A Study of the Safety and Efficacy of Pimavanserin in Patients With Parkinson's Disease Psychosis

• Sponsor: ACADIA Pharmaceuticals Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01174004
• Collaborator: (none)
• Enrollment: 199
• Locations: 63
• Arms: 2
• Duration (Months): 28.1
• Patients Per Site: 3.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of 40 mg pimavanserin compared to placebo in patients with Parkinson's disease psychosis (PDP).

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease Psychosis	Drug: pimavanserin tartrate; Drug: placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 199 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multi-Center, Placebo-Controlled, Double-Blind Trial to Examine the Safety and Efficacy of Pimavanserin in the Treatment of Psychosis in Parkinson's Disease
• Study Start Date: Jul 1, 2010
• Actual Primary Completion Date: Nov 1, 2012
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 pimavanserin tartrate, 40 mg, tablet, once daily by mouth for 6 weeks	Drug: pimavanserin tartrate; pimavanserin tartrate, 40 mg, tablet, once daily by mouth for 6 weeks; Other Names: ACP-103
Placebo Comparator: 2 placebo, tablet, once daily by mouth for 6 weeks	Drug: placebo; placebo, tablet, once daily by mouth for 6 weeks

Outcome Measures

Primary Outcome Measures

1. Antipsychotic Efficacy [Each study visit (i.e. Days 1, 15, 29 and 43)]

   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 43 in the Scale for the Assessment of Positive Symptoms 9-item sum score for Parkinson's Disease (SAPS-PD). The possible total score is 0 to 45 and a negative change in score indicates improvement. Analysis Method: Mixed Model Repeated Measures (MMRM)

Secondary Outcome Measures

1. Motor Symptoms Change From Baseline (Negative = Improvement) [Study Days 1 and 43]

   Motor symptoms were measured using the change from baseline to Day 43 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 possible total score is 0 to 160 and a negative change in score indicates improvement. Analysis Method: Analysis of Covariance (ANCOVA). The UPDRS Parts II+III score was analyzed by constructing 2-sided 95% confidence intervals (CIs) on the difference between the 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 Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts 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 Parkinson's disease diagnosis was established

• Subjects that are on anti-Parkinson's medication must be on a stable dose 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

• Subject and caregiver are willing and able to adequately communicate in English for the purposes of the primary assessment

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Gilbert	Arizona	United States	85234
2		Phoenix	Arizona	United States	85004
3		Phoenix	Arizona	United States	85013
4		Tucson	Arizona	United States	85724
5		Carson	California	United States	90746
6		Fountain Valley	California	United States	92708
7		Fresno	California	United States	93720
8		Fullerton	California	United States	92835
9		Irvine	California	United States	92697
10		La Habra	California	United States	90631
11		La Jolla	California	United States	92037
12		Loma Linda	California	United States	92354
13		Oxnard	California	United States	93030
14		Pasadena	California	United States	91105
15		Reseda	California	United States	91335
16		Sunnyvale	California	United States	94085
17		Ventura	California	United States	93003
18		Danbury	Connecticut	United States	06810
19		Boca Raton	Florida	United States	33486
20		Bradenton	Florida	United States	34205
21		Naples	Florida	United States	34102
22		Orlando	Florida	United States	32806
23		Ormond Beach	Florida	United States	32174
24		Panama City	Florida	United States	32405
25		Port Charlotte	Florida	United States	33980
26		St. Petersburg	Florida	United States	33713
27		Augusta	Georgia	United States	30912
28		Decatur	Georgia	United States	30033
29		Elk Grove Village	Illinois	United States	60007
30		Glenview	Illinois	United States	60026
31		Kansas City	Kansas	United States	66160
32		Louisville	Kentucky	United States	40202
33		Scarborough	Maine	United States	04074
34		Baltimore	Maryland	United States	21287
35		Boston	Massachusetts	United States	02215
36		Novi	Michigan	United States	48377
37		Roseville	Michigan	United States	48066
38		Traverse City	Michigan	United States	49684
39		Flowood	Mississippi	United States	39232
40		St. Louis	Missouri	United States	63110
41		Missoula	Montana	United States	59802
42		Toms River	New Jersey	United States	08755
43		Albany	New York	United States	12208
44		Commack	New York	United States	11725
45		Kingston	New York	United States	12401
46		New York	New York	United States	10016
47		Durham	North Carolina	United States	27705
48		Raleigh	North Carolina	United States	27607
49		Salisbury	North Carolina	United States	28144
50		Cincinnati	Ohio	United States	45219
51		Cleveland	Ohio	United States	44195
52		Columbus	Ohio	United States	43210
53		Toledo	Ohio	United States	43614
54		Greensburg	Pennsylvania	United States	15601
55		Providence	Rhode Island	United States	02906
56		Brentwood	Tennessee	United States	37027
57		Houston	Texas	United States	77030
58		Salt Lake City	Utah	United States	84108
59		Alexandria	Virginia	United States	22311
60		Roanoke	Virginia	United States	24018
61		Virginia Beach	Virginia	United States	23456
62		Milwaukee	Wisconsin	United States	53233
63		Ottawa	Ontario	Canada	K1G 4G3

Sponsors and Collaborators

• ACADIA Pharmaceuticals Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: ACADIA Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT01174004
• Other Study ID Numbers: ACP-103-020
• First Posted: Aug 3, 2010
• Last Update Posted: Mar 26, 2014
• Last Verified: Feb 1, 2014

• Additional relevant MeSH terms: Parkinson Disease; Psychotic Disorders; Mental Disorders; Pimavanserin

