Single-center, open-label, non-randomized study investigating the excretion balance, pharmacokinetics and metabolism of a single oral dose of [14C]-labeled RO5285119 in healthy male subjects

RO5285119 is a new investigational compound that may eventually be used for the
treatment of Autism Spectrum Disorders (ASD), a group of neurodevelopmental
disorders including Autism Disorder, Asperger*s syndrome, and pervasive
developmental disorder * not otherwise specified (PDD-NOS). These disorders are
typically characterized by social deficits, communication difficulties,
stereotyped or repetitive behaviors and interests, and in some cases, cognitive
delays. Evidence implicates that vasopressin may play a role in autism.
Vasopressin is a hormone that is involved in the regulation of blood pressure
and the retention of water in the kidneys in the periphery and in the
regulation of stress, anxiety and social behavior in the central nervous
system. RO5285119 blocks activation of the vasopressin receptor and is in
development for treatment of the core deficits in ASD.
RO5285119 is not registered as a drug but has been given to humans before.

The purpose of the study is to investigate how quickly and to what extent the
study medication is absorbed, distributed, metabolized (broken down) and
eliminated from the body (this is called pharmacokinetics). The compound to be
administered will be labeled with 14-Carbon (14C) and is thus radioactive (also
called radiolabeled). This enables the investigator to trace the compound in
blood, plasma, urine and feces.

This study will be performed in 6 healthy male volunteers.

The actual study will consist of 1 period during which you will stay in the
clinical research center in Zuidlaren for a minimum of 8 days (7 nights) and a
maximum of 12 days (11 nights), followed by minimal 1 and maximal 4 additional
short visits to the clinical research center in Zuidlaren.

During the study the volunteer will receive the study medication after an
overnight fast (at least 8 hours) as an oral solution of 10 milliliters. After
administration of the study medication, the volunteer is required to drink an
additional amount of 220 milliliters water. After this the vial that contained
the study medication will be rinsed twice with 10 milliliters of water, which
the volunteer will also be required to drink. Fasting will continue until 4
hours after administration of the study medication. During fasting and after
intake of the study medication, the volunteer is allowed to drink water ad
libitum with the exception of 1 hour prior to until 2 hours after
administration of study medication.

To date, 3 studies testing the study medication have been carried out in
healthy volunteers. A total of 129 healthy subjects participated in these
studies: 43 healthy volunteers received single oral doses and 83 healthy
volunteers received multiple doses of the study medication. Single doses up to
the highest dose tested of 76 mg and multiple doses up to the highest tested
dose of 52 mg once daily for 14 days were well tolerated. Overall, the most
common adverse events were headache, myalgia (muscle pain), diarrhoea,
somnolence, abdominal pain, dizziness (postural) and back pain. One subject
reported headache, aggression, and anxiety after a single dose of 32 mg. One
subject was withdrawn from treatment due to muscle pain after receiving
multiple doses of the study medication.

Procedurs: pain, minor bleeding, bruising, possible infection