SINGLE-CENTER, SINGLE DOSE ORAL EXCRETION BALANCE
STUDY OF RO5200628 IN HEALTHY MALE VOLUNTEERS

The drug to be given RO5200628 is a new, investigational compound that may
eventually be used for the treatment of major depressive disorder. Depressive
disorders are associated with a disruption in the levels of serotonin,
norepinephrine and dopamine, substances that are present in the human brain.
Normally conventional anti-depressants only effect serotonin levels. This
compound, however, is expected to target the levels of all three substances.
This expected triple action of the investigational drug may enhance the onset
of action, which with anti-depressants currently on the market is usually up to
6 weeks. In addition, the investigational compound may have less effect on
sexual functions and body weight compared to conventional anti-depressants.

Primary:
to explore the routes and rates of elimination of [14C]-radio labeled RO5200628
after oral administration
to determine the pharmacokinetics of total drug related material, RO5200628and
its metabolites as appropriate

Secundary:
to investigate metabolic profiles of the RO5200628 in plasma and excreta and
characterize any major metabolites

Procedures and assessments:
Screening and follow up visit:
clinical laboratory (including TSH and T4), vital signs (including body
temperature), physical examination, 12-lead ECG (in triplicate); at eligibility
screening: medical history, height, alcohol breath test, urine drug screen,
coagulation (PT and aPTT), HBsAg, anti HCV, anti-HIV 1/2; vital signs, 12-lead
ECG (in triplicate), clinical laboratory, alcohol breath test and urine drug
screen to be repeated upon admission

Treatment period:
Involving administration of a single oral dose of RO5200628. One period in
clinic from -17 h up to 366 h (Day 15) after drug administration; if discharge
criteria (the radioactivity in urine and faeces (and plasma) has decreased to
approximately twice background levels and after review of cumulative total
recovery of radioactivity (at least 90% of the total radioactivity has been
recovered in urine and feces or < 1% of the administered dose excreted over a
48-hour period) by the Investigator and Clinical Pharmacologist) are not met on
Day 11 additional urine and faeces collection may be requested up to Day 15; if
the subject fulfils the discharge criteria on Day 11, the subject can be
released and no further sampling will be done; if the subject does not fulfil
discharge criteria on Day 15, subject will be discharged and sampling will be
collected at home for up to 5 days or until discharge criteria are met.

Blood sampling:
for pharmacokinetics of RO5200628 and its known metabolites in plasma: pre-dose
and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, 24, 26, 36, 38, 48, 72, 74, 96, 120
and 144 h post-dose
for total radioactivity in plasma and/or whole blood: pre-dose and 0.5, 1, 1.5,
2, 3, 4, 5, 6, 8, 12, 14, 24, 26, 36, 38, 48, and 72 h post-dose and will
continue in 24 h intervals until discharge criteria are met
for metabolic profiling: pre-dose and 1, 3, 8, 14, 24 and 48 h post-dose
for genotyping: once on Day 1

Urine sampling:
for pharmacokinetics of RO5200628, total radioactivity and metabolic profiling:
intervals 0-6, 6-12 and 12-24 h post-dose and in 24 h intervals thereafter
until discharge criteria are met

Feces sampling:
for total radioactivity and metabolic profiling: 24 h intervals until discharge
criteria are met

Safety assessments:
adverse events: throughout the study; vital signs: pre-dose and 5, 8, 24, 38
and 72 h post-dose and once of day of discharge; 12-lead ECG (in triplicate):
pre-dose and 1, 1.5, 3, 5, 8, 12, 24, 38 and 72 h post-dose and once on day of
discharge; clinical laboratory: 24 h post-dose

Bioanalysis:
analysis of plasma and urine RO5200628 and its known metabolites samples using
validated methods by Sponsor
analysis of total radioactivity in plasma, whole blood, urine and faeces using
validated methods by PRA
quick counts by PRA
metabolic profiling by Sponsor
genotyping by Sponsor

Active substance: RO5200628

In single doses up to 130 mg, RO5200628 was very well tolerated by healthy
volunteers. The most frequently reported adverse effects up to now were
headache, nausea, dizziness and hot flush. The adverse effects were moderate in
severity and resolved within a few hours after onset. In this study 45 mg of
the study medication will be administered.