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
Condition: Healthy
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): JNJ-42165279; 11C-MK-3168
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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.
Intervention MeSH terms: JNJ-42165279
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Healthy; Positron Emission Tomography; 11C-MK-3168; JNJ-42165279; Human Brain