ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03088644
Recruitment Status : Completed
First Posted : March 23, 2017
Last Update Posted : March 29, 2018
Sponsor:
Information provided by (Responsible Party):
Janssen-Cilag International NV

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).

Condition or disease Intervention/treatment Phase
Healthy Drug: JNJ-54175446 Drug: 18F-JNJ-64413739 Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
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
Actual Study Start Date : March 24, 2017
Actual Primary Completion Date : November 14, 2017
Actual Study Completion Date : November 14, 2017

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.




Primary Outcome Measures :
  1. Part A: Effective Radiation Dose Following Injection of 18F-JNJ-64413739 [ Time Frame: Up to 4 Weeks ]
    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.

  2. Part B: Total and Regional Brain Compartmental Kinetics for Volume of Distribution of 18F-JNJ-64413739 [ Time Frame: Up to 4 Weeks ]
    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.

  3. Part C: Test Retest Variability in the Distribution of 18F-JNJ-64413739 [ Time Frame: Up to 5 Weeks ]
    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].

  4. Part D: Plasma Concentrations of JNJ-54175446 [ Time Frame: Up to 5 Weeks ]
    Descriptive statistics will be calculated for the plasma concentrations of JNJ-54175446.

  5. Part D: Percentage of P2X7 Receptor Occupancy [ Time Frame: Up to 5 Weeks ]
    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.


Secondary Outcome Measures :
  1. Part A, B and C: Number of Subjects With Adverse Events as a Measure of Safety and Tolerability of 18F-JNJ-64413739 [ Time Frame: Part A and B: Up to 4 Weeks; Part C: Up to 5 Weeks ]
    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.

  2. Part D: Number of Subjects With Adverse Events as a Measure of Safety and Tolerability of JNJ-54175446 [ Time Frame: Up to 5 Weeks ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03088644


Locations
Belgium
UZ Leuven
Leuven, Belgium, 3000
Sponsors and Collaborators
Janssen-Cilag International NV
Investigators
Study Director: Janssen-Cilag International NV Clinical Trial Janssen-Cilag International NV

Responsible Party: Janssen-Cilag International NV
ClinicalTrials.gov Identifier: NCT03088644     History of Changes
Other Study ID Numbers: CR108269
2016-004007-31 ( EudraCT Number )
54175446EDI1004 ( Other Identifier: Janssen-Cilag International NV )
First Posted: March 23, 2017    Key Record Dates
Last Update Posted: March 29, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No