Study To Evaluate the Efficacy, Safety and Tolerability of E2027 (Hereinafter Referred to as Irsenontrine) in Participants With Dementia With Lewy Bodies

July 29, 2022 updated by: Eisai Inc.

A Placebo-Controlled, Double-Blind, Parallel-Group, Randomized, Study To Evaluate the Efficacy, Safety and Tolerability of E2027 in Subjects With Dementia With Lewy Bodies

This study will be conducted to compare Irsenontrine to placebo on the cognitive endpoint of Montreal Cognitive Assessment (MoCA) and the global clinical endpoint of Clinician's Interview Based Impression of Change Plus (CIBIC-Plus) Caregiver Input in participants with dementia with Lewy bodies after 12 weeks of treatment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

326

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Lille, France, 59037
        • Centre Memoire du CHRU de Lille
      • Lyon, France, 69677
        • Hôpital Neurologique de Lyon
      • Marseille, France, 13385
        • University Hospital de la Timone
      • Strasbourg, France, 67000
        • Centre d'Investigation Clinique (CIC) Hopitaux universitaires Strasbourg HOPITAL DE HAUTEPIERRE - BATIMENT AX5
    • Meurthe-et-Moselle
      • Vandœuvre-lès-Nancy, Meurthe-et-Moselle, France, 54500
        • CHRU Nancy- CMRR de lorraine Hôpital de Brabois-Service de Gériatrie
    • Villeurbanne
      • Lyon, Villeurbanne, France, 69100
        • Centre de Recherche Clinique - Viellissement-Cerveau-Fragilite (CRC-VCF), Hopital des Charpennes
  • Germany
      • Berlin, Germany, 12203
        • Eisai Trial Site #3
      • Kassel, Germany, 34128
        • Eisai Trial Site #1
      • Westerstede, Germany, 26655
        • Eisai Trial Site #2
  • Italy
      • Chieti, Italy, 66100
        • Universita Chieti, CeSI Met
      • Padova, Italy, 35128
        • Clinica Neurologica Azienda Ospedaliera di Padova
  • Japan
      • Hiroshima, Japan, 732-0066
        • Eisai Trial Site #25
      • Osaka, Japan, 550-0012
        • Eisai Trial Site #21
    • Chiba
      • Chiba-shi, Chiba, Japan, 263-0043
        • Eisai Trial Site #20
    • Fukuoka
      • Fukuoka-shi, Fukuoka, Japan, 814-0180
        • Eisai Trial Site #17
    • Gunma
      • Fujioka-shi, Gunma, Japan, 375-0017
        • Eisai Trial Site #8
      • Maebashi-shi, Gunma, Japan, 371-8511
        • Eisai Trial Site #12
    • Hiroshima
      • Miyoshi-shi, Hiroshima, Japan, 728-0013
        • Eisai Trial Site #14
      • Otake-shi, Hiroshima, Japan, 739-0651
        • Eisai Trial Site #4
    • Hyogo
      • Himeji-shi, Hyogo, Japan, 670-0981
        • Eisai Trial Site #2
    • Kanagawa
      • Yokohama-shi, Kanagawa, Japan, 225-0013
        • Eisai Trial Site #23
    • Kumamoto
      • Kumamoto-shi, Kumamoto, Japan, 860-8556
        • Eisai Trial Site #11
    • Nagasaki
      • Nishisonogigun, Nagasaki, Japan, 851-2103
        • Eisai Trial Site #5
    • Niigata
      • Nagaoka-shi, Niigata, Japan, 940-2302
        • Eisai Trial Site #9
    • Okayama
      • Kurashiki-shi, Okayama, Japan, 710-0813
        • Eisai Trial Site #3
    • Osaka
      • Naniwa-ku, Osaka, Japan, 556-0017
        • Eisai Trial Site #1
      • Sakai-ku, Sakai-shi, Osaka, Japan, 590-0018
        • Eisai Trial Site #16
      • Suita-shi, Osaka, Japan, 565-0871
        • Eisai Trial Site #24
      • Suita-shi, Osaka, Japan, 565-0874
        • Eisai Trial Site #13
    • Saga
      • Kanzaki-gun, Saga, Japan, 842-0192
        • Eisai Trial Site #6
    • Tokyo
      • Bunkyo-ku, Tokyo, Japan, 113-0034
        • Eisai Trial Site #10
      • Mitaka-shi, Tokyo, Japan, 181-0013
        • Eisai Trial Site #22
      • Setagaya-Ku, Tokyo, Japan, 158-0098
        • Eisai Trial Site #18
    • Yamaguchi
      • Yanai-shi, Yamaguchi, Japan, 742-1352
        • Eisai Trial Site #19
  • Spain
      • Barcelona, Spain, 08006
        • Institut Internacional de Neurociències Aplicades
      • Barcelona, Spain, 08228
        • Fundacio ACE
      • Barcelona, Spain, 08235
        • Hospital Universitari Vall d'Hebron
      • Madrid, Spain, 28007
        • Hospital General Universitario Gregorio Maranon
    • Barcelona
      • Terrassa, Barcelona, Spain, 08221
        • Hospital Mutua De Terrassa
    • Madrid
      • Majadahonda, Madrid, Spain, 28222
        • Hospital Universitario Puerta de Hierro - Majadahonda
  • United Kingdom
      • Isleworth, United Kingdom, TW7 6FY
        • West london Mental Health Trust
      • London, United Kingdom, SE5 8AF
        • Kings College
      • London, United Kingdom, W1G 9JF
        • Cognition Health
      • Manchester, United Kingdom, M25 3BL
        • Manchester Mental Health and Social Care Trust
      • Newcastle, United Kingdom, NE45PL
        • Newcastle General Hospital
    • East Sussex
      • Crowborough, East Sussex, United Kingdom, TN6 1HB
        • Dementia Research Unit
