Parkinson's Disease Psychosis
Conditions
Keywords
Parkinson's disease, psychotic disorders
Brief summary
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.
Interventions
10 mg, tablet, once daily by mouth, 6 weeks
DRUGPlacebo
tablet, once daily by mouth, 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 PD 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Antipsychotic Efficacy | Each study visit (i.e. Days 1, 8, 15, 29 and 42) | 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 0 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Motor Symptoms Change From Baseline (Negative = Improvement) | Each study visit (i.e. Days 1, 8, 15, 29 and 42) | 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) using the per-protocol (PP) analysis set. The possible total score is 0 to 160 and a negative change in score indicates improvement. Analysis Method: ANCOVA, and missing data was imputed using LOCF. 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. |
Countries
Bulgaria, France, India, Russia, Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo tablet, once daily by mouth, 6 weeks | 98 |
| Pimavanserin 10 mg Pimavanserin tartrate (ACP-103) 10 mg, tablet, once daily by mouth, 6 weeks | 99 |
| Pimavanserin 40 mg Pimavanserin tartrate (ACP-103) 40 mg, tablet, once daily by mouth, 6 weeks | 98 |
| Total | 295 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 5 | 6 |
| Overall Study | Consent withdrawn | 2 | 5 | 10 |
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | Discretion of Sponsor | 1 | 2 | 0 |
| Overall Study | Disease progression | 0 | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 0 |
| Overall Study | Protocol noncompliance | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo | Pimavanserin 10 mg | Pimavanserin 40 mg | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 71 Participants | 69 Participants | 75 Participants | 215 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 30 Participants | 23 Participants | 80 Participants |
| Age, Continuous | 69.6 years STANDARD_DEVIATION 9.67 | 69.0 years STANDARD_DEVIATION 8.61 | 69.4 years STANDARD_DEVIATION 7.84 | 69.3 years STANDARD_DEVIATION 8.71 |
| Region of Enrollment Europe | 44 participants | 44 participants | 43 participants | 131 participants |
| Region of Enrollment India | 10 participants | 10 participants | 10 participants | 30 participants |
| Region of Enrollment United States | 44 participants | 45 participants | 45 participants | 134 participants |
| Sex: Female, Male Female | 47 Participants | 36 Participants | 24 Participants | 107 Participants |
| Sex: Female, Male Male | 51 Participants | 63 Participants | 74 Participants | 188 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 34 / 98 | 29 / 99 | 27 / 98 |
| serious Total, serious adverse events | 2 / 98 | 5 / 99 | 5 / 98 |
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 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 0 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.
Time frame: Each study visit (i.e. Days 1, 8, 15, 29 and 42)
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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Antipsychotic Efficacy | Change from Baseline | -5.9 Score on the SAPS H+D scale | 95% Confidence Interval 7.9 |
| Placebo | Antipsychotic Efficacy | Difference of Least Squares Mean versus Placebo | NA Score on the SAPS H+D scale | — |
| Pimavanserin 10 mg | Antipsychotic Efficacy | Change from Baseline | -5.8 Score on the SAPS H+D scale | 95% Confidence Interval 9.77 |
| Pimavanserin 10 mg | Antipsychotic Efficacy | Difference of Least Squares Mean versus Placebo | 0.1 Score on the SAPS H+D scale | — |
| Pimavanserin 40 mg | Antipsychotic Efficacy | Change from Baseline | -6.7 Score on the SAPS H+D scale | 95% Confidence Interval 7.87 |
| Pimavanserin 40 mg | Antipsychotic Efficacy | Difference of Least Squares Mean versus Placebo | -0.8 Score on the SAPS H+D scale | — |
Secondary
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) using the per-protocol (PP) analysis set. The possible total score is 0 to 160 and a negative change in score indicates improvement. Analysis Method: ANCOVA, and missing data was imputed using LOCF. 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.
Time frame: Each study visit (i.e. Days 1, 8, 15, 29 and 42)
Population: This is the Per Protocol population, which includes subjects in the ITT analysis set, who were free of important protocol deviations, as defined before database lock and unblinding. Subjects were analyzed according to the treatment actually received.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Motor Symptoms Change From Baseline (Negative = Improvement) | Change from Baseline | -2.94 Score on UPDRS-II+III |
| Placebo | Motor Symptoms Change From Baseline (Negative = Improvement) | Difference of Least Square Mean versus Placebo | NA Score on UPDRS-II+III |
| Pimavanserin 10 mg | Motor Symptoms Change From Baseline (Negative = Improvement) | Change from Baseline | -1.41 Score on UPDRS-II+III |
| Pimavanserin 10 mg | Motor Symptoms Change From Baseline (Negative = Improvement) | Difference of Least Square Mean versus Placebo | 1.53 Score on UPDRS-II+III |
| Pimavanserin 40 mg | Motor Symptoms Change From Baseline (Negative = Improvement) | Change from Baseline | -3.13 Score on UPDRS-II+III |
| Pimavanserin 40 mg | Motor Symptoms Change From Baseline (Negative = Improvement) | Difference of Least Square Mean versus Placebo | -0.19 Score on UPDRS-II+III |