Relapse Prevention Study of Pimavanserin in Dementia-related Psychosis

NCT03325556 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: ACP-103-0452017-002227-13
• Study Type: interventional
• Target: 392
• Locations: 13 countries
• Sites: 83

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.

Conditions

Dementia-related Psychosis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 (1)

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

  From randomization in the DB period through 26 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Drug - Pimavanserin

EXPERIMENTAL

Drug: Pimavanserin 34 mg; Drug: Pimavanserin 20 mg

Interventions

Placebo DRUG

Placebo, tablets, once daily by mouth

Placebo

Pimavanserin 34 mg DRUG

Pimavanserin 34 mg total daily dose, tablets, once daily by mouth

Drug - Pimavanserin

Pimavanserin 20 mg DRUG

Pimavanserin 20 mg total daily dose, tablets, once daily by mouth

Drug - Pimavanserin

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ACADIA Pharmaceuticals Inc.: lead

Study Sites (83)

ATP Clinical Research Inc.

Costa Mesa, California, 92626, United States

Location

Neurology Center of North Orange County

Fullerton, California, 92835, United States

Location

Visionary Investigators Network (Aventura Neurologic Associates)

Aventura, Florida, 33180, United States

Location

Parkinson's Disease and Movement Disorders Center of Boca Raton

Boca Raton, Florida, 33486, United States

Location

Premier Clinical Research Institute, Inc.

Miami, Florida, 33122, United States

Location

Visionary Investigators Network (First Choice Neurology Group)

Miami, Florida, 33176, United States

Location

Novel Clinical Research Center, LLC

Miami, Florida, 33186, United States

Location

Collier Neurologic Specialists LLC

Naples, Florida, 34102, United States

Location

Bioclinica Research

Orlando, Florida, 32806, United States

Location

Neurology Associates of Ormond Beach

Ormond Beach, Florida, 32174, United States

Location

Quantum Laboratories

Pompano Beach, Florida, 33064, United States

Location

Neuroscience Research Institute

Winfield, Illinois, 60190, United States

Location

University of Kansas Medical Center Research Institute, Inc.

Kansas City, Kansas, 66160, United States

Location

Alzheimer Disease Center

Quincy, Massachusetts, 02169, United States

Location

Clinical Research Professionals

Chesterfield, Missouri, 63005, United States

Location

Millennium Psychiatric Associates, LLC; DBA Millennium Center for Clinical Research

St Louis, Missouri, 63132, United States

Location

Neurology Center of Las Vegas

Las Vegas, Nevada, 89128, United States

Location

Memory Enhancement Center of America, Inc.

Eatontown, New Jersey, 07724, United States

Location

BioBehavioral Health

Toms River, New Jersey, 08755, United States

Location

Neurological Associates of Albany, PC

Albany, New York, 12208, United States

Location

Manhattan Behavioral Medicine, PLLC

New York, New York, 10036, United States

Location

Richmond Behavioral Associates

Staten Island, New York, 10312, United States

Location

Neuro-Behavioral Clinical Research, Inc.

North Canton, Ohio, 44720, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Abington Neurological Associates Ltd.

Willow Grove, Pennsylvania, 19090, United States

Location

University of Tennessee Medical Center

Knoxville, Tennessee, 37920, United States

Location

University of Virginia Adult Neurology

Charlottesville, Virginia, 22903, United States

Location

Mental Health Center - Ruse EOOD

Rousse, 7003, Bulgaria

Location

Psicomed Estudios Medicos

Antofagasta, 1270244, Chile

Location

Biomedica Research Group

Santiago, 7500710, Chile

Location

Especialidades Médicas L y S

Santiago, 7560356, Chile

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 50005, Czechia

Location

Clintrial s.r.o.

Prague, 10000, Czechia

Location

AD71, s.r.o.

Prague, 10900, Czechia

Location

Vestra Clinics, s.r.o

Rychnov nad Kněžnou, 51601, Czechia

Location

Assistance Publique Hopitaux de Marseille (AP-HM) - Hopital de La Timone - Service de Neurologie et Pathologie du Mouvement du Pr Azulay

Marseille, 13385, France

Location

Centre de Recherche du Gerontopole - CHU de Toulouse

Toulouse, 31059, France

Location

Klinik für Psychiatrie und Psychotherapie der Universität Tübingen

Tübingen, 72076, Germany

Location

Azienda Ospedaliera di Padova Clinica Neurologica

Padua, 35121, Italy

Location

IRCCS San Raffaele Pisanna

Rome, 00163, Italy

Location

IRCCS Fondazione Santa Lucia, Dipartimento di Neurologia e Psichiatria

Rome, 00179, Italy

Location

Universita degli Studi di ROMA "La Sapienza" Dipartimento di NEUROLOGIA E PSICHIATRIA

Rome, 00185, Italy

Location

Azienda Ospedaliero-Universitaria Citta della Salute a della Scienza di Torino - c/o Presidio Ospedaliero Molinette Clinica Neurologica I

Torino, 10126, Italy

Location

Przychodnia Śródmieście Sp. z o.o.

Bydgoszcz, 85-080, Poland

Location

ISPL Wieslaw Jerzy Cubala

Gdansk, 80-438, Poland

Location

Care Clinic

Katowice, 40-060, Poland

Location

Specjalistyczna Praktyka Lekarska

Lublin, 20-582, Poland

Location

NZOZ Neuro-Kard Ilkowski i Partnerzy Spółka Partnerska Lekarzy

Poznan, 61-853, Poland

Location

NEURO-CARE Sp. z o.o. Sp. Komandytowa

Siemianowice Śląskie, 41-100, Poland

Location

Euromedis Sp z. o. o.

