A Safety Study of Pimavanserin in Adult and Elderly Subjects Experiencing Neuropsychiatric Symptoms Related to Neurodegenerative Disease

Neuropsychiatric Symptoms Related to Neurodegenerative Disease Clinical Trial

Official title:

A Phase 3b, Multicenter, Randomized, Double-blind, Placebo-controlled, Safety Study of Pimavanserin Therapy in Adult and Elderly Subjects Experiencing Neuropsychiatric Symptoms Related to Neurodegenerative Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03575052
• Other study ID #: ACP-103-046
• Secondary ID: 2017-003536-36
• Status: Completed
• Phase: Phase 3
• Start date: May 21, 2018
• Est. completion date: May 6, 2022

Study information

• Verified date: August 2022
• Source: ACADIA Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the safety and tolerability of pimavanserin compared to placebo in adult and elderly subjects with neuropsychiatric symptoms related to neurodegenerative disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 784
• Est. completion date: May 6, 2022
• Est. primary completion date: May 6, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

Inclusion Criteria:

1. Can understand the nature of the trial and protocol requirements and provide written informed consent. If the subject is deemed not competent to provide informed consent, the following requirements for consent must be met:

1. The subject's legally acceptable representative (LAR) (or study partner/caregiver, if local regulations allow) must provide written informed consent

2. The subject must provide written (if capable) informed assent

2. Subject requires some or complete assistance with one or more of the following:

1. Instrumental activities of daily living (communication, transportation, meal preparation, shopping, housework, managing medications, managing personal finances) OR

2. Basic activities of daily living (personal hygiene, dressing, eating, maintaining continence or transferring)

3. Meets clinical criteria for at least one of the following disorders, with or without cerebrovascular disease (CVD):

1. Parkinson's disease with or without dementia as defined by the Movement Disorder Society's Task Force

2. Dementia with Lewy bodies (DLB)

3. All-cause dementia, possible or probable Alzheimer's disease (AD)

4. Frontotemporal degeneration spectrum disorders, including possible or probable:

i. Behavioral variant frontotemporal dementia

ii. Progressive supranuclear palsy

iii. Corticobasal degeneration

e. Vascular dementia, including post-stroke dementia multi-infarct dementia and/or subcortical ischemic vascular dementia (SIVD)

4. Has a designated study partner/caregiver

5. Can come to the clinic for study visits with a study partner/caregiver

6. If the subject is female, she must not be pregnant or breastfeeding. She must also be of non-childbearing potential (defined as either surgically sterilized or at least 1 year postmenopausal) or must agree to use a clinically acceptable method of contraception or be abstinent.

7. If the subject is taking an antipsychotic medication at the time of screening, the antipsychotic medication must be discontinued 2 weeks or 5 half-lives (whichever is longer)

Exclusion Criteria:

1. Is in hospice, is receiving end-of-life palliative care, or is bedridden

2. Has psychotic symptoms that are primarily attributable to delirium or substance abuse (i.e., neuropsychiatric symptoms not related to neurodegenerative disease)

3. Has current evidence of an unstable neurological, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical disorder, including cancer or malignancies that, in the judgment of the Investigator, would jeopardize the safe participation of the subject in the study or significantly interfere with the conduct or interpretation of the study

4. Has a known personal or family history of long QT syndrome or family history of sudden cardiac death

5. Has a clinical significant CNS abnormality that is most likely contributing to the dementia or findings on MRI or CT including:

1. intracranial mass lesion

2. vascular malformation

3. evidence of >4 hemosiderin deposits

6. The urine drug screen result at Visit 1 (Screening) indicates the presence of amphetamine/methamphetamine, barbiturates, cocaine, or phencyclidine (PCP). Subjects who test positive for amphetamines and who have a valid prescription may be retested if they agree to abstain from the medication for the length of their participation in the study. The presence of benzodiazepines, marijuana (THC), or opiates does not necessarily exclude the subject from the study, as assessed by the Investigator in consultation with the Medical Monitor.

7. Has previously been enrolled in any prior clinical study with pimavanserin or is currently taking pimavanserinIs judged by the Investigator or the Medical Monitor to be inappropriate for the study for any reason

Additional inclusion/exclusion criteria apply. Patients will be evaluated at screening to ensure that all criteria for study participation are met. 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 pre-specified entry criteria).

