Excretion balance, pharmacokinetics and metabolism of S 47445 after single oral administration of 20mg [14C]-S 47445 in young healthy male volunteers.

The drug to be given (S 47445) is a new, investigational compound that may
eventually be used for the
treatment of Alzheimer*s disease; the drug is still in developmental phase.
Alzheimer*s disease is the most prevalent cause of dementia in elderly people.
It not only causes memory loss but also a deterioration of cognitive function
(learning ability, attention).
Alzheimer*s disease is associated with disturbances/deficiencies in numerous
neurotransmitters
(*messenger* molecules that are being exchanged between cells in the brain and
nervous system).
S 47445 is developed to enhance the function of one of these pathways. In
animal studies S 47445 was
found to enhance cognitive function.
This new compound is not registered as a drug but has been given to humans
before.

- to assess the excretion balance of total radioactivity in urine and faeces
after single oral dose of 20 mg 2.35 MBq (64 µCi) of [14C]-S 47445,
- to determine the pharmacokinetics of the total radioactivity in whole blood,
plasma and urine after single oral dose of 20 mg-2.35MBq (64 µCi) of [14C]-S
47445,
- to investigate the pharmacokinetics of S 47445 in blood and urine after a
single oral dose of 20 mg-2.35 MBq (64 µCi) of [14C]-S 47445,
- to investigate the metabolite profile of S 47445 in plasma, urine and faeces
after a single oral dose of 20 mg-2.35 MBq (64 µCi) of [14C]-S 47445.
- to assess the safety of S 47445 after a single oral dose of 20 mg-2.35 MBq
(64 µCi) of [14C]-S 47445.

This is a study in healthy male volunteers into the Absorption, Distribution,
Metabolism and Excretion (ADME) of 14C labeled S-47445. The study is open label
and not randomized.
The volunteers stay in the clinic for 10 Days (9 nights) where blood samples
are collected and urine and feaces is collected. If the volunteer does not meet
the criteria on excetion of radioactivity at the end of this period, he will be
asked to continue coleecting urine and feaces at home and to deliver this at
the unit every 2nd day.

Single oral dose of 20 mg, 2,35MBq of [14C] S-47445 as a capsule.

In previous clinical studies with S 47445 in a total of 100 healthy volunteers,
with doses up to 800 mg (single dose) and up to 100 mg 1 times daily for 21
days or placebo, 78 volunteers received S 47445 and 22 received placebo. The
following adverse events were reported with S 47445: a feeling of thirst,
dizziness when in standing position, an orthostatic hypotension, a haematoma, a
nasopharyngitis, a headache, a hot flush, and erythema.
With the dose used in this study no serious adverse effects are expected.
However, the possibility that any of the above-mentioned or other adverse
effects could occur cannot be entirely excluded.
The insertion of the indwelling canula and the venepuncture may cause some
pain, and sometimes lead to a bruise, but the actual collection of blood will
not be painful. Light bleeding and possibly an infection may occur. However,
the chance that these complications will occur is limited.