A Study in Healthy Participants to Evaluate the Effect of JNJ-54175446 on Amyloid Biomarkers and Cytokine Profiles in Cerebrospinal Fluid and Plasma

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Placebo; Drug: JNJ-54175446

• Registration Number: NCT02933762
• Lead Sponsor: Janssen Research & Development, LLC

Brief Summary

The primary purpose of this study is to investigate the effects of JNJ-54175446 (dose response) on levels of Aβ fragments (Aβ1-42, Aβ1-40, Aβ1-38, Aβ1-37) in plasma and cerebrospinal fluid (CSF), the effects of JNJ-54175446 on markers of (neuro) inflammation/protection in blood and CSF and the pharmacokinetics of JNJ-54175446 followed by single and multiple dose administration.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Study Start: 2016-09
• Study First Submitted: 2016-09-21
• Study First Submitted QC: 2016-10-12
• Study First Posted: 2016-10-14
• Primary Completion: 2016-11
• Study Completion: 2016-11
• Status Verified: 2017-01
• Last Update Submitted: 2017-01-13
• Last Update Posted: 2017-01-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

• Participants must have a body mass index (BMI) between 18 and 32 kilogram (kg)/ meter (m)^2, inclusive (BMI = weight/height^2)
• Participant must be healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG)

Part 1 and 2 (Elderly Participants):

• 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

Part 1 (Young Participants):

• Healthy male participants between 18 and 45 years of age, inclusive

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Exclusion Criteria

• Participant has a history of or current liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances, any inflammatory illness or any other illness that the Investigator considers should exclude the participant
• 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 (per Screening evaluations)
• Participant has a history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening (per Screening evaluations)
• Participant has a history of malignancy within 5 years before Screening
• Participant has signs of increased intracranial pressure based on fundoscopy at Screening

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part 2: Cohort B3 (Placebo)	Placebo	Healthy elderly participants will receive placebo determined based on the results from Cohort A1
Part 1: Cohort A1 (Placebo)	Placebo	Healthy elderly participants will receive single dose of placebo.
Part 2: Cohort B1 (Placebo)	Placebo	Healthy elderly participants will receive placebo determined based on the results from Cohort A1.
Part 1: Cohort A3 (Placebo)	Placebo	Healthy young participants will receive a single dose of placebo.
Part 2: Cohort B1 (JNJ-54175446 D3 mg)	JNJ-54175446	Healthy elderly participants will receive multiple dose levels D3 mg (\<= 450 mg) of JNJ-54175446 determined based on the results from Cohort A1.
Part 2: Cohort B2 (Placebo)	Placebo	Healthy elderly participants will receive placebo determined based on the results from Cohort A1
Part 1: Cohort A1 (JNJ-54175446 300mg)	JNJ-54175446	Healthy elderly participants will receive single dose of 300mg JNJ-54175446.
Part 1: Cohort A1 (JNJ-54175446 100mg)	JNJ-54175446	Healthy elderly participants will receive single dose of 100mg JNJ-54175446.
Part 1: Cohort A2 (JNJ-54175446 D1 mg)	JNJ-54175446	Healthy elderly participants will receive an additional dose D1 mg \[less than or equal to (\<=) 600 mg\] of JNJ-54175446, to be determined.
Part 1: Cohort A3 (JNJ-54175446 D2 mg)	JNJ-54175446	Healthy young participants will receive a single dose D2 mg (\<= 600 mg) of JNJ-54175446, to be determined.
Part 2: Cohort B2 (JNJ-54175446 D4 mg)	JNJ-54175446	Healthy elderly participants will receive multiple dose levels D4 mg (\<= 450 mg) of JNJ-54175446 determined based on the results from Cohort A1.
Part 1: Cohort A1 (JNJ-54175446 30 milligram[mg])	JNJ-54175446	Healthy elderly participants will receive single dose of 30mg JNJ-54175446.
Part 2: Cohort B3 (JNJ-54175446 D5 mg)	JNJ-54175446	Healthy elderly participants will receive multiple dose levels D5 mg (\<= 450 mg) of JNJ-54175446 determined based on the results from Cohort A1.

Primary Outcome Measures

Name	Time	Method
Area Under The Concentration-Time Curve From 0 To t Hours Postdosing (AUCt)	Part 1: Day 1 - Day 2; Part 2: Day 1 to Day 8
The Effects of JNJ-54175446 (Dose Response) on Markers of (Neuro)Inflammation / Protection in Blood	Part 2: Up to Day 8
The Effects of JNJ-54175446 (Dose Response) on Markers of (Neuro)Inflammation / Protection in CSF	Part 2: Up to Day 8
The Effects of JNJ-54175446 (Dose Response) on Levels of Aβ Fragments in Plasma	Part 2: Up to Day 8
The Effects of JNJ-54175446 (Dose Response) on Levels of Aβ Fragments in Cerebrospinal Fluid (CSF)	Part 2: Up to Day 8
Maximum Observed Plasma Concentration (Cmax) After Single- and Multiple-Dose Administration	Part 1: Day 1 - Day 2; Part 2: Day 1 to Day 8
Minimum Observed Plasma Concentration (Cmin)During Dosing Interval	Part 1: Day 1 - Day 2; Part 2: Day 1 to Day 8
The Observed Plasma Concentration Just Prior to the Beginning or at the end of a Dosing Interval of any Dose Other Than the First Dose (Ctrough)	Part 1: Day 1 - Day 2; Part 2: Day 1 to Day 8
Average Plasma Concentration at Steady State Over the Dosing Interval (Cavg)	Part 1: Day 1 - Day 2; Par 2: Day 1, Day 2 to 6, Day 7, Day 8
Time to Reach the Maximum Plasma Concentration, After Single- and Multiple-Dose Administration (Tmax)	Part 1: Day 1 - Day 2; Part 2: Day 1 to Day 8
Area Under the Concentration-Time Curve From 0 to 24 Hours Postdosing (AUC24h)	Part 1: Day 1 - Day 2; Part 2: Day 1 to Day 8
The Ratio of the Maximum Plasma Concentration (Peak) to Trough Observed Concentration (Peak/Trough Ratio)	Part 1: Day 1 - Day 2; Part 2: Day 1 to Day 8

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events as a Measure of Safety and Tolerability	Screening up to follow-up (in part 1 and part 2 [approximately up to 8 weeks])