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

NCT01483469 | Completed Phase 1

• 1 other identifier: BP27890
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 2

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.

Conditions

Healthy Volunteer

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (3)

• 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

Study Arms (2)

Concept Proof

ACTIVE COMPARATOR

Drug: RO5011232

Receptor Occupancy

EXPERIMENTAL

Drug: RO4917523; Drug: RO5011232

Interventions

RO4917523 DRUG

orally daily, 14 days

Receptor Occupancy

RO5011232 DRUG

\[11C\]-RO5011232 intravenously

Concept Proof; Receptor Occupancy

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (2)

Unknown Facility

Baltimore, Maryland, 21224, United States

Location

Unknown Facility

Baltimore, Maryland, 21225, United States

Location

MeSH Terms

Interventions

2-chloro-4-(1-(4-fluorophenyl)-2,5-dimethyl-1H-imidazol-4-ylethynyl)pyridine

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2011
• First Posted: December 1, 2011
• Study Start: December 1, 2011
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: November 2, 2016

Record last verified: 2016-11

Locations

US (2)