    • Hampshire
      • Southampton, Hampshire, United Kingdom, S030 3JB
        • Memory Assessment and Research Centre, Moorgreen Hospital
    • Scotland
      • Dundee, Scotland, United Kingdom, DD1 9SY
        • Clinical Research Centre (CRC)
      • Glasgow, Scotland, United Kingdom, G51 4TF
        • Queen Elizabeth University Hospital
  • United States
    • Arizona
      • Sun City, Arizona, United States, 85351
        • Banner Sun Health Research Institute
    • California
      • Anaheim, California, United States, 92805
        • Advanced Research Center Inc
      • Fountain Valley, California, United States, 92708
        • Parkinsons and Movement Disorders Institute
      • San Diego, California, United States, 92117
        • Paradigm Clinical Research Centers, Inc
      • Santa Ana, California, United States, 92705
        • Syrentis Clinical Research
    • Connecticut
      • Stamford, Connecticut, United States, 06905
        • New England Institute for Clinical Research
    • Florida
      • Miami, Florida, United States, 33155
        • Elias Research Associates (Allied Biomedical Research Institute)
      • Miami, Florida, United States, 33137
        • Miami Jewish Health-Clinical Research
      • Miami, Florida, United States, 33175
        • Pharmax Research of South Florida; Elias Research Associates
      • Orlando, Florida, United States, 32806
        • Compass Research-Bioclinica
      • Ormond Beach, Florida, United States, 32174
        • Neurology Associates of Ormond Beach
      • Palm Beach Gardens, Florida, United States, 33410
        • Advanced Research Consultants, Inc.
      • Pensacola, Florida, United States, 32502
        • Anchor Neuroscience
      • The Villages, Florida, United States, 32162
        • Compass Research-Bioclinica
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University, Dept of Neurology
    • Kentucky
      • Lexington, Kentucky, United States, 40504
        • University of Kentucky, Dept of Neurology Sanders Brown Center on Aging
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
        • University of Michigan
    • New York
      • Albany, New York, United States, 12208
        • Neurological Associates of Albany, PC
      • New York, New York, United States, 10032
        • Columbia University
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27103
        • PMG Research of Winston-Salem, LLC
    • Ohio
      • Lakewood, Ohio, United States, 44107
        • Cleveland Clinic, Lou Ruvo Center for Brain Health at Lakewood Hospital
    • Oregon
      • Portland, Oregon, United States, 97210
        • Summit Research Network (Oregon) Inc.
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • New Orleans Center for Clinical Research
    • Texas
      • Dallas, Texas, United States, 75231-4350
        • Kerwin Research Center, LLC
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • University of Virginia Adult Neurology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Male or female, age 50 to 85 years, inclusive at time of consent.
  • Meet criteria for probable dementia with Lewy bodies (DLB) (as defined by the 4th report of the DLB Consortium).
  • Mini-Mental State Examination greater than or equal to (≥)14 and less than or equal to (≤) 26 at Screening Visit.
  • Has experienced visual hallucinations during the past 4 weeks before Screening Visit.
  • If receiving acetylcholinesterase inhibitors (AChEI), must have been on a stable dose for at least 12 weeks before Screening Visit, with no plans for dose adjustment during the study. Treatment-naive participants can be entered into the study but there should be no plans to initiate treatment with AChEIs from Screening to the end of the study.
  • If receiving memantine, must have been on a stable dose for at least 12 weeks before Screening Visit, with no plans for dose adjustment during the study. Treatment naive participants can be entered into the study but there should be no plans to initiate treatment with memantine from Screening to the end of the study.
  • Must have an identified caregiver or informant who is willing and able to provide follow-up information on the participant throughout the course of the study.
  • Provide written informed consent. If a participant lacks capacity to consent in the investigator's opinion, the participant's assent should be obtained, as required in accordance with local laws, regulations and customs, plus the written informed consent of a legal representative should be obtained (capacity to consent and definition of legal representative should be determined in accordance with applicable local laws and regulations). In countries where local laws, regulations, and customs do not permit participants who lack capacity to consent to participate in this study, they will not be enrolled.

