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

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.

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: RO5011232; Drug: RO4917523

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
    • Baltimore, Maryland, United States, 21225

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: November 29, 2011
• First Submitted That Met QC Criteria: November 29, 2011
• First Posted (Estimate): December 1, 2011

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Other Study ID Numbers: BP27890