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Study Investigating the Effects of JNJ-54861911 on Amyloid-beta Processing in Cerebrospinal Fluid (CSF) and Plasma in Japanese Participants Asymptomatic at Risk for Alzheimer Dementia

Primary Purpose

Alzheimer's Disease

Status

Completed

Phase

Phase 1

Locations

Japan

Study Type

Interventional

Intervention

JNJ-54861911, 10 mg

JNJ-54861911, 50 mg

Placebo

About this trial

This is an interventional treatment trial for Alzheimer's Disease focused on measuring Alzheimer's Disease, Alzheimer Dementia, JNJ-54861911, Beta Secretase Inhibitor

Eligibility Criteria

65 Years - 85 Years (Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Participant must have had sufficient education or work experience to exclude mental retardation based on Diagnostic and Statistical Manual of Mental Disorders 4th edition, Text Revision (DSM-IV-TR) and must be able to read and write and must have adequate hearing and visual acuity to complete the required psychometric tests
Participant must have a Clinical Dementia Rating Scale- Japanese version (CDR-J) score of '0' and as such rated as normal
Participant must have evidence of amyloid deposition as demonstrated by low Cerebrospinal Fluid (CSF) Amyloid (A)-beta 1-42 levels at Screening
Participant must have a body mass index between 18 and 35 kilogram per square meter, inclusive, at Screening
Participant must be otherwise healthy for their age group or medically stable with or without medication on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at Screening or at Baseline

Exclusion Criteria:

Participant has evidence of any brain disease other than potential very early signs of Alzheimer's disease (AD) or typical age related changes, or any other abnormality that could explain a possible cognitive deficit
Participant has been diagnosed with dementia due to AD, due to other diseases, or with AD and contribution of other disorders (mixed dementia)
Participant has evidence of familial autosomal dominant AD
Participant has any contra-indications for Magnetic Resonance Imaging (MRI) (for example, prostheses, implants, claustrophobia, pacemakers, and others)
Participant has a clinically significant abnormal physical- or neurological examination, vital signs or 12-lead ECG (including QTc greater than 450 millisecond for males and females, left bundle branch block, atrio-ventricular [AV] block second degree or higher, permanent pacemaker or implantable cardioverter defibrillator [ICD]) at Screening or Baseline, which in the opinion of the investigator is not appropriate and reasonable for the population under study

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

JNJ-54861911, 10 mg

JNJ-54861911, 50 mg

Placebo

Arm Description

JNJ-54861911, 10 milligram (mg) (2*5 mg tablet) orally once daily for 4 weeks.

JNJ-54861911, 50 mg (2*25 mg tablet) orally once daily for 4 weeks.

Placebo matching to JNJ-54861911 tablet orally once daily for 4 weeks.

Outcomes

Primary Outcome Measures

Levels of Amyloid (A)-beta1-40 in Cerebrospinal Fluid (CSF) After Treatment at the Intended Target Dose Range

Levels of A-beta1-40 in Plasma After Treatment at the Intended Target Dose Range

Maximum Observed Plasma Concentration (Cmax) of JNJ 54861911

The Cmax is the maximum observed plasma concentration.

Minimum Observed Plasma Concentration (Cmin) of JNJ 54861911

The Cmin is the minimum observed plasma concentration.

Time to Reach Maximum Observed Concentration (Tmax) of JNJ 54861911

The Tmax is time to reach the maximum observed plasma concentration.

Area Under the Curve From Time Zero to end of Dosing Interval (AUCtau)

The AUCtau is a measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption.

Cerebrospinal Fluid Exposure of JNJ-54861911

The Number of Participants who Experienced Adverse Events as a Measure of Safety and Tolerability of JNJ-54861911 After Multiple-Dose Administration in the Anticipated Target Dose Range

An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Secondary Outcome Measures

Levels of A-beta Fragments (A-beta1-37, A-beta1-38, and A-beta1-42) in CSF After Treatment at the Intended Target Dose Range

Levels of A-beta Fragments (A-beta1-37, A-beta1-38, and A-beta1-42) in Plasma After Treatment at the Intended Target Dose Range

Levels of Soluble Amyloid Precursor Protein (APP) Fragments in CSF (sAPP-alpha, sAPP-beta, totalAPP) After Treatment at the Intended Target Dose Range

Compare the Relationship of A-beta1-40 Levels in Plasma and CSF After Treatment at the Intended Dose Range

Full Information

NCT ID

NCT02360657

First Posted

February 5, 2015

Last Updated

January 31, 2019

Sponsor

Janssen Pharmaceutical K.K.