Related Conditions & MeSH terms

• Neurodegenerative Diseases
• Neuropsychiatric Symptoms Related to Neurodegenerative Disease

Intervention

Drug:
• Pimavanserin
Pimavanserin 34 mg total daily dose, tablets, once daily by mouth (provided as two 17 mg NUPLAZID® tablets)
• Placebo
Placebo, tablets, once daily by mouth (provided as two placebo tablets)

Locations

Country	Name	City	State
Bulgaria	Centre for Mental Health Prof. Dr. Ivan Temkov, Lazur Compl., Park Ezero	Bourgas
Bulgaria	UMHAT Psych clin for gen psychiatry and addictions	Pleven
Bulgaria	DCC Sv. Vrach and Sv. Sv. Kozma and Damyan	Sofia
Bulgaria	Diagnostic Consultative Centre, 2, N. Vaptzarov Street	Varna
Bulgaria	Diagnostic Consultative Centre-Mladost-Psychiatry, 15, Republika Blvd	Varna
Bulgaria	Mental Health Center Vratza EOOD, 1 Belasitsa St	Vratsa
Colombia	Centr Investigaciones y Proyectos en Neurociencias	Barranquilla	Atlantico
Colombia	E.S.E. Hospital Mental de Antioquia	Bello	Antioquia
Colombia	Centro de Investigaciones del Sistema Nervioso	Bogota
Colombia	Psynapsis Salud Mental S.A.	Pereira	Risaralda
Czechia	BRAIN-SOULTHERAPY s.r.o., , Lekarna Jalta, Namesti Jana Masaryka 3113	Kladno
Czechia	Fakultni nemocnice Olomouc	Olomouc
Czechia	A-shine s.r.o./ Lekarna Centrum	Plzen
Czechia	AD71, s.r.o.,/Hostivarska Iekarna	Praha 10
Czechia	Axon Clinical	Praha 5
Czechia	Neuropsychiatrie, s.r.o., Lekarna 6ka, Fajtlova 1	Praha 6
Czechia	AD71, s.r.o., /,Lekarna DPS Recruiting	Rícany
Georgia	Health Institute LLC	Tbilisi
Georgia	Petre Sarajishvili Institute of Neurology LLC	Tbilisi
Georgia	Pineo Medical Ecosystem LTD	Tbilisi
Georgia	S. Khechinashvili University Hospital LLC	Tbilisi
Georgia	Tbilisi Heart and Vascular Clinic LTD	Tbilisi
Mexico	Instituto Nacional de Neurologia y Neurocirugia	Ciudad de Mexico	Delegacion Tlalpan
Mexico	Centro Regional para Adulto Mayor, Hsp Univ, JEG	Monterrey	Nuevo Leon
Mexico	Christus Muguerza Hospital Sur	Monterrey	Nuevo Leon
Mexico	Clinicos y Especialidades Medicas	Monterrey	Nuevo Leon
Mexico	Hospital Universitario Saltillo	Saltillo	Coahuila
Poland	MlynowaMed SP Psych Dr. Joanna Lazarcyck	Bialystok
Poland	Wlokiennicza Me Sp Prak Lekarska Dromasz Markowski	Bialystok
Poland	Przychodnia Srodmiescie Sp. z.o.o.	Bydgoszcz
Poland	ISPL Wieslaw Jerzy Cubala	Gdansk
Poland	NZOZ Wielospecjalistyczna Poradnia Lekarska Synap	Katowice
Poland	Silmedic Sp. z.o.o.	Katowice
Poland	Krakowska Ak Neuro Sp.- Centrum Neuro Klinicznej, ul. Arianska 7/3	Kraków
Poland	Neurologi ZOZ Cntr Leczenia SM Badan Klinicznych	Plewiska	Poznan
Poland	Centrum Medyczne HCP Sp. z.o.o.	Poznan
Poland	NZOZ Syntonia Poradnia Zdrowia Psychicznego, ul. Cyprysowa 2F/ 9,10, Pruszcz	Pruszcz Gdanski
Poland	Neuro-care	Siemianowice Slaskie
Poland	Neuro-Care Sp. z.o.o. sp. Komandytowa	Siemianowice Slaskie
Poland	RCMed Oddzial Sochaczew, ul. _eromskiego 41A	Sochaczew
Romania	Spitalul Clinic Judetean de Urgenta Cluj-Napoca	Cluj-Napoca	Cluj
Romania	Spitalul clinic CF Constanta, Sectia Neurologie	Constanta
Romania	Med Anima SRL, Clinica de psihiatrie	Iasi
Romania	S.C. Carpe Diem SRL	Sibiu
Russian Federation	Federal Siberian Sci Clinical Center of Med and Bio	Krasnoyarsk	Krasnoyarksk Region
Russian Federation	Mental Health Research Center	Moscow
Russian Federation	City Clinical Hospital #34	Novosibirsk
Russian Federation	Leningrad Regional Psychoneurological Dispensary	Roshchino
Russian Federation	City Psychiatric Hospital #3	Saint Petersburg
Russian Federation	FSBI NMRC PN n.a. V.M. Bekhterev	Saint Petersburg
Russian Federation	St. Nicholas the Wonder Worker Psychiatric Hospital	Saint Petersburg
Russian Federation	Samara Psychiatric Hospital	Samara
Russian Federation	Saratov City Clinical Hospital V. I. Razumovsky	Saratov
Russian Federation	Smolensk State Medical University	Smolensk
Russian Federation	Stavropol Regional Clin Spec Psych Hospital #1	Stavropol'
Russian Federation	Clinic "Hundred Years"	Tomsk	Tomsk Region
Russian Federation	Regional Specialized Psychiatric Hospital #2	Tonnel'nyy	Kochubeev District
