A Safety Study of Pimavanserin in Adult and Elderly Subjects Experiencing Neuropsychiatric Symptoms Related to Neurodegenerative Disease

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability of pimavanserin compared to placebo in adult and elderly subjects with neuropsychiatric symptoms related to neurodegenerative disease.

Official Title
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A Phase 3b, Multicenter, Randomized, Double-blind, Placebo-controlled, Safety Study of Pimavanserin Therapy in Adult and Elderly Subjects Experiencing Neuropsychiatric Symptoms Related to Neurodegenerative Disease

Conditions
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Neuropsychiatric Symptoms Related to Neurodegenerative Disease

Intervention / Treatment
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* Drug: Pimavanserin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Can understand the nature of the trial and protocol requirements and provide written informed consent. If the subject is deemed not competent to provide informed consent, the following requirements for consent must be met: The subject's legally acceptable representative (LAR) (or study partner/caregiver, if local regulations allow) must provide written informed consent The subject must provide written (if capable) informed assent Subject requires some or complete assistance with one or more of the following: Instrumental activities of daily living (communication, transportation, meal preparation, shopping, housework, managing medications, managing personal finances) OR Basic activities of daily living (personal hygiene, dressing, eating, maintaining continence or transferring) Meets clinical criteria for at least one of the following disorders, with or without cerebrovascular disease (CVD): Parkinson's disease with or without dementia as defined by the Movement Disorder Society's Task Force Dementia with Lewy bodies (DLB) All-cause dementia, possible or probable Alzheimer's disease (AD) Frontotemporal degeneration spectrum disorders, including possible or probable: i. Behavioral variant frontotemporal dementia ii. Progressive supranuclear palsy iii. Corticobasal degeneration e. Vascular dementia, including post-stroke dementia multi-infarct dementia and/or subcortical ischemic vascular dementia (SIVD) Has a designated study partner/caregiver Can come to the clinic for study visits with a study partner/caregiver If the subject is female, she must not be pregnant or breastfeeding. She must also be of non-childbearing potential (defined as either surgically sterilized or at least 1 year postmenopausal) or must agree to use a clinically acceptable method of contraception or be abstinent. If the subject is taking an antipsychotic medication at the time of screening, the antipsychotic medication must be discontinued 2 weeks or 5 half-lives (whichever is longer) Exclusion Criteria: Is in hospice, is receiving end-of-life palliative care, or is bedridden Has psychotic symptoms that are primarily attributable to delirium or substance abuse (i.e., neuropsychiatric symptoms not related to neurodegenerative disease) Has current evidence of an unstable neurological, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical disorder, including cancer or malignancies that, in the judgment of the Investigator, would jeopardize the safe participation of the subject in the study or significantly interfere with the conduct or interpretation of the study Has a known personal or family history of long QT syndrome or family history of sudden cardiac death Has a clinical significant CNS abnormality that is most likely contributing to the dementia or findings on MRI or CT including: intracranial mass lesion vascular malformation evidence of >4 hemosiderin deposits The urine drug screen result at Visit 1 (Screening) indicates the presence of amphetamine/methamphetamine, barbiturates, cocaine, or phencyclidine (PCP). Subjects who test positive for amphetamines and who have a valid prescription may be retested if they agree to abstain from the medication for the length of their participation in the study. The presence of benzodiazepines, marijuana (THC), or opiates does not necessarily exclude the subject from the study, as assessed by the Investigator in consultation with the Medical Monitor. Has previously been enrolled in any prior clinical study with pimavanserin or is currently taking pimavanserinIs judged by the Investigator or the Medical Monitor to be inappropriate for the study for any reason Additional inclusion/exclusion criteria apply. Patients will be evaluated at screening to ensure that all criteria for study participation are met. Patients may be excluded from the study based on these assessments (and specifically, if it is determined that their baseline health and psychiatric condition do not meet all pre-specified entry criteria).

Ages Eligible for Study
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Minimum Age: 60 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 |
| --- | --- |
| Experimental: Drug - Pimavanserin<br> | Drug: Pimavanserin<br>* Pimavanserin 34 mg total daily dose, tablets, once daily by mouth (provided as two 17 mg NUPLAZID® tablets)<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo, tablets, once daily by mouth (provided as two placebo tablets)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-emergent adverse events (TEAEs) | Safety and tolerability of pimavanserin compared to placebo in adult and elderly subjects with neuropsychiatric symptoms related to neurodegenerative disease | Treatment Period: 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Week 8 in Extrapyramidal Symptom Rating Scale-Abbreviated (ESRS-A) |  | Treatment Period: 8 weeks | 
| Change from Baseline to Week 8 in Mini-Mental State Examination (MMSE) |  | Treatment Period: 8 weeks |