A Human Proof of Concept Study for [11C]-RO5011232 as Radiotracer and Study of the Binding of RO4917523 to Human mGlu5 Brain Receptor at Steady-State in Healthy Volunteers

Study Overview
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Brief Summary
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This open label, non-randomized, parallel group study will evaluate [11C]-RO5011232 as radiotracer for brain mGlu5 receptor occupancy and investigate the binding of RO49917523 to human mGlu5 brain receptor at steady-state in healthy volunteers. In Parts I, II and III, positron emission tomography (PET) assessments of specific uptake of the radiotracer and whole body dosimetry will be made after intravenous injection of [11C]-RO5011232. In Part IV, subjects will receive RO4917523 orally daily for 14 days while receiving three single intravenous bolus injections of [11C]-RO5011232. The anticipated time on study treatment is up to 4 weeks.

Official Title
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Human Proof of Concept Positron Emission Tomography Study to Investigate [11C]-RO5011232 as a Radiotracer for Brain mGlu5 Receptor Occupancy and to Investigate the Binding of RO4917523 to Human mGlu5 Brain Receptor at Steady-state.

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: RO4917523
* Drug: RO5011232


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female volunteers as determined by medical history, physical examination, 12-lead ECG, and routine clinical laboratory measurements Age 18 to 65 years inclusive Body mass index (BMI) between 18 to30 kg/m2 inclusive and body weight at least 50 kg Appropriate body size (less than 195 cm [6 feet and 5 inches]) in order to accommodate the whole body scanning Exclusion Criteria: History of or presence of clinically significant psychiatric condition, as evaluated by a psychiatrist before enrolment History of head trauma with prolonged loss of consciousness (>10 minutes) or any neurological condition or a history of migraine headaches Contraindications to MRI procedures (Part I, III and IV) Subjects suffering from claustrophobia or who would be unable to undergo magnetic resonance imaging (MRI) or PET scanning Positive pregnancy test at screening or on any day preceding a PET scan Lactating women Positive for hepatitis B, hepatitis C or HIV infection Any history of alcohol or drug abuse within the last 6 months Regular smoker or nicotine user (>10 cigarettes per day) Participation in an investigational drug or device study within three months prior to screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Concept Proof<br> | Drug: RO5011232<br>* [11C]-RO5011232 intravenously<br>|
| Experimental: Receptor Occupancy<br> | Drug: RO4917523<br>* orally daily, 14 days<br>Drug: RO5011232<br>* [11C]-RO5011232 intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part I: mGlu5 receptor binding of [11C]-RO5011232 radiotracer in human brain, assessed by positron emission tomography (PET) |  | approximately 6 months | 
| Part II: Dosimetry/radiation safety of [11C]-RO5011232 assessments by whole body PET scan |  | approximately 6 months | 
| Part III: Measurement of test-retest precision of PET images of regions of interest in the human brain |  | approximately 6 months | 
| Part IV: Correlation between RO4917523 plasma concentration and R04917523 binding to mGlu5 receptor in brain |  | approximately 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of [11C]-RO5011232 administered intravenously at microdose level: Incidence of adverse events |  | approximately 6 months | 
| Part IV: In vitro binding potential (reference region with no specific binding of radiotracer) assessed by PET |  | approximately 6 months | 
| Part IV: Safety of 14-day treatment with RO4917523: Incidence of adverse events |  | approximately 6 months |