A Single-Center, Randomized, Investigator/Subject-Blind, Adaptive Single Ascending-Dose, Placebo-Controlled, Parallel Study to Investigate the Safety, Tolerability, Pharmacokinetics (Including the Effect of Food), and Pharmacodynamics of RO5545965 Following Oral Administration in Healthy Subjects.

RO5545965 is a new investigational compound that may eventually be used for the
treatment of psychosis and schizophrenia. RO5545965 is not registered as a
drug. This is the first time that this compound is being given to humans.
RO5545965 will be administered in form of a capsule.

to assess the safety and tolerability of single ascending doses of RO5545965 in
healthy subjects
to investigate the pharmacokinetics (PK) of RO5545965 (and its metabolite(s) if
appropriate)
to investigate the pharmacodynamic (PD) effects of RO5545965
to assess the effect of food on the PK of a single dose of RO5545965

Procedures and assessments
Screening and follow-up:
clinical laboratory, physical examination,12-lead ECG, vital signs; at
eligibility screening: medical history, drug- and alcohol screen, HBsAg, anti
HCV, anti-HIV 1/2

Observation period:
each period in clinic from -42h (Day -2) up to 48h (Day 3) after drug
administration (Day 1) with an ambulatory visit on Day 5

Blood sampling:
For pharmacokinetics: Day 1 pre-dose and at 30 minutes and 1, 1.5, 1.75, 2, 2,5
, 3, 4, 5, 6, 8, 10, 12, 24 and 48 hours post-dose;
For pharmacodynamics (prolactine measurements): pre-dose on Day 1 and 0.5, 1,
1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8 and 10 hours post-dose and time-matched on Day
-1
For genotyping; on Day 1 (mandatory)

Urine sampling:
For pharmacokinetics: Day 1 pre-dose and at intervals 0-4h, 4-12h, 12-24h and
24-48h

Safety assessments:
Adverse events throughout the study. Clinical laboratory, hematology,
urinalysis, coagulation (screening only), physical examination, vital signs,
12-lead-ECG and weight at screening and follow-up

Special safety assessments:
Bond & Lader VAS, DSST (Digit Symbol Substitution Test), ESRS - A
(Extrapyramidal Symptom Rating Scale - Abbreviated)

Part 1: subjects will receive a single dose of RO5545965 as an oral capsule
Part 2: subjects will receive a single dose per period of RO5545965 as an oral
capsule

Registration of adverse effects: During the entire investigation all adverse
effect will be documented.

Blood draw (for pharmacokinetics & pharmacodynamics and lab safety tests),
indwelling canula: During this study blood will be drawn. It is anticipated
that an indwelling canula will be used and blood draws will be drawn by direct
puncture of the vein.

Collection of urine: Urine will be collected until 48 hours after
administration of RO5545965 or placebo.

Heart trace (ECGs): ECGs will be made regularly.

Blood pressure and pulse rate (vital signs): Vital signs will be measured
regularly.

Blood sample for DNA tests: On Day 1 a blood sample will be taken for possible
DNA tests. Participation in this part of the study is mandatory.

Bond & Lader VAS: This Visual Analogue Scale will be used to assess alertness,
calmness and contentment.

DSST: This digit symbol substitution test, consisting of a combination of
symbols and numbers will test the mental status

ESRS-A: A physician will examine on Days -1, 1 and 3 using the Extrapyramidal
Symptoms Rating Scale - Abbreviated; a combination of a clinical interview, as
well as motor examination to test the physical status.