A Study of LY3154207 in Participants With Dementia Due to Lewy Body Dementia (LBD) Associated With Idiopathic Parkinson's Disease (PD) or Dementia With Lewy Bodies (DLB)

NCT ID: NCT03305809

Last Updated: 2021-07-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 344 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-09
• Study Completion Date: 2020-07-10

Brief Summary

A randomized placebo-controlled trial to evaluate the safety and efficacy of three doses of study drug LY3154207 treated for 12 weeks in participants with mild-to-moderate dementia associated with LBD (PDD or DLB).

Conditions

Lewy Body Dementia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Participants received placebo administered orally once a day (QD).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Administered orally.

10 milligram (mg) LY3154207

Participants received 10 mg LY3154207 administered orally QD.

Group Type: EXPERIMENTAL

LY3154207

Intervention Type: DRUG

Administered orally.

30 mg LY3154207

Participants received 30 mg LY3154207 administered orally QD.

Group Type: EXPERIMENTAL

LY3154207

Intervention Type: DRUG

Administered orally.

75 mg LY3154207

Participants received 75 mg LY3154207 administered orally QD.

Group Type: EXPERIMENTAL

LY3154207

Intervention Type: DRUG

Administered orally.

Interventions

LY3154207

Administered orally.

Intervention Type: DRUG

Placebo

Administered orally.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Have dementia as defined by a decline in cognitive function, which in the opinion of the investigator has resulted in functional impairment.
• Meet diagnostic criteria for PD per MDS criteria or DLB per 4th Consensus Report of the DLB Consortium.
• Have a score on the MoCA of 10 - 23.
• Are Modified Hoehn and Yahr Stages 0 - 4.
• Have a blood pressure (BP) or pulse rate at screening and randomization, as determined by three sequential BP/pulse rate measurements in a seated position:

• Participants <60 years old:

1. A mean systolic BP less than or equal to 140 millimeters of mercury (mmHg), a mean diastolic BP less than or equal to 90 mmHg and a mean pulse rate less than or equal 90 beats/minute in a seated position.

2. Each of the 3 systolic BP measurement must be less than 180 mmHg

• Participants ≥60 years old:

1. A mean systolic BP less than or equal to 150 mmHg, a mean diastolic BP less than or equal to 90 mmHg and a mean pulse rate less than or equal to 90 beats/min in a seated position.

2. Each of the 3 systolic BP measurement must be less than 180 mmHg

• If on anti-parkinsonian agents, participants must be on stable dosage for at least 3 weeks prior to screening, and should remain on stable doses during the course of the study.
• If on medications affecting cognition (rivastigmine, galantamine, donepezil, memantine), participants must be on stable dosage for at least 3 weeks prior to screening and should remain at a stable dosage during the course of the study.
• If on antidepressant medications, participants must be on stable dosage for at least 3 weeks prior to screening and should remain at a stable dosage during the course of the study.
• If on clozapine, quetiapine, and pimavanserin to address drug induced or disease related psychosis, participants must be on stable dosage for 3 weeks prior to screening and should remain at a stable dosage during the course of the study.
• If on antihypertensive medications, participants must be on stable dosage for at least 3 weeks prior to screening.
• Men should use appropriate contraception.
• All participants must have a reliable caregiver who is in frequent contact with the participant (defined as at least 10 hours per week) and will accompany the participant to screening, baseline, day 7, day 42, day 84 and follow-up.

Exclusion Criteria

• Are women of childbearing potential.
• Have significant central nervous system or psychiatric disease, other than PD or DLB, that in the investigator's opinion may affect cognition or the ability to complete the study.
• Have a history in the last 6 months of transient ischemic attacks or ischemic stroke.
• Have a history of intra cerebral hemorrhage due to hypertension.
• Have a history of hypertensive encephalopathy.
• Have atypical or secondary parkinsonism due to drugs (e.g., antipsychotics) or disease (such as progressive supranuclear palsy, essential tremor, multiple system atrophy (e.g. striatonigral degeneration, olivopontocerebellar atrophy), or postencephalitic parkinsonism).
• Have a current implantable intracranial stimulator or history of intracranial ablation surgery (e.g., subthalamic, globus pallidus-internal segment [GPi]).
• Have a history of substance abuse within the past 1 year (drug categories defined by the Diagnostic and Statistical Manual of Mental Disorder, 5th Edition [DSM-5], and/or substance dependence within the past 1 year, not including caffeine and nicotine.
• Have a serious or unstable medical illness, other than idiopathic LBD (PDD or DLB), including cardiovascular, hepatic, respiratory, hematologic, endocrinologic, neurologic, or renal disease, or clinically significant laboratory or electrocardiogram (ECG) abnormality as determined by the investigator.

