Study to Evaluate Safety and Daytime Sedation in Subjects With Parkinson's Disease With Neuropsychiatric Symptoms Treated With Pimavanserin or Low-Dose Quetiapine

Study Overview
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Brief Summary
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This is a pilot study to explore the effects of pimavanserin and low-dose quetiapine in subjects with Parkinson's disease with neuropsychiatric symptoms.

Official Title
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A Pilot Randomized, Double-blind, Placebo-controlled Study to Evaluate Safety and Daytime Sedation in Subjects With Parkinson's Disease With Neuropsychiatric Symptoms Treated With Pimavanserin or Low-Dose Quetiapine

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: Pimavanserin
* Other: Placebo
* Drug: Quetiapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects 50 to 85 years of age, inclusive Able to understand the protocol requirements and provide written informed consent Able to complete questions on a handheld device / tablet, is willing to wear an actigraph and can be reliably rated on assessment scales Able to designate an 'informant' (relative, housemate, friend) who can provide information about the subject's well being and attend clinic visits with the subject Is able to swallow the test capsule without difficulty during the Screening visit Has a Mini-Mental State Examination (MMSE) score ≥19 Has a diagnosis of idiopathic Parkinson's disease, without any other known or suspected cause of parkinsonism. Initial diagnosis of PD must have been made more than 1 year prior to Screening. Has non-motor neuropsychiatric symptoms severe enough to warrant treatment with an antipsychotic agent based on investigator judgement and CGI-S score If the subject is on anti-Parkinsonian medication, they must be on a stable regimen for 1 month prior to Baseline and not planning (at the time of the Baseline visit) to make a major change in dose(s) 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 or be abstinent for at least 1 month prior to the Baseline visit, during the study, and 41 days following completion of double-blind treatment. Exclusion Criteria: Has atypical parkinsonism or secondary parkinsonism variants such as tardive or medication induced parkinsonism Is in hospice, is receiving end-of-life palliative care, or is bedridden or confined to a wheelchair Has neuropsychiatric symptoms that are primarily attributable to current delirium or substance abuse Has current evidence of an unstable neurological, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical or psychiatric 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 orthostatic hypotension as judged by the investigator and medical monitor Is judged by the Investigator or the Medical Monitor to be inappropriate for the study for any reason, including if the subject is judged to be a danger to self or others 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 condition do not meet all pre-specified entry criteria).

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 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>Pimavanserin 34 mg provided as 2 x 17 mg encapsulated tablets | Drug: Pimavanserin<br>* Pimavanserin 34 mg (provided as 2×17 mg encapsulated tablets) administered orally as a single dose once daily<br>|
| Placebo Comparator: Placebo<br>Placebo encapsulated tablet | Other: Placebo<br>* Placebo (provided as 2 × placebo encapsulated tablets) administered orally as a single dose once daily<br>|
| Active Comparator: Quetiapine<br>Immediate release Quetiapine encapsulated tablets | Drug: Quetiapine<br>* Quetiapine 25 mg (provided as 1×25 mg quetiapine encapsulated tablet and 1 × placebo encapsulated tablet), OR 50 mg (provided as 2×25 mg quetiapine encapsulated tablets), OR 100 mg (provided as 2×50 mg quetiapine encapsulated tablets) administered orally as a single dose once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-emergent Adverse Events (TEAEs) | Assess the safety and tolerability of pimavanserin in patients with PD in terms of treatment-emergent adverse events. | 4-week treatment duration, plus 30 days treatment-free safety follow-up |