Serbia	CHC Dr Dragisa Misovic- Dedinje	Belgrade
Serbia	Clinic for Psychiatric Diseases Dr. Laza Lazarevic	Belgrade
Serbia	Clinical Center of Serbia, Clinic for Psychiatry	Belgrade
Serbia	Klinicki Centar Srbije (KCS)- Klinika za nerurologiju	Belgrade
Serbia	Military Medical Academy	Belgrade
Serbia	Special Hospital for Psychiatric Diseases "Kovin"	Kovin
Serbia	Clinical Center Kragujevac, Clinic for Neurology	Kragujevac
Serbia	Clinical Center Kragujevac, Clinic of Psychiatry	Kragujevac
Serbia	Clinical Center Nis, Clinic for Psychiatry	Toponica
Serbia	General Hospital Valjevo, Department for Neurology	Valjevo
South Africa	Flexivest Fourteen Research Centre Potocnik F C V	Durbanville	Western Cape
South Africa	Neurology Practice	Pretoria	Gauteng
South Africa	Dr. Stanley Lipshitz Clinic Inc.	Sandton	Gauteng
Ukraine	Dnipr Regional Clinical Hospital n.a. Mechnikov	Dnipro
Ukraine	Dnipropetrovsk Regional Rehabilitation Hospital	Dnipro
Ukraine	I.I. Mechnykov Dnipropetrovsk Regional Clinical Hospital	Dnipro
Ukraine	Ivano-Frankivsk Nat Med Uni Dep Psychiatry, Regional Hospital	Ivano-Frankivsk
Ukraine	Institute of Neruology, Nat Acad of Med Sci of UKR	Kharkiv
Ukraine	Institute of Neurology	Kharkiv
Ukraine	Municipal Non-Commercial Institution of Kharkiv Regional Council "Kharkiv Regional Clinical Psychiatric Hospital # 3" 46, Ac. Pavlova str	Kharkiv
Ukraine	Kyiv Regional Medical Incorp. Psychiatria, Center	Kyiv
Ukraine	Kyiv Regional Psychiatric and Narcological Medical Association 8, Vokzalna str	Kyiv
Ukraine	Ternopil Regional Communal Clinical Psychoneurological Hospital 14, Troleibusna str.	Ternopil'
Ukraine	Municipal Institution "Vinnytsya Regional Psychoneurological Hospital n.a. Acad. O.I.Yushchenko", Male Department #7, Female Department #10, Vinnytsya, National Medical University n.a. M.I.Pyrogov, 109 Pyrogova str.	Vinnytsia
Ukraine	Municipal Unst Zaporizhzhya Reg Clinical Hosp Neurology	Zaporizhzhya
Ukraine	Zaporizhzhya Reg. Hospital, Neurology Dpt	Zaporizhzhya
United States	UNC Hospital	Chapel Hill	North Carolina
United States	ATP Clinical Research, Inc.	Costa Mesa	California
United States	Cognitive Clinical Trials	Gilbert	Arizona
United States	Indago Research & Health Center Inc	Hialeah	Florida
United States	Reliable Clinical Research, LLC	Hialeah	Florida
United States	Central for Biomedical Research, LLC	Knoxville	Tennessee
United States	Axcess Medical Research	Loxahatchee Groves	Florida
United States	Suburban Research Associates	Media	Pennsylvania
United States	Future Care Solution, LLC	Miami	Florida
United States	Global Medical Institutes	Miami	Florida
United States	MediClear Medical & Research Center, Inc.	Miami	Florida
United States	Novel Clinical Research LLC	Miami	Florida
United States	Premier Clinical Research Institute, Inc.	Miami	Florida
United States	The NeuroCognitive Institute	Mount Arlington	New Jersey
United States	Boston Center Memory	Newton	Massachusetts
United States	Laszlo J Mate, MD, PA	North Palm Beach	Florida
United States	Cognitive Clinical Trials LLC	Papillion	Nebraska
United States	Syrentis Clinical Research	Santa Ana	California
United States	Insight Clinical Trials LLC	Shaker Heights	Ohio
United States	University of South Florida	Tampa	Florida
United States	Synexus Clinical Research US	The Villages	Florida

Sponsors (1)

Lead Sponsor	Collaborator
ACADIA Pharmaceuticals Inc.

Countries where clinical trial is conducted

United States,  Bulgaria,  Colombia,  Czechia,  Georgia,  Mexico,  Poland,  Romania,  Russian Federation,  Serbia,  South Africa,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment-emergent adverse events (TEAEs)	Safety and tolerability of pimavanserin compared to placebo in adult and elderly subjects with neuropsychiatric symptoms related to neurodegenerative disease	Treatment Period: 8 weeks
Secondary	Change from Baseline to Week 8 in Extrapyramidal Symptom Rating Scale-Abbreviated (ESRS-A)		Treatment Period: 8 weeks
Secondary	Change from Baseline to Week 8 in Mini-Mental State Examination (MMSE)		Treatment Period: 8 weeks