Clinical trial NCT03088644: A Study to Investigate P2X7 Receptor Occupancy by JNJ-54175446 With the Newly Developed P2X7 Receptor Positron Emission Tomography (PET) Tracer 18F-JNJ-64413739
Official title: An Open-label Study to Investigate P2X7 Receptor Occupancy by JNJ-54175446 With the Newly Developed P2X7 Receptor PET Tracer 18F-JNJ-64413739
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Janssen-Cilag International NV
Sponsor class: INDUSTRY
First posted: 2017-03-23
Enrollment: 16
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Part A: Effective Radiation Dose Following Injection of 18F-JNJ-64413739
timeFrame: Up to 4 Weeks
measure: Part B: Total and Regional Brain Compartmental Kinetics for Volume of Distribution of 18F-JNJ-64413739
timeFrame: Up to 4 Weeks
measure: Part C: Test Retest Variability in the Distribution of 18F-JNJ-64413739
timeFrame: Up to 5 Weeks
measure: Part D: Plasma Concentrations of JNJ-54175446
timeFrame: Up to 5 Weeks
measure: Part D: Percentage of P2X7 Receptor Occupancy
timeFrame: Up to 5 Weeks
Secondary outcomes:
measure: Part A, B and C: Number of Subjects With Adverse Events as a Measure of Safety and Tolerability of 18F-JNJ-64413739
timeFrame: Part A and B: Up to 4 Weeks; Part C: Up to 5 Weeks
measure: Part D: Number of Subjects With Adverse Events as a Measure of Safety and Tolerability of JNJ-54175446
timeFrame: Up to 5 Weeks
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: UZ Leuven
Study officials:
affiliation: Janssen-Cilag International NV
name: Janssen-Cilag International NV Clinical Trial
role: STUDY_DIRECTOR
References: