Relapse Prevention Study of Pimavanserin in Dementia-related Psychosis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of pimavanserin compared to placebo in preventing relapse of psychotic symptoms in subjects with dementia-related psychosis who responded to 12 weeks of open label pimavanserin treatment.

Official Title
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A Double-blind, Placebo-controlled, Relapse Prevention Study of Pimavanserin for the Treatment of Hallucinations and Delusions Associated With Dementia-related Psychosis

Conditions
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Dementia-related Psychosis

Intervention / Treatment
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* Drug: Placebo
* Drug: Pimavanserin 34 mg
* Drug: Pimavanserin 20 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets criteria for All-cause Dementia according to NIA-AA guidelines Meets clinical criteria for one of the following disorders: Dementia associated with Parkinson's disease, Dementia with Lewy bodies, Possible or probable Alzheimer's disease, Frontotemporal degeneration spectrum disorders, Vascular dementia Has an MMSE score ≥6 and ≤24 Has had psychotic symptoms for at least 2 months Must be on a stable does of cholinesterase inhibitor or memantine, if applicable If the subject is female, she must not be pregnant or breastfeeding. She must also be of non-childbearing potential or must agree to use a clinically acceptable method of contraception for the duration of the study Exclusion Criteria: Has psychotic symptoms that are primarily attributable to a condition other than dementia Has had a recent major depressive episode Has experienced suicidal ideation or behavior within 3 months prior to study enrollment Has evidence of a non-neurologic medical comorbidity or medication use that could substantially impair cognition Has a history of ischemic stroke within the last 12 months or any evidence of hemorrhagic stroke Has a known history of cerebral amyloid angiopathy (CAA), epilepsy, CNS neoplasm, or unexplained syncope Has any of the following: greater than New York Heart Association (NYHA) Class 2 congestive heart failure, Grade 2 or greater angina pectoris, sustained ventricular tachycardia, ventricular fibrillation, torsade de pointes, syncope due to an arrhythmia, an implantable cardiac defibrillator Had a myocardial infarction within the last 6 months Has a known personal or family history or symptoms of long QT syndrome Has a significant unstable medical condition that could interfere with subject's ability to complete the study or comply with study procedures Requires treatment with a medication or other substance that is prohibited by the protocol Additional inclusion/exclusion criteria apply. Subjects will be evaluated at screening to ensure that all criteria for study participation are met.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo, tablets, once daily by mouth<br>|
| Experimental: Drug - Pimavanserin<br> | Drug: Pimavanserin 34 mg<br>* Pimavanserin 34 mg total daily dose, tablets, once daily by mouth<br>Drug: Pimavanserin 20 mg<br>* Pimavanserin 20 mg total daily dose, tablets, once daily by mouth<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time From Randomization to Relapse in the Double-blind (DB) Period | The time from randomization to relapse in the DB period was compared between treatment groups using a Cox regression model. The treatment effect was measured by the hazard ratio (HR). Relapse was defined as (1) ≥30% increase in SAPS-H+D total score from DB baseline (BL) and CGI-I score ≥6 relative to DB BL, (2) treatment with antipsychotic for dementia-related delusions/hallucinations, (3) treatment/study discontinuation due to lack of efficacy, and/or (4) hospitalization for worsening dementia-related psychosis. SAPS-H+D is a 20-item scale; the total score is the sum of the 20 item scores (range 0-100); higher scores denote more severe symptoms. CGI-I is a clinician-rated 7-point scale to rate improvement in hallucinations/delusions relative to BL (range 1-7); higher scores denote less improvement or worsening. A pre-specified IA was conducted after accrual of 40 adjudicated relapse events. The prespecified stopping criterion was met; the study was stopped for efficacy. | From randomization in the DB period through 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time From Randomization to Discontinuation From the DB Period for Any Reason | The endpoint of time from randomization to discontinuation from the DB period for any reason (other than termination of the study by the sponsor) was compared between treatment groups using a Cox regression model. The treatment effect was measured by the HR. | From randomization in the DB period through 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dementia, Dementia-related psychosis, Dementia associated with Parkinson's disease, Dementia with Lewy bodies, Alzheimer's disease, Behavioral variant frontotemporal dementia, Progressive supranuclear palsy, Corticobasal degeneration, Vascular dementia, Hallucinations, Delusions, Psychosis