A Study to Investigate Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA Gamma 8) Receptor Occupancy of JNJ-64140284 With Newly Developed Transmembrane AMPA Receptor Regulatory Protein (TARP)-Gamma 8 Positron Emission Tomography (PET) [18F]JNJ-64511070 in Healthy Men

NCT03693391 | Terminated Phase 1 DMC

• 3 other identifiers: CR10850864140284EDI10032018-002539-98
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to measure the blocking of \[18F\]JNJ-64511070 binding in the brain at the time after administration of a drug when the maximum plasma concentration is reached; when the rate of absorption equals the rate of elimination (tmax) of JNJ-64140284 and determine the exposure/receptor interaction of JNJ-64140284 in healthy male participants following single oral dose administration of JNJ-64140284.

Conditions

Healthy

Outcome Measures

Primary Outcomes (2)

• Total and Regional Brain Compartmental Kinetics for Volume of Distribution (V[t]) of 18FJNJ-64511070

  The distribution of \[18F\]JNJ-64511070 in brain will be measured by positron emission tomography (PET) scans obtained 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-64511070.

  Approximately up to 1 hour on Day 2

• Percentage of Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA gamma 8) Receptor Occupancy

  Percentage of AMPAgamma8 receptor occupancy will be assessed by measuring the blocking of fluorine-18 labeled\[18F\]JNJ-64511070 uptake in the human brain by JNJ-64140284 using \[18F\]JNJ-64511070 positron emission tomography-computed tomography (PET-CT) scan and a post JNJ-64140284 scan obtained around tmax (approximately up to 1 hour on Day 2).

  Approximately up to 1 hour on Day 2

Secondary Outcomes (2)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  Approximately 6 weeks

• Change from Baseline in Electroencephalogram (EEG) Power at Day 2

  Baseline and Day 2

Study Arms (4)

Cohort 1: JNJ-64140284

EXPERIMENTAL

Participants in cohort 1 will receive single oral dose of JNJ-64140284 at a starting dose of 0.5 milligram (mg) under fasted conditions. The dose levels of JNJ-64140284 will be escalated sequentially based on the decisions of an independent Data Review Committee (iDRC), the clinical team and the investigator. First 3 participants will also receive an intravenous (IV) bolus injection of \[18F\]JNJ-64511070 at a dose of 185 megaBecquerel (MBq). Participants with no measurable brain receptor occupancy will receive second (escalated) dosing with JNJ-64140284 and subsequent positron emission tomography-computed tomography (PET-CT) scan.

Drug: JNJ-64140284; Drug: Fluorine-18 Labeled [18F]-JNJ-64511070

Cohort 2: JNJ-64140284

EXPERIMENTAL

Participants in cohort 2 will receive next dose level of JNJ-64140284 based upon the data-review from the previous cohort and on the decisions of an iDRC, the clinical team and the investigator. At least 3 participants will receive an IV bolus injection of \[18F\]JNJ-64511070 at a dose of 185 MBq. Participants with no measurable brain receptor occupancy will receive second (escalated) dosing with JNJ-64140284 and subsequent PET-CT scan.

Drug: JNJ-64140284; Drug: Fluorine-18 Labeled [18F]-JNJ-64511070

Cohort 3: JNJ-64140284

EXPERIMENTAL

Participants in cohort 3 will receive next dose level of JNJ-64140284 based upon the data-review from the previous cohort and on the decisions of an iDRC, the clinical team and the investigator. At least 3 participants will receive an IV bolus injection of \[18F\]JNJ-64511070 at a dose of 185 MBq. Participants with no measurable brain receptor occupancy will receive second (escalated) dosing with JNJ-64140284 and subsequent PET-CT scan.

Drug: JNJ-64140284; Drug: Fluorine-18 Labeled [18F]-JNJ-64511070

Cohort 4: JNJ-64140284

EXPERIMENTAL

Participants in cohort 4 will receive next dose level of JNJ-64140284 based upon the data-review from the previous cohort and on the decisions of an iDRC, the clinical team and the investigator. At least 3 participants will receive an IV bolus injection of \[18F\]JNJ-64511070 at a dose of 185 MBq. Participants with no measurable brain receptor occupancy will receive second (escalated) dosing with JNJ-64140284 and subsequent PET-CT scan.

Drug: JNJ-64140284; Drug: Fluorine-18 Labeled [18F]-JNJ-64511070

Interventions

JNJ-64140284 DRUG

Single dose of JNJ-64140284 up to 3 mg oral solution will be administered under fasted conditions.

Cohort 1: JNJ-64140284; Cohort 2: JNJ-64140284; Cohort 3: JNJ-64140284; Cohort 4: JNJ-64140284

Fluorine-18 Labeled [18F]-JNJ-64511070 DRUG

An intravenous (IV) bolus injection of 185 MegaBecquerel (MBq) \[18F\]JNJ-64511070 will be administered.

Cohort 1: JNJ-64140284; Cohort 2: JNJ-64140284; Cohort 3: JNJ-64140284; Cohort 4: JNJ-64140284

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Body mass index (BMI) between 18 and 30 kilogram per meter square (kg/m\^2) inclusive (Body Mass Index \[BMI\] = weight/height\^2)
• Non-smoker (not smoked for 3 months prior to screening) or/and has not used nicotine -containing products (for example, nicotine patch) 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 candidate for arterial catheter placement
• Has no history or laboratory evidence of a coagulopathy. (for participants undergoing positron emission tomography \[PET\] scan only)
• 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 a) who is sexually active with a woman of childbearing potential and has not had vasectomy must agree to use a condom and their female partner should also use oral contraception or user independent method such as intrauterine device (IUD) or hormonal implant for at least the same duration; b) who is sexually active with a woman who is pregnant, must use a condom; c) must agree not to donate sperm

You may not qualify if:

• Exposed to greater than (\>)1 milliSievert (mSv) of ionizing radiation participating as a participant in research studies 12 months before the start of this study
• Clinically significant abnormal values for hematology, clinical chemistry or urinalysis at screening. It is expected that laboratory values will generally be within the normal range for the laboratory, though minor deviations, which are not considered to be of clinical significance to the investigator are acceptable
• 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, liver or renal disease or obstruction to urinary flow, infection, or any other condition that the Investigator considers significant should exclude the participant. 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 unless the participant has been successfully treated for HCV or HIV. Successful treatment should be confirmed by a negative ribonucleic acid (RNA) test for the virus

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2018
• First Posted: October 3, 2018
• Study Start: October 17, 2018
• Primary Completion: March 2, 2019
• Study Completion: March 13, 2019
• Last Updated: April 27, 2025

Record last verified: 2025-04

Locations

BE (1)