A Study of 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: NCT00658567
• Collaborator: (none)
• Enrollment: 123
• Locations: 50
• Arms: 3
• Duration (Months): 21
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

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: Pimavanserin tartrate (ACP-103)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 123 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Study Start Date: Mar 1, 2008
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
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: 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

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 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) [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 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

• 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		La Habra	California	United States	90631
2		Laguna Hills	California	United States	92653
3		Reseda	California	United States
4		Ventura	California	United States	93003
5		Englewood	Colorado	United States	80113
6		Farmington	Connecticut	United States	06030
7		Deerfield Beach	Florida	United States	33064
8		Panama City	Florida	United States	32405
9		Sarasota	Florida	United States	34233
10		Boston	Massachusetts	United States	02215
11		Worcester	Massachusetts	United States	01655
12		Clinton	Michigan	United States	48035
13		Detroit	Michigan	United States	48201
14		East Lansing	Michigan	United States	48824
15		Columbia	Missouri	United States	65201
16		Omaha	Nebraska	United States	68131
17		Albany	New York	United States	12208
18		Commack	New York	United States	11725
19		Charlotte	North Carolina	United States	28204
20		Durham	North Carolina	United States	27705
21		New Bern	North Carolina	United States
22		Toledo	Ohio	United States	43614
23		Philadelphia	Pennsylvania	United States	19131
24		Philadelphia	Pennsylvania	United States	19141
25		Houston	Texas	United States	77030
26		Burlington	Vermont	United States	05401
27		Innsbruck		Austria	6020
28		Brussels		Belgium	1090
29		Ottignies		Belgium	1340
30		Roeselare		Belgium	8800
31		Chieti Scalo		Italy	66013
32		Grossetto		Italy	58100
33		Roma		Italy	00163
34		Roma		Italy	00185
35		Bydgoszcz		Poland	85-096
36		Katowice		Poland	40-752
37		Lodz		Poland	90-130
38		Lublin		Poland	20-090
39		Coimbra		Portugal	3000-548
40		Lisboa		Portugal	1649-028
41		Porto		Portugal	4099-001
42		Belgrade		Serbia	11000
43		Barcelona		Spain	08003
44		Barcelona		Spain	08036
45		Barcelona		Spain	08195
46		San Sebastian		Spain	20009
47		Santiago De Compostela		Spain	15706
48		Jonkoping		Sweden	SE-551 85
49		Linkoping		Sweden	SE-581 85
50		Stockholm		Sweden	SE-112 45

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: NCT00658567
• Other Study ID Numbers: ACP-103-014
• First Posted: Apr 15, 2008
• Last Update Posted: May 19, 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
• Additional relevant MeSH terms: Parkinson Disease; Psychotic Disorders; Mental Disorders; Pimavanserin

Study Results

Participant Flow

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

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 Participants	39	41	41	121
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	7 17.9%	7 17.1%	7 17.1%	21 17.4%
>=65 years	32 82.1%	34 82.9%	34 82.9%	100 82.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	73.0 (7.91)	71.0 (7.44)	72.1 (8.15)	72.0 (7.82)
Sex: Female, Male (Count of Participants)
Female	12 30.8%	15 36.6%	17 41.5%	44 36.4%
Male	27 69.2%	26 63.4%	24 58.5%	77 63.6%
Region of Enrollment (participants) [Number]
United States	18 46.2%	17 41.5%	18 43.9%	53 43.8%
Europe	21 53.8%	24 58.5%	23 56.1%	68 56.2%

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
Measure Participants	38	38	41
Change from Baseline	-4.4	NA	-6.5
Difference of Least Squares Mean versus Placebo	NA	NA	-2.1

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
Measure Participants	38	38	41
Change from Baseline	-1.8	NA	-3.9
Difference of Least Squares Mean versus Placebo	NA	NA	-2.1

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	/ (NaN)		/ (NaN)		/ (NaN)
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 (5.1%)		3/41 (7.3%)		1/41 (2.4%)
Infections and infestations
Gastroenteritis	1/39 (2.6%)	1	0/41 (0%)	0	0/41 (0%)	0
Injury, poisoning and procedural complications
Fall	0/39 (0%)	0	1/41 (2.4%)	1	0/41 (0%)	0
Hip fracture	0/39 (0%)	0	1/41 (2.4%)	1	0/41 (0%)	0
Nervous system disorders
Parkinson's disease	0/39 (0%)	0	0/41 (0%)	0	1/41 (2.4%)	1
Psychiatric disorders
Delusion	0/39 (0%)	0	1/41 (2.4%)	2	0/41 (0%)	0
Delusional disorder, persecutory type	0/39 (0%)	0	1/41 (2.4%)	1	0/41 (0%)	0
Delirium	1/39 (2.6%)	1	0/41 (0%)	0	0/41 (0%)	0
Mental status changes	1/39 (2.6%)	1	0/41 (0%)	0	0/41 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Pimavanserin 10 mg		Pimavanserin 20 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/39 (30.8%)		4/41 (9.8%)		8/41 (19.5%)
Injury, poisoning and procedural complications
Fall	3/39 (7.7%)	5	2/41 (4.9%)	3	3/41 (7.3%)	3
Nervous system disorders
Somnolence	2/39 (5.1%)	2	1/41 (2.4%)	1	1/41 (2.4%)	1
Dizziness	2/39 (5.1%)	2	0/41 (0%)	0	1/41 (2.4%)	1
Psychiatric disorders
Insomnia	1/39 (2.6%)	1	0/41 (0%)	0	3/41 (7.3%)	3
Hallucination	2/39 (5.1%)	2	0/41 (0%)	0	2/41 (4.9%)	2
Vascular disorders
Orthostatic hypotension	3/39 (7.7%)	3	2/41 (4.9%)	2	0/41 (0%)	0

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.