Evaluation of E2609 in Subjects With Mild Cognitive Impairment or Mild Dementia Due to Alzheimer's Disease (Study: E2609-A001-101 Amendment 02)

A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Oral Doses of E2609 in Subjects With Mild Cognitive Impairment or Mild Dementia Due to Alzheimer's Disease

Subjects will be adults aged 50 to 85 years who have subjective memory complaints and mild cognitive impairment or mild dementia due to Alzheimer's disease (AD). Subjects taking thyroxine or thyroid supplements and subjects receiving an acetylcholinesterase inhibitor (AChEI) and/or memantine for AD must be on a stable dose for at least 12 weeks prior to Screening and remain on their stable dose throughout the trial. Subjects will receive placebo or a single oral dose of E2609. Safety assessments will be conducted. Additionally, the pharmacokinetics of E2609 and drug effects will be evaluated using cerebrospinal fluid biomarkers and cognitive and psychological measures.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: E2609; Drug: Placebo for E2609

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States
  • Maryland
    • Baltimore, Maryland, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Meets the current cognitive classification of MCI or mild dementia due to AD pathology (all subjects having a "positive" biomarker for amyloid β) as defined by the National Institute on Aging - Alzheimer's Association (NIA-AA) research criteria
• Aged 50 to 85 years, inclusive at time of consent

Exclusion criteria:

• Currently has any neurological condition other than AD (Alzheimer's disease)-related that could be contributing to the subject's cognitive impairment
• Significant pathological findings on brain MRI at Screening, including but not limited to multiple microhemorrhages
• Any psychiatric diagnosis or symptoms, e.g., hallucinations, major depression,anxiety or delusions that in the Investigator's opinion could interfere with assessment of cognition or confound the diagnosis of MCI or mild dementia due to AD in the subject.
• A lifetime history of cerebrovascular events or non-vasovagal related loss of consciousness within the last 10 years
• Any other abnormality of the ECG at Screening and/or Baseline (including QRS > 110 ms, abnormal electrical axis, PR interval > 220 ms and conduction abnormalities) considered clinically significant by the investigator
• History of cardiac arrhythmias, ischemic heart disease or cerebrovascular disease
• Lower spinal malformation on physical or lumbar spine radiography, local spinal infection, or other abnormality, including but not limited to obesity, that would prevent LP or insertion of an indwelling catheter for CSF sampling
• Any history of seizure disorder, symptomatic seizures (not including a history of simple febrile seizures in childhood) or any past or present medical condition which, in the opinion of the investigator has the potential to reduce seizure threshold (e.g., history of head trauma or concussion, previous alcohol abuse, substance abuse).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: E2609	Drug: E2609; E2609 capsules: 5 mg, 25 mg, 50 mg, and 200 mg E2609 doses: 5 mg, 10 mg, 25 mg, 50 mg, 100 mg, 200 mg, and 400 mg According to the randomized study design, participants who are assigned to receive E2609 will each receive a single assigned dose consisting of two capsules of E2609 or in some cases one capsule of E2609 and one of placebo
PLACEBO_COMPARATOR: Placebo for E2609	Drug: Placebo for E2609; Placebo capsules According to the randomized study design, participants who are assigned to receive placebo will each receive a single dose consisting of two capsules of placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent change from baseline in cerebrospinal fluid amyloid-beta levels	baseline to 36 hours post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of adverse events	8 days

Collaborators and Investigators

• Sponsor: Eisai Inc.
• Investigators: Principal Investigator: Hakop Gevorkyan, California Clinical Trials Medical Group Inc.; Principal Investigator: Olukemi Olugemo, MD, PAREXEL International - EPCU Baltimore

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (ACTUAL): September 1, 2013
• Study Completion (ACTUAL): October 1, 2013

Study Registration Dates

• First Submitted: May 15, 2012
• First Submitted That Met QC Criteria: May 15, 2012
• First Posted (ESTIMATE): May 17, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): December 30, 2016
• Last Update Submitted That Met QC Criteria: December 29, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Tauopathies; Cognition Disorders; Dementia; Alzheimer Disease; Cognitive Dysfunction
• Other Study ID Numbers: E2609-A001-101