A First-in-Human Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Escalating Oral Doses of JNJ 28431754 in Healthy Male Subjects

JNJ-28431754 is an investigational drug being developed for the treatment of
type 2 diabetes mellitus.

Part 1 of the study has two objectives. Firstly, we will study the safety and
tolerability of the drug after the administration of single ascending oral
doses of the drug. Secondly we will study the pharmacokinetics and
pharmacodynamics. This means that we investigate the effect of the study drug
and the speed at which the drug is absorbed, distributed, broken down and
eliminated in the body.
In Part 2 of the study we will investigate whether food, when given together
with JNJ-28431754, will affect the safety, tolerability, pharmacodynamics and
pharmacokinetics of JNJ-28431754.

This is a single center study in healthy male subjects who will receive a
single ascending dose of JNJ-28431754 or placebo. The study consist of Part 1
and Part 2.
Part 1:
Six or more groups of each eight healthy male volunteers, will participate in
this part of the study. The study will include a medical screening, one
admission period of 7 days and finally a follow-up visit 10 to 14 days after
dosing. The current Amendment describes the investigation of the effect of
twice daily dosing. For that reason an additional group will be added.
The subjects will be admitted to the unit on Day -2.
On Day -1, the baseline assessments will be done.
In the morning of Day 1 the subjects will receive a single oral dose of study
drug JNJ-28431754 or placebo in a fasted state.
The doses of JNJ-28431754 will be escalated in a stepwise fashion if the
safety, tolerability and pharmacokinetic profile (uo to 48 hours post dosing)
is found acceptable after assessments of preceding dose level(s).
Part 2:
One group of 8 healthy male volunteers will participate in this part of the
study.
Part 2 consists of two periods. The study will include a medical screening, two
admission periods of 6 days and finally a follow-up visit 10 to 14 days after
the last dosing.
The subjects will be admitted to the unit on Day -1.
In the morning of *Day 1* of each period one single oral dose of JNJ-28431754
or placebo with or without a standardized high fat meal will be administered.
This will be determined by chance. The two periods will be separated by about
14-days wash out period.

Each subject is only allowed to participate after randomisation to one of the
cohorts.
During part 1, a one single dose of JNJ-28431754 or placebo is administered.
The extra group will be dosed, twice daily.
Part 2, consist of 2 periods, separated by about 14-days wash out period.
On day 1 of each period the subject receives a one single dose of JNJ-28431754
or placebo, with or without a standardized high fat meal.

The associated risks to this study are the occurence of possibility side
effects of the use of JNJ-28431754. The burden of the subjects are the
confinement period in the unit, venapuncture, the insertion of the canula and
connection of the telemetry equipment. All subjects will be carefully monitored
regarding possible adverse events by experienced study personnel and
physicians.