Relapse Prevention Study of Pimavanserin in Dementia-rela... | NCT03325556

ID	Type	Description	Link
2017-002227-13	EudraCT Number

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator		Drug: Placebo
Drug - Pimavanserin	Experimental		Drug: Pimavanserin 34 mg Drug: Pimavanserin 20 mg

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug	Placebo, tablets, once daily by mouth	Placebo
Pimavanserin 34 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Time From Randomization to Relapse in the Double-blind (DB) Period	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.	From randomization in the DB period through 26 weeks

Secondary Outcomes

Measure	Description	Time Frame
Time From Randomization to Discontinuation From the DB Period for Any Reason	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.	From randomization in the DB period through 26 weeks

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Meets criteria for All-cause Dementia according to NIA-AA guidelines
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
Has an MMSE score ≥6 and ≤24
Has had psychotic symptoms for at least 2 months
Must be on a stable does of cholinesterase inhibitor or memantine, if applicable
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:

Has psychotic symptoms that are primarily attributable to a condition other than dementia
Has had a recent major depressive episode
Has experienced suicidal ideation or behavior within 3 months prior to study enrollment
Has evidence of a non-neurologic medical comorbidity or medication use that could substantially impair cognition
Has a history of ischemic stroke within the last 12 months or any evidence of hemorrhagic stroke
Has a known history of cerebral amyloid angiopathy (CAA), epilepsy, CNS neoplasm, or unexplained syncope
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
Had a myocardial infarction within the last 6 months
Has a known personal or family history or symptoms of long QT syndrome
Has a significant unstable medical condition that could interfere with subject's ability to complete the study or comply with study procedures
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.

Facility	Status	City	State	ZIP	Country	Contacts
ATP Clinical Research Inc.		Costa Mesa	California	92626	United States
Neurology Center of North Orange County

PubMed Identifier	Type	Citation	Retractions
41286676	Derived	Torres-Yaghi Y, Chrones L, Abler V, Brunson G. Safety and efficacy of pimavanserin in patients with Lewy body dementia experiencing dementia-related psychosis in the HARMONY study. BMC Neurol. 2025 Nov 24;25(1):479. doi: 10.1186/s12883-025-04496-8.
34934801	Derived	Cummings JL, Ismail Z, Dickerson BC, Ballard C, Grossberg G, McEvoy B, Foff E, Atri A. Development and assessment of a brief screening tool for psychosis in dementia. Alzheimers Dement (Amst). 2021 Dec 7;13(1):e12254. doi: 10.1002/dad2.12254. eCollection 2021.

Label	URL
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	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Pimavanserin Open-Label Period	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.
FG001	Pimavanserin Double-Blind Period

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 16, 2018	Mar 10, 2021

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

- ParticipantsBG000392

Title	Measurements
	BG00074.5± 8.28

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

- ParticipantsBG000392

Title	Measurements
Female	BG000229
Male

Race (NIH/OMB)

For 8 patients, Information on race was not available.

Count of Participants

Participants

Title

Denominators

Categories

- ParticipantsBG000384

Title	Measurements
American Indian or Alaska Native	BG000

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

- ParticipantsBG000392

Title	Measurements
	BG000118

Czechia

Dementia severity

Count of Participants

Participants

Title

Denominators

Categories

- ParticipantsBG000392

Title	Measurements
Mild	BG00065
Moderate

Scale for the Assessment of Positive Symptoms-Hallucinations+Delusions (SAPS-H+D) total score

The Scale for the Assessment of Positive Symptoms-Hallucinations and Delusions (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.

Mean

Standard Deviation

Score on a scale

Title

Denominators

Categories

- ParticipantsBG000392

Title	Measurements
	BG000

Clinical Global Impression-Severity (CGI-S)

The Clinical Global Impression-Severity (CGI-S) is a clinician-rated, 7-point scale to rate the severity of the patient's hallucinations and delusions at the time of assessment. Scores range from 1 to 7, with a higher score marking a more severe state.

Mean

Standard Deviation

units on a scale

Title

Denominators

Categories

- ParticipantsBG000392

Title	Measurements
	BG000

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

Time From Randomization to Relapse in the Double-blind (DB) Period

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.

