Relapse Prevention Study of Pimavanserin in Dementia-related Psychosis

• Sponsor: ACADIA Pharmaceuticals Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03325556
• Collaborator: (none)
• Enrollment: 392
• Locations: 83
• Arms: 2
• Actual Duration (Months): 25.1
• Patients Per Site: 4.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy of pimavanserin compared to placebo in preventing relapse of psychotic symptoms in subjects with dementia-related psychosis who responded to 12 weeks of open label pimavanserin treatment.

Condition or Disease	Intervention/Treatment	Phase
Dementia-related Psychosis	Drug: Placebo; Drug: Pimavanserin 34 mg; Drug: Pimavanserin 20 mg	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 392 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-blind, Placebo-controlled, Relapse Prevention Study of Pimavanserin for the Treatment of Hallucinations and Delusions Associated With Dementia-related Psychosis
• Actual Study Start Date: Sep 27, 2017
• Actual Primary Completion Date: Jul 31, 2019
• Actual Study Completion Date: Oct 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo, tablets, once daily by mouth
Experimental: Drug - Pimavanserin	Drug: Pimavanserin 34 mg; Pimavanserin 34 mg total daily dose, tablets, once daily by mouth; Drug: Pimavanserin 20 mg; Pimavanserin 20 mg total daily dose, tablets, once daily by mouth

Outcome Measures

Primary Outcome Measures

1. Time From Randomization to Relapse in the Double-blind (DB) Period [From randomization in the DB period through 26 weeks]

   The time from randomization to relapse in the DB period was compared between treatment groups using a Cox regression model. The treatment effect was measured by the hazard ratio (HR). Relapse was defined as (1) ≥30% increase in SAPS-H+D total score from DB baseline (BL) and CGI-I score ≥6 relative to DB BL, (2) treatment with antipsychotic for dementia-related delusions/hallucinations, (3) treatment/study discontinuation due to lack of efficacy, and/or (4) hospitalization for worsening dementia-related psychosis. SAPS-H+D is a 20-item scale; the total score is the sum of the 20 item scores (range 0-100); higher scores denote more severe symptoms. CGI-I is a clinician-rated 7-point scale to rate improvement in hallucinations/delusions relative to BL (range 1-7); higher scores denote less improvement or worsening. A pre-specified IA was conducted after accrual of 40 adjudicated relapse events. The prespecified stopping criterion was met; the study was stopped for efficacy.

Secondary Outcome Measures

1. Time From Randomization to Discontinuation From the DB Period for Any Reason [From randomization in the DB period through 26 weeks]

   The endpoint of time from randomization to discontinuation from the DB period for any reason (other than termination of the study by the sponsor) was compared between treatment groups using a Cox regression model. The treatment effect was measured by the HR.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Meets criteria for All-cause Dementia according to NIA-AA guidelines

2. Meets clinical criteria for one of the following disorders: Dementia associated with Parkinson's disease, Dementia with Lewy bodies, Possible or probable Alzheimer's disease, Frontotemporal degeneration spectrum disorders, Vascular dementia

3. Has an MMSE score ≥6 and ≤24

4. Has had psychotic symptoms for at least 2 months

5. Must be on a stable does of cholinesterase inhibitor or memantine, if applicable

6. If the subject is female, she must not be pregnant or breastfeeding. She must also be of non-childbearing potential or must agree to use a clinically acceptable method of contraception for the duration of the study

Exclusion Criteria:

1. Has psychotic symptoms that are primarily attributable to a condition other than dementia

2. Has had a recent major depressive episode

3. Has experienced suicidal ideation or behavior within 3 months prior to study enrollment

4. Has evidence of a non-neurologic medical comorbidity or medication use that could substantially impair cognition

5. Has a history of ischemic stroke within the last 12 months or any evidence of hemorrhagic stroke

6. Has a known history of cerebral amyloid angiopathy (CAA), epilepsy, CNS neoplasm, or unexplained syncope

7. Has any of the following: greater than New York Heart Association (NYHA) Class 2 congestive heart failure, Grade 2 or greater angina pectoris, sustained ventricular tachycardia, ventricular fibrillation, torsade de pointes, syncope due to an arrhythmia, an implantable cardiac defibrillator

