Clinical trial NCT03467152: Study To Evaluate the Efficacy, Safety and Tolerability of E2027 (Hereinafter Referred to as Irsenontrine) in Participants With Dementia With Lewy Bodies
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dementia With Lewy Bodies
Keywords: Irsenontrine
Montreal Cognitive Assessment
Neuropsychiatric Inventory
Mini-Mental State Examination
Cognitive Fluctuation Inventory
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2018-03-15
Enrollment: 326
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in the Montreal Cognitive Assessment (MoCA) Total Score at Week 12 of Treatment
timeFrame: Baseline and Week 12
measure: Number of Participants Based on Clinician's Interview Based Impression of Change Plus Caregiver Input (CIBIC-Plus) Scale at Week 12 of Treatment
timeFrame: Week 12
Secondary outcomes:
measure: Clinician's Global Impression of Change - In Dementia With Lewy Bodies (CGIC-DLB) Scale at Week 12 of Treatment
timeFrame: Week 12
measure: Mean Change From Baseline in the Cognitive Fluctuation Inventory (CFI) Score at Week 12 of Treatment
timeFrame: Baseline and Week 12
measure: Mean Change From Baseline in the Mini-Mental State Examination (MMSE) Total Score Week 12 of Treatment
timeFrame: Baseline and Week 12
measure: Mean Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Total Score at Week 12 of Treatment
timeFrame: Baseline and Week 12
measure: Change From Baseline in NPI-4 Subscore at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in NPI-10 Subscore at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in NPI-D (Caregiver Distress) Total Score at Week 12
timeFrame: Baseline and Week 12
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation
timeFrame: From first dose of study drug up to Week 16
measure: Number of Participants With Orthostatic Hypotension
timeFrame: Week 2, Week 4, Week 6, Week 9 and Week 12
measure: Number of Participants With Orthostatic Tachycardia
timeFrame: From first dose of study drug up to Week 16
measure: Number of Participants With Markedly Abnormal Laboratory Values
timeFrame: From first dose of study drug up to Week 16
measure: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
timeFrame: From first dose of study drug up to Week 16
measure: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: From first dose of study drug up to Week 16
measure: Change From Baseline in Total Score of Unified Parkinson's Disease Rating Scale Part III: Motor Examination (UPDRS-III)
timeFrame: Baseline up to Week 16
Other outcomes:
Locations:
city: Sun City
country: United States
facility: Banner Sun Health Research Institute
state: Arizona
city: Anaheim
country: United States
facility: Advanced Research Center Inc
state: California
city: Fountain Valley
country: United States
facility: Parkinsons and Movement Disorders Institute
state: California
city: San Diego
country: United States
facility: Paradigm Clinical Research Centers, Inc
state: California
city: Santa Ana
country: United States
facility: Syrentis Clinical Research
state: California
city: Stamford
country: United States
facility: New England Institute for Clinical Research
state: Connecticut
city: Miami
country: United States
facility: Miami Jewish Health-Clinical Research
state: Florida
city: Miami
country: United States
facility: Elias Research Associates (Allied Biomedical Research Institute)
state: Florida
city: Miami
country: United States
facility: Pharmax Research of South Florida; Elias Research Associates
state: Florida
city: Orlando
country: United States
facility: Compass Research-Bioclinica
state: Florida
city: Ormond Beach
country: United States
facility: Neurology Associates of Ormond Beach
state: Florida
city: Palm Beach Gardens
country: United States
facility: Advanced Research Consultants, Inc.
state: Florida
city: Pensacola
country: United States
facility: Anchor Neuroscience
state: Florida
city: The Villages
country: United States
facility: Compass Research-Bioclinica
state: Florida
city: Indianapolis
country: United States
facility: Indiana University, Dept of Neurology
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky, Dept of Neurology Sanders Brown Center on Aging
state: Kentucky
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Albany
country: United States
facility: Neurological Associates of Albany, PC
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Winston-Salem
country: United States
facility: PMG Research of Winston-Salem, LLC
state: North Carolina
city: Lakewood
country: United States
facility: Cleveland Clinic, Lou Ruvo Center for Brain Health at Lakewood Hospital
state: Ohio
city: Portland
country: United States
facility: Summit Research Network (Oregon) Inc.