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

Posted

Median

Full Range

days

From randomization in the DB period through 26 weeks

ID	Title	Description
OG000	Pimavanserin Double-Blind Period	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
OG001	Placebo Double-Blind Period	Placebo once daily for 26 weeks or until relapse

Units	Counts
Participants	OG00095 OG00199

Title

Denominators

Categories

Title	Measurements
	OG000NA(NA to NA)The median time to relapse could not be estimated as the Kaplan-Meier probability estimate of relapse over the 26-week DB period did not exceed 50%. OG001NA(NA to NA)The median time to relapse could not be estimated as the Kaplan-Meier probability estimate of relapse over the 26-week DB period did not exceed 50%.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Regression, Cox		0.0023	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	Hazard Ratio (HR)	0.353	Standard Error of the Mean	0.3676	2-Sided	95	0.172	0.727			Model included covariates for Treatment group, dementia subtype, and region, and robust sandwich-type variance estimator.		Superiority

Secondary

Time From Randomization to Discontinuation From the DB Period for Any Reason

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.

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

Posted

Median

Full Range

days

From randomization in the DB period through 26 weeks

ID	Title	Description
OG000	Pimavanserin Double-Blind Period	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
OG001	Placebo Double-Blind Period	Placebo once daily for 26 weeks or until relapse

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cardiac failure congestive	Cardiac disorders	MedDRA 22.0	Non-systematic Assessment	EG0001 events1 affected392 at risk EG0010 events0 affected105 at risk EG0020 events0 affected112 at risk
Myocardial infarction	Cardiac disorders	MedDRA 22.0	Non-systematic Assessment	EG0001 events1 affected392 at risk EG0010 events0 affected105 at risk EG0020 events0 affected112 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA 22.0	Non-systematic Assessment	EG0001 events1 affected392 at risk EG0010 events0 affected105 at risk EG0020 events0 affected112 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 22.0	Non-systematic Assessment	EG0001 events1 affected392 at risk EG0010 events0 affected105 at risk EG0020 events0 affected112 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 22.0	Non-systematic Assessment	EG0001 events1 affected392 at risk EG0010 events0 affected105 at risk EG0020 events0 affected112 at risk
Haematemesis	Gastrointestinal disorders	MedDRA 22.0	Non-systematic Assessment	EG0001 events1 affected392 at risk EG0010 events0 affected105 at risk EG0021 events1 affected112 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 22.0	Non-systematic Assessment	EG0001 events1 affected392 at risk EG0010 events0 affected105 at risk EG0020 events0 affected112 at risk
Oedema peripheral	General disorders	MedDRA 22.0	Non-systematic Assessment	EG0001 events1 affected392 at risk EG0010 events0 affected105 at risk EG0020 events0 affected112 at risk
Urinary tract infection	Infections and infestations	MedDRA 22.0	Non-systematic Assessment	EG0002 events2 affected392 at risk EG0011 events1 affected105 at risk EG0021 events1 affected112 at risk
Abscess jaw	Infections and infestations	MedDRA 22.0	Non-systematic Assessment	EG0001 events1 affected392 at risk EG0010 events0 affected105 at risk EG0020 events0 affected112 at risk
Diverticulitis	Infections and infestations	MedDRA 22.0	Non-systematic Assessment	EG0001 events1 affected392 at risk EG0010 events0 affected105 at risk EG0020 events0 affected112 at risk
Erysipelas	Infections and infestations	MedDRA 22.0	Non-systematic Assessment	EG0001 events1 affected392 at risk EG0010 events0 affected105 at risk EG0020 events0 affected112 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 22.0	Non-systematic Assessment	EG0002 events2 affected392 at risk EG0010 events0 affected105 at risk EG0020 events0 affected112 at risk
Bone fissure	Injury, poisoning and procedural complications	MedDRA 22.0	Non-systematic Assessment	EG0001 events1 affected392 at risk EG0010 events0 affected105 at risk EG0020 events0 affected112 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 22.0	Non-systematic Assessment	EG0002 events2 affected392 at risk EG0010 events0 affected105 at risk EG0020 events0 affected112 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA 22.0	Non-systematic Assessment	EG0001 events1 affected392 at risk EG0010 events0 affected105 at risk EG0020 events0 affected112 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Non-systematic Assessment	EG0001 events1 affected392 at risk EG0010 events0 affected105 at risk EG0020 events0 affected112 at risk
Pneumonia	Infections and infestations	MedDRA 22.0	Non-systematic Assessment	EG0000 events0 affected392 at risk EG0010 events0 affected105 at risk EG0021 events1 affected112 at risk
Sepsis	Infections and infestations	MedDRA 22.0	Non-systematic Assessment	EG0000 events0 affected392 at risk EG0011 events1 affected105 at risk EG0020 events0 affected112 at risk
Septic encephalopathy	Infections and infestations	MedDRA 22.0	Non-systematic Assessment	EG0000 events0 affected392 at risk EG0011 events1 affected105 at risk EG0020 events0 affected112 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 22.0	Non-systematic Assessment	EG0000 events0 affected392 at risk EG0010 events0 affected105 at risk EG0021 events1 affected112 at risk
Prostate cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Non-systematic Assessment	EG0000 events0 affected392 at risk EG0011 events1 affected105 at risk EG0020 events0 affected112 at risk
Metabolic encephalopathy	Nervous system disorders	MedDRA 22.0	Non-systematic Assessment	EG0000 events0 affected392 at risk EG0011 events1 affected105 at risk EG0020 events0 affected112 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 22.0	Non-systematic Assessment	EG0000 events0 affected392 at risk EG0011 events1 affected105 at risk EG0020 events0 affected112 at risk
Agression	Psychiatric disorders	MedDRA 22.0	Non-systematic Assessment	EG0001 events1 affected392 at risk EG0011 events1 affected105 at risk EG0020 events0 affected112 at risk
Dementia Alzheimer's type	Nervous system disorders	MedDRA 22.0	Non-systematic Assessment	EG0001 events1 affected392 at risk EG0010 events0 affected105 at risk EG0020 events0 affected112 at risk
Agitation	Psychiatric disorders	MedDRA 22.0	Non-systematic Assessment	EG0001 events1 affected392 at risk EG0010 events0 affected105 at risk EG0020 events0 affected112 at risk
Mental status changes	Psychiatric disorders	MedDRA 22.0	Non-systematic Assessment	EG0001 events1 affected392 at risk EG0010 events0 affected105 at risk EG0020 events0 affected112 at risk
Neuropsychiatric symptoms	Psychiatric disorders	MedDRA 22.0	Non-systematic Assessment	EG0001 events1 affected392 at risk EG0010 events0 affected105 at risk EG0020 events0 affected112 at risk
Psychotic disorder	Psychiatric disorders	MedDRA 22.0	Non-systematic Assessment	EG0001 events1 affected392 at risk EG0010 events0 affected105 at risk EG0020 events0 affected112 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 22.0	Non-systematic Assessment	EG0001 events1 affected392 at risk EG0010 events0 affected105 at risk EG0020 events0 affected112 at risk
Syncope	Nervous system disorders	MedDRA 22.0	Non-systematic Assessment	EG0000 events0 affected392 at risk EG0010 events0 affected105 at risk EG0021 events1 affected112 at risk