8. Had a myocardial infarction within the last 6 months

9. Has a known personal or family history or symptoms of long QT syndrome

10. Has a significant unstable medical condition that could interfere with subject's ability to complete the study or comply with study procedures

11. Requires treatment with a medication or other substance that is prohibited by the protocol

Additional inclusion/exclusion criteria apply. Subjects will be evaluated at screening to ensure that all criteria for study participation are met.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ATP Clinical Research Inc.	Costa Mesa	California	United States	92626
2	Neurology Center of North Orange County	Fullerton	California	United States	92835
3	Visionary Investigators Network (Aventura Neurologic Associates)	Aventura	Florida	United States	33180
4	Parkinson's Disease and Movement Disorders Center of Boca Raton	Boca Raton	Florida	United States	33486
5	Premier Clinical Research Institute, Inc.	Miami	Florida	United States	33122
6	Visionary Investigators Network (First Choice Neurology Group)	Miami	Florida	United States	33176
7	Novel Clinical Research Center, LLC	Miami	Florida	United States	33186
8	Collier Neurologic Specialists LLC	Naples	Florida	United States	34102
9	Bioclinica Research	Orlando	Florida	United States	32806
10	Neurology Associates of Ormond Beach	Ormond Beach	Florida	United States	32174
11	Quantum Laboratories	Pompano Beach	Florida	United States	33064
12	Neuroscience Research Institute	Winfield	Illinois	United States	60190
13	University of Kansas Medical Center Research Institute, Inc.	Kansas City	Kansas	United States	66160
14	Alzheimer Disease Center	Quincy	Massachusetts	United States	02169
15	Clinical Research Professionals	Chesterfield	Missouri	United States	63005
16	Millennium Psychiatric Associates, LLC; DBA Millennium Center for Clinical Research	Saint Louis	Missouri	United States	63132
17	Neurology Center of Las Vegas	Las Vegas	Nevada	United States	89128
18	Memory Enhancement Center of America, Inc.	Eatontown	New Jersey	United States	07724
19	BioBehavioral Health	Toms River	New Jersey	United States	08755
20	Neurological Associates of Albany, PC	Albany	New York	United States	12208
21	Manhattan Behavioral Medicine, PLLC	New York	New York	United States	10036
22	Richmond Behavioral Associates	Staten Island	New York	United States	10312
23	Neuro-Behavioral Clinical Research, Inc.	North Canton	Ohio	United States	44720
24	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
25	Abington Neurological Associates Ltd.	Willow Grove	Pennsylvania	United States	19090
26	University of Tennessee Medical Center	Knoxville	Tennessee	United States	37920
27	University of Virginia Adult Neurology	Charlottesville	Virginia	United States	22903
28	Mental Health Center - Ruse EOOD	Russe		Bulgaria	7003
29	Psicomed Estudios Medicos	Antofagasta		Chile	1270244
30	Biomedica Research Group	Santiago		Chile	7500710
31	Especialidades Médicas L y S	Santiago		Chile	7560356
32	Fakultni nemocnice Hradec Kralove	Hradec Králové		Czechia	50005
33	Clintrial s.r.o.	Praha 10		Czechia	10000
34	AD71, s.r.o.	Praha 10		Czechia	10900
35	Vestra Clinics, s.r.o	Rychnov nad Kněžnou		Czechia	51601
36	Assistance Publique Hopitaux de Marseille (AP-HM) - Hopital de La Timone - Service de Neurologie et Pathologie du Mouvement du Pr Azulay	Marseille		France	13385
37	Centre de Recherche du Gerontopole - CHU de Toulouse	Toulouse		France	31059
38	Klinik für Psychiatrie und Psychotherapie der Universität Tübingen	Tuebingen		Germany	72076
39	Azienda Ospedaliera di Padova Clinica Neurologica	Padova		Italy	35121
40	IRCCS San Raffaele Pisanna	Rome		Italy	00163
41	IRCCS Fondazione Santa Lucia, Dipartimento di Neurologia e Psichiatria	Rome		Italy	00179
