A Randomized, Double-Blind, Placebo-Controlled Study in Healthy Male Subjects to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Ascending Oral Doses of JNJ-26070109

The study has three objectives. Firstly, we will study the safety and
tolerability of JNJ-26070109 after single increasing dose administration of the
drug. Secondly, we will study the speed at which the drug is absorbed in the
body, as well as the effects of the drug and the extent to which it is
metabolised. Thirdly, we will investigate the maximum tolerated concentration
in the body.

JNJ-2607019 is an investigational drug being developed for gastroesophageal
reflux disease (GERD) to reduce the complaints of abdominal pain and heartburn
in people with this disease. JNJ-26070109 inhibits the gastrin receptor in the
stomach. The gastrin receptors are small particles in the stomach. When the
gastrin receptor is triggered the stomach will produce acid. In people with
GERD the acid in the stomach is the cause for the abdominal pain and heartburn.
By blocking the gastrin receptor the acid production will decrease and the
complaints of pain and heartburn will diminish.

This is a single center study in healthy male subjects, and consists of 2 parts.
Part One is a double-blind, randomized, placebo-controlled single ascending
dose design. Subjects will participate in one of seven (7) cohorts (n = 10) and
will receive either JNJ 26070109 oral suspension (n = 7) or placebo (n = 3)
after an overnight fast. Dose escalation will continue until maximum tolerated
dose (MTD) is reached per the dose limiting toxicity (DLT) described in Section
(4.7.6). The doses of JNJ 26070109 will be escalated in a stepwise fashion if
the safety, tolerability and pharmacokinetic profile (up to 24 hours post
dosing) is found acceptable after assessment of the preceding dose level(s).
Each dose escalation will not exceed 4 fold of the previous dose and the dose
will not exceed 1000 mg.
Part Two of the study is an open-label, single dose design to evaluate the
effect of JNJ-26070109 on intra-gastric pH. Subjects that participated in Part
One are not eligible to participate in Part Two. Twelve (12) healthy male
subjects will be enrolled. Subjects will have 24-hour intra-gastric pH
measurements on two consecutive days: at baseline for 24 hours prior to dosing
(first 24 hours; Day *1) and following dosing with JNJ 26070109 oral suspension
(second 24 hours; Day 1). The dose to be administered in Part Two will be the
MTD, or the highest dose administered in Part One, if the MTD is not reached.
This dose may be administered as a single dose or in divided doses on Day 1
based on Part One results.
The total duration per subject is 38 days at a maximum. The study will include
a medical examination, one admission period of 5 days, one visit and finally a
follow-up. For the last group of 12 healthy male volunteers the study will
include a medical examination, one admission period of 6 days, one visit and
finally a follow-up. The following assessments will be taken; physical exam,
blood-and urine sample collections, alcohol breath test, blood sample for
DNA-assessment, vital signs, ECG*s and continuously hearth rhythm (telemetry).
For group 8, also intra gastric pH monitoring will be assessed for a period of
48 hours.

Every subject is only allowed to participate after randomisation to one of the
cohorts.

Cohort 1: single oral dose of 5 mg of JNJ-26070109 suspension or placebo
Cohort 2: single oral dose of 15 mg of JNJ-26070109 suspension or placebo
Cohort 3: single oral dose of 50mg of JNJ-26070109 suspension or placebo
Cohort 4: single oral dose of 150mg of JNJ-26070109 suspension or placebo
Cohort 5: single oral dose of 400 mg of JNJ-26070109 suspension or placebo
Cohort 6: single oral dose of 700 mg of JNJ-26070109 suspension or placebo
Cohort 7: single oral dose of 1000 mg of JNJ-26070109 suspension or placebo


Cohort 8: Dose administration ofxxxx mg of JNJ-26070109 suspension or placebo.
The dose to be administered will be the MTD, or the highest dose administered
in the previous cohorts, if the MTD is not reached. This dose may be
administered as a single dose or in divided doses on Day 1 based on Part One
results.

The associated risks to this study are the occurrence of possibility side
effects of the use of JNj-26070109. The burden of the subjects are the
confinement period in the unit, venipuncture, the insertion of the cannula and
connection of the telemetry equipment. For cohort 8 also the insertion of the
gastric tube. All subjects will be carefully monitored regarding possible
adverse events by experienced study personnel and physicians.