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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-004007-31 | EudraCT Number | ||
| 54175446EDI1004 | Other Identifier | Janssen-Cilag International NV |
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The primary purpose of this study is to measure the whole body distribution and radiation dosimetry of 18F-JNJ-64413739 (Part A), to measure the uptake, distribution, and clearance (CL) of 18F-JNJ-64413739 in the brain of healthy male subjects by Positron Emission Tomography (PET) and to model tissue specific kinetics of 18F-JNJ-64413739 with the appropriate input function (IF) (Part B), to measure subject test retest variability in the distribution of 18F-JNJ-64413739 in the brain of healthy male subjects by comparing PET scans obtained at least 1 week apart (Part C) and following single oral dose administration of JNJ-54175446, to measure the blocking of 18F-JNJ-64413739 uptake in the brain at the time to reach maximum plasma concentration (tmax) of JNJ-54175446 and model the exposure/receptor interaction of JNJ-54175446 in healthy male subjects (Part D).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A: 18F-JNJ-64413739 | Experimental | Subjects will receive an intravenous (IV) bolus injection of 18F-JNJ-64413739 at a dose between 150 and 185 megaBecquerel (MBq) on Day 1 of Part A to investigate the total body biodistribution and measure the radiation dosimetry. |
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| Part B: 18F-JNJ-64413739 | Experimental | Subjects will receive an IV bolus injection of 18F-JNJ-64413739 at a dose between 150 and 185 MBq on Day 1 of Part B to measure the uptake, distribution, and clearance in brain. |
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| Part C: 18F-JNJ-64413739 | Experimental | Subjects will receive an IV bolus injection of 18F-JNJ-64413739 for a PET/MR scan on Day 1 and a repeat 18F-JNJ-64413739 PET/magnetic resonance (MR) scan at least 1 week later to determine the test-retest variability in V[t]. 18F-JNJ-64413739 doses will be between 150 and 185 MBq. |
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| Part D: JNJ-54175446 + 18F-JNJ-64413739 | Experimental | Subjects will have a baseline 18F-JNJ-64413739 PET/MR scan on Day 1. On Day 2 they will receive JNJ-54175446 (maximum 600 milligram [mg]) orally (after light breakfast) and then an IV injection of 18F-JNJ-64413739 four hours after dosing for a PET/MR scan. At least 1 week later, they will receive another dose of JNJ-54175446, and then an IV injection of 18F-JNJ-64413739 four hours later for a second post-treatment PET/MR scan. 18F-JNJ-64413739 doses will be between 150 and 185 MBq. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| JNJ-54175446 | Drug | JNJ-54175446 up to 600 mg suspension for oral dose administration. |
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| Measure | Description | Time Frame |
|---|---|---|
| Part A: Effective Radiation Dose Following Injection of 18F-JNJ-64413739 | The tissue radioactivity will be measured per organ for up to 5 hours after injection of up to 185 megaBecquerel (MBq) of 18F-JNJ-64413739 and corrected for attenuation by computed tomography (CT) transmission scans using PET/CT. These measurements will be used to estimate effective radiation dose per organ and total body. | Up to 4 Weeks |
| Part B: Total and Regional Brain Compartmental Kinetics for Volume of Distribution of 18F-JNJ-64413739 | The Distribution of 18F-JNJ-64413739 in brain will be measured by dynamic PET/magnetic resonance (MR) scans obtained from the time of injection for up to 120 minutes along with measurement of the tracer input function with arterial samples for intact tracer and metabolites to establish the total and regional compartmental kinetics and volume of distribution (V[t]) of 18F-JNJ-64413739. | Up to 4 Weeks |
| Part C: Test Retest Variability in the Distribution of 18F-JNJ-64413739 | Test Retest Variability within subjects will be assessed based on percent difference in V[t] following 18F-JNJ-64413739 PET/MR scans obtained at least 1 Week apart. V[t] will be the parameter for the estimated volume of distribution of the tracer derived from the kinetic model that best fits the data from Part B. It will be calculated by formula [100*abs (V[t]test - V[t]retest)/[( V[t]test+ V[t]retest)/2].](streamdown:incomplete-link) | Up to 5 Weeks |
| Part D: Plasma Concentrations of JNJ-54175446 | Descriptive statistics will be calculated for the plasma concentrations of JNJ-54175446. | Up to 5 Weeks |
| Part D: Percentage of P2X7 Receptor Occupancy | Percent reduction in V[t] of 18F-JNJ-64413739 in brain regions of interest will be calculated by PET/MR scans obtained at pre and post treatment with single doses of JNJ-54175446. |
| Measure | Description | Time Frame |
|---|---|---|
| Part A, B and C: Number of Subjects With Adverse Events as a Measure of Safety and Tolerability of 18F-JNJ-64413739 | An adverse event is any untoward medical event that occurs in a subject administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. | Part A and B: Up to 4 Weeks; Part C: Up to 5 Weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Janssen-Cilag International NV Clinical Trial | Janssen-Cilag International NV | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UZ Leuven | Leuven | 3000 | Belgium |
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| 18F-JNJ-64413739 | Drug | 18F-JNJ-64413739 fluid for injection administered intravenously. |
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| Up to 5 Weeks |
| Part D: Number of Subjects With Adverse Events as a Measure of Safety and Tolerability of JNJ-54175446 | An adverse event is any untoward medical event that occurs in a subject administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. | Up to 5 Weeks |
| ID | Term |
|---|---|
| C000655225 | JNJ-54175446 |
| C000706135 | (18)F-JNJ-64413739 |
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