42	Universita degli Studi di ROMA "La Sapienza" Dipartimento di NEUROLOGIA E PSICHIATRIA	Rome		Italy	00185
43	Azienda Ospedaliero-Universitaria Citta della Salute a della Scienza di Torino - c/o Presidio Ospedaliero Molinette Clinica Neurologica I	Torino		Italy	10126
44	Przychodnia Śródmieście Sp. z o.o.	Bydgoszcz		Poland	85-080
45	ISPL Wieslaw Jerzy Cubala	Gdańsk		Poland	80-438
46	Care Clinic	Katowice		Poland	40-060
47	Specjalistyczna Praktyka Lekarska	Lublin		Poland	20-582
48	NZOZ Neuro-Kard Ilkowski i Partnerzy Spółka Partnerska Lekarzy	Poznan		Poland	61-853
49	NEURO-CARE Sp. z o.o. Sp. Komandytowa	Siemianowice Śląskie		Poland	41-100
50	Euromedis Sp z. o. o.	Szczecin		Poland	70-111
51	Centrum Medyczne NeuroProtect	Warszawa		Poland	01-697
52	Clinical center of Serbia, Clinic for Neurology	Belgrade		Serbia	11 000
53	Military Medical Academy, Clinic for Neurology	Belgrade		Serbia	11 000
54	Clinical Hospital Center Dr Dragisa Misovic-Dedinje	Belgrade		Serbia	11000
55	Institut of Mental Health	Belgrade		Serbia	11000
56	Psychiatric Clinic, Military Medical Academy	Belgrade		Serbia	11000
57	Clinic for Psychiatry, Clinical Center Kragujevac	Kragujevac		Serbia	34 000
58	Department of addictive disorders of the Clinic for Psychiatry, Clinical center Kragujevac	Kragujevac		Serbia	34 000
59	Clinic for Psychiatry	Nis		Serbia	18 000
60	MUDr. Beata Dupejova, neurologicka ambulancia s.r.o	Banska Bystrica		Slovakia	974 04
61	Epamed s.r.o., Psychiatricka ambulancia	Košice		Slovakia	040 01
62	NEURES s.r.o. neurologicka ambulancia	Krompachy		Slovakia	053 42
63	Centrum Zdravia R.B.K., s.r.o.	Svidnik		Slovakia	089 01
64	Crystal Comfort, s.r.o.	Vranov nad Toplou		Slovakia	093 01
65	Clinica IINA	Barcelona		Spain	08006
66	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
67	Hospital General de Cataluña	Sant Cugat Del Vallès		Spain	08195
68	Estudio de Psiquiatría	Sevilla		Spain	41003
69	Hospital Universitario Virgen del Rocío	Sevilla		Spain	41013
70	Municipal Institution "Odesa Regional Psychiatric Hospital #2", Female Gerontological Department # 5, Male Gerontological Department #1	Oleksandrivka	Odessa Region	Ukraine	67513
71	Communal Institution "Dnipropetrovsk Regional Clinical Hospital n.a. I. I. Mechnikov"	Dnipro		Ukraine	49005
72	Municipal Institution of Health Care "Kharkiv Regional Clinical Psychiatric Hospital #3"	Kharkiv		Ukraine	61068
73	State Institution "Institute of Neurology, Psychiatry, and Narcology of the National Academy of Medical Sciences of Ukraine", Department of Clinical, Social, and Paediatric Psychiatry	Kharkiv		Ukraine	61068
74	Kherson Regional Psychiatric Hospital	Kherson		Ukraine	73488
75	Lviv Regional State Clinical Psychiatric Hospital	Lviv		Ukraine	79021
76	Municipal Institution "Odesa Regional Medical Center of Mental Health", Department #18	Odesa		Ukraine	65006
77	Poltava Regional Clinical Psychiatric Hospital named after O.F. Maltsev	Poltava		Ukraine	36013
78	Municipal Institution "Vinnytsya Regional Psychoneurological Hospital n.a. Acad. O.I.Yushchenko", Male Department #14, Female Department #15, Vinnytsya National Medical University n.a. M.I.Pyrogov, Department of Psychiatry, Narcology and Psychotherapeutic	Vinnytsya		Ukraine	21005
79	Municipal Institution "Zaporizhzhya Regional Clinical Hospital of Zaporizhzhya Regional Council"	Zaporizhzhya		Ukraine	69600
80	Royal United Hospital - The Research Institute for the Care of Older People (RICE) Centre	Bath		United Kingdom	BA1 3NG
81	MAC Clinical Research - Blackpool	Blackpool		United Kingdom	FY2 0JH
82	Re:Cognition Health Ltd.	London		United Kingdom	W1G 9JF
83	MAC Clinical Research - Manchester	Manchester		United Kingdom	M13 9NQ

