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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02169973
• Other study ID #: CR103601
• Secondary ID: 42165279EDI10032
• Status: Completed
• Phase: Phase 1
• First received: February 26, 2014
• Last updated: September 25, 2015
• Start date: February 2014
• Est. completion date: July 2014

Study information

• Verified date: September 2015
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health Products
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy

Intervention

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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	Correlation Between Fatty Acid Amide Hydrolase (FAAH) Occupancy in Brain With Peripheral FAAH inhibition	Correlation between peripheral and central FAAH inhibitions in white blood cells by JNJ 42165279 will be measured.	Postdose Day 1 and Day 8	No
Secondary	Effect of FAAH C385A polymorphism on the distribution volume of 11C-MK-3168 in human brain	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	No
Secondary	Number of participants with adverse events	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	Yes