A Blinded, Placebo-Controlled, Randomized, Single Ascending Dose Study in Healthy Male Subjects to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-37822681

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.

The objectives for the study are:
to investigate the safety and tolerability of JNJ-37822681 following single
dose administrations in healthy male subjects.
to investigate the plasma pharmacokinetic profile of JNJ-37822681 and
metabolites after single ascending dose administration
to investigate renal excretion of JNJ-37822681
·to investigate the pharmacodynamic effect of JNJ-37822681 (specifically:
effect on prolactine (PRL) concentrations, saccadic eye movements, smooth
pursuit eye movements, adaptive tracking, Bond and Lader Visual Analogue
Scales, Bowdle VAS, body sway, tapping, and pharmacoelectroencephalogram
(pEEG).

This is an alternating panel, randomized, blinded, placebo-controlled study in
healthy male subjects. Two panels of each 12 subjects will participate in the
study. Each subject will receive 3 doses of JNJ 37822681 and 1 placebo dose,
randomized over 4 study periods. Panels will alternate. At each dosing occasion
9 subjects will receive JNJ-37822681 and 3 placebo. It is planned that subjects
will receive escalating doses of JNJ-37822681.

At periods 1 - 3 subjects will be admitted to the study unit in the morning of
Day -1. On Day 1 the study medication will be administered and the subjects
will be discharged on Day 3. In period 4 the subjects will be discharged on Day
4, 72 hours after the study medication administration.

Doses will be escalated only if acceptable safety and tolerability was
demonstrated at the preceding, lower, dose level. Selected pharmacokinetic and
pharmacodynamic endpoints will also be generated following each dose
administration and will be available to support dose escalation in the same
subject. If peak concentration-related dose-limiting side effects are observed,
it may be decided to administer the same dose but divided over multiple
administrations during Day 1 for the next period.

Each subject will receive 3 doses of JNJ-37822681 and 1 placebo dose,
randomized over 4 study periods. It is planned that the subjects will receive
escalating doses of JNJ-37822681. The starting dose will be 0,5 mg JNJ-37822681

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 be carefully monitored for possible adverse events by
experienced study personnel and physicians.