Trial Outcomes & Findings for A Study of Safety and Efficacy of Pimavanserin (ACP-103) in Patients With Parkinson's Disease Psychosis (NCT NCT00658567)

Last Updated: 2017-05-19

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

123 participants

Primary outcome timeframe

Each study visit (i.e. Days 1, 8, 15, 29 and 42)

Results posted on

2017-05-19

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Placebo tablet, once daily by mouth, 6 weeks	Pimavanserin 10 mg Pimavanserin tartrate (ACP-103) 10 mg, tablet, once daily by mouth, 6 weeks	Pimavanserin 20 mg Pimavanserin tartrate (ACP-103) 20 mg, tablet, once daily by mouth, 6 weeks
Overall Study STARTED	40	42	41
Overall Study COMPLETED	32	38	35
Overall Study NOT COMPLETED	8	4	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo tablet, once daily by mouth, 6 weeks	Pimavanserin 10 mg Pimavanserin tartrate (ACP-103) 10 mg, tablet, once daily by mouth, 6 weeks	Pimavanserin 20 mg Pimavanserin tartrate (ACP-103) 20 mg, tablet, once daily by mouth, 6 weeks
Overall Study Adverse Event	5	2	3
Overall Study Voluntary Withdrawal of Consent	2	0	2
Overall Study Physician Decision	0	1	0
Overall Study At Discretion of Sponsor	1	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=39 Participants Placebo tablet, once daily by mouth, 6 weeks	10 mg n=41 Participants Pimavanserin tartrate (ACP-103) 10 mg, tablet, once daily by mouth, 6 weeks	20 mg n=41 Participants Pimavanserin tartrate (ACP-103) 20 mg, tablet, once daily by mouth, 6 weeks	Total n=121 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=99 Participants	7 Participants n=107 Participants	7 Participants n=206 Participants	21 Participants n=7 Participants
Age, Categorical >=65 years	32 Participants n=99 Participants	34 Participants n=107 Participants	34 Participants n=206 Participants	100 Participants n=7 Participants
Age, Continuous	73.0 years STANDARD_DEVIATION 7.91 • n=99 Participants	71.0 years STANDARD_DEVIATION 7.44 • n=107 Participants	72.1 years STANDARD_DEVIATION 8.15 • n=206 Participants	72.0 years STANDARD_DEVIATION 7.82 • n=7 Participants
Sex: Female, Male Female	12 Participants n=99 Participants	15 Participants n=107 Participants	17 Participants n=206 Participants	44 Participants n=7 Participants
Sex: Female, Male Male	27 Participants n=99 Participants	26 Participants n=107 Participants	24 Participants n=206 Participants	77 Participants n=7 Participants
Region of Enrollment United States	18 participants n=99 Participants	17 participants n=107 Participants	18 participants n=206 Participants	53 participants n=7 Participants
Region of Enrollment Europe	21 participants n=99 Participants	24 participants n=107 Participants	23 participants n=206 Participants	68 participants n=7 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Placebo tablet, once daily by mouth, 6 weeks	Pimavanserin 10 mg n=38 Participants Pimavanserin tartrate (ACP-103) 10 mg, tablet, once daily by mouth, 6 weeks	Pimavanserin 20 mg n=41 Participants Pimavanserin tartrate (ACP-103) 20 mg, tablet, once daily by mouth, 6 weeks
Antipsychotic Efficacy Change from Baseline	-4.4 Scores on the SAPS H+D scale Interval -6.5 to -2.3	NA Scores on the SAPS H+D scale Only the high dose comparison was incorporated in the ANCOVA model analysis following the early termination of the study. The prospective SAP eliminated the analysis of the low dose, 10 mg arm.	-6.5 Scores on the SAPS H+D scale Interval -8.5 to -4.5
Antipsychotic Efficacy Difference of Least Squares Mean versus Placebo	NA Scores on the SAPS H+D scale Calculation is a comparison of active arm versus placebo.	NA Scores on the SAPS H+D scale Only the high dose comparison was incorporated in the ANCOVA model analysis following the early termination of the study. The prospective SAP eliminated the analysis of the low dose, 10 mg arm.	-2.1 Scores on the SAPS H+D scale Interval -4.9 to 0.8

SECONDARY outcome

Timeframe: 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). 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.

