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

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ClinicalTrials.gov Identifier: NCT00477672
Recruitment Status : Completed
First Posted : May 24, 2007
Results First Posted : March 26, 2014
Last Update Posted : May 17, 2017
Sponsor:
Information provided by (Responsible Party):
ACADIA Pharmaceuticals Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Parkinson's Disease Psychosis
Interventions Drug: Pimavanserin tartrate (ACP-103)
Drug: Placebo
Enrollment 298

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo Pimavanserin 10 mg Pimavanserin 40 mg
Hide 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) 40 mg, tablet, once daily by mouth, 6 weeks
Period Title: Overall Study
Started 98 101 99
Completed 91 85 83
Not Completed 7 16 16
Reason Not Completed
Adverse Event             3             5             6
Death             0             1             0
Disease progression             0             1             0
Physician Decision             1             0             0
Protocol noncompliance             0             2             0
Consent withdrawn             2             5             10
Discretion of Sponsor             1             2             0
Arm/Group Title Placebo Pimavanserin 10 mg Pimavanserin 40 mg Total
Hide 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) 40 mg, tablet, once daily by mouth, 6 weeks Total of all reporting groups
Overall Number of Baseline Participants 98 99 98 295
Hide Baseline Analysis Population Description
Safety Analysis Set
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 98 participants 99 participants 98 participants 295 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
27
  27.6%
30
  30.3%
23
  23.5%
80
  27.1%
>=65 years
71
  72.4%
69
  69.7%
75
  76.5%
215
  72.9%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 98 participants 99 participants 98 participants 295 participants
69.6  (9.67) 69.0  (8.61) 69.4  (7.84) 69.3  (8.71)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 98 participants 99 participants 98 participants 295 participants
Female
47
  48.0%
36
  36.4%
24
  24.5%
107
  36.3%
Male
51
  52.0%
63
  63.6%
74
  75.5%
188
  63.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 98 participants 99 participants 98 participants 295 participants
United States 44 45 45 134
India 10 10 10 30
Europe 44 44 43 131
1.Primary Outcome
Title Antipsychotic Efficacy
Hide 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 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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 40 mg
Hide 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) 40 mg, tablet, once daily by mouth, 6 weeks
Overall Number of Participants Analyzed 95 96 91
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Score on the SAPS H+D scale
Change from Baseline
-5.9
(-7.3 to -4.5)
-5.8
(-7.2 to -4.3)
-6.7
(-8.1 to -5.2)
Difference of Least Squares Mean versus Placebo
NA [1] 
(NA to NA)
0.1
(-1.7 to 2.0)
-0.8
(-2.7 to 1.1)
[1]
Calculation is a comparison of active arm versus placebo.
2.Secondary Outcome
Title Motor Symptoms Change From Baseline (Negative = Improvement)
Hide 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) 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Placebo Pimavanserin 10 mg Pimavanserin 40 mg
Hide 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) 40 mg, tablet, once daily by mouth, 6 weeks
Overall Number of Participants Analyzed 90 88 85
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Score on UPDRS-II+III
Change from Baseline
-2.94
(-5.08 to -0.80)
-1.41
(-3.58 to 0.76)
-3.13
(-5.34 to -0.91)
Difference of Least Square Mean versus Placebo
NA [1] 
(NA to NA)
1.53
(-1.24 to 4.31)
-0.19
(-2.99 to 2.62)
[1]
Calculation is a comparison of active arm versus placebo.
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 40 mg
Hide 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) 40 mg, tablet, once daily by mouth, 6 weeks
All-Cause Mortality
Placebo Pimavanserin 10 mg Pimavanserin 40 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Pimavanserin 10 mg Pimavanserin 40 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/98 (2.04%)      5/99 (5.05%)      5/98 (5.10%)    
Blood and lymphatic system disorders       
Anemia  1  1/98 (1.02%)  1 0/99 (0.00%)  0 0/98 (0.00%)  0
Cardiac disorders       
Myocardial infarction  1  0/98 (0.00%)  0 1/99 (1.01%)  1 0/98 (0.00%)  0
Gastrointestinal disorders       
Gastrointestinal hemorrhage  1  1/98 (1.02%)  1 0/99 (0.00%)  0 0/98 (0.00%)  0
Infections and infestations       
Bronchitis  1  1/98 (1.02%)  1 0/99 (0.00%)  0 0/98 (0.00%)  0
Cellulitis  1  0/98 (0.00%)  0 1/99 (1.01%)  1 0/98 (0.00%)  0
Sepsis  1  0/98 (0.00%)  0 1/99 (1.01%)  1 0/98 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Breast cancer  1  0/98 (0.00%)  0 0/99 (0.00%)  0 1/98 (1.02%)  1
Nervous system disorders       
Encephalopathy  1  0/98 (0.00%)  0 1/99 (1.01%)  1 0/98 (0.00%)  0
Headache  1  0/98 (0.00%)  0 0/99 (0.00%)  0 1/98 (1.02%)  1
Syncope  1  0/98 (0.00%)  0 1/99 (1.01%)  1 0/98 (0.00%)  0
Psychiatric disorders       
Confusional state  1  0/98 (0.00%)  0 0/99 (0.00%)  0 1/98 (1.02%)  1
Dementia  1  0/98 (0.00%)  0 1/99 (1.01%)  1 0/98 (0.00%)  0
Hallucination  1  0/98 (0.00%)  0 0/99 (0.00%)  0 1/98 (1.02%)  1
Mental status changes  1  0/98 (0.00%)  0 0/99 (0.00%)  0 1/98 (1.02%)  1
Respiratory, thoracic and mediastinal disorders       
Respiratory distress  1  0/98 (0.00%)  0 0/99 (0.00%)  0 1/98 (1.02%)  1
Surgical and medical procedures       
Inguinal hernia repair  1  0/98 (0.00%)  0 1/99 (1.01%)  1 0/98 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (11.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5.00%
Placebo Pimavanserin 10 mg Pimavanserin 40 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   34/98 (34.69%)      29/99 (29.29%)      27/98 (27.55%)    
Gastrointestinal disorders       
Nausea  1  4/98 (4.08%)  4 4/99 (4.04%)  5 8/98 (8.16%)  10
Constipation  1  3/98 (3.06%)  4 4/99 (4.04%)  5 5/98 (5.10%)  5
General disorders       
Edema  1  1/98 (1.02%)  1 2/99 (2.02%)  3 7/98 (7.14%)  7
Injury, poisoning and procedural complications       
Fall  1  11/98 (11.22%)  12 5/99 (5.05%)  5 4/98 (4.08%)  4
Nervous system disorders       
Dizziness  1  4/98 (4.08%)  4 7/99 (7.07%)  7 7/98 (7.14%)  7
Headache  1  6/98 (6.12%)  6 4/99 (4.04%)  4 4/98 (4.08%)  4
Psychiatric disorders       
Confusional state  1  3/98 (3.06%)  3 5/99 (5.05%)  5 5/98 (5.10%)  5
Vascular disorders       
Orthostatic hypotension  1  9/98 (9.18%)  10 4/99 (4.04%)  4 2/98 (2.04%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (11.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators 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/Title: Roger Mills, MD
Organization: ACADIA Pharmaceuticals Inc.
Phone: 858-202-7563
Responsible Party: ACADIA Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT00477672     History of Changes
Other Study ID Numbers: ACP-103-012
First Submitted: May 22, 2007
First Posted: May 24, 2007
Results First Submitted: February 6, 2014
Results First Posted: March 26, 2014
Last Update Posted: May 17, 2017