# History of Changes for Study: NCT00658567

History of Changes for Study: NCT00658567
A Study of Safety and Efficacy of Pimavanserin (ACP-103) in Patients With Parkinson's Disease Psychosis
Latest version (submitted April 18, 2017) on ClinicalTrials.gov

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Study Record Versions

Version | A | B | Submitted Date | Changes
--- | --- | --- | --- | ---
1 |  |  | April 10, 2008 | None (earliest Version on record)
2 |  |  | May 19, 2008 | Study Status and Contacts/Locations
3 |  |  | August 25, 2008 | Study Status and Contacts/Locations
4 |  |  | September 24, 2008 | Study Status and Contacts/Locations
5 |  |  | October 20, 2008 | Study Status and Contacts/Locations
6 |  |  | November 17, 2008 | Study Status and Contacts/Locations
7 |  |  | December 17, 2008 | Contacts/Locations, Study Status and Eligibility
8 |  |  | February 16, 2009 | Study Status and Contacts/Locations
9 |  |  | March 26, 2009 | Study Status and Contacts/Locations
10 |  |  | April 16, 2009 | Study Status and Contacts/Locations
11 |  |  | June 16, 2009 | Contacts/Locations and Study Status
12 |  |  | July 16, 2009 | Study Status and Contacts/Locations
13 |  |  | August 4, 2010 | Recruitment Status, Study Status, Contacts/Locations and Sponsor/Collaborators
14 |  |  | August 29, 2014 | Study Status, Outcome Measures, Sponsor/Collaborators, Arms and Interventions, Study Design, Results and Eligibility
15 |  |  | April 18, 2017 | Oversight, Study Status, IPDSharing and Contacts/Locations

Comparison Format:

- Merged
- Side-by-Side

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Changes (Merged) for Study: NCT00658567
April 10, 2008 (v1) -- April 18, 2017 (v15)
Changes in: Study Status, Sponsor/Collaborators, Oversight, Study Design, Arms and Interventions, Outcome Measures, Eligibility, Contacts/Locations, IPDSharing and Results
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Study Identification

Unique Protocol ID: | ACP-103-014
Brief Title: | A Study of Safety and Efficacy of Pimavanserin (ACP-103) in Patients With Parkinson's Disease Psychosis
Official Title: |
Secondary IDs: |

Study Status

Record Verification: | April 2008 2017
Overall Status: | Recruiting Completed
Study Start: | March 2008
Primary Completion: | December 2009 [Actual]
Study Completion: | December 2009 [ Anticipated Actual]
First Submitted: | April 10, 2008
First Submitted that Met QC Criteria: | April 10, 2008
First Posted: | April 15, 2008 [Estimate]
Results First Submitted: | February 6, 2014
Results First Submitted that Met QC Criteria: | August 29, 2014
Results First Posted: | September 9, 2014 [Estimate]
Last Update Submitted that Met QC Criteria: | April 10 18, 2008 2017
Last Update Posted: | April 15, 2008 [Estimate] May 19, 2017 [Actual]

Sponsor/Collaborators

Sponsor: | ACADIA Pharmaceuticals Inc.
Responsible Party: | Sponsor
Collaborators: |

Oversight

U.S. FDA-regulated Drug: | Yes
U.S. FDA-regulated Device: | No
Data Monitoring: | No

Study Description

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.
Detailed Description: |

Conditions

Conditions: | Parkinson's Disease Psychosis
Keywords: |

Study Design

Study Type: | Interventional
Primary Purpose: | Treatment
Study Phase: | Phase 3
Interventional Study Model: | Parallel Assignment
Number of Arms: | 3
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation: | Randomized
Enrollment: | 240 [Anticipated] 123 [Actual]

Arms and Interventions

Arms | Assigned Interventions
--- | ---
Experimental: 2 pimavanserin tartrate (ACP-103) 20 mg, tablet, once daily by mouth, 6 weeks | Drug: Pimavanserin tartrate (ACP-103) 20 mg, tablet, once daily by mouth, for six weeks
Placebo Comparator: 3 Placebo Placebo tablet, once daily by mouth, 6 weeks | Drug: Pimavanserin tartrate (ACP-103) Placebo, tablet, once daily by mouth, for six weeks
Experimental: 1 pimavanserin tartrate (ACP-103) 10 mg, tablet, once daily by mouth, 6 weeks | Drug: Pimavanserin tartrate (ACP-103) 10 mg, tablet, once daily by mouth, for six weeks

Outcome Measures

[See Results Section.]
Primary Outcome Measures: |

1.

