A Study of Safety and Efficacy of Pimavanserin (ACP-103) in Patients With Parkinson's Disease Psychosis

Study Overview
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Brief Summary
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This study will evaluate the safety and efficacy of two dose levels of pimavanserin (ACP-103) compared to placebo in patients with Parkinson's disease psychosis.

Conditions
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Parkinson's Disease Psychosis

Intervention / Treatment
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* Drug: Pimavanserin tartrate (ACP-103)
* Drug: Pimavanserin tartrate (ACP-103)
* Drug: Pimavanserin tartrate (ACP-103)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A clinical diagnosis of Parkinson's disease with a minimum duration of 1 year Presence of visual and/or auditory hallucinations, and/or delusions, occurring during the four weeks prior to study screening Psychotic symptoms must have developed after Parkinson's disease diagnosis was established Subject must be on stable dose of anti-Parkinson's medication for 1 month prior to Study Day 1 (Baseline) and during the trial Subject that has received stereotaxic surgery for subthalamic nucleus deep brain stimulation must be at least 6 months post surgery and the stimulator settings must have been stable for at least 1 month prior to Study Day 1 (Baseline) and must remain stable during the trial The subject is willing and able to provide consent Caregiver is willing and able to accompany the subject to all visits Exclusion Criteria: Subject has a history of significant psychotic disorders prior to or concomitantly with the diagnosis of Parkinson's disease including, but not limited to, schizophrenia or bipolar disorder Subject has received previous ablative stereotaxic surgery (i.e., pallidotomy and thalamotomy) to treat Parkinson's disease Subject has current evidence of a serious and or unstable cardiovascular, respiratory, gastrointestinal, renal, hematologic or other medical disorder Subject has had a myocardial infarction in last six months Subject has any surgery planned during the screening, treatment or follow-up periods Patients will be evaluated at screening to ensure that all criteria for study participation are met. These evaluations will include specific measures of psychosis severity, delirium, dementia, cardiovascular condition, and pregnancy status. 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 protocol-specified entry criteria).

Ages Eligible for Study
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Minimum Age: 40 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: 2<br>pimavanserin tartrate (ACP-103) 20 mg, tablet, once daily by mouth, 6 weeks | Drug: Pimavanserin tartrate (ACP-103)<br>* 20 mg, tablet, once daily by mouth, for six weeks<br>|
| Placebo Comparator: Placebo<br>Placebo tablet, once daily by mouth, 6 weeks | Drug: Pimavanserin tartrate (ACP-103)<br>* Placebo, tablet, once daily by mouth, for six weeks<br>|
| Experimental: 1<br>pimavanserin tartrate (ACP-103) 10 mg, tablet, once daily by mouth, 6 weeks | Drug: Pimavanserin tartrate (ACP-103)<br>* 10 mg, tablet, once daily by mouth, for six weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antipsychotic Efficacy | Antipsychotic efficacy was defined as a decrease in the severity and/or frequency of hallucinations and/or delusions. This is measured as the change from baseline (Day 1) to Day 42 in the Scale for the Assessment of Positive Symptoms - Hallucinations and Delusions scales (SAPS-H+D) score for the ITT Analysis Set. The possible total score is 1 to 100 and a negative change in score indicates improvement. Analysis Method: Analysis of Covariance (ANCOVA) and missing data was imputed using Last Observation Carried Forward (LOCF) method. | Each study visit (i.e. Days 1, 8, 15, 29 and 42) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Motor Symptoms Change From Baseline (Negative = Improvement) | Motor symptoms were measured using the change from baseline (Day 1) to Day 42 in the combined score of the Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living) and Part III (Motor Examination). The total possible score is 0 to 160 and a negative change in score indicates improvement. Analysis Method: ANCOVA, and missing data was imputed using LOCF method. The UPDRS Parts II+III score was analyzed by constructing 2-sided 95% confidence intervals (CIs) on the difference between each pimavanserin dose group and placebo mean change from baseline. Non-inferiority was concluded if the upper limit of the CI was less than or equal to 5. | Each study visit (i.e. Days 1, 8, 15, 29 and 42) |