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

NCT02360657 | Completed Phase 1

• 2 other identifiers: CR10639754861911ALZ1008
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

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.

Conditions

Alzheimer's Disease

Keywords

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

Outcome Measures

Primary Outcomes (8)

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

  Up to 4 weeks

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

  Up to 4 weeks

• Maximum Observed Plasma Concentration (Cmax) of JNJ 54861911

  The Cmax is the maximum observed plasma concentration.

  Up to 4 weeks

• Minimum Observed Plasma Concentration (Cmin) of JNJ 54861911

  The Cmin is the minimum observed plasma concentration.

  Up to 4 weeks

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

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

  Up to 4 weeks

• 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.

  Up to 4 weeks

• Cerebrospinal Fluid Exposure of JNJ-54861911

  Up to 4 weeks

• 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.

  Up to 4 weeks

Secondary Outcomes (4)

• 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

  Up to 4 weeks

• 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

  Up to 4 weeks

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

  Up to 4 weeks

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

  Up to 4 weeks

Study Arms (3)

JNJ-54861911, 10 mg

EXPERIMENTAL

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

Drug: JNJ-54861911, 10 mg

JNJ-54861911, 50 mg

EXPERIMENTAL

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

Drug: JNJ-54861911, 50 mg

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

JNJ-54861911, 10 mg DRUG

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

JNJ-54861911, 10 mg

JNJ-54861911, 50 mg DRUG

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

JNJ-54861911, 50 mg

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 65 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Pharmaceutical K.K.: lead

Study Sites (2)

Unknown Facility

Fukuoka, Japan

Location

Unknown Facility

Tokyo, Japan

Location

Related Publications (1)

• 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.

  PMID: 30134967 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

atabecestat

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Janssen Pharmaceutical K.K., Japan Clinical Trial

  Janssen Pharmaceutical K.K.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2015
• First Posted: February 10, 2015
• Study Start: February 16, 2015
• Primary Completion: September 8, 2015
• Study Completion: September 8, 2015
• Last Updated: February 4, 2019

Record last verified: 2019-01

Locations

JP (2)