Exclusion Criteria:

  • Any neurological condition that may be contributing to cognitive impairment above and beyond those caused by the participant's DLB, including any comorbidities detected by clinical assessment or magnetic resonance imaging (MRI).
  • History of transient ischemic attacks or stroke within 12 months of Screening.
  • Modified Hachinski Ischemic Scale greater than (>) 4.
  • Parkinsonian (extrapyramidal) features with Hoehn and Yahr stage 4 intravenous or higher.
  • Any major psychiatric diagnosis, including schizophrenia, bipolar disorder and current major depressive disorder as per Diagnostic and Statistical Manual of Mental Disorders Fifth Edition.
  • Geriatric Depression Scale score > 8.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Irsenontrine
Participants will be randomized to receive a 50 milligram (mg) once daily oral dose of Irsenontrine for 12 weeks.
Drug: Irsenontrine
Oral hypromellose capsules.
Other Names:
  • E2027
Placebo Comparator: Placebo
Participants will be randomized to receive a 50 mg once daily oral dose of Irsenontrine-matched placebo for 12 weeks.
Drug: Placebo
Oral hypromellose capsules.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in the Montreal Cognitive Assessment (MoCA) Total Score at Week 12 of Treatment
Time Frame: Baseline and Week 12
The MoCA scale is used for detecting cognitive impairment. The scores range between 0 to 30 points; a score of 26 or above was considered normal. Higher values represent a better outcome.
Baseline and Week 12
Number of Participants Based on Clinician's Interview Based Impression of Change Plus Caregiver Input (CIBIC-Plus) Scale at Week 12 of Treatment
Time Frame: Week 12
Number of participants are reported categorized in grades based on the CIBIC-Plus scale. The CIBIC-Plus scale is designed to measure various domains that describe participant function: general, mental/cognitive state, behavior, and activities of daily living. It is a semi-structured global rating derived from a comprehensive interview with the participant and caregiver or informant by an independent rater who has no access to the source data or other psychometric test scores conducted post-randomization as part of the protocol. The CIBIC-Plus was a 7-point scale and scores were: 1 (marked improvement), 2 (moderate improvement), 3 (minimal improvement), 4 (no change), 5 (minimal worsening), 6 (moderate worsening), and 7 (marked worsening). Higher values represent a worse outcome.
Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinician's Global Impression of Change - In Dementia With Lewy Bodies (CGIC-DLB) Scale at Week 12 of Treatment
Time Frame: Week 12
Number of participants are reported categorized in grades based on the CGIC-DLB scale. The CGIC-DLB scale provided an overall clinician-determined summary measure of change from the participant's clinical status that takes into account all available information from the efficacy endpoints (which include cognitive function, non-cognitive symptoms, behavior, and the impact of the symptoms on the participant's ability to function) and safety data. The (CGIC-DLB) was a 7-point scale and scores were: 1 (marked improvement), 2 (moderate improvement), 3 (minimal improvement), 4 (no change), 5 (minimal worsening), 6 (moderate worsening), and 7 (marked worsening). Higher values represent a worse outcome.
Week 12
Mean Change From Baseline in the Cognitive Fluctuation Inventory (CFI) Score at Week 12 of Treatment
Time Frame: Baseline and Week 12
The CFI scale assessed cognitive fluctuation. It evaluates fluctuation in various domains including attention, ability to perform daily functions, orientation, verbal communication and behavior. The score was based on frequency and severity with a score range of 0 to 12. The scale also assessed the degree of caregiver or informant distress engendered by the symptoms. Higher scores indicating greater impairment.
Baseline and Week 12
