NCT03305809

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).

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
344

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Nov 2017

Geographic Reach
3 countries

77 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 4, 2017

Completed
6 days until next milestone

First Posted

Study publicly available on registry

October 10, 2017

Completed
1 month until next milestone

Study Start

First participant enrolled

November 9, 2017

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 10, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 10, 2020

Completed
1 year until next milestone

Results Posted

Study results publicly available

July 23, 2021

Completed
Last Updated

July 23, 2021

Status Verified

July 1, 2021

Enrollment Period

2.7 years

First QC Date

October 4, 2017

Results QC Date

July 2, 2021

Last Update Submit

July 2, 2021

Conditions

Keywords

Parkinson Disease DementiaParkinson DiseaseDopamineCognitionLewy Body DementiaDementia with Lewy Bodies

Outcome Measures

Primary Outcomes (1)

  • Change From Baseline in the Continuity of Attention (CoA) Composite Score of the Cognitive Drug Research Computerized Cognition Battery (CDR-CCB)

    The CDR-CCB tests is designed to evaluate the effects of novel compounds on the quality of cognitive functioning which includes tests of attention (simple and choice reaction time, digit vigilance), working memory (spatial and numeric) and episodic memory (word recognition, picture recognition). Continuity of attention measures speed and accuracy and is calculated from 3 attentional tasks on the CDR computerized battery tests. For continuity of attention, the score range is -999 to 35. A high score reflects someone able to keep his/her mind on a single task for a prolonged period. A negative change from baseline reflects impairment compared to baseline. Data presented are model-based bayesian posterior mean response rates with 95% credible interval.

    Baseline, Week 12

Secondary Outcomes (19)

  • Change From Baseline on the Alzheimer's Disease Cooperative Study-Clinician Global Impression of Change (ADCS-CGIC) Score

    Baseline, Week 12

  • Change From Baseline on the CDR-CCB Power of Attention (PoA) Composite Score

    Baseline, Week 12

  • Change From Baseline in the 13-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13)

    Baseline, Week 12

  • Change From Screening in the Montreal Cognitive Assessment (MoCA) Score

    Screening (Baseline), Week 12

  • Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score and Individual Item Scores

    Baseline, Week 12

  • +14 more secondary outcomes

Study Arms (4)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

10 milligram (mg) LY3154207

EXPERIMENTAL

Participants received 10 mg LY3154207 administered orally QD.

Drug: LY3154207

30 mg LY3154207

EXPERIMENTAL

Participants received 30 mg LY3154207 administered orally QD.

Drug: LY3154207

75 mg LY3154207

EXPERIMENTAL

Participants received 75 mg LY3154207 administered orally QD.

Drug: LY3154207

Interventions

Administered orally.

10 milligram (mg) LY315420730 mg LY315420775 mg LY3154207

Administered orally.

Placebo

Eligibility Criteria

Age40 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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:
  • 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.
  • Each of the 3 systolic BP measurement must be less than 180 mmHg
  • Participants ≥60 years old:
  • 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.
  • 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.
  • +3 more criteria

You may not qualify if:

  • 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.
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (77)

University of Alabama Birmingham

Birmingham, Alabama, 35233, United States

Location

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

Mayo Clinic of Scottsdale

Scottsdale, Arizona, 85259, United States

Location

Banner Sun Health Research Institute

Sun City, Arizona, 85351, United States

Location

University of Arizona Health Sciences

Tucson, Arizona, 85724, United States

Location

Parkinson'S & Movement Disorder Institute

Fountain Valley, California, 92708, United States

Location

University of CA, Irvine

Irvine, California, 92697, United States

Location

Collaborative Neuroscience Network - CNS

Long Beach, California, 90806, United States

Location

University of Southern California School of Medicine

Los Angeles, California, 90033, United States

Location

Pacific Neuroscience Medical Group

Oxnard, California, 93030, United States

Location

Stanford Neuroscience Health Center

Palo Alto, California, 94304, United States

Location

SC3 Research Group Inc Pasadena

Pasadena, California, 91105, United States

Location

SC3 Research Group Inc Reseda

Reseda, California, 91335, United States

Location

University of California, Davis - Health Systems

Sacramento, California, 95817, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Denver Neurological Research

Denver, Colorado, 80210, United States

Location

Rocky Mountain Movement Disorders Center

Englewood, Colorado, 80113, United States

Location

New England Institute for Clinical Research

Stamford, Connecticut, 06905, United States

Location

Hartford Healthcare Chase Movement Disorders Center

Vernon, Connecticut, 06066, United States

Location

Christiana Care Health Service

Newark, Delaware, 19713, United States

Location

Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

JEM Research Institute

Atlantis, Florida, 33462, United States

Location

Visionary Investigators Network

Aventura, Florida, 33180, United States

Location

Parkinson's Disease and Movement Disorders

Boca Raton, Florida, 33486, United States

Location

Norman Fixel Institute for Neurological Diseases (FIND)

