Relapse Prevention Study of Pimavanserin in Dementia-related Psychosis

Phase 3

Completed

Conditions: Dementia-related Psychosis

Interventions: Drug: Placebo
Drug: Pimavanserin 34 mg
Drug: Pimavanserin 20 mg

Registration Number: NCT03325556

Lead Sponsor: ACADIA Pharmaceuticals Inc.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 392

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Drug - Pimavanserin	Pimavanserin 34 mg	-
Drug - Pimavanserin	Pimavanserin 20 mg	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.

Trial Locations

Locations (83): Municipal Institution "Odesa Regional Medical Center of Mental Health", Department #18
🇺🇦
Odesa, Ukraine
University of Tennessee Medical Center
🇺🇸
Knoxville, Tennessee, United States
Institut of Mental Health
🇷🇸
Belgrade, Serbia
NEURES s.r.o. neurologicka ambulancia
🇸🇰
Krompachy, Slovakia
Department of addictive disorders of the Clinic for Psychiatry, Clinical center Kragujevac
🇷🇸
Kragujevac, Serbia
Epamed s.r.o., Psychiatricka ambulancia
🇸🇰
Košice, Slovakia
Crystal Comfort, s.r.o.
🇸🇰
Vranov nad Toplou, Slovakia
ATP Clinical Research Inc.
🇺🇸
Costa Mesa, California, United States
Novel Clinical Research Center, LLC
🇺🇸
Miami, Florida, United States
Visionary Investigators Network (Aventura Neurologic Associates)
🇺🇸
Aventura, Florida, United States
Millennium Psychiatric Associates, LLC; DBA Millennium Center for Clinical Research
🇺🇸
Saint Louis, Missouri, United States
Neurology Center of Las Vegas
🇺🇸
Las Vegas, Nevada, United States
Richmond Behavioral Associates
🇺🇸
Staten Island, New York, United States
Clinical center of Serbia, Clinic for Neurology
🇷🇸
Belgrade, Serbia
Hospital General de Cataluña
🇪🇸
Sant Cugat Del Vallès, Spain
Centrum Medyczne NeuroProtect
🇵🇱
Warszawa, Poland
Abington Neurological Associates Ltd.
🇺🇸
Willow Grove, Pennsylvania, United States
Military Medical Academy, Clinic for Neurology
🇷🇸
Belgrade, Serbia
Psychiatric Clinic, Military Medical Academy
🇷🇸
Belgrade, Serbia
Biomedica Research Group
🇨🇱
Santiago, Chile
Centrum Zdravia R.B.K., s.r.o.
🇸🇰
Svidnik, Slovakia
Municipal Institution "Odesa Regional Psychiatric Hospital #2", Female Gerontological Department # 5, Male Gerontological Department #1
🇺🇦
Oleksandrivka, Odessa Region, Ukraine
Communal Institution "Dnipropetrovsk Regional Clinical Hospital n.a. I. I. Mechnikov"
🇺🇦
Dnipro, Ukraine
Kherson Regional Psychiatric Hospital
🇺🇦
Kherson, Ukraine
Clinical Hospital Center Dr Dragisa Misovic-Dedinje
🇷🇸
Belgrade, Serbia
Estudio de Psiquiatría
🇪🇸
Sevilla, Spain
Lviv Regional State Clinical Psychiatric Hospital
🇺🇦
Lviv, Ukraine
Clinic for Psychiatry, Clinical Center Kragujevac
🇷🇸
Kragujevac, Serbia
Clinic for Psychiatry
🇷🇸
Nis, Serbia
Municipal Institution of Health Care "Kharkiv Regional Clinical Psychiatric Hospital #3"
🇺🇦
Kharkiv, Ukraine
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
Royal United Hospital - The Research Institute for the Care of Older People (RICE) Centre
🇬🇧
Bath, United Kingdom
Centre de Recherche du Gerontopole - CHU de Toulouse
🇫🇷
Toulouse, France
Re:Cognition Health Ltd.
🇬🇧
London, United Kingdom
Clinica IINA
🇪🇸
Barcelona, Spain
Hospital Universitari Vall d'Hebron
🇪🇸
Barcelona, Spain
Mental Health Center - Ruse EOOD
🇧🇬
Russe, Bulgaria
Neurology Center of North Orange County
🇺🇸