Antipsychotic efficacy will be assessed using the scale for the assessment of Positive Symptoms (SAPS) Antipsychotic Efficacy
[ Time Frame: 6 weeks 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 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.

Secondary Outcome Measures: |

1.

Motor Symptoms Change From Baseline (Negative = Improvement)
[ Time Frame: 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.

Eligibility

Minimum Age: | 40 Years
Maximum Age: |
Sex: | All
Gender Based: |
Accepts Healthy Volunteers: | No

Criteria:

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 ( is i.e., pallidotomy and thalamotomy) to treat Parkinson's disease
- Subject has current evidence of a serious and or unstable cardiovascular, respiratory, gastrointestinal, renal, mematologic 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).

Contacts/Locations

Central Contact Person: | Kimberly Wilson Email: ACP-103clintrials@acadia-pharm.com
Locations: | United States, California
| La Habra, California, United States, 90631
| Laguna Hills, California, United States, 92653
| United States, California
| [Recruiting] Reseda, California, United States
| Ventura, California, United States, 93003
| United States, Colorado
| Englewood, Colorado, United States, 80113
| United States, Connecticut
| Farmington, Connecticut, United States, 06030
| United States, Florida
| Deerfield Beach, Florida, United States, 33064
| Panama City, Florida, United States, 32405
| Sarasota, Florida, United States, 34233
| United States, Massachusetts
| Boston, Massachusetts, United States, 02215
| Worcester, Massachusetts, United States, 01655
| United States, Michigan
| Clinton, Michigan, United States, 48035
| Detroit, Michigan, United States, 48201
| East Lansing, Michigan, United States, 48824
| United States, Missouri
| Columbia, Missouri, United States, 65201
| United States, Nebraska
| Omaha, Nebraska, United States, 68131
| United States, New York
| Albany, New York, United States, 12208
| Commack, New York, United States, 11725
| United States, North Carolina
| Charlotte, North Carolina, United States, 28204
| Durham, North Carolina, United States, 27705
| United States, North Carolina
| [Recruiting] New Bern, North Carolina, United States
| United States, Ohio
| Toledo, Ohio, United States, 43614
| United States, Pennsylvania
| Philadelphia, Pennsylvania, United States, 19131
| Philadelphia, Pennsylvania, United States, 19141
| United States, Texas
| Houston, Texas, United States, 77030
| United States, Vermont
| Burlington, Vermont, United States, 05401
| Austria
| Innsbruck, Austria, 6020
| Belgium
| Brussels, Belgium, 1090
| Ottignies, Belgium, 1340
| Roeselare, Belgium, 8800
| Italy
| Chieti Scalo, Italy, 66013
| Grossetto, Italy, 58100
| Roma, Italy, 00163
| Roma, Italy, 00185
| Poland
| Bydgoszcz, Poland, 85-096
| Katowice, Poland, 40-752
| Lodz, Poland, 90-130
| Lublin, Poland, 20-090
| Portugal
| Coimbra, Portugal, 3000-548
| Lisboa, Portugal, 1649-028
| Porto, Portugal, 4099-001
| Serbia
| Belgrade, Serbia, 11000
| Spain
| Barcelona, Spain, 08003
| Barcelona, Spain, 08036
| Barcelona, Spain, 08195
| San Sebastian, Spain, 20009
| Santiago De Compostela, Spain, 15706
| Sweden
| Jonkoping, Sweden, SE-551 85
| Linkoping, Sweden, SE-581 85
| Stockholm, Sweden, SE-112 45

IPDSharing

Plan to Share IPD: | No

References

Citations: |
Links: |
Available IPD/Information: |

Study Results

Participant Flow

Recruitment Details |
Pre-assignment Details |

Arm/Group Title | Placebo
--- | ---

Pimavanserin 10 mg

Pimavanserin 20 mg

Arm/Group Description | Placebo tablet, once daily by mouth, 6 weeks | Pimavanserin tartrate (ACP-103) 10 mg, tablet, once daily by mouth, 6 weeks | Pimavanserin tartrate (ACP-103) 20 mg, tablet, once daily by mouth, 6 weeks
Period Title: Overall Study
Started | 40 | 42 | 41
Completed | 32 | 38 | 35
Not Completed | 8 | 4 | 6
Reason Not Completed |  |  |
Adverse Event | 5 | 2 | 3
Voluntary Withdrawal of Consent | 2 | 0 | 2
Physician Decision | 0 | 1 | 0
At Discretion of Sponsor | 1 | 1 | 1