state: Oregon
city: Knoxville
country: United States
facility: New Orleans Center for Clinical Research
state: Tennessee
city: Dallas
country: United States
facility: Kerwin Research Center, LLC
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Adult Neurology
state: Virginia
city: Vandœuvre-lès-Nancy
country: France
facility: CHRU Nancy- CMRR de lorraine Hôpital de Brabois-Service de Gériatrie
state: Meurthe-et-Moselle
city: Lyon
country: France
facility: Centre de Recherche Clinique - Viellissement-Cerveau-Fragilite (CRC-VCF), Hopital des Charpennes
state: Villeurbanne
city: Lille
country: France
facility: Centre Memoire du CHRU de Lille
city: Lyon
country: France
facility: Hopital Neurologique de Lyon
city: Marseille
country: France
facility: University Hospital de la Timone
city: Strasbourg
country: France
facility: Centre d'Investigation Clinique (CIC) Hopitaux universitaires Strasbourg HOPITAL DE HAUTEPIERRE - BATIMENT AX5
city: Berlin
country: Germany
facility: Eisai Trial Site #3
city: Kassel
country: Germany
facility: Eisai Trial Site #1
city: Westerstede
country: Germany
facility: Eisai Trial Site #2
city: Chieti
country: Italy
facility: Universita Chieti, CeSI Met
city: Padova
country: Italy
facility: Clinica Neurologica Azienda Ospedaliera di Padova
city: Chiba-shi
country: Japan
facility: Eisai Trial Site #20
state: Chiba
city: Fukuoka-shi
country: Japan
facility: Eisai Trial Site #17
state: Fukuoka
city: Fujioka-shi
country: Japan
facility: Eisai Trial Site #8
state: Gunma
city: Maebashi-shi
country: Japan
facility: Eisai Trial Site #12
state: Gunma
city: Miyoshi-shi
country: Japan
facility: Eisai Trial Site #14
state: Hiroshima
city: Otake-shi
country: Japan
facility: Eisai Trial Site #4
state: Hiroshima
city: Himeji-shi
country: Japan
facility: Eisai Trial Site #2
state: Hyogo
city: Yokohama-shi
country: Japan
facility: Eisai Trial Site #23
state: Kanagawa
city: Kumamoto-shi
country: Japan
facility: Eisai Trial Site #11
state: Kumamoto
city: Nishisonogigun
country: Japan
facility: Eisai Trial Site #5
state: Nagasaki
city: Nagaoka-shi
country: Japan
facility: Eisai Trial Site #9
state: Niigata
city: Kurashiki-shi
country: Japan
facility: Eisai Trial Site #3
state: Okayama
city: Naniwa-ku
country: Japan
facility: Eisai Trial Site #1
state: Osaka
city: Sakai-ku, Sakai-shi
country: Japan
facility: Eisai Trial Site #16
state: Osaka
city: Suita-shi
country: Japan
facility: Eisai Trial Site #24
state: Osaka
city: Suita-shi
country: Japan
facility: Eisai Trial Site #13
state: Osaka
city: Kanzaki-gun
country: Japan
facility: Eisai Trial Site #6
state: Saga
city: Bunkyo-ku
country: Japan
facility: Eisai Trial Site #10
state: Tokyo
city: Mitaka-shi
country: Japan
facility: Eisai Trial Site #22
state: Tokyo
city: Setagaya-Ku
country: Japan
facility: Eisai Trial Site #18
state: Tokyo
city: Yanai-shi
country: Japan
facility: Eisai Trial Site #19
state: Yamaguchi
city: Hiroshima
country: Japan
facility: Eisai Trial Site #25
city: Osaka
country: Japan
facility: Eisai Trial Site #21
city: Terrassa
country: Spain
facility: Hospital Mutua de Terrassa
state: Barcelona
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda
state: Madrid
city: Barcelona
country: Spain
facility: Institut Internacional de Neurociències Aplicades
city: Barcelona
country: Spain
facility: Fundacio ACE
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Crowborough
country: United Kingdom
facility: Dementia Research Unit
state: East Sussex
city: Southampton
country: United Kingdom
facility: Memory Assessment and Research Centre, Moorgreen Hospital
state: Hampshire
city: Dundee
country: United Kingdom
facility: Clinical Research Centre (CRC)
state: Scotland
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
state: Scotland
city: Isleworth
country: United Kingdom
facility: West London Mental Health Trust
city: London
country: United Kingdom
facility: Kings College
city: London
country: United Kingdom
facility: Cognition Health
city: Manchester
country: United Kingdom
facility: Manchester Mental Health and Social Care Trust
city: Newcastle
country: United Kingdom
facility: Newcastle General Hospital
Study officials:
References: