Microdose (i.v.) and oral potential therapeutic dose administration of S 47445 to assess absolute bioavailability and pharmacokinetic parameters of S 47445 in healthy young male volunteers. An open label 1 period study.

The drug to be given (S 47445) is a new, investigational compound that may
eventually be used for the treatment of Alzheimer*s disease. Alzheimer*s
disease is the most prevalent cause of dementia in elderly people. It not only
causes memory loss but also difficulties in cognitive function. Alzheimer*s
disease is associated with deficiencies in numerous neurotransmitters
(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.

primary:
To assess absolute bioavailability of S 47445 after administration of a single
oral potential therapeutic dose and to determine the blood and urinary
pharmacokinetic parameters of S 47445 after administration of a single i.v.
microdose of [14C]-S 47445 and a single oral potential therapeutic dose of S
47445.
The secondary objective of the study is to assess the safety and the
tolerability of S 47445 after administration of a single i.v. microdose of
[14C]-S 47445 and a single oral potential therapeutic dose of S 47445.

Procedures and assessments:
Screening and Run-Out Visit:
Clinical laboratory, vital signs, physical examination, 12-lead ECG; at
eligibility screening: medical history, CYP2D6 genotyping, standard EEG, drug
screen, HBsAg, anti HCV, anti-HIV 1/2; drug screen to be repeated upon
admission. Run-out visit at release form the clinical unit.

Treatment period:
Involving administration of a single oral dose S 47445 and a single i.v.
microdose [14C] S 47445. One period in clinic from -17 h up to 72 h after drug
administration.

Blood Sampling:
for pharmacokinetics of S 47445, radioactivity associated to [14C]-S 47445 and
total radioactivity in plasma: pre-dose and 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8,
12, 16, 24, 48 and 72 h post-dose
a single sample for genetic profiling

Urine sampling:
for pharmacokinetics of S 47445, radioactivity associated to [14C]-S 47445 and
total radioactivity: pre-dose and intervals 0-12, 12-24, 24-48 and 48-72 h
post-dose

Safety assessments:
adverse events: throughout the study, vital signs, Clinical laboratory, 12 lead
ECG.

Bioanalysis:
analysis of total radioactivity and radioactivity associated to [14C]-S 47445
in plasma and urine using a validated AMS method by Xceleron under Sponsor
responsibility
analysis of S 47445 in plasma using a LC-MS method by Covance UK under Sponsor
responsibility
genotyping (CYP2D6) by PRA
genotypeing (general) by Integragen

Active substance S47445 and [14C]- S47445

As S 47445 will be administered to men for the first time shortly before this
study, to date adverse effects in man have not been reported. In previous
studies with rats and monkeys, in which S 47445 was administered daily in high
doses over a period of 4 weeks, the following adverse effects were observed:
increased saliva production, minor changes in blood cell production
(extramedullary haemopoiesis) and whitish feaces.
With the dose used in this study no serious adverse effects are expected..