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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:
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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
Open or close this module 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:
Open or close this module 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]
Open or close this module Sponsor/Collaborators
Sponsor: ACADIA Pharmaceuticals Inc.
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module 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:
Open or close this module Conditions
Conditions: Parkinson's Disease Psychosis
Keywords:
Open or close this module 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]
Open or close this module 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
Open or close this module 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.

Open or close this module 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).
Open or close this module 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
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Citations:
Links:
Available IPD/Information:
Study Results
Open or close this module 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
Open or close this module 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
Open or close this module 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.
Open or close this module 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)
Open or close this module Limitations and Caveats
[Not specified]
Open or close this module 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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