AN OPEN-LABEL, SINGLE-DOSE, SINGLE-PERIOD STUDY DESIGNED TO ASSESS THE MASS BALANCE RECOVERY, METABOLITE PROFILE AND METABOLITE IDENTIFICATION OF [14C]-OLOROFIM ADMINISTERED VIA THE ORAL ROUTE TO HEALTHY MALE SUBJECTS.

Olorofim is a new compound that may eventually be used for the treatment of
serious fungal infections. Fungal infections are especially dangerous for
patients with an immune system that is not working properly, like cancer
patients, patients in the intensive care unit and transplantation patients.
With an improperly working immune system a fungus could invade the blood stream
which can be fatal.
The currently available treatments have limitations, such as causing
significant adverse reactions, they interact with other medications, and some
strains of fungus have become resistant to some antifungal drugs (meaning the
drugs do not work anymore).
Olorofim has a new mechanism of action compared to the available antifungal
treatments. Olorofim inhibits a substance (enzyme) that is involved in cell
multiplication. In this way olorofim prevents the growth and spread of the
fungus in the body.

The purpose of this study is to investigate how quickly and to what extent
olorofim is absorbed and eliminated from the body. Olorofim will be labelled
with 14 Carbon (14C) and is thus radioactive. In this way olorofim can be
traced in blood, urine and stool and bile.

The bile will be collected via a nasoduodenal tube.

It will also be investigated how safe the new compound olorofim is and how well
it is tolerated when it is administered to healthy volunteers. Olorofim has
been administered to humans before.

The volunteer is given 120 mg of [14 C] olorofim as a drink of approximately 30
milliliters (mL). After the administration of the test substance, the bottle
will be rinsed a few times with water, which you should also drink. A total of
240 ml of the test substance / water should be drunk.

During the first 2 hours after administration of the test substance, the
volunteer should not lie down (except when indicated by one of the
researchers), as this may influence the uptake of the test substance.

Part A:
The study will consist of 1 group with 6 volunteers.
The actual study will consist of 1 period during which they will stay in the
research center for up to 16 days (15 nights). If necessary, they will return
to the research center for one or two 24-hour collection of urine and feces on
Day 21 and Day 28. For these collection intervals, they are expected in the
research center at 11.00 hour in the morning of Day 21 and Day 28, and they can
leave after the 24-hour collection interval (Day 22 and/or Day 29).

Day 1 is the day of administration of the study compound. The volunteers are
expected at the research center at 14:00 h in the afternoon prior to the day of
administration of the study compound. They will leave the research center on
Day 15 of the study (unless radioactivity levels permits to leave earlier).

Part B:
The study will consist of 2 groups (Group B1 and Group B2) with a total of 6
volunteers (with at least 2 volunteers in a group). One can participate in one
of the groups. The actual study consists of 1 period during which the
volunteers will stay in the research center for 6 days (5 nights).

Day 1 is the day of administration of the study compound. They are expected at
the research center at 14:00 h in the afternoon prior to the day of
administration of the study compound. They will leave the research center on
Day 5 of the study.

On Day 1, approximately 2 hours before administration of the study compound, a
nasoduodenal tube will be inserted through the nose into the duodenum . A
nasoduodenal tube is a slim flexible tube that under local anesthesia, is
inserted via the nose, through the esophagus (gullet) and stomach, placed with
its tip in the duodenum (first part of the intestines) to take samples of the
liquid (bile) in the duodenum. The tube will be inserted once and will remain
in place for up to 8 hours (for Group B1) or 14 hours (Group B2).

Not applicable.

Drawing blood and/or insertion of the indwelling cannula (tube in an arm vein)
may be painful or cause some bruising.

In total, we will take maximally resp. 450 milliliters (mL) or 300 milliliters
(mL) of blood. This amount does not cause any problems in adults. To compare: a
blood donation involves 500 mL of blood being taken each time.

To make a heart tracing, electrodes (small, plastic patches) will be pasted at
specific locations on the arms, chest and legs. Prolonged use of these
electrodes can cause skin irritation (rash and itching).

During a period of 6 hours (Group B1) or 12 hours (Group B2) after
administration of the study compound on Day 1 they will have samples of the
fluid (bile) in the duodenum collected via the nasoduodenal tube.