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

Phase 1

Completed

• Conditions: Healthy Volunteer
• Interventions: Drug: RO5011232; Drug: RO4917523

• Registration Number: NCT01483469
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-11-29
• Study First Submitted QC: 2011-11-29
• Study Start: 2011-12
• Study First Posted: 2011-12-01
• Primary Completion: 2013-10
• Study Completion: 2013-10
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-01
• Last Update Posted: 2016-11-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 56

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Concept Proof	RO5011232	-
Receptor Occupancy	RO5011232	-
Receptor Occupancy	RO4917523	-

Primary Outcome Measures

Name	Time	Method
Part I: mGlu5 receptor binding of [11C]-RO5011232 radiotracer in human brain, assessed by positron emission tomography (PET)	approximately 6 months
Part IV: Correlation between RO4917523 plasma concentration and R04917523 binding to mGlu5 receptor in brain	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

Secondary Outcome Measures

Name	Time	Method
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
Safety of [11C]-RO5011232 administered intravenously at microdose level: Incidence of adverse events	approximately 6 months