Study Results

Participant Flow

Arm/Group Title	Placebo	Pimavanserin 40 mg
Arm/Group Description	Placebo 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	94	105
COMPLETED	87	89
NOT COMPLETED	7	16

Baseline Characteristics

Arm/Group Title	Placebo	Pimavanserin 40 mg	Total
Arm/Group Description	Placebo 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 Participants	94	104	198
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	11 11.7%	12 11.5%	23 11.6%
>=65 years	83 88.3%	92 88.5%	175 88.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	72.7 (8.03)	72.6 (6.49)	72.7 (7.25)
Sex: Female, Male (Count of Participants)
Female	38 40.4%	34 32.7%	72 36.4%
Male	56 59.6%	70 67.3%	126 63.6%
Region of Enrollment (participants) [Number]
United States	92 97.9%	101 97.1%	193 97.5%
Canada	2 2.1%	3 2.9%	5 2.5%

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 43 in the Scale for the Assessment of Positive Symptoms 9-item sum score for Parkinson's Disease (SAPS-PD). The possible total score is 0 to 45 and a negative change in score indicates improvement. Analysis Method: Mixed Model Repeated Measures (MMRM)
Time Frame	Each study visit (i.e. Days 1, 15, 29 and 43)

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 collected no later than 3 days after the last dose date.

Arm/Group Title	Placebo	Pimavanserin 40 mg
Arm/Group Description	Placebo tablet, once daily by mouth, 6 weeks	Pimavanserin tartrate (ACP-103), 40 mg, tablet, once daily by mouth, 6 weeks
Measure Participants	90	95
Change from Baseline	-2.73	-5.79
Difference of Least Squares Mean versus Placebo	NA	-3.06

2. Secondary Outcome

Title	Motor Symptoms Change From Baseline (Negative = Improvement)
Description	Motor symptoms were measured using the change from baseline to Day 43 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 possible total score is 0 to 160 and a negative change in score indicates improvement. Analysis Method: Analysis of Covariance (ANCOVA). The UPDRS Parts II+III score was analyzed by constructing 2-sided 95% confidence intervals (CIs) on the difference between the 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	Study Days 1 and 43

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 collected no later than 3 days after the last dose date.

Arm/Group Title	Placebo	Pimavanserin 40 mg
Arm/Group Description	Placebo tablet, once daily by mouth, 6 weeks	Pimavanserin tartrate (ACP-103), 40 mg, tablet, once daily by mouth, 6 weeks
Measure Participants	90	95
Change from Baseline	-1.69	-1.40
Difference of Least Squares Mean versus Placebo	NA	0.29

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, 15, 29, 43 and Day 71 or 4 weeks after the last dose for subjects who do not continue into the open-label, extension protocol.
Arm/Group Title	Placebo		Pimavanserin 40 mg
Arm/Group Description	Placebo 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 40 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Pimavanserin 40 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/94 (4.3%)		11/104 (10.6%)
Cardiac disorders
Arrhythmia	1/94 (1.1%)	1	0/104 (0%)	0
Atrial fibrillation	0/94 (0%)	0	1/104 (1%)	1
Cardio-respiratory arrest	1/94 (1.1%)	1	0/104 (0%)	0
Gastrointestinal disorders
Hemorrhoids	0/94 (0%)	0	1/104 (1%)	1
General disorders
Asthenia	0/94 (0%)	0	1/104 (1%)	1
Fatigue	0/94 (0%)	0	1/104 (1%)	1
Multi-organ failure	0/94 (0%)	0	1/104 (1%)	1
Infections and infestations
Urinary tract infection	1/94 (1.1%)	1	3/104 (2.9%)	3
Bronchitis	0/94 (0%)	0	1/104 (1%)	1
Sepsis	0/94 (0%)	0	1/104 (1%)	1
Septic shock	0/94 (0%)	0	1/104 (1%)	1
Injury, poisoning and procedural complications
Fall	0/94 (0%)	0	1/104 (1%)	1
Fracture	1/94 (1.1%)	1	0/104 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/94 (0%)	0	1/104 (1%)	1
Nervous system disorders
Parkinson's disease	0/94 (0%)	0	1/104 (1%)	1
Transient ischemic attack	1/94 (1.1%)	1	0/104 (0%)	0
Psychiatric disorders
Psychotic disorder	0/94 (0%)	0	2/104 (1.9%)	2
Hallucination	0/94 (0%)	0	1/104 (1%)	1
Mental status changes	0/94 (0%)	0	1/104 (1%)	1
Sleep disorder	0/94 (0%)	0	1/104 (1%)	1
Skin and subcutaneous tissue disorders
Decubitus ulcer	1/94 (1.1%)	1	0/104 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Pimavanserin 40 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/94 (33%)		41/104 (39.4%)
Gastrointestinal disorders
Nausea	6/94 (6.4%)	6	6/104 (5.8%)	7
General disorders
Edema peripheral	3/94 (3.2%)	3	7/104 (6.7%)	7
Infections and infestations
Urinary tract infection	11/94 (11.7%)	12	14/104 (13.5%)	16
Injury, poisoning and procedural complications
Fall	8/94 (8.5%)	9	11/104 (10.6%)	14
Nervous system disorders
Confusional state	3/94 (3.2%)	4	6/104 (5.8%)	6
Headache	5/94 (5.3%)	5	1/104 (1%)	1
Psychiatric disorders
Hallucination	1/94 (1.1%)	1	7/104 (6.7%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.