Mean Change From Baseline in the Mini-Mental State Examination (MMSE) Total Score Week 12 of Treatment
Time Frame: Baseline and Week 12
The MMSE is a 30-point scale that measured orientation to time and place, registration, immediate and delayed recall, attention, language, and drawing. The total score ranges from 0 (most impaired) to 30 (no impairment). The lower score means severe cognitive deficit and higher score indicates better function.
Baseline and Week 12
Mean Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Total Score at Week 12 of Treatment
Time Frame: Baseline and Week 12
The NPI-12 scale assessed the frequency and severity of 12 neuropsychiatric symptoms commonly described in dementia participants: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, nighttime behaviors, and appetite/eating changes. The scale also assessed the degree of caregiver or informant distress engendered by each of the symptoms. The sum of the composite scores for the 12 domains yielded the NPI-12 total score. NPI-12 total score ranged from 0 (minimum severity) to 144 (maximum severity); higher score indicates greater neuropsychiatric disturbance.
Baseline and Week 12
Change From Baseline in NPI-4 Subscore at Week 12
Time Frame: Baseline and Week 12
The NPI scale assesses the frequency and severity of 12 neuropsychiatric symptoms commonly described in dementia participants: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, nighttime behaviors, and appetite/eating changes. NPI-4 is the subscore covering the domains of delusions, hallucinations, apathy and depression. NPI-4 total subscore ranged from 0 to 48, with higher scores indicating a greater neuropsychiatric disturbance.
Baseline and Week 12
Change From Baseline in NPI-10 Subscore at Week 12
Time Frame: Baseline and Week 12
The NPI-10 assessed range of behaviors seen in dementia for both frequency and severity. It is a 10 item questionnaire with the following domains: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/liability and aberrant motor behavior. The total score was a sum of the 10 domains, where the score of each domain was calculated as frequency (scale: 1=occasionally to 4=very frequently)*Severity (scale: 1=Mild to 3=Severe). Each domain has a maximum score of 12 and all domains were equally weighted for total score, the range for total score is 0 to 120. Higher scores indicating a greater neuropsychiatric disturbance.
Baseline and Week 12
Change From Baseline in NPI-D (Caregiver Distress) Total Score at Week 12
Time Frame: Baseline and Week 12
The NPI-D scale assesses the frequency and severity of 12 neuropsychiatric symptoms commonly described in dementia participants: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, nighttime behaviors, and appetite/eating changes. The scale assesses the degree of caregiver distress engendered by each of the symptoms. The caregiver distress (NPI-D) is rated by caregiver based on his or her own stress on a five point scale from 0 to 5, where: 0(no distress), 1(minimal), 2(mild), 3(moderate), 4(moderately severe), 5(very severe or extreme). NPI-D total score is calculated by summing the scores of the 12 sub-scale distress scores. The NPI-D total scores ranges from 0 to 60 with higher scores indicating greater distress.
Baseline and Week 12
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation
Time Frame: From first dose of study drug up to Week 16
A TEAE was defined as an AE that emerged or worsened in severity relative to baseline during treatment or within 28 days after the last dose of study drug. Severe TEAE was defined as inability to work or to perform normal daily activity. A Serious TEAE is any untoward medical occurrence that at any dose: results in death; is life threatening (that is, the participant was at immediate risk of death from the adverse event as it occurred; this does not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death) requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is medically important due to other reasons than the above mentioned criteria. An adverse event (AE) was defined as any untoward medical occurrence in a participant administered an investigational product.
