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

• Sponsor: ACADIA Pharmaceuticals Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00477672
• Collaborator: (none)
• Enrollment: 298
• Locations: 78
• Arms: 3
• Duration (Months): 25
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.2

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease Psychosis	Drug: Pimavanserin tartrate (ACP-103); Drug: Pimavanserin tartrate (ACP-103); Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 298 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 ACP-103 in the Treatment of Psychosis in Parkinson's Disease
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 2 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, 6 weeks
Experimental: 3 Pimavanserin tartrate (ACP-103), 40 mg, tablet, once daily by mouth, 6 weeks	Drug: Pimavanserin tartrate (ACP-103); 40 mg, tablet, once daily by mouth, 6 weeks
Placebo Comparator: 1 Placebo tablet, once daily by mouth, 6 weeks	Drug: Placebo; tablet, once daily by mouth, 6 weeks

Outcome Measures

Primary Outcome Measures

1. Antipsychotic Efficacy [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 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.

Secondary Outcome Measures

1. Motor Symptoms Change From Baseline (Negative = Improvement) [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) 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.

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 PD 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 (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	85013
3		Berkeley	California	United States	94705
4		Carson	California	United States	90746
5		Fountain Valley	California	United States	92708
6		Irvine	California	United States	92697
7		Sunnyvale	California	United States	94805
8		Danbury	Connecticut	United States	06810
9		Fairfield	Connecticut	United States	06824
10		Boca Raton	Florida	United States	33486
11		Gainesville	Florida	United States	32610
12		Jacksonville	Florida	United States	32209
13		Miami	Florida	United States	33136
14		Pompano Beach	Florida	United States	33060
15		Port Charlotte	Florida	United States	33952
16		Saint Petersburg	Florida	United States	33701
17		Sarasota	Florida	United States	34239
18		Tampa	Florida	United States	33606
19		Augusta	Georgia	United States	30912
20		Springfield	Illinois	United States	62794
21		Scarborough	Maine	United States	04074
22		Worcester	Massachusetts	United States	01655
23		Southfield	Michigan	United States	48034
24		Traverse City	Michigan	United States	49684
25		Toms River	New Jersey	United States	08755
26		Kingston	New York	United States	12401
27		Rochester	New York	United States	14618
28		Asheville	North Carolina	United States	28806
29		Salisbury	North Carolina	United States	28144
30		Columbus	Ohio	United States	43210
31		Warwick	Rhode Island	United States	02886
32		Brentwood	Tennessee	United States	37027
33		San Antonio	Texas	United States	78258
34		Richmond	Virginia	United States	23229
35		Kirkland	Washington	United States	98034
36		Spokane	Washington	United States	99204
37		Pleven		Bulgaria	5800
38		Rousse		Bulgaria	7003
39		Sofia		Bulgaria	1113
40		Varna		Bulgaria	9010
41		Clermont ferrand		France	63003
42		Marseille		France	13385
43		Nantes		France	44093
44		Pessac		France	33604
45		Strasbourg		France	67091
46		Toulouse		France	35059
47		Bangalore		India	560034
48		Hyderabad		India	500003
49		Karnataka		India	575001
50		Mangalore		India	575002
51		Mumbai		India	400016
52		Mumbai		India	400036
53		New Dalhi		India	110060
54		Pune		India	411004
55		Pune		India	411030
56		Tamil Nadu		India	600006
57		Tamil Nadu		India	625020
58		Visakhapatnam		India	530001
59		Kazan		Russian Federation	420061
60		Kirov		Russian Federation	610014
61		Moscow		Russian Federation	125284
62		Samara		Russian Federation	443095
63		Smolensk		Russian Federation	214018
64		St. Petersburg		Russian Federation	194044
65		Kharkiv		Ukraine	61068
66		Kiev		Ukraine	04080
67		Kiev		Ukraine	04114
68		Lugansk		Ukraine	91045
69		Lviv		Ukraine	79010
70		Vinnytsia		Ukraine	21005
71		Barnsley		United Kingdom	S75 2EP
72		Blackburn		United Kingdom	BB3 2HH
73		Brighton		United Kingdom	BN2 5BE
74		Dorset		United Kingdom	BH23 2JX
75		London		United Kingdom	NW3 2PF
76		Newcastle upon Tyne		United Kingdom	NE4 6BE
77		North Shields		United Kingdom	NE29 8NH
78		Salford		United Kingdom	M6 8HD

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: NCT00477672
• Other Study ID Numbers: ACP-103-012
• First Posted: May 24, 2007
• Last Update Posted: May 17, 2017
• Last Verified: Apr 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by ACADIA Pharmaceuticals Inc.: Parkinson's disease, psychotic disorders
• Additional relevant MeSH terms: Parkinson Disease; Psychotic Disorders; Mental Disorders; Pimavanserin

