted conditions. This means that the volunteer is not
allowed to eat for at least 4 hours before administration of the study
compound. During fasting the volunteer is allowed to drink water. Fasting will
continue until 1 hour after administration of the study compound. Then the
volunteer will receive a breakfast. During the first 2 hours after
administration of BIM23B065 the volunteer will have to lie down (if allowed by
the procedures).

A single dose of 1.2 milligrams (mg) radiolabeled BIM23B065 as an injection
under the skin (subcutaneous).

A clinical study with BIM23B065 has been previously conducted where 29 healthy
volunteers received a single subcutaneous dose of BIM23B065 at dose levels
between 0.1 and 1.5 mg. Common adverse effects observed in that study were skin
reactions, such as local redness of the skin, at the site where the
subcutaneous injection was given; these effects typically resolved within 2
hours after the injection with BIM23B065 was given. Other common adverse
effects were nausea, hypotension (low blood pressure) and orthostatic
hypotension (drop in blood pressure on standing from a sitting or lying
position that may be accompanied by lightheadedness and/or dizziness); these
effects were expected since they are known adverse effects of compounds that
bind to dopamine receptors.