An Open-Label, Single Dose Study to Investigate Striatal Dopamine D2 Receptor Binding of JNJ-37822681 Using [11C]Raclopride Positron Emission Tomography in Healthy Male Subjects

JNJ-37822681 is a selective, fast-dissociating, dopamine D2 antagonist for the
treatment of psychosis. Because the compound is selective and fast
dissociating, it is expected that treatment with JNJ 37822681 will result in
less side effects than those experienced with currently marketed therapies.
JNJ-37822681 is hypothesized to have clinical effects through interactions with
the dopamine D2 receptor. In this study, [11C]raclopride PET will be used to
directly investigate the interaction of JNJ-37822681 with striatal dopamine D2
receptors. Understanding the relationship between plasma concentrations and
occupancy will support rational dose selection for Phase II efficacy studies in
patients with schizophrenia.

The objective of this study is to investigate the relationship between
JNJ-37822681 plasma concentration and striatal dopamine D2 receptor occupancy
in healthy male subjects.
The secondary objective of this study is to investigate the safety and
tolerability of JNJ-37822681 in healthy male subjects.

This is an open label, randomized study. 8 subjects are planned to participate
in this study. Each subject will receive 2 dose levels of JNJ-37822681 and 3
[11C]raclopride PET scans.

During the screening subjects will be checked for eligibility. Subjects who are
eligible to participate in the study will have an MR scan and the baseline PET
scan.

The volunteerd will be admitted to the study unit in the afternoon of Day -1.
On Day 1 the subjects will be taken to the PET centre of the VUMC and they will
receive the study medication followed by a PET scan approximately 2 hours
later. The subjects will then be taken back to the study unit. Subjects will be
released in the morning of Day 2.

Subjects 1 and 2 will receive a single oral dose of 10 mg JNJ-37822681. Further
dose levels will be determined based on the results obtained from previous
subjects, and on tolerability/safety observations from parallel ongoing single
and multiple dose studies. If appropriate, > 1 measurements may be made at 1
dose level.

Each subject will receive 2 dose levels of JNJ-37822681 and 3 [11C]raclopride
PET scans.

The associated risks are the occurence of possible side effects of the use of
JNJ-37822681.
The burden of the subjects are the confinement period in the unit,
venapuncture, and the insertion of the canula.

All subjects will receive 3 PET scans. The total radiation is 6 mSv, which is
largely within the legal limits.

All subjects will be carefully monitored for possible adverse events by
experienced study personnel and physicians