Sponsors and Collaborators

• ACADIA Pharmaceuticals Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Aug 16, 2018
• Statistical Analysis Plan - Jul 26, 2019

More Information

Additional Information:

• Tariot P, et al. HARMONY study: pimavanserin significantly prolongs time to relapse of dementia-related psychosis. Innov Aging. 2020; 4(suppl 1):163-164.
• Tariot P, et al. HARMONY relapse-prevention study: pimavanserin significantly prolongs time to relapse of dementia-related psychosis. J Prev Alz Dis. 2019; 6(suppl 1):S30-S31

Publications

None provided.

• Responsible Party: ACADIA Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT03325556
• Other Study ID Numbers: ACP-103-045; 2017-002227-13
• First Posted: Oct 30, 2017
• Last Update Posted: Jun 21, 2021
• Last Verified: May 1, 2021

• 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.: Dementia; Dementia-related psychosis; Dementia associated with Parkinson's disease; Dementia with Lewy bodies; Alzheimer's disease; Behavioral variant frontotemporal dementia; Progressive supranuclear palsy; Corticobasal degeneration; Vascular dementia; Hallucinations; Delusions; Psychosis
• Additional relevant MeSH terms: Dementia; Psychotic Disorders; Mental Disorders; Pimavanserin

Study Results

Participant Flow

Recruitment Details	The study was performed in subjects with all-cause dementia according to NIA-AA guidelines, including dementia associated with Parkinson's disease, dementia with Lewy Bodies, possible or probable Alzheimer's disease, frontotemporal degeneration spectrum disorder, and/or vascular dementia, and were to have had at least a 2-month history of psychotic symptoms.
Pre-assignment Detail	During the screening period, subjects were assessed for study eligibility and prohibited medications were discontinued when medically appropriate. Subjects and partner/caregivers also received a standardized psychosocial therapy training.

Arm/Group Title	Pimavanserin Open-Label Period	Pimavanserin Double-Blind Period	Placebo Double-Blind Period
Arm/Group Description	Pimavanserin 34 mg once daily, with the possibility to adjust to pimavanserin 20 mg once daily between Weeks 1 and 4 based on tolerability. After Week 4, the dose of study drug remained fixed at either 34 or 20 mg once daily.	Pimavanserin 34 mg once daily or pimavanserin 20 mg once daily (the dose at which patients completed the Open-Label Period) for 26 weeks or until relapse	Placebo once daily for 26 weeks or until relapse
Period Title: Open-label Period
STARTED	392	0	0
COMPLETED	217	0	0
NOT COMPLETED	175	0	0
Period Title: Open-label Period
STARTED	0	105	112
COMPLETED	0	44	35
NOT COMPLETED	0	61	77

Baseline Characteristics

Arm/Group Title	Pimavanserin Open-Label Period
Arm/Group Description	Pimavanserin 34 mg once daily, with the possibility to adjust to pimavanserin 20 mg once daily between Weeks 1 and 4 based on tolerability. After Week 4, the dose of study drug remained fixed at either 34 or 20 mg once daily.
Overall Participants	392
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	74.5 (8.28)
Sex: Female, Male (Count of Participants)
Female	229 58.4%
Male	163 41.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	10 2.6%
White	371 94.6%
More than one race	0 0%
Unknown or Not Reported	3 0.8%
Region of Enrollment (participants) [Number]
United States	118 30.1%
Czechia	11 2.8%
Ukraine	74 18.9%
United Kingdom	8 2%
Spain	9 2.3%
Poland	42 10.7%
Italy	13 3.3%
Slovakia	35 8.9%
Bulgaria	3 0.8%
Chile	27 6.9%
France	7 1.8%
Serbia	44 11.2%
Germany	1 0.3%
Dementia severity (Count of Participants)
Mild	65 16.6%
Moderate	275 70.2%
Severe	52 13.3%
Scale for the Assessment of Positive Symptoms-Hallucinations+Delusions (SAPS-H+D) total score (Score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Score on a scale]	24.4 (9.22)
Clinical Global Impression-Severity (CGI-S) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	4.7 (0.69)