Baseline Characteristics

Arm/Group Title | Placebo | 10 mg | 20 mg | Total
Arm/Group Description | Placebo tablet, once daily by mouth, 6 weeks | Pimavanserin tartrate (ACP-103) 10 mg, tablet, once daily by mouth, 6 weeks | Pimavanserin tartrate (ACP-103) 20 mg, tablet, once daily by mouth, 6 weeks | Total of all reporting groups
Overall Number of Baseline Participants | 39 | 41 | 41 | 121
Baseline Analysis Population Description | [Not Specified]
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants | Number Analyzed | 39 Participants | 41 Participants | 41 Participants | 121 Participants
<=18 years | 0 0% | 0 0% | 0 0% | 0 0%
Between 18 and 65 years | 7 17.95% | 7 17.07% | 7 17.07% | 21 17.36%
>=65 years | 32 82.05% | 34 82.93% | 34 82.93% | 100 82.64%
Age, Continuous Mean ( Standard Deviation) Unit of measure: years | Number Analyzed | 39 Participants | 41 Participants | 41 Participants | 121 Participants
| 73.0 (7.91) | 71.0 (7.44) | 72.1 (8.15) | 72.0 (7.82)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants | Number Analyzed | 39 Participants | 41 Participants | 41 Participants | 121 Participants
Female | 12 30.77% | 15 36.59% | 17 41.46% | 44 36.36%
Male | 27 69.23% | 26 63.41% | 24 58.54% | 77 63.64%
Region of Enrollment Measure Type: Number Unit of measure: participants | Number Analyzed | 39 Participants | 41 Participants | 41 Participants | 121 Participants
United States |  | 18 | 17 | 18 | 53
Europe |  | 21 | 24 | 23 | 68

Outcome Measures

1. Primary Outcome:

Title | Antipsychotic Efficacy

Description

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.

Time Frame | Each study visit (i.e. Days 1, 8, 15, 29 and 42)
Outcome Measure Data
Analysis Population Description
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/Group Title | Placebo | Pimavanserin 10 mg | Pimavanserin 20 mg
Arm/Group Description | Placebo tablet, once daily by mouth, 6 weeks | Pimavanserin tartrate (ACP-103) 10 mg, tablet, once daily by mouth, 6 weeks | Pimavanserin tartrate (ACP-103) 20 mg, tablet, once daily by mouth, 6 weeks
Overall Number of Participants Analyzed | 38 | 38 | 41
Least Squares Mean (95% Confidence Interval) Unit of Measure: Scores on the SAPS H+D scale |  |  |
Change from Baseline | -4.4 (-6.5 to -2.3) | NA (NA to NA) [1] | -6.5 (-8.5 to -4.5)
Difference of Least Squares Mean versus Placebo | NA (NA to NA) [2] | NA (NA to NA) [1] | -2.1 (-4.9 to 0.8)

[1] | NA Explanation: 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] | NA Explanation: Calculation is a comparison of active arm versus placebo.

2. Secondary Outcome:

Title | Motor Symptoms Change From Baseline (Negative = Improvement)

Description

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.

Time Frame | Each study visit (i.e. Days 1, 8, 15, 29 and 42)
Outcome Measure Data
Analysis Population Description
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/Group Title | Placebo | Pimavanserin 10 mg | Pimavanserin 20 mg
Arm/Group Description | Placebo tablet, once daily by mouth, 6 weeks | Pimavanserin tartrate (ACP-103) 10 mg, tablet, once daily by mouth, 6 weeks | Pimavanserin tartrate (ACP-103) 20 mg, tablet, once daily by mouth, 6 weeks
Overall Number of Participants Analyzed | 38 | 38 | 41
Least Squares Mean (95% Confidence Interval) Unit of Measure: Score on UPDRS-II+III scale. |  |  |
Change from Baseline | -1.8 (-4.6 to 1.0) | NA (NA to NA) [1] | -3.9 (-6.6 to -1.2)
Difference of Least Squares Mean versus Placebo | NA (NA to NA) [2] | NA (NA to NA) [1] | -2.1 (-5.9 to 1.8)

[1] | NA Explanation: 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] | NA Explanation: Calculation is a comparison of active arm versus placebo.

