An open label, single dose, single period study to assess the mass balance recovery, metabolite profile and metabolite identification of [14C] APD421 administered via the intravenous route to healthy male subjects

APD421 is a new formulation for intravenous administration of the already
registered drug amisulpride. Thus, the active compound in APD421 is no new
drug; the active compound is already available on the market in other
formulations and under several dosages for the treatment of schizophrenia and
other psychoses. APD421 is being developed for the treatment of nausea and
vomiting following operations or chemotherapy. This new formulation is in
development and is not registered as a drug but has been given to humans
before. Amisulpride blocks some of the effects of a substance known as
dopamine. Dopamine is a neurotransmitter that occurs naturally in the body and
plays a role in the brain and nervous system, including triggering nausea and
vomiting. Amisulpride binds to specific dopamine receptors and, like other
dopamine antagonists, may be useful in prevention and treatment of nausea and
vomiting.

The purpose of the study is to investigate how quickly and to what extent
APD421 is absorbed, distributed, metabolized (broken down) and eliminated from
the body (this is called pharmacokinetics). APD421 to be administered will be
labelled with 14-Carbon (14C) and is thus radioactive (also called
radiolabeled). In this way APD421 can be traced in blood, urine and faeces. It
will also be investigated to what extent APD421 is tolerated.

The study will consist of 1 period during which you will stay in the clinical
research centre in Groningen for a maximum of 9 days (8 nights).

The volunteer will receive a single dose of 10 mg radiolabeled APD421 as an
intravenous infusion (in a vein) during 4 minutes (with a possible extension up
to 8 minutes).

All potential drugs cause adverse effects; the extent to which this occurs
differs. Amisulpride is already approved in tablet form for treatment of some
psychiatric illnesses (under brand names such as Solian®), when it is given at
5 to 100 times higher doses than the dose given in the current study. For
adverse effects, please see the patient information leaflet for Solian. In 7
clinical studies with APD421 to date, the only adverse effects considered
related to study drug and occurring more frequently than with placebo (placebo
is the same formulation without the active ingredient) have been:
* short-lived pain at the infusion site, at doses of 20 mg and above, and
* short-lived increase in prolactin levels in the blood. Prolactin is a hormone
which is normally high during pregnancy and lactation and also in severe stress.
In these clinical studies, no other medical problems were associated with these
adverse effects. You should be aware that the aforementioned adverse effects
and possibly other, still unknown adverse effects, may occur during the study.
However, with the dose used in this study no serious adverse effects are
expected.

In this study radiolabeled APD421 will be used. The amount of radioactivity in
this dose will be maximally 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 = millisievert, 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 APD421 is calculated to be
less than 0.1 mSv. This is maximally 5% of the average annual radiation burden.

Procedures: pain, minor bleeding, bruising, possible infection