Clinical trial NCT02169973: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
Positron Emission Tomography
11C-MK-3168
JNJ-42165279
Human Brain
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2014-06-23
Enrollment: 15
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Part A: Compartmental Model of the Volume of Distribution of 11C-MK-3168 in Brain by Positron Emission Tomography (PET)
timeFrame: Day 1
measure: Part B: Dose Dependent Occupancy of Fatty Acid Amide Hydrolase (FAAH) After Single Dose of JNJ-42165279
timeFrame: Up to 5 weeks
measure: Part C: Dose and Time Dependent Occupancy of FAAH After Repeat Dose of JNJ-42165279
timeFrame: Upto 5 weeks
Secondary outcomes:
measure: Correlation Between Fatty Acid Amide Hydrolase (FAAH) Occupancy in Brain With Peripheral FAAH inhibition
timeFrame: Postdose Day 1 and Day 8
measure: Effect of FAAH C385A polymorphism on the distribution volume of 11C-MK-3168 in human brain
timeFrame: Postdose Day 1 and Day 8
measure: Number of participants with adverse events
timeFrame: Up to 5 weeks
Other outcomes:
Locations:
city: Leuven
country: Belgium
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: