Purpose

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).

Condition

Eligibility

Eligible Ages
Between 40 Years and 85 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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:
  • 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.
  • 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.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
LY3154207 High Dose
LY3154207 administered orally.
  • Drug: LY3154207
    Administered orally.
Experimental
LY3154207 Mid Dose
LY3154207 administered orally.
  • Drug: LY3154207
    Administered orally.
Experimental
LY3154207 Low Dose
LY3154207 administered orally.
  • Drug: LY3154207
    Administered orally.
Placebo Comparator
Placebo
Placebo administered orally.
  • Drug: Placebo
    Administered orally.

Recruiting Locations

Georgetown University Hospital
Washington, District of Columbia 20007
Contact:
202-444-6087

More Details

NCT ID
NCT03305809
Status
Recruiting
Sponsor
Eli Lilly and Company

Study Contact

There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or
1-317-615-4559
Clinicaltrials.gov@lilly.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.