1. Study Identification

Unique Protocol Identification Number

NCT02360657

Brief Title

Study Investigating the Effects of JNJ-54861911 on Amyloid-beta Processing in Cerebrospinal Fluid (CSF) and Plasma in Japanese Participants Asymptomatic at Risk for Alzheimer Dementia

Official Title

A Double-blind, Placebo-controlled, Randomized, 4-Week, Multiple-dose, Proof of Mechanism (POM) Study in Japanese Subjects Asymptomatic at Risk for Alzheimer Dementia (ARAD) Investigating the Effects of JNJ-54861911 on A-beta Processing in Cerebrospinal Fluid (CSF) and Plasma

Study Type

Interventional

2. Study Status

Record Verification Date

January 2019

Overall Recruitment Status

Completed

Study Start Date

February 16, 2015 (Actual)

Primary Completion Date

September 8, 2015 (Actual)

Study Completion Date

September 8, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Janssen Pharmaceutical K.K.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to determine the safety, tolerability and effect of JNJ-54861911 on level of amyloid-beta in Cerebrospinal Fluid (CSF) and plasma following 4 weeks of treatment in Japanese participants asymptomatic at risk for Alzheimer Dementia (ARAD) at the intended target dose range.

Detailed Description

This is a multi-center (when more than one hospital or medical school team work on a medical research study), double-blind (neither physician nor participant knows the treatment that the participant receives), placebo-controlled (the experimental treatment or procedure is compared to an inactive substance), randomized (study medication assigned by chance), multiple dose, Proof of Mechanism (POM) study in Japanese participants ARAD. All eligible participants will be randomly assigned to 1 of 3 treatment groups (that is, placebo, JNJ-54861911 10 milligram [mg] or JNJ-54861911 50 mg once daily regimen). This study will consist of Screening Phase (8-week), Double blind Treatment Phase (4-week), and Follow-up Phase (2-week). The maximum study duration for a participant will be 14 weeks. Participant's safety will be monitored throughout the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alzheimer's Disease

Keywords

Alzheimer's Disease, Alzheimer Dementia, JNJ-54861911, Beta Secretase Inhibitor

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

JNJ-54861911, 10 mg

Arm Type

Experimental

Arm Description

JNJ-54861911, 10 milligram (mg) (2*5 mg tablet) orally once daily for 4 weeks.

Arm Title

JNJ-54861911, 50 mg

Arm Type

Experimental

Arm Description

JNJ-54861911, 50 mg (2*25 mg tablet) orally once daily for 4 weeks.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo matching to JNJ-54861911 tablet orally once daily for 4 weeks.

Intervention Type

Drug

Intervention Name(s)

JNJ-54861911, 10 mg

Intervention Description

JNJ-54861911, 10 mg (2*5 mg tablet) orally once daily for 4 weeks.

Intervention Type

Drug

Intervention Name(s)

JNJ-54861911, 50 mg

Intervention Description

JNJ-54861911, 50 mg (2*25 mg tablet) orally once daily for 4 weeks.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo matching to JNJ-54861911 tablet orally once daily for 4 weeks.

Primary Outcome Measure Information:

Title

Levels of Amyloid (A)-beta1-40 in Cerebrospinal Fluid (CSF) After Treatment at the Intended Target Dose Range

Time Frame

Up to 4 weeks

Title

Levels of A-beta1-40 in Plasma After Treatment at the Intended Target Dose Range

Time Frame

Up to 4 weeks

Title

Maximum Observed Plasma Concentration (Cmax) of JNJ 54861911

Description

The Cmax is the maximum observed plasma concentration.

Time Frame

Up to 4 weeks

Title

Minimum Observed Plasma Concentration (Cmin) of JNJ 54861911

Description

The Cmin is the minimum observed plasma concentration.

Time Frame

Up to 4 weeks

Title

Time to Reach Maximum Observed Concentration (Tmax) of JNJ 54861911

Description

The Tmax is time to reach the maximum observed plasma concentration.