Fullerton, California, United States
Parkinson's Disease and Movement Disorders Center of Boca Raton
🇺🇸
Boca Raton, Florida, United States
Premier Clinical Research Institute, Inc.
🇺🇸
Miami, Florida, United States
Visionary Investigators Network (First Choice Neurology Group)
🇺🇸
Miami, Florida, United States
Neurology Associates of Ormond Beach
🇺🇸
Ormond Beach, Florida, United States
Bioclinica Research
🇺🇸
Orlando, Florida, United States
Quantum Laboratories
🇺🇸
Pompano Beach, Florida, United States
Neuroscience Research Institute
🇺🇸
Winfield, Illinois, United States
Memory Enhancement Center of America, Inc.
🇺🇸
Eatontown, New Jersey, United States
Clinical Research Professionals
🇺🇸
Chesterfield, Missouri, United States
Alzheimer Disease Center
🇺🇸
Quincy, Massachusetts, United States
Neuro-Behavioral Clinical Research, Inc.
🇺🇸
North Canton, Ohio, United States
Manhattan Behavioral Medicine, PLLC
🇺🇸
New York, New York, United States
BioBehavioral Health
🇺🇸
Toms River, New Jersey, United States
Neurological Associates of Albany, PC
🇺🇸
Albany, New York, United States
University of Virginia Adult Neurology
🇺🇸
Charlottesville, Virginia, United States
Psicomed Estudios Medicos
🇨🇱
Antofagasta, Chile
Especialidades Médicas L y S
🇨🇱
Santiago, Chile
Klinik für Psychiatrie und Psychotherapie der Universität Tübingen
🇩🇪
Tuebingen, Germany
Clintrial s.r.o.
🇨🇿
Praha 10, Czechia
AD71, s.r.o.
🇨🇿
Praha 10, Czechia
Fakultni nemocnice Hradec Kralove
🇨🇿
Hradec Králové, Czechia
Vestra Clinics, s.r.o
🇨🇿
Rychnov nad Kněžnou, Czechia
Azienda Ospedaliera di Padova Clinica Neurologica
🇮🇹
Padova, Italy
Assistance Publique Hopitaux de Marseille (AP-HM) - Hopital de La Timone - Service de Neurologie et Pathologie du Mouvement du Pr Azulay
🇫🇷
Marseille, France
IRCCS San Raffaele Pisanna
🇮🇹
Rome, Italy
IRCCS Fondazione Santa Lucia, Dipartimento di Neurologia e Psichiatria
🇮🇹
Rome, Italy
Universita degli Studi di ROMA "La Sapienza" Dipartimento di NEUROLOGIA E PSICHIATRIA
🇮🇹
Rome, Italy
Azienda Ospedaliero-Universitaria Citta della Salute a della Scienza di Torino - c/o Presidio Ospedaliero Molinette Clinica Neurologica I
🇮🇹
Torino, Italy
Przychodnia Śródmieście Sp. z o.o.
🇵🇱
Bydgoszcz, Poland
NZOZ Neuro-Kard Ilkowski i Partnerzy Spółka Partnerska Lekarzy
🇵🇱
Poznan, Poland
ISPL Wieslaw Jerzy Cubala
🇵🇱
Gdańsk, Poland
NEURO-CARE Sp. z o.o. Sp. Komandytowa
🇵🇱
Siemianowice Śląskie, Poland
Euromedis Sp z. o. o.
🇵🇱
Szczecin, Poland
MUDr. Beata Dupejova, neurologicka ambulancia s.r.o
🇸🇰
Banska Bystrica, Slovakia
Hospital Universitario Virgen del Rocío
🇪🇸
Sevilla, Spain
Poltava Regional Clinical Psychiatric Hospital named after O.F. Maltsev
🇺🇦
Poltava, Ukraine
Municipal Institution "Zaporizhzhya Regional Clinical Hospital of Zaporizhzhya Regional Council"
🇺🇦
Zaporizhzhya, Ukraine
MAC Clinical Research - Manchester
🇬🇧
Manchester, United Kingdom
MAC Clinical Research - Blackpool
🇬🇧
Blackpool, United Kingdom
Collier Neurologic Specialists LLC
🇺🇸
Naples, Florida, United States
University of Kansas Medical Center Research Institute, Inc.
🇺🇸
Kansas City, Kansas, United States
Care Clinic
🇵🇱
Katowice, Poland
Specjalistyczna Praktyka Lekarska
🇵🇱
Lublin, Poland
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
Thomas Jefferson University
🇺🇸
Philadelphia, Pennsylvania, United States