An Open-Label Drug-Drug Interaction Study in Healthy Male Subjects to Explore the Effects of Single and Multiple Doses of JNJ-39393406 on the Pharmacokinetics of a Single Oral Dose of Midazolam

JNJ-39393406 is a new medication developed for the treatment of symptoms of
decreased cognition in schizophrenia and Alzheimer disease.

The purpose of this investigation is:
• To examine the effect of single and multiple doses of the new drug
JNJ-39393406 (the study medication) on absorption, metabolism and excretion by
the body after single administration of the drug midazolam.
• To examine the safety and tolerability of the new drug JNJ-39393406 (the
study medication).

This investigation is a open label drug-drug interaction study.

The study will start with a screening. A physical examination and different
standard test (ECG, blood pressure) will be performed during the screening
appointment. Blood and urine samples will be taken for laboratorium tests and
an alcohol breath test and drug screen will be performed.

During the confinement the medication will be administered to the subjects on
different occasions. Blood
samples will also be taken at several occasions. Adverse events will be
registered. ECG and vitals will be judged.

At the end of the study a follow-up visit will take place.

The trial medication JNJ-39393406 is not a registered drug. This drug has been
given to volunteer before and was well tolerated. Side effects were mentioned
which are probably due to the medication. These were dizziness, headache and
feeling tired.

NJ-39393406 has been extensively tested on animals according to official
guidelines. Comparison of the results in the animal studies of the clinical
starting doses showed no undesired effects. At higher doses the following
undesired effects were seen: rise of liver values, small changes of the
clotting parameters, increase of the white blood cell values and increase of
red blood cells. At highest doses there were indications of increased breaking
up of red blood cells, accumulation of pigment in the liver and excessive iron
deposits near the spleen after investigation of the tissue of the laboratory
animals. The drug can also give a light irritation of the eyes and occasionally
an effect was seen on coordination and grip. After a recovery period of 4 weeks
following treatment of 4 weeks the animals recovered and no effects could be
seen anymore.

Testing of the heart showed no undesired effects within the investigated dose
ranges compared with the doses used for this study.

Midazolam (Dormicum®) is a registered drug belonging to the group of
benzodiazepines. They work relaxing, give muscle relaxation and decrease
feeling of fear. Physicians prescribe it for sleeplessness and for a short
period for anxiety . The most common side effects are drowsiness during the
day, muscle weakness, feelings of confusion, tiredness and double vision. You
will get midazolam in a low dose (2 mg) because the effect can be increased by
the drug medication JNJ-39393406.