• Have a history in the last 6 months of exertional angina, unstable angina, myocardial infarction, and acute coronary syndrome.
• Have a history of heart failure of either New York Heart Association Class III or IV.
• A history of additional risk factors for Torsades de Pointes (TdP; [e.g., chronic hypokalemia, family history of Long QT Syndrome]).
• Participants with acute liver disease (e.g. acute viral hepatitis, alcoholic hepatitis); participants with a known chronic liver disease (e.g. hepatitis B, C, alcoholic liver disease, cirrhosis); alanine aminotransferase (ALT) or aspartate aminotransferase (AST) equal to or higher than 2X upper limit of normal (ULN); total bilirubin (TBL) equal to or higher than 1.5X ULN; (except for participants with Gilbert's syndrome); or alkaline phosphatase (ALP) equal to or higher than 2X ULN.
• Participants have answered 'yes' to either Question 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) or Question 5 (Active Suicidal Ideation with Specific Plan and Intent) on the "Suicidal Ideation" portion of the Columbia Suicide Severity Rating Scale (C-SSRS)- Children's version, or answer "yes" to any of the suicide-related behaviors (actual attempt, interrupted attempt, aborted attempt).
• Have used antipsychotic medications, with the exception of clozapine, quetiapine, pimavanserin in the 6 months prior to screening and at any time during the course of the study.
• Have used anticholinergics trihexyphenidyl and benztropine in the 4 weeks prior to screening and at any time during the course of the study.
• Have motor conditions for which the antiparkinsonian treatment is expected to change during the course of the study, as well as unpredictable motor fluctuations that in the investigator's opinion would interfere with administering assessments.
• Are taking any medications or food, herbal or dietary supplements that are inhibitors (e.g., ketoconazole, grapefruit juice), or strong/moderate inducers of cytochrome P450 3A4 (CYP3A4) (e.g., rifampicin) or are unable or unwilling to discontinue usage of them 4 weeks prior to first dose of study drug.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Call 1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

University of Alabama Birmingham

Birmingham, Alabama, United States

Barrow Neurological Institute

Phoenix, Arizona, United States

Mayo Clinic of Scottsdale

Scottsdale, Arizona, United States

Banner Sun Health Research Institute

Sun City, Arizona, United States

University of Arizona Health Sciences

Tucson, Arizona, United States

Parkinson'S & Movement Disorder Institute

Fountain Valley, California, United States

University of CA, Irvine

Irvine, California, United States

Collaborative Neuroscience Network - CNS

Long Beach, California, United States

University of Southern California School of Medicine

Los Angeles, California, United States

Pacific Neuroscience Medical Group

Oxnard, California, United States

Stanford Neuroscience Health Center

Palo Alto, California, United States

SC3 Research Group Inc Pasadena

Pasadena, California, United States

SC3 Research Group Inc Reseda

Reseda, California, United States

University of California, Davis - Health Systems

Sacramento, California, United States

University of Colorado Hospital

Aurora, Colorado, United States

Denver Neurological Research

Denver, Colorado, United States

Rocky Mountain Movement Disorders Center

Englewood, Colorado, United States

New England Institute for Clinical Research

Stamford, Connecticut, United States

Hartford Healthcare Chase Movement Disorders Center

Vernon, Connecticut, United States

Christiana Care Health Service

Newark, Delaware, United States

Georgetown University Hospital

Washington D.C., District of Columbia, United States

JEM Research Institute

Atlantis, Florida, United States

Visionary Investigators Network

Aventura, Florida, United States

Parkinson's Disease and Movement Disorders

Boca Raton, Florida, United States

Norman Fixel Institute for Neurological Diseases (FIND)

