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| ID | Type | Description | Link |
|---|---|---|---|
| 42165279EDI1003 | Other Identifier | Janssen Research & Development, LLC | |
| 2013-004199-37 | EudraCT Number |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A | Experimental | 3 to 5 participants will undergo Positron Emission Tomography (PET)/computed tomography scan after administration of 11C-MK-3168 on Day 1. |
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| Part B | Experimental | 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. |
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| Part C | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| JNJ-42165279 | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Effect of FAAH C385A polymorphism on the distribution volume of 11C-MK-3168 in human brain |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Leuven | Belgium |
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| 11C-MK-3168 | Drug | 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. |
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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 |
| 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 |
| ID | Term |
|---|---|
| C000632387 | JNJ-42165279 |
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