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

NCT02169973 | Completed Phase 1

• 3 other identifiers: CR10360142165279EDI10032013-004199-37
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Keywords

Healthy; Positron Emission Tomography; 11C-MK-3168; JNJ-42165279; Human Brain

Outcome Measures

Primary Outcomes (3)

• Part A: Compartmental Model of the Volume of Distribution of 11C-MK-3168 in Brain by Positron Emission Tomography (PET)

  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

  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

  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 Outcomes (3)

• Correlation Between Fatty Acid Amide Hydrolase (FAAH) Occupancy in Brain With Peripheral FAAH inhibition

  Postdose Day 1 and Day 8

• Effect of FAAH C385A polymorphism on the distribution volume of 11C-MK-3168 in human brain

  Postdose Day 1 and Day 8

• Number of participants with adverse events

  Up to 5 weeks

Study Arms (3)

Part A

EXPERIMENTAL

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

Part B

EXPERIMENTAL

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: JNJ-42165279; Drug: 11C-MK-3168

Part C

EXPERIMENTAL

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: JNJ-42165279; Drug: 11C-MK-3168

Interventions

JNJ-42165279 DRUG

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.

Part B; Part C

11C-MK-3168 DRUG

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.

Part A; Part B; Part C

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Unknown Facility

Leuven, Belgium

Location

MeSH Terms

Interventions

JNJ-42165279

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: February 26, 2014
• First Posted: June 23, 2014
• Study Start: February 1, 2014
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: September 28, 2015

Record last verified: 2015-09

Locations

BE (1)