Gainesville, Florida, United States

ClinCloud, LLC

Maitland, Florida, United States

Visionary Investigators Network

Miami, Florida, United States

Suncoast Research Group, LLC

Miami, Florida, United States

VIN - Victor Faradji

Miami, Florida, United States

Collier Neurologic Specialists

Naples, Florida, United States

Renstar Medical Research

Ocala, Florida, United States

Compass Research

Orlando, Florida, United States

Neurology Associates of Ormond Beach

Ormond Beach, Florida, United States

Visionary Investigators Network -VIN-Margarita Almeida

Pembroke Pines, Florida, United States

Axiom Research

Tampa, Florida, United States

Emory University

Atlanta, Georgia, United States

Atlanta Center of Medical Research

Atlanta, Georgia, United States

Central DuPage Hospital

Winfield, Illinois, United States

Indiana University School of Medicine

Indianapolis, Indiana, United States

Josephson Wallack Munshower Neurology

Indianapolis, Indiana, United States

University of Kansas School of Medicine

Kansas City, Kansas, United States

Maine Neurology

Scarborough, Maine, United States

New England Neurological Associates, PC

Methuen, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

QUEST Research Institute

Farmington Hills, Michigan, United States

Clinical Research Professionals

Chesterfield, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

Cleveland Clinic of Las Vegas

Las Vegas, Nevada, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

The Cognitive and Research Center of NJ

Springfield, New Jersey, United States

Bio Behavioral Health

Toms River, New Jersey, United States

Dent Neurological Institute

Amherst, New York, United States

Alzheimer's Disease and Memory Disorders Center

Buffalo, New York, United States

Adirondack Medical Research

Glens Falls, New York, United States

Parker Jewish Insititue for Heatlh Care and Rehabilition

New Hyde Park, New York, United States

NYU Langone

New York, New York, United States

Carolinas Healthcare System

Charlotte, North Carolina, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Penn State Univ. Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Abington Neurological Associates

Willow Grove, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Texas Neurology, PA

Dallas, Texas, United States

Neurology Consultants of Dallas, PA

Dallas, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

Houston Methodist Research Ins

Houston, Texas, United States

Sentara Neurology Specialists

Virginia Beach, Virginia, United States

Northwest Clinical Research Center

Bellevue, Washington, United States

Evergreen Professional Plaza

Kirkland, Washington, United States

University of Wisconsin-Madison Hospital and Health Clinic

Madison, Wisconsin, United States

Toronto Memory Program

Toronto, Ontario, Canada

Ottawa Hospital Research Institute

Ottawa, , Canada

Cortex, PSC

Las Piedras, PR, Puerto Rico

Instituto de Neurologia Dra. Ivonne Fraga

San Juan, PR, Puerto Rico

University of Puerto Rico

San Juan, PR, Puerto Rico

Santa Cruz Behavioral PSC

Bayamón, , Puerto Rico

Countries

United States; Canada; Puerto Rico

References

Chen C, Kowahl NR, Rainaldi E, Burq M, Munsie LM, Battioui C, Wang J, Biglan K, Marks WJ Jr, Kapur R. Wrist-worn sensor-based measurements for drug effect detection with small samples in people with Lewy Body Dementia. Parkinsonism Relat Disord. 2023 Apr;109:105355. doi: 10.1016/j.parkreldis.2023.105355. Epub 2023 Mar 4.

Reference Type: DERIVED

PMID: 36905719 (View on PubMed)

Wilbraham D, Biglan KM, Svensson KA, Tsai M, Kielbasa W. Safety, Tolerability, and Pharmacokinetics of Mevidalen (LY3154207), a Centrally Acting Dopamine D1 Receptor-Positive Allosteric Modulator (D1PAM), in Healthy Subjects. Clin Pharmacol Drug Dev. 2021 Apr;10(4):393-403. doi: 10.1002/cpdd.874. Epub 2020 Oct 7.

Reference Type: DERIVED

PMID: 33029934 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.lillytrialguide.com/en-US/studies/parkinson-s-disease-dementia/HBEH#?postal=

A Study of LY3154207 in Participants With Dementia Due to Lewy Body Dementia (LBD) Associated With Idiopathic Parkinson's Disease (PD) or Dementia With Lewy Bodies (DLB) (PRESENCE)

Other Identifiers

I7S-MC-HBEH

Identifier Type: OTHER

Identifier Source: secondary_id

16261

Identifier Type: -

Identifier Source: org_study_id