A Study to Investigate P2X7 Receptor Occupancy by JNJ-54175446 With the Newly Developed P2X7 Receptor Positron Emission Tomography (PET) Tracer 18F-JNJ-64413739

An Open-label Study to Investigate P2X7 Receptor Occupancy by JNJ-54175446 With the Newly Developed P2X7 Receptor PET Tracer 18F-JNJ-64413739

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).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: 18F-JNJ-64413739; Drug: JNJ-54175446

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Body mass index (BMI) between 18 and 30 kilogram per square meter (kg/m^2) inclusive (BMI = weight/height^2)
• Nonsmoker (not smoked for 3 months prior to screening)
• Is willing to allow the investigators to place an arterial catheter in the radial artery, is assessed via physical examination (Allen Test) to be a good subject for arterial catheter placement and should not be allergic to local anesthetics for catheter placement (Part B-C-D)
• During the study and for a minimum of 1 spermatogenesis cycle (defined as approximately 90 days) after receiving the last dose of study drug, in addition to the highly effective method of contraception, a man: who is sexually active with a woman of childbearing potential and has not had vasectomy must agree to use a barrier method of contraception (e.g., condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository). In addition, their female partner should also use an highly effective method of birth control (e.g. hormonal contraception) for at least the same duration; who is sexually active with a woman who is pregnant must use a condom; must agree not to donate sperm
• Subjects must have signed an informed consent document indicating that they understand the purpose of, and procedures required for the study and are willing to participate in the study and comply with the study procedures and restrictions

Exclusion Criteria:

• Exposed to greater than (>)1 millisievert (mSv) of ionizing radiation participating as a subject in research studies in the 12 months before the start of this study
• Clinically significant abnormal physical and neurological examination, vital signs or 12-lead electrocardiogram (ECG) at screening or admission
• History of or current significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematological disease, lipid abnormalities, bronchospastic respiratory disease, diabetes mellitus, renal or hepatic insufficiency, thyroid disease, parkinson's disease, infection, or any other illness that the Investigator considers should exclude the subject. History of epilepsy or fits or unexplained black-outs
• Serology positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies or human immunodeficiency virus (HIV) antibodies
• Subject has a history of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-V) criteria within 6 months before Screening or positive test result(s) for alcohol and/or drugs of abuse (opiates (including methadone), cocaine, amphetamines, methamphetamines, cannabinoids, barbiturates, ecstasy and benzodiazepines) at screening or admission of each period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: 18F-JNJ-64413739; 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.	Drug: 18F-JNJ-64413739; 18F-JNJ-64413739 fluid for injection administered intravenously.
Experimental: Part B: 18F-JNJ-64413739; 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.	Drug: 18F-JNJ-64413739; 18F-JNJ-64413739 fluid for injection administered intravenously.
Experimental: Part C: 18F-JNJ-64413739; 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.	Drug: 18F-JNJ-64413739; 18F-JNJ-64413739 fluid for injection administered intravenously.
Experimental: Part D: JNJ-54175446 + 18F-JNJ-64413739; 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.	Drug: JNJ-54175446; JNJ-54175446 up to 600 mg suspension for oral dose administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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].	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.	Up to 5 Weeks

Secondary Outcome Measures

Outcome Measure	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
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

Collaborators and Investigators

• Sponsor: Janssen-Cilag International NV
• Investigators: Study Director: Janssen-Cilag International NV Clinical Trial, Janssen-Cilag International NV

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2017
• Primary Completion (Actual): November 14, 2017
• Study Completion (Actual): November 14, 2017

Study Registration Dates

• First Submitted: March 17, 2017
• First Submitted That Met QC Criteria: March 17, 2017
• First Posted (Actual): March 23, 2017

Study Record Updates

• Last Update Posted (Actual): April 27, 2025
• Last Update Submitted That Met QC Criteria: April 25, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; (18)F-JNJ-64413739
• Other Study ID Numbers: CR108269; 2016-004007-31 (EudraCT Number); 54175446EDI1004 (Other Identifier: Janssen-Cilag International NV)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No