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Placebo tablet, once daily by mouth, 6 weeks	Pimavanserin 10 mg n=38 Participants Pimavanserin tartrate (ACP-103) 10 mg, tablet, once daily by mouth, 6 weeks	Pimavanserin 20 mg n=41 Participants Pimavanserin tartrate (ACP-103) 20 mg, tablet, once daily by mouth, 6 weeks
Motor Symptoms Change From Baseline (Negative = Improvement) Change from Baseline	-1.8 Score on UPDRS-II+III scale. Interval -4.6 to 1.0	NA Score on UPDRS-II+III scale. Only the high dose comparison was incorporated in the ANCOVA model analysis following the early termination of the study. The prospective SAP eliminated the analysis of the low dose, 10 mg arm.	-3.9 Score on UPDRS-II+III scale. Interval -6.6 to -1.2
Motor Symptoms Change From Baseline (Negative = Improvement) Difference of Least Squares Mean versus Placebo	NA Score on UPDRS-II+III scale. Calculation is a comparison of active arm versus placebo.	NA Score on UPDRS-II+III scale. Only the high dose comparison was incorporated in the ANCOVA model analysis following the early termination of the study. The prospective SAP eliminated the analysis of the low dose, 10 mg arm.	-2.1 Score on UPDRS-II+III scale. Interval -5.9 to 1.8

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 12 other events

Deaths: 0 deaths

Pimavanserin 10 mg

Serious events: 3 serious events

Other events: 4 other events

Deaths: 0 deaths

Pimavanserin 20 mg

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=39 participants at risk Placebo tablet, once daily by mouth, 6 weeks	Pimavanserin 10 mg n=41 participants at risk Pimavanserin tartrate (ACP-103) 10 mg, tablet, once daily by mouth, 6 weeks	Pimavanserin 20 mg n=41 participants at risk Pimavanserin tartrate (ACP-103) 20 mg, tablet, once daily by mouth, 6 weeks
Infections and infestations Gastroenteritis	2.6% 1/39 • Number of events 1 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	0.00% 0/41 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	0.00% 0/41 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.
Injury, poisoning and procedural complications Fall	0.00% 0/39 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	2.4% 1/41 • Number of events 1 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	0.00% 0/41 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/39 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	2.4% 1/41 • Number of events 1 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	0.00% 0/41 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.
Nervous system disorders Parkinson's disease	0.00% 0/39 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	0.00% 0/41 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	2.4% 1/41 • Number of events 1 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.
Psychiatric disorders Delusion	0.00% 0/39 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	2.4% 1/41 • Number of events 2 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	0.00% 0/41 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.
Psychiatric disorders Delusional disorder, persecutory type	0.00% 0/39 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	2.4% 1/41 • Number of events 1 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	0.00% 0/41 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.
Psychiatric disorders Delirium	2.6% 1/39 • Number of events 1 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	0.00% 0/41 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	0.00% 0/41 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.
Psychiatric disorders Mental status changes	2.6% 1/39 • Number of events 1 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	0.00% 0/41 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	0.00% 0/41 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.

Other adverse events

Other adverse events
Measure	Placebo n=39 participants at risk Placebo tablet, once daily by mouth, 6 weeks	Pimavanserin 10 mg n=41 participants at risk Pimavanserin tartrate (ACP-103) 10 mg, tablet, once daily by mouth, 6 weeks	Pimavanserin 20 mg n=41 participants at risk Pimavanserin tartrate (ACP-103) 20 mg, tablet, once daily by mouth, 6 weeks
Nervous system disorders Somnolence	5.1% 2/39 • Number of events 2 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	2.4% 1/41 • Number of events 1 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	2.4% 1/41 • Number of events 1 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.
Nervous system disorders Dizziness	5.1% 2/39 • Number of events 2 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	0.00% 0/41 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	2.4% 1/41 • Number of events 1 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.
Psychiatric disorders Insomnia	2.6% 1/39 • Number of events 1 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	0.00% 0/41 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	7.3% 3/41 • Number of events 3 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.
Vascular disorders Orthostatic hypotension	7.7% 3/39 • Number of events 3 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	4.9% 2/41 • Number of events 2 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	0.00% 0/41 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.
Injury, poisoning and procedural complications Fall	7.7% 3/39 • Number of events 5 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	4.9% 2/41 • Number of events 3 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	7.3% 3/41 • Number of events 3 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.
Psychiatric disorders Hallucination	5.1% 2/39 • Number of events 2 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	0.00% 0/41 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.	4.9% 2/41 • Number of events 2 • 6 weeks From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 8, 15, 29, 42 and Day 70 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.

Additional Information

Roger Mills, MD

ACADIA Pharmaceuticals Inc.

Phone: 858-202-7563

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Investigator may publish the study results, relative to his/her own patients, only after review, comment and approval by the sponsor. No publication of confidential information shall be made without the sponsor's prior written consent. At least 60 days prior to submitting a manuscript or prior to any public presentation, a copy of the manuscript or presentation will be provided to the sponsor for review and comment. The sponsor has 60 days to review and comment.
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Restriction type: OTHER