NCT02475148

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
76

participants targeted

Target at P75+ for phase_1 healthy

Timeline
Completed

Started Jun 2015

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2015

Completed
15 days until next milestone

First Submitted

Initial submission to the registry

June 16, 2015

Completed
2 days until next milestone

First Posted

Study publicly available on registry

June 18, 2015

Completed
4 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2015

Completed
Last Updated

February 3, 2025

Status Verified

January 1, 2025

Enrollment Period

4 months

First QC Date

June 16, 2015

Last Update Submit

January 31, 2025

Conditions

Healthy

Keywords

JNJ-54175446Healthy

Outcome Measures

Primary Outcomes (12)

  • Number of Participants with Adverse Events

    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

    Baseline up to 24 Hours after study drug administration

  • Maximum Observed Plasma and Cerebrospinal Fluid (CSF) Concentration (Cmax)

    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)

    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)

    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)

    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)

    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])

    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])

    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)

    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)

    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

    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

Study Arms (8)

Part 1: Cohort 1

EXPERIMENTAL

Participants will receive either JNJ-54175446 0.5 milligram (mg) or placebo on Day 1.

Drug: JNJ 54175446Drug: Placebo

Part 1: Cohort 2

EXPERIMENTAL

Participants will receive either JNJ-54175446 2.5 mg or placebo on Day 1.

Drug: JNJ 54175446Drug: Placebo

Part 1: Cohort 3

EXPERIMENTAL

Participants will receive either JNJ-54175446 10 mg or placebo on Day 1.

Drug: JNJ 54175446Drug: Placebo

Part 1: Cohort 4

EXPERIMENTAL

Participants will receive either JNJ-54175446 30 mg or placebo on Day 1.

Drug: JNJ 54175446Drug: Placebo

Part 1: Cohort 5

EXPERIMENTAL

Participants will receive either JNJ-54175446 100 mg or placebo on Day 1.

Drug: JNJ 54175446Drug: Placebo

Part 1: Cohort 6

EXPERIMENTAL

Participants will receive either JNJ-54175446 200 mg or placebo on Day 1.

Drug: JNJ 54175446Drug: Placebo

Part 2: Cohort 7

EXPERIMENTAL

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

Part 3: Cohort 8

EXPERIMENTAL

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: JNJ 54175446Drug: PlaceboOther: High fat/high Calorie Breakfast

Interventions

JNJ 54175446DRUG
Part 1: Cohort 1Part 1: Cohort 2Part 1: Cohort 3Part 1: Cohort 4Part 1: Cohort 5Part 1: Cohort 6Part 2: Cohort 7Part 3: Cohort 8
PlaceboDRUG
Part 1: Cohort 1Part 1: Cohort 2Part 1: Cohort 3Part 1: Cohort 4Part 1: Cohort 5Part 1: Cohort 6Part 3: Cohort 8
High fat/high Calorie BreakfastOTHER
Part 3: Cohort 8

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Unknown Facility

Merksem, Belgium

Location

Related Publications (1)

  • Triana-Baltzer G, Timmers M, De Boer P, Schoene M, Furey M, Bleys C, Vrancken I, Slemmon R, Ceusters M, van Nueten L, Kolb H. Profiling classical neuropsychiatric biomarkers across biological fluids and following continuous lumbar puncture: A guide to sample type and time. Compr Psychoneuroendocrinol. 2022 Jan 15;10:100116. doi: 10.1016/j.cpnec.2022.100116. eCollection 2022 May.

    PMID: 35774109DERIVED

Study Officials

  • Janssen-Cilag International NV Clinical Trial

    Janssen-Cilag International NV

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 16, 2015

First Posted

June 18, 2015

Study Start

June 1, 2015

Primary Completion

October 1, 2015

Study Completion

October 1, 2015

Last Updated

February 3, 2025

Record last verified: 2025-01

Locations

BE(1)