Outcome Measures

1. Primary Outcome

Title	Time From Randomization to Relapse in the Double-blind (DB) Period
Description	The time from randomization to relapse in the DB period was compared between treatment groups using a Cox regression model. The treatment effect was measured by the hazard ratio (HR). Relapse was defined as (1) ≥30% increase in SAPS-H+D total score from DB baseline (BL) and CGI-I score ≥6 relative to DB BL, (2) treatment with antipsychotic for dementia-related delusions/hallucinations, (3) treatment/study discontinuation due to lack of efficacy, and/or (4) hospitalization for worsening dementia-related psychosis. SAPS-H+D is a 20-item scale; the total score is the sum of the 20 item scores (range 0-100); higher scores denote more severe symptoms. CGI-I is a clinician-rated 7-point scale to rate improvement in hallucinations/delusions relative to BL (range 1-7); higher scores denote less improvement or worsening. A pre-specified IA was conducted after accrual of 40 adjudicated relapse events. The prespecified stopping criterion was met; the study was stopped for efficacy.
Time Frame	From randomization in the DB period through 26 weeks

Outcome Measure Data

Analysis Population Description

All patients randomized on or before the database cutoff date for the IA (i.e., when 40 adjudicated relapse events had accrued).

Arm/Group Title	Pimavanserin Double-Blind Period	Placebo Double-Blind Period
Arm/Group Description	Pimavanserin 34 mg once daily or pimavanserin 20 mg once daily (the dose at which patients completed the Open-Label Period) for 26 weeks or until relapse	Placebo once daily for 26 weeks or until relapse
Measure Participants	95	99
Median (Full Range) [days]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pimavanserin Double-Blind Period, Placebo Double-Blind Period
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0023
	Comments	1-sided p-value reported. The protocol-defined O'Brien Flemming stopping boundary for the planned IA was a 1-sided p-value equal to 0.0033
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.353
	Confidence Interval	(2-Sided) 95%; 0.172 to 0.727
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3676
	Estimation Comments	Model included covariates for Treatment group, dementia subtype, and region, and robust sandwich-type variance estimator.

2. Secondary Outcome

Title	Time From Randomization to Discontinuation From the DB Period for Any Reason
Description	The endpoint of time from randomization to discontinuation from the DB period for any reason (other than termination of the study by the sponsor) was compared between treatment groups using a Cox regression model. The treatment effect was measured by the HR.
Time Frame	From randomization in the DB period through 26 weeks

Outcome Measure Data

Analysis Population Description

All patients randomized on or before the database cutoff date for the IA (i.e., when 40 adjudicated relapse events had accrued).

Arm/Group Title	Pimavanserin Double-Blind Period	Placebo Double-Blind Period
Arm/Group Description	Pimavanserin 34 mg once daily or pimavanserin 20 mg once daily (the dose at which patients completed the Open-Label Period) for 26 weeks or until relapse	Placebo once daily for 26 weeks or until relapse
Measure Participants	95	99
Median (Full Range) [days]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pimavanserin Double-Blind Period, Placebo Double-Blind Period
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0024
	Comments	1-sided p-value
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.452
	Confidence Interval	(2-Sided) 95%; 0.261 to 0.785
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.2812
	Estimation Comments	Model included covariates for Treatment group, dementia subtype, and region, and robust sandwich-type variance estimator.

