Healthy
Conditions
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.
Interventions
DRUGJNJ-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.
DRUGPlacebo
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.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| The Effects of JNJ-54175446 (Dose Response) on Levels of Aβ Fragments in Plasma | Part 1: Up to Day 2 |
| The Effects of JNJ-54175446 (Dose Response) on Levels of Aβ Fragments in Cerebrospinal Fluid (CSF) | Part 1: Up to Day 2 |
| The Effects of JNJ-54175446 (Dose Response) on Markers of (Neuro)Inflammation / Protection in Blood | Part 1: Up to Day 2 |
| The Effects of JNJ-54175446 (Dose Response) on Markers of (Neuro)Inflammation / Protection in CSF | Part 1: Up to Day 2 |
| 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 t Hours Postdosing (AUCt) | 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 |
Secondary
| Measure | Time frame |
|---|---|
| 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]) |
Countries
Belgium
Outcome results
None listed