Study Results

Participant Flow

Arm/Group Title	Placebo	Pimavanserin 10 mg	Pimavanserin 40 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) 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

Baseline Characteristics

Arm/Group Title	Placebo	Pimavanserin 10 mg	Pimavanserin 40 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) 40 mg, tablet, once daily by mouth, 6 weeks	Total of all reporting groups
Overall Participants	98	99	98	295
Age (Count of Participants)
<=18 years	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 (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.6 (9.67)	69.0 (8.61)	69.4 (7.84)	69.3 (8.71)
Sex: Female, Male (Count of Participants)
Female	47 48%	36 36.4%	24 24.5%	107 36.3%
Male	51 52%	63 63.6%	74 75.5%	188 63.7%
Region of Enrollment (participants) [Number]
United States	44 44.9%	45 45.5%	45 45.9%	134 45.4%
India	10 10.2%	10 10.1%	10 10.2%	30 10.2%
Europe	44 44.9%	44 44.4%	43 43.9%	131 44.4%

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 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)

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 40 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) 40 mg, tablet, once daily by mouth, 6 weeks
Measure Participants	95	96	91
Change from Baseline	-5.9 (7.90)	-5.8 (9.77)	-6.7 (7.87)
Difference of Least Squares Mean versus Placebo	NA	0.1	-0.8

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) 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)

Outcome Measure Data

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
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
Measure Participants	90	88	85
Change from Baseline	-2.94	-1.41	-3.13
Difference of Least Square Mean versus Placebo	NA	1.53	-0.19

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 40 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) 40 mg, tablet, once daily by mouth, 6 weeks
All Cause Mortality
	Placebo		Pimavanserin 10 mg		Pimavanserin 40 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
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%)		5/99 (5.1%)		5/98 (5.1%)
Blood and lymphatic system disorders
Anemia	1/98 (1%)	1	0/99 (0%)	0	0/98 (0%)	0
Cardiac disorders
Myocardial infarction	0/98 (0%)	0	1/99 (1%)	1	0/98 (0%)	0
Gastrointestinal disorders
Gastrointestinal hemorrhage	1/98 (1%)	1	0/99 (0%)	0	0/98 (0%)	0
Infections and infestations
Bronchitis	1/98 (1%)	1	0/99 (0%)	0	0/98 (0%)	0
Cellulitis	0/98 (0%)	0	1/99 (1%)	1	0/98 (0%)	0
Sepsis	0/98 (0%)	0	1/99 (1%)	1	0/98 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	0/98 (0%)	0	0/99 (0%)	0	1/98 (1%)	1
Nervous system disorders
Encephalopathy	0/98 (0%)	0	1/99 (1%)	1	0/98 (0%)	0
Headache	0/98 (0%)	0	0/99 (0%)	0	1/98 (1%)	1
Syncope	0/98 (0%)	0	1/99 (1%)	1	0/98 (0%)	0
Psychiatric disorders
Confusional state	0/98 (0%)	0	0/99 (0%)	0	1/98 (1%)	1
Dementia	0/98 (0%)	0	1/99 (1%)	1	0/98 (0%)	0
Hallucination	0/98 (0%)	0	0/99 (0%)	0	1/98 (1%)	1
Mental status changes	0/98 (0%)	0	0/99 (0%)	0	1/98 (1%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory distress	0/98 (0%)	0	0/99 (0%)	0	1/98 (1%)	1
Surgical and medical procedures
Inguinal hernia repair	0/98 (0%)	0	1/99 (1%)	1	0/98 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Pimavanserin 10 mg		Pimavanserin 40 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/98 (34.7%)		29/99 (29.3%)		27/98 (27.6%)
Gastrointestinal disorders
Nausea	4/98 (4.1%)	4	4/99 (4%)	5	8/98 (8.2%)	10
Constipation	3/98 (3.1%)	4	4/99 (4%)	5	5/98 (5.1%)	5
General disorders
Edema	1/98 (1%)	1	2/99 (2%)	3	7/98 (7.1%)	7
Injury, poisoning and procedural complications
Fall	11/98 (11.2%)	12	5/99 (5.1%)	5	4/98 (4.1%)	4
Nervous system disorders
Dizziness	4/98 (4.1%)	4	7/99 (7.1%)	7	7/98 (7.1%)	7
Headache	6/98 (6.1%)	6	4/99 (4%)	4	4/98 (4.1%)	4
Psychiatric disorders
Confusional state	3/98 (3.1%)	3	5/99 (5.1%)	5	5/98 (5.1%)	5
Vascular disorders
Orthostatic hypotension	9/98 (9.2%)	10	4/99 (4%)	4	2/98 (2%)	2

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.