A Study to Investigate the Regional Brain Kinetics of the Positron Emission Tomography Ligand 11C-MK-3168 and the Blocking of the Retention of the Ligand in the Human Brain by JNJ-42165279

September 25, 2015 updated by: Janssen Research & Development, LLC

An Open-Label Study to Investigate the Regional Brain Kinetics of the Positron Emission Tomography Ligand 11C-MK-3168 and the Blocking of the Retention of the Ligand in the Human Brain by JNJ-42165279

The purpose of the study is to measure the uptake, distribution, and clearance of 11C-MK-3168 by Positron Emission Tomography (PET) scan and to model the tissue specific kinetics of 11C-MK-3168 with the appropriate input function in human brain in Part A; to measure blocking of retention of 11C-MK-3168 at the estimated time to maximum plasma concentration after dosing (tmax) following each single oral doses of JNJ-42165279 and model the exposure/enzyme interaction of JNJ-42165279 in Part B; to measure the saturation of enzyme inhibition in the brain at steady state plasma concentrations of JNJ-42165279 (on Day 8) after 7 once-daily doses of JNJ-42165279 by conducting PET studies with 11C-MK-3168 at trough plasma concentrations on Day 2 in Part C.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is an open-label (both [participants and investigator] know what treatment participants will receive) study. This study consists of 3 consecutive parts: A, B, and C. Each part will consist of a screening phase (between 21 to 2 days prior to the study medication), a treatment phase (Part A: 1 day; Part B: 8 days; Part C: 8 days), and the end-of-study/ follow-up visit (within 5 to 7 days after last PET scan). In the treatment phase of the Part A, participants will undergo a baseline PET/computed tomography scan (after administration of 11C-MK-3168 on Day 1); In Part B, participants will undergo a baseline PET scan, followed by 2 post-treatment PET scans after 2 single doses of JNJ-42165279 on Days 1 and 8; in Part C, participants will undergo a baseline PET scan, followed by 2 post-treatment PET scans after 24 hours postdose of JNJ-42165279 on Days 1 and 7. Safety will be evaluated by the assessment of adverse events, vital signs, 12-lead electrocardiogram, clinical laboratory testing, physical examination (including weight and tympanic temperature [temperature measure in an ear]), and neurological examination. The total duration of study participation for a participant will be approximately 4 weeks for Part A and approximately 5 weeks for Parts B and C.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Body mass index (BMI) between 18 and 30 kg/m2 inclusive (BMI = weight/height2)
  • Non-smoker (not smoked for 3 months prior to screening)
  • Agree to use one of the protocol mentioned barrier methods of birth control

Exclusion Criteria:

  • Exposed to 1 millisievert or more of ionizing radiation in the year before the start of this study
  • Clinically significant abnormal laboratory values and abnormal physical and neurological examination at screening
  • Any clinically significant Magnetic Resonance Imaging (MRI) abnormalities at screening, as determined by a neuroradiologist, which are relevant for the study
  • Allen test (test to assess the arterial blood flow to the hand) indicating abnormal blood supply to the hand
  • Has implanted or embedded metal objects, or fragments in the head or body that would present a risk during the MRI scanning procedure