ID	Term
D003704	Dementia
D020961	Lewy Body Disease
D000544	Alzheimer Disease
D013494	Supranuclear Palsy, Progressive
D000088282	Corticobasal Degeneration
D015140	Dementia, Vascular
D006212	Hallucinations
D003702	Delusions
D011618	Psychotic Disorders

ID	Term
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D019965	Neurocognitive Disorders
D001523	Mental Disorders
D020734	Parkinsonian Disorders
D001480	Basal Ganglia Diseases
D009069	Movement Disorders
D000080874	Synucleinopathies
D019636	Neurodegenerative Diseases
D024801	Tauopathies
D009886	Ophthalmoplegia
D015835	Ocular Motility Disorders
D003389	Cranial Nerve Diseases
D010243	Paralysis
D009461	Neurologic Manifestations
D005128	Eye Diseases
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D002561	Cerebrovascular Disorders
D002537	Intracranial Arteriosclerosis
D020765	Intracranial Arterial Diseases
D056784	Leukoencephalopathies
D001161	Arteriosclerosis
D001157	Arterial Occlusive Diseases
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D010468	Perceptual Disorders
D019954	Neurobehavioral Manifestations
D001526	Behavioral Symptoms
D001519	Behavior
D019967	Schizophrenia Spectrum and Other Psychotic Disorders

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pimavanserin Open-Label Period	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	1	392	20	392	24	392
EG001	Pimavanserin Double-Blind Period	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	1	105	5	105	16	105
EG002	Placebo Double-Blind Period	Placebo once daily for 26 weeks or until relapse	0	112	4	112	9	112