Gainesville, Florida, 32608, United States

Location

ClinCloud, LLC

Maitland, Florida, 32751, United States

Location

Visionary Investigators Network

Miami, Florida, 33133, United States

Location

Suncoast Research Group, LLC

Miami, Florida, 33135, United States

Location

VIN - Victor Faradji

Miami, Florida, 33176, United States

Location

Collier Neurologic Specialists

Naples, Florida, 34105, United States

Location

Renstar Medical Research

Ocala, Florida, 34470, United States

Location

Compass Research

Orlando, Florida, 32806, United States

Location

Neurology Associates of Ormond Beach

Ormond Beach, Florida, 32174, United States

Location

Visionary Investigators Network -VIN-Margarita Almeida

Pembroke Pines, Florida, 33026, United States

Location

Axiom Research

Tampa, Florida, 33609, United States

Location

Emory University

Atlanta, Georgia, 30329, United States

Location

Atlanta Center of Medical Research

Atlanta, Georgia, 30331, United States

Location

Central DuPage Hospital

Winfield, Illinois, 60190, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

Josephson Wallack Munshower Neurology

Indianapolis, Indiana, 46256, United States

Location

University of Kansas School of Medicine

Kansas City, Kansas, 66160, United States

Location

Maine Neurology

Scarborough, Maine, 04074, United States

Location

New England Neurological Associates, PC

Methuen, Massachusetts, 01844, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

QUEST Research Institute

Farmington Hills, Michigan, 48334, United States

Location

Clinical Research Professionals

Chesterfield, Missouri, 63005, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Cleveland Clinic of Las Vegas

Las Vegas, Nevada, 89106, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756-0001, United States

Location

The Cognitive and Research Center of NJ

Springfield, New Jersey, 07081, United States

Location

Bio Behavioral Health

Toms River, New Jersey, 08755, United States

Location

Dent Neurological Institute

Amherst, New York, 14226, United States

Location

Alzheimer's Disease and Memory Disorders Center

Buffalo, New York, 14203, United States

Location

Adirondack Medical Research

Glens Falls, New York, 12801, United States

Location

Parker Jewish Insititue for Heatlh Care and Rehabilition

New Hyde Park, New York, 11040, United States

Location

NYU Langone

New York, New York, 10016, United States

Location

Carolinas Healthcare System

Charlotte, North Carolina, 28207, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Penn State Univ. Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Pennsylvania Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Abington Neurological Associates

Willow Grove, Pennsylvania, 19090, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Texas Neurology, PA

Dallas, Texas, 75214, United States

Location

Neurology Consultants of Dallas, PA

Dallas, Texas, 75243, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Houston Methodist Research Ins

Houston, Texas, 77030, United States

Location

Sentara Neurology Specialists

Virginia Beach, Virginia, 23456, United States

Location

Northwest Clinical Research Center

Bellevue, Washington, 98007-4209, United States

Location

Evergreen Professional Plaza

Kirkland, Washington, 98034, United States

Location

University of Wisconsin-Madison Hospital and Health Clinic

Madison, Wisconsin, 53705, United States

Location

Toronto Memory Program

Toronto, Ontario, M3B 2S7, Canada

Location

Ottawa Hospital Research Institute

Ottawa, K1Y 4E9, Canada

Location

Cortex, PSC

Las Piedras, PR, 00771, Puerto Rico

Location

Instituto de Neurologia Dra. Ivonne Fraga

San Juan, PR, 00918, Puerto Rico

Location

University of Puerto Rico

San Juan, PR, 00936, Puerto Rico

Location

Santa Cruz Behavioral PSC

Bayamón, 00961-6911, Puerto Rico

Location

Related Publications (2)

  • 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.

  • 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.

Related Links

MeSH Terms

Conditions

Lewy Body DiseaseParkinson Disease

Interventions

LY3154207

Condition Hierarchy (Ancestors)

Parkinsonian DisordersBasal Ganglia DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesDementiaMovement DisordersSynucleinopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental Disorders

Results Point of Contact

Title
Chief Medical Officer
Organization
Eli Lilly and Company

Study Officials

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

    Eli Lilly and Company

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
GT60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 4, 2017

First Posted

October 10, 2017

Study Start

November 9, 2017

Primary Completion

July 10, 2020

Study Completion

July 10, 2020

Last Updated

July 23, 2021

Results First Posted

July 23, 2021

Record last verified: 2021-07

Data Sharing

IPD Sharing
Will share

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Shared Documents
STUDY PROTOCOL, SAP, CSR
Time Frame
Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
Access Criteria
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
More information

Locations