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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 15
- 主要终点
- Part A: Compartmental Model of the Volume of Distribution of 11C-MK-3168 in Brain by Positron Emission Tomography (PET)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Part A
3 to 5 participants will undergo Positron Emission Tomography (PET)/computed tomography scan after administration of 11C-MK-3168 on Day 1.
干预措施: 11C-MK-3168 (Drug)
Part B
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.
干预措施: JNJ-42165279 (Drug)
Part B
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.
干预措施: 11C-MK-3168 (Drug)
Part C
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.
干预措施: JNJ-42165279 (Drug)
Part C
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.
干预措施: 11C-MK-3168 (Drug)
结局指标
主要结局
Part A: Compartmental Model of the Volume of Distribution of 11C-MK-3168 in Brain by Positron Emission Tomography (PET)
时间窗: Day 1
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.
Part B: Dose Dependent Occupancy of Fatty Acid Amide Hydrolase (FAAH) After Single Dose of JNJ-42165279
时间窗: Up to 5 weeks
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.
Part C: Dose and Time Dependent Occupancy of FAAH After Repeat Dose of JNJ-42165279
时间窗: Upto 5 weeks
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.
次要结局
- 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)