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A
3 to 5 participants will undergo Positron Emission Tomography (PET)/computed tomography scan after administration of 11C-MK-3168 on Day 1.
Drug: 11C-MK-3168
Participants will receive 11C-MK-3168 in the target range of 185 to 370 megabecquerel (MBq) intravenously (into a vein) before every positron emission tomography scan in Parts A, B, and C.
Experimental: Part B
3 to 12 participants will undergo PET scan after administration of 11C-MK-3168 on Day 1. Participants will receive 2 single doses of JNJ-42165279: 100 mg on Days 1 and up to 250 mg on Day 8. Participants will undergo PET scans after 1 hour of each administration of JNJ-42165279 on Days 1 and 8, with 11C-MK-3168 administration.
Drug: 11C-MK-3168
Participants will receive 11C-MK-3168 in the target range of 185 to 370 megabecquerel (MBq) intravenously (into a vein) before every positron emission tomography scan in Parts A, B, and C.
Drug: JNJ-42165279
Participants will receive oral suspension of JNJ-42165279 in Part B as single dose on Day 1 (100 mg) and on Day 8 (up to 250 mg); in Part C as once daily dose (up to 100 mg) from Day 1 to Day 7.
Experimental: Part C
4 to 8 participants will undergo PET scan after administration of 11C-MK-3168 on Day 1. Participants will receive once daily dose of JNJ-42165279 (up to 100 mg) from Day 1 to Day 7. Participants will undergo PET scans after 24 hour of administration of JNJ-42165279 on Days 1 and 7, with 11C-MK-3168 administration.
Drug: 11C-MK-3168
Participants will receive 11C-MK-3168 in the target range of 185 to 370 megabecquerel (MBq) intravenously (into a vein) before every positron emission tomography scan in Parts A, B, and C.
Drug: JNJ-42165279
Participants will receive oral suspension of JNJ-42165279 in Part B as single dose on Day 1 (100 mg) and on Day 8 (up to 250 mg); in Part C as once daily dose (up to 100 mg) from Day 1 to Day 7.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A: Compartmental Model of the Volume of Distribution of 11C-MK-3168 in Brain by Positron Emission Tomography (PET)
Time Frame: Day 1
Uptake, distribution, and clearance of 11C-MK-3168 in the brain and plasma of healthy male participants will be evaluated by PET scan and arterial sampling.
Day 1
Part B: Dose Dependent Occupancy of Fatty Acid Amide Hydrolase (FAAH) After Single Dose of JNJ-42165279
Time Frame: Up to 5 weeks
Occupancy of the FAAH in brain by JNJ-42165279 will be evaluated by comparing the distribution volume of 11C-MK-3168 after single dose JNJ-42165279 to the distribution volume at baseline.
Up to 5 weeks
Part C: Dose and Time Dependent Occupancy of FAAH After Repeat Dose of JNJ-42165279
Time Frame: Upto 5 weeks
Occupancy of FAAH in brain by JNJ-42165279 at steady state will be evaluated by comparing the distribution volume of 11C-MK-3168 at Tmax after single dose JNJ-42165279 and then at trough after dosing for seven days with JNJ-42165279 to the distribution volume prior to treatment.
Upto 5 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation Between Fatty Acid Amide Hydrolase (FAAH) Occupancy in Brain With Peripheral FAAH inhibition
Time Frame: Postdose Day 1 and Day 8
Correlation between peripheral and central FAAH inhibitions in white blood cells by JNJ 42165279 will be measured.
Postdose Day 1 and Day 8
Effect of FAAH C385A polymorphism on the distribution volume of 11C-MK-3168 in human brain
Time Frame: Postdose Day 1 and Day 8
Effect of FAAH C385A polymorphism on the distribution volume of 11C-MK-3168 in human brain will be assessed.
Postdose Day 1 and Day 8
Number of participants with adverse events
Time Frame: Up to 5 weeks
Number of participants with adverse events will be reported as an assessment of safety and tolerability of 11C-MK-3168 and JNJ-42165279.
Up to 5 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Janssen Research & Development, LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2014

Primary Completion (Actual)

July 1, 2014

Study Completion (Actual)

July 1, 2014

Study Registration Dates

First Submitted

February 26, 2014

First Submitted That Met QC Criteria

June 19, 2014

First Posted (Estimate)

June 23, 2014

Study Record Updates

Last Update Posted (Estimate)

September 28, 2015

Last Update Submitted That Met QC Criteria

September 25, 2015

Last Verified

September 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR103601
  • 42165279EDI1003 (Other Identifier: Janssen Research & Development, LLC)
  • 2013-004199-37 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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