A Study to Investigate Safety and Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of JNJ-54175446 in Healthy Participants

January 31, 2025 updated by: Janssen-Cilag International NV

A Randomized, Placebo-controlled, Double-blind, Single Ascending Dose Study to Investigate Safety and Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of JNJ-54175446 in Healthy Subjects

The purpose of this study is to investigate the safety and tolerability of JNJ-54175446 versus placebo after single oral dose administration (ascending dose levels), to determine the maximal tolerated dose (MTD) or the safety and tolerability at exposures resulting in full target engagement for at least 24 hours in all participants (whichever comes first), to characterize the pharmacokinetics of JNJ-54175446 in plasma, cerebrospinal fluid (CSF) and urine and to investigate the effect of food (high fat/high calorie) on the pharmacokinetics of JNJ 54175446 after single oral dose administration.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a double-blind, placebo-controlled, randomized, single ascending dose study in healthy participants for JNJ-54175446. The study will consist of 3 phases: a screening phase (between 21 and 2 days prior to dose administration), a double-blind treatment phase (8 days; Part 1 and Part 3) or an open-label treatment phase (8 days; Part 2), and a follow-up examination (within 14 to 21 days after dose administration). The maximal study duration for a participant will not exceed 6 weeks. In each cohort of Part 1 (6 cohorts) and Part 3 (1 cohort), participants will be randomly assigned to receive JNJ-54175446 or matching placebo and in cohort of part 2, all participants will be assigned to JNJ-54175446 treatment. In part 1, primarily maximum tolerated dose (MTD) will be assessed, along with safety and tolerability of JNJ-54175446. In part 2, pharmacokinetics (PK) of JNJ-54175446 in cerebrospinal fluid (CSF) will be assessed. In part 3, the effect of food on the plasma PK of JNJ-54175446 in young healthy male participants will be assessed. Safety will be monitored throughout the study.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
76

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Participants must have a body mass index (BMI) between 18 and 32 kg/m^2, inclusive (BMI = weight/height^2)
  • Participants must be healthy on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel[excluding liver function tests], hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities to be not clinically significant. This determination must be recorded in the subject's source documents and initialed by the investigator
  • A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control e.g., either 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, and all men must also not donate sperm during the study and for 3 months after receiving the last dose of study drug. In addition, their female partner should also use an appropriate method of birth control for at least the same duration

For Part 1 and 3:

- Healthy male participants between 18 and 54 years of age, inclusive

For Part 2:

  • Healthy male or female participants between 55 and 75 years of age, inclusive
  • Participant must be healthy on the basis of both physical and neurological examination performed at screening and at admission to the clinical unit
  • Women must not be of childbearing potential (i.e., must be postmenopausal with amenorrhea for at least 12 months); permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy); or otherwise be incapable of pregnancy

Exclusion Criteria:

  • Participant has a history of or current liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic (including coagulation disorders), rheumatologic, psychiatric, or metabolic disturbances, any inflammatory illness or any other illness that the Investigator considers should exclude the participant
  • Participant has any liver function test (including alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyltransferase [gamma-GT], alkaline phosphatase [ALP] and bilirubin) at screening exceeding the upper limit of normal
  • Participant has a history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening
  • Participant has a history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening
  • Participant has a Prothrombin time [PT] >14 seconds and/or an activated partial thromboplastin time [aPTT] >35 seconds

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Part 1: Cohort 1
Participants will receive either JNJ-54175446 0.5 milligram (mg) or placebo on Day 1.
Drug: Placebo
Drug: JNJ 54175446
Experimental: Part 1: Cohort 2
Participants will receive either JNJ-54175446 2.5 mg or placebo on Day 1.
Drug: Placebo
Drug: JNJ 54175446
Experimental: Part 1: Cohort 3
Participants will receive either JNJ-54175446 10 mg or placebo on Day 1.
Drug: Placebo
Drug: JNJ 54175446
Experimental: Part 1: Cohort 4
Participants will receive either JNJ-54175446 30 mg or placebo on Day 1.
Drug: Placebo
Drug: JNJ 54175446
Experimental: Part 1: Cohort 5
Participants will receive either JNJ-54175446 100 mg or placebo on Day 1.
Drug: Placebo
Drug: JNJ 54175446
Experimental: Part 1: Cohort 6
Participants will receive either JNJ-54175446 200 mg or placebo on Day 1.
Drug: Placebo
Drug: JNJ 54175446
Experimental: Part 2: Cohort 7
Participants will receive JNJ-54175446 on Day 1. The dose of JNJ-54175446 will be determined in part 1 as suitable dose.
Drug: JNJ 54175446
Experimental: Part 3: Cohort 8
Participants will receive JNJ-54175446 on Day 1 along with high fat/high calorie breakfast. The dose of JNJ-54175446 will be determined in part 1 as suitable dose.
Drug: Placebo
Drug: JNJ 54175446
Other: High fat/high Calorie Breakfast

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants with Adverse Events
Time Frame: Baseline up to 14 or 21 days after study drug administration
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Baseline up to 14 or 21 days after study drug administration
Maximum Tolerated Dose of JNJ-54175446 in Part 1
Time Frame: Baseline up to 24 Hours after study drug administration
Baseline up to 24 Hours after study drug administration
Maximum Observed Plasma and Cerebrospinal Fluid (CSF) Concentration (Cmax)
Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration
The Cmax is the maximum observed concentration.
Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration
Last Quantifiable Plasma and Cerebrospinal Fluid (CSF) Concentration (Clast)
Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration
Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration
Time to Reach Maximum Observed Plasma and Cerebrospinal Fluid Concentration (Tmax)
Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration
Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration
Time to Last Quantifiable Plasma and Cerebrospinal Fluid Concentration (Tlast)
Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration
Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration
Area Under Curve From Time of Administration up to the Last Time Point with a Measurable Plasma and Cerebrospinal Fluid Concentration (AUClast)
Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration
Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration
Area Under the Plasma and Cerebrospinal Fluid Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])
Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration
Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration
First-order Rate Constant (Lambda[z])
Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration
Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration
Elimination Half-Life (t1/2)
Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration
The elimination half-life (t1/2) is the time measured for the plasma/CSF concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration
Total Clearance (CL/F)
Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration
Total clearance of drug after extravascular administration, uncorrected for absolute bioavailability
Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration
Creatinine Clearance
Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration
Creatinine clearance was calculated by Cockroft-Gault formula. Creatinine clearance is equal to 140 minus age multiplied by weight and constant (1 for men and 0.85 for women) divided by creatinine in (micro mole per liter).
Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Janssen-Cilag International NV

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Janssen-Cilag International NV Clinical Trial, Janssen-Cilag International NV

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 16, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 16, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 18, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 31, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2025

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CR107482
  • 2015-000942-53 (EudraCT Number)
  • 54175446EDI1001 (Other Identifier: Janssen-Cilag International NV)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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