A Study To Examine Safety, Pharmacokinetics, And Pharmacodynamic Of Pf 06412562 In Healthy Males

This study is designed to investigate the safety, tolerability pharmacokinetics and
pharmacodynamic effects of PF-06412562 following multiple dose administration as MR tablets
in healthy adult males. The study will be comprised of 2 analytical stages. Both analytical
stages will be conducted as randomized, subject and investigator blind, sponsor open,
placebo-controlled, parallel design. Study enrollment will be continuous through Stage I and
Stage II. Stage I consists of approximately 45 completer subjects (approximately 15 per
arm). Stage I is an exploratory hypothesis generation stage. No multiple comparison
adjustment will be conducted for the Stage I analysis. The sample size in Stage I is based
on operational feasibility. All endpoints including the composite scores will be tested at
the end of Stage I. Each PF-06412562 dose (3 mg BID and 15 mg BID) will be compared to the
placebo arm for each endpoint. Up to 5 comparisons that meet Stage I decision criteria will
be treated as primary comparisons in Stage II (see Data Analysis section). Stage II is a
hypothesis testing stage in which multiple comparisons will be adjusted and overall type I
error rate will be controlled across all primary comparisons. Stage II will be formally
powered to study those endpoints/doses most likely to demonstrate the strongest
pharmacodynamic signal. Stage II will not exceed 56 completers (~21 in each PF-06412562 arm
and ~14 in placebo arm). Study enrollment will be continuous through Stage I and Stage II.
The three treatments in both stages include (i) PF-06412562 3 mg BID (ii) PF-06412562 15 mg
BID, and (iii) placebo. Separate placebo groups, contemporaneous with the treatment groups,
will be recruited for Stage I and Stage II. A total of approximately 101 subjects will be
randomly assigned to one of the 3 treatments. If a subject drops out before completing the
study, or withdraws for reasons unrelated to the safety of the test treatment, the subject
will be replaced at the discretion of the Sponsor in consultation with the investigator.
Subjects with fMRI or ERP data that does not pass imaging or ERP data QC will also be
replaced.

Subjects will be randomized to a specific treatment arm according to the randomization
schedule provided to the site by Pfizer. Two doses of PF-06412562 (3 mg and 15 mg),
administered as MR tablets, will be given twice daily (BID) from Day 1 through Day 6. A
loading dose of PF-06412562 will be administered as an IR tablet on Day 1 only to facilitate
rapid attainment of concentration into the target range. For subjects assigned to the 3 mg
BID group, one 3 mg MR tablet and one

1 mg PF-06412562 IR tablet will be administered. For subjects assigned to the 15 mg BID
group, one 15 mg MR tablet and one 5 mg IR dose of PF-06412562 will be administered.

On Day 7 only the morning dose will be administered. Subject participation will be
approximately 12 days (and 11 nights), excluding screening and follow-up. Screening
activities will be completed up to 28 days prior to admission to the study on Day -3. The
follow-up visit is conducted approximately 7 to 10 days after the last dose of study drug
administration. Medically healthy, right-handed male subjects, aged 18-45 will be screened
for working memory capacity, psychiatric disorders and other cognitive/educational
constrains. Subjects who meet all entry criteria will be randomized into one of the three
treatment arms.

Inclusion Criteria:

- Medically healthy

- Male

- Right-handed aged

- 18-45 years

- BMI 17.5 to 35kg/m2.

Exclusion Criteria:

- Females

- Evidence or history of clinically significant hematological, renal, endocrine,
pulmonary, gastrointestinal, cardiovascular, hepatic, neurologic, or allergic disease
(including drug allergies, but excluding untreated, asymptomatic, seasonal allergies
at time of screening and at the time of dosing).