A single-center, randomized, double-blind, adaptive, parallel study to investigate the safety, tolerability, pharmacokinetics (Including the effect of food), and pharmacodynamics of RO6806127 in healthy male subjects.

RO6806127 is a new investigational compound that may eventually be used for the
treatment of schizophrenia. RO6806127 stimulates glutamate-mediated
transmission of information in the brain. Glutamate is a neurotransmitter
(messenger molecule) that carries information from one brain cell to another
(neurotransmission). Dysfunctional glutamate-mediated transmission of
information is thought to play a role in schizophrenia.
This is the first time that RO6806127 is being given to humans.

The study will be performed in 2 parts, Parts 1 and 2. The volunteers can only
participate in one of the two parts of this study. The purpose of Part 1 of the
study is to investigate to what extent RO6806127 is tolerated. It will also be
investigated how quickly and to what extent RO6806127 is absorbed, distributed
and eliminated from the body (this is called pharmacokinetics). In addition,
the effect of RO6806127 on blood and urine parameters, brain activity and your
mental state will be investigated (this is called pharmacodynamics).

Part 2 will investigate the effect of food on the pharmacokinetics of
RO6806127.

Before the study the volunteer will undergo a pre-study screening during which
you will be subjected to a number of medical examinations.
Similar examinations will be performed after the study at the post-study
screening.

At the pre-study screening an EEG (brain scan) will be made. This will be done
in the Martini hospital in Groningen.

The actual study will consist of 1 period during which the volunteers will stay
in the clinical research center in Groningen for 6 days (5 nights) followed by
1 day (Day 6) during which they will visit the clinical research center in
Groningen.

The volunteers will leave the clinical research center on Day 4. This stay can
be prolonged due to safety reasons. A follow-up visit is planned 2-3 weeks
after the actual study.

The participation to the entire study, from pre-study screening until the post
study screening , will be for group 1 up to 50 days, group 2 maximum 74 days.

During the study the volunteers will receive RO6806127 or placebo after a
fasting period (no food) of at least 10 hours in the form of an oral solution
of at least 5 mL. Within 5 minutes after administration of the study
medication, they are required to drink an additional amount of 240 milliliters
of a buffered solution (i.e., a solution with a stabilized acidity). The study
medication might give the volunteers an unusual taste experience and can cause
a warm and/or dry feeling in the mouth. If taste is reported for RO6806127 a
mouth-wash will be provided before the administration to all subsequent
participants. There will be asked to rinse the mouth for 30 seconds with a 15
mL Hexetidine mouth wash.

For all groups it is applicable that on Day 1 fasting will continue until 4
hours after drug administration. Then the volunteers will receive a lunch.
During fasting and after intake of the study medication, they are allowed to
drink water except for 2 hours after administration of the study medication.

The study will consist of 1 period during which the volunteer will receive a
single dose of RO6806127 or placebo.

Whether the volunteer will receive RO6806127 or placebo will be determined by
chance. Per group a minimum of 3 and a maximum of 12 participants will receive
RO6806127, and a minimum of 1 and a maximum of 4 participants will receive
placebo.

All potential drugs cause adverse events; the extent to which this occurs
differs. As RO6806127 will be administered to man for the first time in this
study, adverse effects of RO6806127 in man are not known to date. However,
RO6806127 has been studied in animals. The observed adverse effects in animals
were: vomiting, increase in respiration, increase in body temperature,
increased glucose levels, anxiety, restlessness, hyperactivity,
gastro-esophageal reflux (regurgitation), flatulence and diarrhea.

The Hexetidine mouth wash may cause mild irritation of the mouth (sore mouth,
burning or itching) or, very rare, transient insensitivity and change of taste.