A RANDOMIZED, DOUBLE BLIND, PLACEBO CONTROLLED, CROSS-OVER, ASCENDING SINGLE ORAL DOSE, SAFETY, TOLERABILITY AND PHARMACOKINETIC STUDY OF CB-189,625 IN HEALTHY MALE SUBJECTS.

CB-189,625 is a new investigational compound that may eventually be used for
the treatment of acute and chronic pain, potentially decreasing the need for
opioids (narcotics). This is the first time that this compound will be given to
humans.

Primary: to assess the safety and tolerability of one oral dose of CB-189,625
at 6 dose levels in healthy male volunteers.
Secondary: to determine the plasma pharmacokinetic profile of one oral dose of
CB 189,625 at 6 dose levels in healthy volunteers.

This is a randomized, double-blind, placebo-controlled, cross-over, single
dose, safety, tolerability and pharmacokinetic study of 6 ascending doses of
CB-189,625 in two cohorts of healthy male volunteers. The first cohort of nine
subjects (Cohort 1) will be sequentially enrolled into 3 of 6 dosing periods
(Dose Levels 1, 3, and 5). The remaining cohort of nine subjects (Cohort 2)
will be enrolled in the other 3 dosing periods (Dose Levels 2, 4, and 6). Each
subject will receive one dose of placebo and two different doses of CB-189,625
over the course of their participation in all three dosing periods.

Procedures and assessments:
Pre-screening, throughout the study and safety days: demographics, medical
history, drug and alcohol screen, vital signs (including body weight and
height, supine systolic and diastolic blood pressure, pulse rate, respiratory
rate and body temperature), 12 lead electrocardiogram (ECG), serology (HBsAg,
anti HCV and anti-HIV 1/2), clinical laboratory (including clinical chemistry,
hematology and urinalysis), physical examination, adverse events (AEs),
previous medication, hot/cold sensation and audiometry.

Blood sampling: Blood for plasma concentration of CB-189,625 and its
metabolites.
Urine sampling: Urine for analysis of levels of CB-189,625 and its metabolites
will be collected.

Cohort 1:
period 1: a single oral dose of 200 mg CB-189,625 or placebo.
period 3: a single oral dose of 800 mg CB-189,625 or placebo.
period 5: a single oral dose of 1600 mg CB-189,625 or placebo.

Cohort 2:
period 2: a single oral dose of 400 mg CB-189,625 or placebo.
period 4: a single oral dose of 1200 mg CB-189,625 or placebo.
period 6: a single oral dose of 2000 mg CB-189,625 or placebo.

Each subject will particpate in three periods, receiving two different doses of
CB-189,625 and one dose of placebo.

As CB-189,625 will be administered to man for the first time in this study, to
date adverse effects in man have not been reported. CB-189,625 has been studied
in animals (rats, dogs and monkeys). The most important adverse events reported
from these animal studies were: diarrhea, changes in clinical laboratory
parameters including cholesterol, liver enzymes, red blood cell indices, and
urine output, and changes to the vital signs and ECG. These events occurred at
much higher doses in animals than will be used in man. One of the inactive
ingredients, hydroxypropyl-beta-cyclodextrin (HPCD) that is used in both the
CB-189,625 compound and the placebo compound can cause diarrhea and stomach
discomfort after multiple high daily doses. The single dose of HPCD that you
receive in this study is not anticipated to cause any discomfort.
With the doses used in this study no serious adverse effects are expected. The
occurrence of known or other effects cannot be excluded.

Registration af adverse effects: During the entire investigation all adverse
effect you report will be documented.

Blood draw, indwelling canula: During this study less then 400 ml of blood will
be drawn. It is anticipated that in every period an indwelling canula will be
used and approximately 4 blood draws will be drawn by direct puncture of the
vein.

Collection of urine: All urine will be collected until 48 hours after
administration of CB-189,625 or placebo (thus until Day 3 of each period).

Heart trace (ECG*s): ECG*s will be made regularly, once before and 4 times
after each time you are administered CB-189, 625 or placebo.

Hot /Cold sensation: During the 24 hours after administration of CB-189,625 or
placebo (thus until Day 2 of each period), you will be regularly tested on your
perception of hot and cold materials on your skin.

Audiometry: Before and 1 hour after administration of CB-189,625 or placebo
your hearing will be tested