Adverse Events

Time Frame	Adverse Events (AEs) were to be documented through 30 days after the last dose in the study.
Arm/Group Title	Pimavanserin Open-Label Period		Pimavanserin Double-Blind Period		Placebo Double-Blind Period
Arm/Group Description	Pimavanserin 34 mg once daily, with the possibility to adjust to pimavanserin 20 mg once daily between Weeks 1 and 4 based on tolerability. After Week 4, the dose of study drug remained fixed at either 34 or 20 mg once daily		Pimavanserin 34 mg once daily or pimavanserin 20 mg once daily (the dose at which patients completed the Open-Label Period) for 26 weeks or until relapse		Placebo once daily for 26 weeks or until relapse
All Cause Mortality
	Pimavanserin Open-Label Period		Pimavanserin Double-Blind Period		Placebo Double-Blind Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/392 (0.3%)		1/105 (1%)		0/112 (0%)
Serious Adverse Events
	Pimavanserin Open-Label Period		Pimavanserin Double-Blind Period		Placebo Double-Blind Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/392 (5.1%)		5/105 (4.8%)		4/112 (3.6%)
Cardiac disorders
Cardiac failure congestive	1/392 (0.3%)	1	0/105 (0%)	0	0/112 (0%)	0
Myocardial infarction	1/392 (0.3%)	1	0/105 (0%)	0	0/112 (0%)	0
Gastrointestinal disorders
Abdominal pain lower	1/392 (0.3%)	1	0/105 (0%)	0	0/112 (0%)	0
Abdominal pain upper	1/392 (0.3%)	1	0/105 (0%)	0	0/112 (0%)	0
Diarrhoea	1/392 (0.3%)	1	0/105 (0%)	0	0/112 (0%)	0
Haematemesis	1/392 (0.3%)	1	0/105 (0%)	0	1/112 (0.9%)	1
Intestinal obstruction	1/392 (0.3%)	1	0/105 (0%)	0	0/112 (0%)	0
General disorders
Oedema peripheral	1/392 (0.3%)	1	0/105 (0%)	0	0/112 (0%)	0
Infections and infestations
Urinary tract infection	2/392 (0.5%)	2	1/105 (1%)	1	1/112 (0.9%)	1
Abscess jaw	1/392 (0.3%)	1	0/105 (0%)	0	0/112 (0%)	0
Diverticulitis	1/392 (0.3%)	1	0/105 (0%)	0	0/112 (0%)	0
Erysipelas	1/392 (0.3%)	1	0/105 (0%)	0	0/112 (0%)	0
Pneumonia	0/392 (0%)	0	0/105 (0%)	0	1/112 (0.9%)	1
Sepsis	0/392 (0%)	0	1/105 (1%)	1	0/112 (0%)	0
Septic encephalopathy	0/392 (0%)	0	1/105 (1%)	1	0/112 (0%)	0
Injury, poisoning and procedural complications
Fall	2/392 (0.5%)	2	0/105 (0%)	0	0/112 (0%)	0
Bone fissure	1/392 (0.3%)	1	0/105 (0%)	0	0/112 (0%)	0
Metabolism and nutrition disorders
Dehydration	2/392 (0.5%)	2	0/105 (0%)	0	0/112 (0%)	0
Malnutrition	1/392 (0.3%)	1	0/105 (0%)	0	0/112 (0%)	0
Decreased appetite	0/392 (0%)	0	0/105 (0%)	0	1/112 (0.9%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/392 (0.3%)	1	0/105 (0%)	0	0/112 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer metastatic	0/392 (0%)	0	1/105 (1%)	1	0/112 (0%)	0
Nervous system disorders
Metabolic encephalopathy	0/392 (0%)	0	1/105 (1%)	1	0/112 (0%)	0
Transient ischaemic attack	0/392 (0%)	0	1/105 (1%)	1	0/112 (0%)	0
Dementia Alzheimer's type	1/392 (0.3%)	1	0/105 (0%)	0	0/112 (0%)	0
Syncope	0/392 (0%)	0	0/105 (0%)	0	1/112 (0.9%)	1
Psychiatric disorders
Agression	1/392 (0.3%)	1	1/105 (1%)	1	0/112 (0%)	0
Agitation	1/392 (0.3%)	1	0/105 (0%)	0	0/112 (0%)	0
Mental status changes	1/392 (0.3%)	1	0/105 (0%)	0	0/112 (0%)	0
Neuropsychiatric symptoms	1/392 (0.3%)	1	0/105 (0%)	0	0/112 (0%)	0
Psychotic disorder	1/392 (0.3%)	1	0/105 (0%)	0	0/112 (0%)	0
Renal and urinary disorders
Acute kidney injury	1/392 (0.3%)	1	0/105 (0%)	0	0/112 (0%)	0
Other (Not Including Serious) Adverse Events
	Pimavanserin Open-Label Period		Pimavanserin Double-Blind Period		Placebo Double-Blind Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/392 (6.1%)		16/105 (15.2%)		9/112 (8%)
Infections and infestations
Urinary tract infection	18/392 (4.6%)	19	6/105 (5.7%)	8	4/112 (3.6%)	5
Nervous system disorders
Headache	6/392 (1.5%)	6	10/105 (9.5%)	13	5/112 (4.5%)	8

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 their 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.