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.
Name: JNJ-42165279
Name: 11C-MK-3168
Description: 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.
Measure: Part A: Compartmental Model of the Volume of Distribution of 11C-MK-3168 in Brain by Positron Emission Tomography (PET) Time: Day 1Description: 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.
Measure: Part B: Dose Dependent Occupancy of Fatty Acid Amide Hydrolase (FAAH) After Single Dose of JNJ-42165279 Time: Up to 5 weeksDescription: 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.
Measure: Part C: Dose and Time Dependent Occupancy of FAAH After Repeat Dose of JNJ-42165279 Time: Upto 5 weeksDescription: Correlation between peripheral and central FAAH inhibitions in white blood cells by JNJ 42165279 will be measured.
Measure: Correlation Between Fatty Acid Amide Hydrolase (FAAH) Occupancy in Brain With Peripheral FAAH inhibition Time: Postdose Day 1 and Day 8Description: Effect of FAAH C385A polymorphism on the distribution volume of 11C-MK-3168 in human brain will be assessed.
Measure: Effect of FAAH C385A polymorphism on the distribution volume of 11C-MK-3168 in human brain Time: Postdose Day 1 and Day 8Description: Number of participants with adverse events will be reported as an assessment of safety and tolerability of 11C-MK-3168 and JNJ-42165279.
Measure: Number of participants with adverse events Time: Up to 5 weeksAllocation: Non-Randomized
Parallel Assignment
There is one SNP
Correlation between peripheral and central FAAH inhibitions in white blood cells by JNJ 42165279 will be measured.. Effect of FAAH C385A polymorphism on the distribution volume of 11C-MK-3168 in human brain. --- C385A ---
Effect of FAAH C385A polymorphism on the distribution volume of 11C-MK-3168 in human brain will be assessed.. Number of participants with adverse events. --- C385A ---