From first dose of study drug up to Week 16
Number of Participants With Orthostatic Hypotension
Time Frame: Week 2, Week 4, Week 6, Week 9 and Week 12
Orthostatic hypotension was defined as drop in standing systolic blood pressure greater than or equal to (>=) 20 Millimeter of mercury (mmHg) compared to supine, or drop in standing diastolic blood pressure >=10 mmHg compared to supine.
Week 2, Week 4, Week 6, Week 9 and Week 12
Number of Participants With Orthostatic Tachycardia
Time Frame: From first dose of study drug up to Week 16
Orthostatic tachycardia by numerical criteria was defined by the following numerical criteria: Standing heart rate (HR) increased by >30 beats/min compared to supine and absolute standing HR was >100 beats/min.
From first dose of study drug up to Week 16
Number of Participants With Markedly Abnormal Laboratory Values
Time Frame: From first dose of study drug up to Week 16
A laboratory value was determined to be a markedly abnormal value if the postbaseline common toxicity criteria grade increased from baseline and the post-baseline grade was greater than or equal to 2.
From first dose of study drug up to Week 16
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Time Frame: From first dose of study drug up to Week 16
From first dose of study drug up to Week 16
Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS)
Time Frame: From first dose of study drug up to Week 16
The C-SSRS (mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories); is an interview-based instrument to systematically assess suicidal ideation and suicidal behavior. C-SSRS assess whether participant experience any of the following: completed suicide; suicide attempt (response of "yes" on "actual attempt"); preparatory acts toward imminent suicidal behavior ("yes" on "preparatory acts or behavior", "aborted attempt" or "interrupted attempt"), suicidal ideation ("yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent ("yes" on "has participant engaged in non-suicidal self-injurious behavior"). Here, number of participants with positive response ("yes") to suicidal behavior or/and Ideation, any non-suicidal self-injurious behavior was reported.
From first dose of study drug up to Week 16
Change From Baseline in Total Score of Unified Parkinson's Disease Rating Scale Part III: Motor Examination (UPDRS-III)
Time Frame: Baseline up to Week 16
The UPDRS scale evaluates extrapyramidal features in motor function in Parkinson's disease. It contains 33 items in 18 categories: (1) speech, (2) facial expression, (3) rigidity, (4) finger tapping, (5) hand movements, (6) supinational and pronation movements of hands, (7) toe tapping, (8) leg agility, (9) arising from chair, (10) gait, (11) freezing of gait, (12) postural stability, (13) posture, (14) body bradykinesia, (15) postural tremor of hands, (16) kinetic tremor of hands, (17) rest tremor amplitude and (18) constancy of rest tremor. Each item is scored 0 to 4, giving a total score range 0 to 132. Higher scores indicating more severe symptoms.
Baseline up to Week 16

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Eisai Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 4, 2018

Primary Completion (Actual)

April 15, 2020

Study Completion (Actual)

April 15, 2020

Study Registration Dates

First Submitted

March 9, 2018

First Submitted That Met QC Criteria

March 9, 2018

First Posted (Actual)

March 15, 2018

Study Record Updates

Last Update Posted (Actual)

August 1, 2022

Last Update Submitted That Met QC Criteria

July 29, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • E2027-G000-201
  • 2017-003728-64 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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