Parkinson's Disease Psychosis
Conditions
Brief summary
The purpose of this study is to evaluate the safety and efficacy of 40 mg pimavanserin compared to placebo in patients with Parkinson's disease psychosis (PDP).
Interventions
pimavanserin tartrate, 40 mg, tablet, once daily by mouth for 6 weeks
DRUGplacebo
placebo, tablet, once daily by mouth for 6 weeks
Sponsors
ACADIA Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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 * Subjects that are on anti-Parkinson's medication must be on a stable dose 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 * Subject and caregiver are willing and able to adequately communicate in English for the purposes of the primary assessment
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Antipsychotic Efficacy | Each study visit (i.e. Days 1, 15, 29 and 43) | 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 43 in the Scale for the Assessment of Positive Symptoms 9-item sum score for Parkinson's Disease (SAPS-PD). The possible total score is 0 to 45 and a negative change in score indicates improvement. Analysis Method: Mixed Model Repeated Measures (MMRM) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Motor Symptoms Change From Baseline (Negative = Improvement) | Study Days 1 and 43 | Motor symptoms were measured using the change from baseline to Day 43 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 possible total score is 0 to 160 and a negative change in score indicates improvement. Analysis Method: Analysis of Covariance (ANCOVA). The UPDRS Parts II+III score was analyzed by constructing 2-sided 95% confidence intervals (CIs) on the difference between the 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. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo tablet, once daily by mouth, 6 weeks | 94 |
| Pimavanserin 40 mg Pimavanserin tartrate (ACP-103), 40 mg, tablet, once daily by mouth, 6 weeks | 104 |
| Total | 198 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 10 |
| Overall Study | At Discretion of Sponsor | 2 | 2 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | Placebo | Pimavanserin 40 mg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 83 Participants | 92 Participants | 175 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 12 Participants | 23 Participants |
| Age, Continuous | 72.7 years STANDARD_DEVIATION 8.03 | 72.6 years STANDARD_DEVIATION 6.49 | 72.7 years STANDARD_DEVIATION 7.25 |
| Region of Enrollment Canada | 2 participants | 3 participants | 5 participants |
| Region of Enrollment United States | 92 participants | 101 participants | 193 participants |
| Sex: Female, Male Female | 38 Participants | 34 Participants | 72 Participants |
| Sex: Female, Male Male | 56 Participants | 70 Participants | 126 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 31 / 94 | 41 / 104 |
| serious Total, serious adverse events | 4 / 94 | 11 / 104 |
Outcome results
Primary
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 43 in the Scale for the Assessment of Positive Symptoms 9-item sum score for Parkinson's Disease (SAPS-PD). The possible total score is 0 to 45 and a negative change in score indicates improvement. Analysis Method: Mixed Model Repeated Measures (MMRM)
Time frame: Each study visit (i.e. Days 1, 15, 29 and 43)
Population: This is the Intent to Treat population, defined as patients who received at least one dose of study drug and had both the baseline SAPS assessment and at least one post-baseline SAPS assessment collected no later than 3 days after the last dose date.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Antipsychotic Efficacy | Change from Baseline | -2.73 Score on the SAPS-PD scale |
| Placebo | Antipsychotic Efficacy | Difference of Least Squares Mean versus Placebo | NA Score on the SAPS-PD scale |
| Pimavanserin 40 mg | Antipsychotic Efficacy | Change from Baseline | -5.79 Score on the SAPS-PD scale |
| Pimavanserin 40 mg | Antipsychotic Efficacy | Difference of Least Squares Mean versus Placebo | -3.06 Score on the SAPS-PD scale |
Secondary
Motor Symptoms Change From Baseline (Negative = Improvement)
Motor symptoms were measured using the change from baseline to Day 43 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 possible total score is 0 to 160 and a negative change in score indicates improvement. Analysis Method: Analysis of Covariance (ANCOVA). The UPDRS Parts II+III score was analyzed by constructing 2-sided 95% confidence intervals (CIs) on the difference between the 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.
Time frame: Study Days 1 and 43
Population: This is the Intent to Treat population, defined as patients who received at least one dose of study drug and had both the baseline SAPS assessment and at least one post-baseline SAPS assessment collected no later than 3 days after the last dose date.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Motor Symptoms Change From Baseline (Negative = Improvement) | Change from Baseline | -1.69 Score on the UPDRS-II+III |
| Placebo | Motor Symptoms Change From Baseline (Negative = Improvement) | Difference of Least Squares Mean versus Placebo | NA Score on the UPDRS-II+III |
| Pimavanserin 40 mg | Motor Symptoms Change From Baseline (Negative = Improvement) | Change from Baseline | -1.40 Score on the UPDRS-II+III |
| Pimavanserin 40 mg | Motor Symptoms Change From Baseline (Negative = Improvement) | Difference of Least Squares Mean versus Placebo | 0.29 Score on the UPDRS-II+III |