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)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03305809
• Date of registration: 04/10/2017
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company
• Public title: 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
• Scientific title: Effect of LY3154207 on Cognition in Mild-to-Moderate Dementia Due to Lewy Body Dementia (LBD) Associated With Idiopathic Parkinson's Disease (PD) or Dementia With Lewy Bodies (DLB)
• Date of first enrolment: November 9, 2017
• Target sample size: 344
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03305809
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

Canada, China, Puerto Rico, United States

Contacts

• Name: Call 1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
• Affiliation: Eli Lilly and Company

Key inclusion & exclusion 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.



Age minimum: 40 Years
Age maximum: 85 Years
Gender: All

Health Condition(s) or Problem(s) studied

Lewy Body Dementia

Intervention(s)

Drug: LY3154207

Drug: Placebo

Primary Outcome(s)

Change from Baseline in the Continuity of Attention (CoA) Composite Score of the Cognitive Drug Research Computerized Cognition Battery (CDR-CCB) [Time Frame: Baseline, Week 12]

Secondary Outcome(s)

Change from Baseline in the Neuropsychiatric Inventory (NPI) Total Score [Time Frame: Baseline, Week 12]

Change from Baseline in the Penn Parkinson's Daily Activities Questionnaire-15 (PDAQ-15) Total Score [Time Frame: Baseline, Week 12]

Change from Baseline in the Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score [Time Frame: Baseline, Week 12]

Change from Baseline in SBP to 8 Hours Post Dose [Time Frame: Baseline, 8 Hours Post Dose]

Change from Baseline in the Epworth Sleepiness Scale (ESS) Score [Time Frame: Baseline, Week 12]

Change from Baseline on the Alzheimer's Disease Cooperative Study-Clinician Global Impression of Change (ADCS-CGIC) Score [Time Frame: Baseline, Week 12]

Change from Baseline in Pulse Rate to 8 Hours Post Dose [Time Frame: Baseline, 8 Hours Post Dose]

Change from Baseline in Pulse Rate to Week 12 [Time Frame: Baseline, Week 12]

Change from Baseline on the CDR-CCB Power of Attention (PoA) Composite Score [Time Frame: Baseline, Week 12]

Change from Week 12 in the Physician Withdrawal Checklist (PWC)-20 Total Score [Time Frame: Week 12, Follow-up (2 Days after Week 12 Visit)]

Change from Baseline in Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency Test Score [Time Frame: Baseline, Week 12]

Change from Screening in the Montreal Cognitive Assessment (MoCA) Score [Time Frame: Screening, Week 12]

Pharmacokinetics (PK): Steady-State Trough Plasma Concentrations of LY3154207 [Time Frame: Week 12]

Change from Baseline in the 13-item Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog13) [Time Frame: Baseline, Week 12]

Change from Baseline in Systolic Blood Pressure (SBP) to Week 12 [Time Frame: Baseline, Week 12]

Secondary ID(s)

16261

I7S-MC-HBEH

Source(s) of Monetary Support

Please refer to primary and secondary sponsors