Adverse Events

Time Frame | 6 weeks
Adverse Event Reporting Description | 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.
Arm/Group Title | Placebo | Pimavanserin 10 mg | Pimavanserin 20 mg
Arm/Group Description | Placebo tablet, once daily by mouth, 6 weeks | Pimavanserin tartrate (ACP-103) 10 mg, tablet, once daily by mouth, 6 weeks | Pimavanserin tartrate (ACP-103) 20 mg, tablet, once daily by mouth, 6 weeks
All-Cause Mortality
| Placebo | Pimavanserin 10 mg | Pimavanserin 20 mg
| Affected / At Risk (%) | # Events | Affected / At Risk (%) | # Events | Affected / At Risk (%) | # Events
Total | / |  | / |  | / |
Serious Adverse Events
| Placebo | Pimavanserin 10 mg | Pimavanserin 20 mg
| Affected / At Risk (%) | # Events | Affected / At Risk (%) | # Events | Affected / At Risk (%) | # Events
Total | 2 / 39 ( 5.13%) |  | 3 / 41 ( 7.32%) |  | 1 / 41 ( 2.44%) |
Infections and infestations
Gastroenteritis † A | 1 / 39 ( 2.56%) | 1 | 0 / 41 ( 0%) | 0 | 0 / 41 ( 0%) | 0
Injury, poisoning and procedural complications
Fall † A | 0 / 39 ( 0%) | 0 | 1 / 41 ( 2.44%) | 1 | 0 / 41 ( 0%) | 0
Hip fracture † A | 0 / 39 ( 0%) | 0 | 1 / 41 ( 2.44%) | 1 | 0 / 41 ( 0%) | 0
Nervous system disorders
Parkinson's disease † A | 0 / 39 ( 0%) | 0 | 0 / 41 ( 0%) | 0 | 1 / 41 ( 2.44%) | 1
Psychiatric disorders
Delirium † A | 1 / 39 ( 2.56%) | 1 | 0 / 41 ( 0%) | 0 | 0 / 41 ( 0%) | 0
Delusion † A | 0 / 39 ( 0%) | 0 | 1 / 41 ( 2.44%) | 2 | 0 / 41 ( 0%) | 0
Delusional disorder, persecutory type † A | 0 / 39 ( 0%) | 0 | 1 / 41 ( 2.44%) | 1 | 0 / 41 ( 0%) | 0
Mental status changes † A | 1 / 39 ( 2.56%) | 1 | 0 / 41 ( 0%) | 0 | 0 / 41 ( 0%) | 0
† Indicates events were collected by systematic assessment. ATerm from vocabulary, MedDRA (11.1)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events | 5.00%
| Placebo | Pimavanserin 10 mg | Pimavanserin 20 mg
| Affected / At Risk (%) | # Events | Affected / At Risk (%) | # Events | Affected / At Risk (%) | # Events
Total | 12 / 39 ( 30.77%) |  | 4 / 41 ( 9.76%) |  | 8 / 41 ( 19.51%) |
Injury, poisoning and procedural complications
Fall † A | 3 / 39 ( 7.69%) | 5 | 2 / 41 ( 4.88%) | 3 | 3 / 41 ( 7.32%) | 3
Nervous system disorders
Dizziness † A | 2 / 39 ( 5.13%) | 2 | 0 / 41 ( 0%) | 0 | 1 / 41 ( 2.44%) | 1
Somnolence † A | 2 / 39 ( 5.13%) | 2 | 1 / 41 ( 2.44%) | 1 | 1 / 41 ( 2.44%) | 1
Psychiatric disorders
Hallucination † A | 2 / 39 ( 5.13%) | 2 | 0 / 41 ( 0%) | 0 | 2 / 41 ( 4.88%) | 2
Insomnia † A | 1 / 39 ( 2.56%) | 1 | 0 / 41 ( 0%) | 0 | 3 / 41 ( 7.32%) | 3
Vascular disorders
Orthostatic hypotension † A | 3 / 39 ( 7.69%) | 3 | 2 / 41 ( 4.88%) | 2 | 0 / 41 ( 0%) | 0
† Indicates events were collected by systematic assessment. ATerm from vocabulary, MedDRA (11.1)

Limitations and Caveats

[Not specified]

More Information

Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between the Principal Investigator and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.

Results Point of Contact:
Name/Official Title: | Roger Mills, MD
Organization: | ACADIA Pharmaceuticals Inc.
Phone: | 858-202-7563
Email: | rmills@acadia-pharm.com

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