Microdose (intravenous and oral) and oral dose of S 47445 to assess absolute bioavailability, pharmacokinetic parameters and excretion balance of S 47445 in healthy young male volunteers.

S 47445 is a new investigational compound that may eventually be used for the
treatment of Alzheimer*s disease. Alzheimer*s disease is associated with
disturbances in the exchange of *messenger* molecules (neurotransmitters)
between cells in the brain and the nervous system. S 47445 is developed to
enhance this exchange.
S 47445 is not registered as a drug but has been given to humans before.

The purpose of the study is to investigate how quickly and to what extent S
47445 is absorbed, distributed, metabolized (broken down) and eliminated from
the body (this is called pharmacokinetics). S 47445 will be labeled with
14-Carbon (14C) and is thus radioactive. This enables the investigator to trace
S 47445 in blood, urine and feces. The safety and tolerability of S 47445 will
also be evaluated. In addition, the bioavailability (measurements of the amount
of drug that is actually absorbed) of S 47445 will be investigated.

Procedures and assessments
Screening and follow-up:
clinical laboratory, full physical examination, ECG, weight, vital signs (BP,
temperature HR) and adverse events; only at screening: medical and surgical
history, relevant previous treatments, psychological examination, alcohol and
drug screen, HBsAg, anti HCV and anti-HIV 1/2, height, EEG and CYP2D6
genotyping; upon admission: medical and surgical history, alcohol and drug
screen and ADME genotyping

Observation period:
two periods in clinic from -17 h up to 144 h (Day 7) after drug administration

Blood sampling:
for pharmacokinetics of S 47445 and total radioactivity in plasma: Period 1 and
2: pre-dose and until 96 hrs post dose
for CYP2D6 genotyping: once during screening
for ADME genotyping: once at Day -1 of period 1

Urine sampling:
for pharmacokinetics of S 47445 and total radioactivity: period 1 and 2:
pre-dose and until 120-144 h post-dose

Faeces sampling:
for pharmacokinetics of S 47445 and total radioactivity: period 1 and: pre-dose
and until 120-144 h post-dose

Safety assessments:
adverse events: throughout the study; physical exam, vital signs (including
body temperature and respiratory rate) and 12-lead ECG: pre-dose and several
time points during the study.

In period 1 the subjects will receive a single oral dose of 20 mg as 4 tablets
of unlabeled S 47445 after an overnight fast (at least 10 hours) with 250 mL of
water. Three hours later, you will receive 50 mcg radio labeled S 47445 in
2.5-mL solution as a single intravenous (IV) infusion over 15 min.

In period 2, the subjects will receive a single oral dose of 50 mcg radio
labeled S 47445 after an overnight fast (at least 10 hours) as a 2.5-mL oral
solution.

Registration of adverse effects

Blood sampling, indwelling cannula: During this study less than 500 ml of blood
will be drawn. It is anticipated that an indwelling cannula will be inserted
for blood samplings on Day 1 and Day 2 of both periods. The blood samplings on
the other days will be drawn by direct puncture of the vein.

IV administration: For the IV administration an indwelling cannula will be
inserted specifically for this purpose in addition to the indwelling cannula
used for blood sampling.

Collection of urine and feces: In both periods urine and feces will be
collected until 144 hours after administration of S 47445 (thus until Day 7). A
blank urine and faeces sample will be obtained before drug administration.

Heart trace (ECG*s): ECG*s will be made regularly: specifically on Day 1.

Electro Encephalogram (EEG): The study medication is expected to act on the
brain, so in order to avoid problems during the study the brain activity is
studied before administration of the study medication.

Genotyping for CYP2D6: Part of the screening visit will be to perform
genotyping in order to assess liver*s capacity to metabolize certain drugs.

Blood sample for DNA tests: On Day 0 an additional blood sample will be taken
in order to perform analyses on genetic material (DNA).

In previous clinical studies with S 47445 in 100 healthy volunteers, with doses
up to 800 mg (single dose) and up to 100 mg (multiple dose, 21 days) the
following adverse events were reported: feeling of thirst, dizziness and low
blood pressure when standing-up, hematoma on the back of the foot, headache,
hot flush, and redness of the skin. Drugs with a comparable action sometimes
induce unrest, anxiety or sleeplessness.