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

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: JNJ-54175446; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02933762

2016-003040-37 (EudraCT Number)

CR108231

54175446EDI1005 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 25 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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25 participants in 13 patient groups

Part 1: Cohort A1 (JNJ-54175446 30 milligram[mg])

Experimental group

Description:

Healthy elderly participants will receive single dose of 30mg JNJ-54175446.

Treatment:

Drug: JNJ-54175446

Part 1: Cohort A1 (JNJ-54175446 100mg)

Experimental group

Description:

Healthy elderly participants will receive single dose of 100mg JNJ-54175446.

Treatment:

Drug: JNJ-54175446

Part 1: Cohort A1 (JNJ-54175446 300mg)

Experimental group

Description:

Healthy elderly participants will receive single dose of 300mg JNJ-54175446.

Treatment:

Drug: JNJ-54175446

Part 1: Cohort A1 (Placebo)

Experimental group

Description:

Healthy elderly participants will receive single dose of placebo.

Treatment:

Drug: Placebo

Part 1: Cohort A2 (JNJ-54175446 D1 mg)

Experimental group

Description:

Healthy elderly participants will receive an additional dose D1 mg \[less than or equal to (\<=) 600 mg\] of JNJ-54175446, to be determined.

Treatment:

Drug: JNJ-54175446

Part 1: Cohort A3 (JNJ-54175446 D2 mg)

Experimental group

Description:

Healthy young participants will receive a single dose D2 mg (\<= 600 mg) of JNJ-54175446, to be determined.

Treatment:

Drug: JNJ-54175446

Part 1: Cohort A3 (Placebo)

Experimental group

Description:

Healthy young participants will receive a single dose of placebo.

Treatment:

Drug: Placebo

Part 2: Cohort B1 (JNJ-54175446 D3 mg)

Experimental group

Description:

Healthy elderly participants will receive multiple dose levels D3 mg (\<= 450 mg) of JNJ-54175446 determined based on the results from Cohort A1.

Treatment:

Drug: JNJ-54175446

Part 2: Cohort B1 (Placebo)

Experimental group

Description:

Healthy elderly participants will receive placebo determined based on the results from Cohort A1.

Treatment:

Drug: Placebo

Part 2: Cohort B2 (JNJ-54175446 D4 mg)

Experimental group

Description:

Healthy elderly participants will receive multiple dose levels D4 mg (\<= 450 mg) of JNJ-54175446 determined based on the results from Cohort A1.

Treatment:

Drug: JNJ-54175446

Part 2: Cohort B2 (Placebo)

Experimental group

Description:

Healthy elderly participants will receive placebo determined based on the results from Cohort A1

Treatment:

Drug: Placebo

Part 2: Cohort B3 (JNJ-54175446 D5 mg)

Experimental group

Description:

Healthy elderly participants will receive multiple dose levels D5 mg (\<= 450 mg) of JNJ-54175446 determined based on the results from Cohort A1.

Treatment:

Drug: JNJ-54175446

Part 2: Cohort B3 (Placebo)

Experimental group

Description:

Healthy elderly participants will receive placebo determined based on the results from Cohort A1

Treatment:

Drug: Placebo