Szczecin, 70-111, Poland

Location

Centrum Medyczne NeuroProtect

Warsaw, 01-697, Poland

Location

Clinical center of Serbia, Clinic for Neurology

Belgrade, 11 000, Serbia

Location

Military Medical Academy, Clinic for Neurology

Belgrade, 11 000, Serbia

Location

Clinical Hospital Center Dr Dragisa Misovic-Dedinje

Belgrade, 11000, Serbia

Location

Institut of Mental Health

Belgrade, 11000, Serbia

Location

Psychiatric Clinic, Military Medical Academy

Belgrade, 11000, Serbia

Location

Clinic for Psychiatry, Clinical Center Kragujevac

Kragujevac, 34 000, Serbia

Location

Department of addictive disorders of the Clinic for Psychiatry, Clinical center Kragujevac

Kragujevac, 34 000, Serbia

Location

Clinic for Psychiatry

Niš, 18 000, Serbia

Location

MUDr. Beata Dupejova, neurologicka ambulancia s.r.o

Banská Bystrica, 974 04, Slovakia

Location

Epamed s.r.o., Psychiatricka ambulancia

Košice, 040 01, Slovakia

Location

NEURES s.r.o. neurologicka ambulancia

Krompachy, 053 42, Slovakia

Location

Centrum Zdravia R.B.K., s.r.o.

Svidník, 089 01, Slovakia

Location

Crystal Comfort, s.r.o.

Vranov nad Topľou, 093 01, Slovakia

Location

Clinica IINA

Barcelona, 08006, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital General de Cataluña

Sant Cugat del Vallès, 08195, Spain

Location

Estudio de Psiquiatría

Seville, 41003, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Municipal Institution "Odesa Regional Psychiatric Hospital #2", Female Gerontological Department # 5, Male Gerontological Department #1

Oleksandrivka, Odesa Oblast, 67513, Ukraine

Location

Communal Institution "Dnipropetrovsk Regional Clinical Hospital n.a. I. I. Mechnikov"

Dnipro, 49005, Ukraine

Location

Municipal Institution of Health Care "Kharkiv Regional Clinical Psychiatric Hospital #3"

Kharkiv, 61068, Ukraine

Location

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, 61068, Ukraine

Location

Kherson Regional Psychiatric Hospital

Kherson, 73488, Ukraine

Location

Lviv Regional State Clinical Psychiatric Hospital

Lviv, 79021, Ukraine

Location

Municipal Institution "Odesa Regional Medical Center of Mental Health", Department #18

Odesa, 65006, Ukraine

Location

Poltava Regional Clinical Psychiatric Hospital named after O.F. Maltsev

Poltava, 36013, Ukraine

Location

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

Vinnytsia, 21005, Ukraine

Location

Municipal Institution "Zaporizhzhya Regional Clinical Hospital of Zaporizhzhya Regional Council"

Zaporizhzhya, 69600, Ukraine

Location

Royal United Hospital - The Research Institute for the Care of Older People (RICE) Centre

Bath, BA1 3NG, United Kingdom

Location

MAC Clinical Research - Blackpool

Blackpool, FY2 0JH, United Kingdom

Location

Re:Cognition Health Ltd.

London, W1G 9JF, United Kingdom

Location

MAC Clinical Research - Manchester

Manchester, M13 9NQ, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 41286676 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.

  PMID: 34934801 DERIVED

• Tariot PN, Cummings JL, Soto-Martin ME, Ballard C, Erten-Lyons D, Sultzer DL, Devanand DP, Weintraub D, McEvoy B, Youakim JM, Stankovic S, Foff EP. Trial of Pimavanserin in Dementia-Related Psychosis. N Engl J Med. 2021 Jul 22;385(4):309-319. doi: 10.1056/NEJMoa2034634.

  PMID: 34289275 DERIVED

Related Links

• 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

MeSH Terms

Conditions

Dementia; Lewy Body Disease; Alzheimer Disease; Supranuclear Palsy, Progressive; Corticobasal Degeneration; Dementia, Vascular; Hallucinations; Delusions; Psychotic Disorders

Interventions

pimavanserin

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Tauopathies; Ophthalmoplegia; Ocular Motility Disorders; Cranial Nerve Diseases; Paralysis; Neurologic Manifestations; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cerebrovascular Disorders; Intracranial Arteriosclerosis; Intracranial Arterial Diseases; Leukoencephalopathies; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Perceptual Disorders; Neurobehavioral Manifestations; Behavioral Symptoms; Behavior; Schizophrenia Spectrum and Other Psychotic Disorders

Results Point of Contact

• Title: Sr. Dir. Medical Information and Medical Communications
• Organization: Acadia Pharmaceuticals Inc.

medicalinformation@acadia-pharm.com

858-261-

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2017
• First Posted: October 30, 2017
• Study Start: September 27, 2017
• Primary Completion: July 31, 2019
• Study Completion: October 30, 2019
• Last Updated: June 21, 2021
• Results First Posted: June 21, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); ES (5); BU (1); CL (3); SE (8); FR (2); US (27); GB (4); IT (5); CZ (4); UA (10); SL (5); PL (8)