A phase I, open-label study to investigate the absorption, metabolism, excretion, and mass balance of [14C]QLT091001 following single oral dose in healthy male subjects

The research medication is a new medication developed for the treatment of
inheretid retinal diseases (IRD).

The study objectives are:
- to characterize the biotransformation pathways, the routes and rates of
excretion, and total recovery of the 14C-labeled research medication and its
radiolabeled metabolites
- to characterize the pharmacokinetics (PK) of the research medication and its
major metabolites
- to document the safety and tolerability

A phase I, open-label study to investigate the absorption, metabolism,
excretion, and mass balance of the research medication following a single oral
dose in healthy male subjects.

The study will start with a screening. At the screening a physical examination
will take place and a few other standard medical assessments will be performed
(ECG, vital signs). Furthermore a blood and urine sample will be taken for
laboratory tests and an alcohol breath test and drug screen will be done.

During the stay in the clinic the subject will receive the 14C-labeled research
medication once on Day 1. On several time points blood will be taken and all
urine and feaces will be collected. The subjects will be asked for possible
side effects on regular basis. Furthermore several safety assessments (ECG,
vital signs) will be done frequently and an ophthalmic examination will be
performed three times. On Day 10 the subjects will be discharged from the
clinic after they have met met the discharge criteria regarding radioactivity
levels in samples of blood, urine and feces. When these criteria have not been
met by the morning on Day 10, they will stay in the clinic until the criteria
are met.

It appeared that the amount of radioactivity was decreased sufficiently for the
subjects to leave the clinic, however, it was not yet totally excreted by the
body. To have a complete insight of the excretion of the research medication
QLT091001, the sponsor would like to further determine the radioactivity in
your samples of blood, urine and feces for maximally 4 times with an interval
of 2 weeks.

The research medication has been previously tested in humans and animals and
was generally well tolerated. A total of 27 humans have received the research
medication in a trial. In healthy subjects (20 volunteers), a number of
side-effects, related to the research medication have been reported. These
side-effects included mild transient headaches and facial flushing and burning
sensation, decreased appetite, lack of energy, sensitivity for light, change of
certain blood parameters (decreased haemoglobine, red blood cells and
triglycerides).
Based on studies with the research medication in animals and human experience
with drugs resembling the research medication effects on the liver are
possible. These effects are expected to be reversible.

The dose level is selected on the basis of research results in animals and
humans. The risk to health at these dose levels is limited but subjects may
experience one of the above mentioned side-effects or other symptoms not
previously reported. The health of the subjects will be closely monitored
during the trial to minimize these risks.

The radioactive substance that is used for this study is broken down rapidly.
The total radiation load in this study is estimated as 1.4 millisievert.