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

Healthy Clinical Trial

Official title:

An Exploratory, Single-Blind, Placebo-Controlled, Randomized, Single- and Multiple-Dose Pharmacodynamics Study in Healthy Subjects to Evaluate the Effect of JNJ-54175446 on Amyloid Biomarkers and Cytokine Profiles in Cerebrospinal Fluid and Plasma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02933762
• Other study ID #: CR108231
• Secondary ID: 2016-003040-3754
• Status: Completed
• Phase: Phase 1
• First received: September 21, 2016
• Last updated: January 13, 2017
• Start date: September 2016
• Est. completion date: November 2016

Study information

• Verified date: January 2017
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: November 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• JNJ-54175446
Participants will receive a single oral dose of JNJ-54175446 suspension orally once on Day 1 of part 1 and Day 1 to Day 7 in part 2.
• Placebo
Participants will receive a single oral dose of JNJ-54175446 suspension orally once on Day 1 of part 1 and Day 1 to Day 7 in part 2.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Effects of JNJ-54175446 (Dose Response) on Levels of Aß Fragments in Plasma		Part 1: Up to Day 2
Primary	The Effects of JNJ-54175446 (Dose Response) on Levels of Aß Fragments in Plasma		Part 2: Up to Day 8
Primary	The Effects of JNJ-54175446 (Dose Response) on Levels of Aß Fragments in Cerebrospinal Fluid (CSF)		Part 1: Up to Day 2
Primary	The Effects of JNJ-54175446 (Dose Response) on Levels of Aß Fragments in Cerebrospinal Fluid (CSF)		Part 2: Up to Day 8
Primary	The Effects of JNJ-54175446 (Dose Response) on Markers of (Neuro)Inflammation / Protection in Blood		Part 1: Up to Day 2
Primary	The Effects of JNJ-54175446 (Dose Response) on Markers of (Neuro)Inflammation / Protection in Blood		Part 2: Up to Day 8
Primary	The Effects of JNJ-54175446 (Dose Response) on Markers of (Neuro)Inflammation / Protection in CSF		Part 1: Up to Day 2
Primary	The Effects of JNJ-54175446 (Dose Response) on Markers of (Neuro)Inflammation / Protection in CSF		Part 2: Up to Day 8
Primary	Maximum Observed Plasma Concentration (Cmax) After Single- and Multiple-Dose Administration		Part 1: Day 1 - Day 2; Part 2: Day 1 to Day 8
Primary	Minimum Observed Plasma Concentration (Cmin)During Dosing Interval		Part 1: Day 1 - Day 2; Part 2: Day 1 to Day 8
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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])