A pilot study exploring the reproducibility and suitability for multi-center clinical trials of fMRI bold signal during a monetary incentive delay task and arterial spin labeling with and without prior administration of Risperidone

The sponsor is interested to increase the number of clinical sites capable of
supporting clinical magnetic resonance imaging (MRI) trials for the development
of drugs acting on the function of the brains (i.e. the Central Nervous System
[CNS]).

Most clinical trials are conducted at several clinical research centers. The
advantages of multicenter studies are a larger number of participants,
different geographic locations, and different population groups. However, a
very limited number of clinic sites can support MRI studies. UMCG Neuroimaging
Center and PRA have experience with the conduct of MRI in combination with
behavioral assessments to study the effect of medical interventions.

The sponsor is also interested in exploring the reproducibility of the specific
imaging methods discussed here which are considered of interest in the context
of The Sponsor*s drug development pipeline across different sites and scanner
platforms.

The study will be performed in up to 5 volunteers who will participate in 2
visits during which MRI and behavioral assessment will be performed, once with
and once without prior administration of risperidone.

The purpose of this study is to explore if the (f)MRI- and behavioral
assessment are reproducible and suitable for drug studies performed at more
than one medical center or clinic.

The actual study will consist of 2 visits during which the volunteer will stay
at the PRA research center in Groningen [clinical site UMCG] for 2 days (1
night). There is a period of 5 days (6 nights) between the 2 visits the
volunteer will stay at home.

The MRI scans and assessments will be at Day 1 and Day 8. The volunteer is
expected at the research center at 14:00 h in the afternoon prior to the day of
the MRI scans and assessments. The volunteer will leave the research center in
the afternoon after completion of all assessments on Day 1 and Day 8,
respectively.
This will be followed by 7-14 days during which the volunteer will be called at
home once. The volunteer will then be asked how he feels and whether he uses
any medication.

This study is an open-label, 2 imaging sessions study in up to 5 healthy male
volunteers, with and without prior administration of risperidone.

The volunteer will be assigned to 2 treatments, one without risperidone
(Treatment A) and one with risperidone (Treatment B; a single dose of 2 mg of
risperidone). Prior to the MRI scan on Day 1, volunteers will be assigned to
receive first Treatment A followed by Treatment B (A/B), or first Treatment B
followed by treatment A (B/A).

Risperidone will be given as an oral tablet with 240 ml of (tap) water 2 hours
before fMRI scanning and should not be chewed.

Group Day Treatment How Often
1 1 A: no risperidone n/a
8 B: 2 mg risperidone 2 hours before MRI once
2 1 B: 2 mg risperidone 2 hours before MRI once
8 A: no risperidone n/a

Risperidone may cause side effects.

The most common adverse reactions in clinical studies were somnolence, appetite
increased, fatigue, common cold (rhinitis), upper respiratory tract infection,
vomiting, coughing, urinary incontinence, saliva increased, constipation,
fever, abdominal pain, nausea, dry mouth, rash, restlessness and compelling
need to be in constant motion (akathisia), Parkinsonism, neurological movement
disorder (dystonia), anxiety, dizziness, unintentional muscle movement
(tremor), restlessness and compelling need to be in constant motion
(akathisia), and feeling of unusual fullness following meals/nausea/heartburn
(dyspepsia).

Side effects may affect the driving skill. Hence the volunteer is not allowed
to drive home after discharge on treatment Day 1 and 8.

Drawing blood may be painful or cause some bruising. We will draw a small
volume of blood during the pre-study screening.

To measure the heart rate, electrodes (small, plastic patches) will be pasted
at specific locations on the chest and abdomen. Use of these electrodes can
cause skin irritation (rash and itching). An ECG will be made during the
pre-study screening.

The MRI/fMRI scans are not associated with any radioactivity and there are no
adverse effects to be expected.