Time Frame

Up to 4 weeks

Title

Area Under the Curve From Time Zero to end of Dosing Interval (AUCtau)

Description

The AUCtau is a measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption.

Time Frame

Up to 4 weeks

Title

Cerebrospinal Fluid Exposure of JNJ-54861911

Time Frame

Up to 4 weeks

Title

The Number of Participants who Experienced Adverse Events as a Measure of Safety and Tolerability of JNJ-54861911 After Multiple-Dose Administration in the Anticipated Target Dose Range

Description

Time Frame

Up to 4 weeks

Secondary Outcome Measure Information:

Title

Levels of A-beta Fragments (A-beta1-37, A-beta1-38, and A-beta1-42) in CSF After Treatment at the Intended Target Dose Range

Time Frame

Up to 4 weeks

Title

Levels of A-beta Fragments (A-beta1-37, A-beta1-38, and A-beta1-42) in Plasma After Treatment at the Intended Target Dose Range

Time Frame

Up to 4 weeks

Title

Levels of Soluble Amyloid Precursor Protein (APP) Fragments in CSF (sAPP-alpha, sAPP-beta, totalAPP) After Treatment at the Intended Target Dose Range

Time Frame

Up to 4 weeks

Title

Compare the Relationship of A-beta1-40 Levels in Plasma and CSF After Treatment at the Intended Dose Range

Time Frame

Up to 4 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

65 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Participant must have had sufficient education or work experience to exclude mental retardation based on Diagnostic and Statistical Manual of Mental Disorders 4th edition, Text Revision (DSM-IV-TR) and must be able to read and write and must have adequate hearing and visual acuity to complete the required psychometric tests Participant must have a Clinical Dementia Rating Scale- Japanese version (CDR-J) score of '0' and as such rated as normal Participant must have evidence of amyloid deposition as demonstrated by low Cerebrospinal Fluid (CSF) Amyloid (A)-beta 1-42 levels at Screening Participant must have a body mass index between 18 and 35 kilogram per square meter, inclusive, at Screening Participant must be otherwise healthy for their age group or medically stable with or without medication on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at Screening or at Baseline Exclusion Criteria: Participant has evidence of any brain disease other than potential very early signs of Alzheimer's disease (AD) or typical age related changes, or any other abnormality that could explain a possible cognitive deficit Participant has been diagnosed with dementia due to AD, due to other diseases, or with AD and contribution of other disorders (mixed dementia) Participant has evidence of familial autosomal dominant AD Participant has any contra-indications for Magnetic Resonance Imaging (MRI) (for example, prostheses, implants, claustrophobia, pacemakers, and others) Participant has a clinically significant abnormal physical- or neurological examination, vital signs or 12-lead ECG (including QTc greater than 450 millisecond for males and females, left bundle branch block, atrio-ventricular [AV] block second degree or higher, permanent pacemaker or implantable cardioverter defibrillator [ICD]) at Screening or Baseline, which in the opinion of the investigator is not appropriate and reasonable for the population under study

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Janssen Pharmaceutical K.K., Japan Clinical Trial

Organizational Affiliation

Janssen Pharmaceutical K.K.

Official's Role

Study Director

Facility Information:

City

Fukuoka

Country

Japan

City

Tokyo

Country

Japan

12. IPD Sharing Statement

Citations:

PubMed Identifier

30134967

Citation

Timmers M, Streffer JR, Russu A, Tominaga Y, Shimizu H, Shiraishi A, Tatikola K, Smekens P, Borjesson-Hanson A, Andreasen N, Matias-Guiu J, Baquero M, Boada M, Tesseur I, Tritsmans L, Van Nueten L, Engelborghs S. Pharmacodynamics of atabecestat (JNJ-54861911), an oral BACE1 inhibitor in patients with early Alzheimer's disease: randomized, double-blind, placebo-controlled study. Alzheimers Res Ther. 2018 Aug 23;10(1):85. doi: 10.1186/s13195-018-0415-6.

Results Reference

derived

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Study Investigating the Effects of JNJ-54861911 on Amyloid-beta Processing in Cerebrospinal Fluid (CSF) and Plasma in Japanese Participants Asymptomatic at Risk for Alzheimer Dementia

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