A Study of the Safety and Efficacy of Pimavanserin in Pat... | NCT01174004

Status Module

Label	Type	Description	Intervention Names
1	Experimental	pimavanserin tartrate, 40 mg, tablet, once daily by mouth for 6 weeks	Drug: pimavanserin tartrate
2	Placebo Comparator	placebo, tablet, once daily by mouth for 6 weeks	Drug: placebo

Name	Type	Description	Arm Group Labels	Other Names
pimavanserin tartrate	Drug	pimavanserin tartrate, 40 mg, tablet, once daily by mouth for 6 weeks	1

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Antipsychotic Efficacy	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)	Each study visit (i.e. Days 1, 15, 29 and 43)

Secondary Outcomes

Measure	Description	Time Frame
Motor Symptoms Change From Baseline (Negative = Improvement)	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 Module

Eligibility 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
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).

PubMed Identifier	Type	Citation	Retractions
24183563	Derived	Cummings J, Isaacson S, Mills R, Williams H, Chi-Burris K, Corbett A, Dhall R, Ballard C. Pimavanserin for patients with Parkinson's disease psychosis: a randomised, placebo-controlled phase 3 trial. Lancet. 2014 Feb 8;383(9916):533-40. doi: 10.1016/S0140-6736(13)62106-6. Epub 2013 Nov 1.

Results Section

Participant Flow Module

ID	Title	Description
FG000	Placebo	Placebo tablet, once daily by mouth, 6 weeks
FG001	Pimavanserin 40 mg	Pimavanserin tartrate (ACP-103), 40 mg, tablet, once daily by mouth, 6 weeks

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Safety Analysis Set

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020
Between 18 and 65 years

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00072.7± 8.03 BG00172.6± 6.49 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00038 BG00134 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00092 BG001101 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Antipsychotic Efficacy

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)

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.

Posted

Least Squares Mean

95% Confidence Interval

Score on the SAPS-PD scale

Each study visit (i.e. Days 1, 15, 29 and 43)

ID	Title	Description
OG000	Placebo	Placebo tablet, once daily by mouth, 6 weeks
OG001	Pimavanserin 40 mg	Pimavanserin tartrate (ACP-103), 40 mg, tablet, once daily by mouth, 6 weeks

Units	Counts
Participants	OG00090 OG00195

Title

Denominators

Categories

Change from Baseline

Title	Measurements
	OG000-2.73(-4.05 to -1.42) OG001-5.79(-7.09 to -4.49)

Difference of Least Squares Mean versus Placebo

Title	Measurements
	OG000

Secondary

Motor Symptoms Change From Baseline (Negative = Improvement)

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.

Posted

Least Squares Mean

95% Confidence Interval

Score on the UPDRS-II+III

Study Days 1 and 43

ID	Title	Description
OG000	Placebo	Placebo tablet, once daily by mouth, 6 weeks
OG001	Pimavanserin 40 mg	Pimavanserin tartrate (ACP-103), 40 mg, tablet, once daily by mouth, 6 weeks

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Arrhythmia	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected94 at risk EG0010 events0 affected104 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected94 at risk EG0011 events1 affected104 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected94 at risk EG0010 events0 affected104 at risk
Hemorrhoids	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected94 at risk EG0011 events1 affected104 at risk
Asthenia	General disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected94 at risk EG0011 events1 affected104 at risk
Fatigue	General disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected94 at risk EG0011 events1 affected104 at risk
Multi-organ failure	General disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected94 at risk EG0011 events1 affected104 at risk
Urinary tract infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected94 at risk EG0013 events3 affected104 at risk
Bronchitis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected94 at risk EG0011 events1 affected104 at risk
Sepsis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected94 at risk EG0011 events1 affected104 at risk
Septic shock	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected94 at risk EG0011 events1 affected104 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected94 at risk EG0011 events1 affected104 at risk
Fracture	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected94 at risk EG0010 events0 affected104 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected94 at risk EG0011 events1 affected104 at risk
Parkinson's disease	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected94 at risk EG0011 events1 affected104 at risk
Transient ischemic attack	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected94 at risk EG0010 events0 affected104 at risk
Psychotic disorder	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected94 at risk EG0012 events2 affected104 at risk
Hallucination	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected94 at risk EG0011 events1 affected104 at risk
Mental status changes	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected94 at risk EG0011 events1 affected104 at risk
Sleep disorder	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected94 at risk EG0011 events1 affected104 at risk
Decubitus ulcer	Skin and subcutaneous tissue disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected94 at risk EG0010 events0 affected104 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0006 events6 affected94 at risk EG0017 events6 affected104 at risk
Edema peripheral	General disorders	MedDRA 13.1	Systematic Assessment	EG0003 events3 affected94 at risk EG0017 events7 affected104 at risk
Urinary tract infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG00012 events11 affected94 at risk EG00116 events14 affected104 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0009 events8 affected94 at risk EG00114 events11 affected104 at risk
Confusional state	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0004 events3 affected94 at risk EG0016 events6 affected104 at risk
Headache	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0005 events5 affected94 at risk EG0011 events1 affected104 at risk
Hallucination	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected94 at risk EG0019 events7 affected104 at risk

Facility	Status	City	State	ZIP	Country	Contacts
		Gilbert	Arizona	85234	United States

ID	Title	Description
BG000	Placebo	Placebo tablet, once daily by mouth, 6 weeks
BG001	Pimavanserin 40 mg	Pimavanserin tartrate (ACP-103), 40 mg, tablet, once daily by mouth, 6 weeks
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Placebo tablet, once daily by mouth, 6 weeks			4	94	31	94
EG001	Pimavanserin 40 mg	Pimavanserin tartrate (ACP-103), 40 mg, tablet, once daily by mouth, 6 weeks			11	104	41	104