Clinical trial NCT04531982: Efficacy and Safety of Pimavanserin as Adjunctive Treatment for the Negative Symptoms of Schizophrenia
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Pimavanserin as Adjunctive Treatment for the Negative Symptoms of Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Lead sponsor: ACADIA Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2020-08-31
Enrollment: 454
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy and safety of adjunctive pimavanserin compared with adjunctive placebo in the treatment of negative symptoms of schizophrenia


Eligibility criteria: Inclusion Criteria:

* Male or female, ≥18 and ≤55 years of age at the time of Screening
* Has a caregiver or some other identified responsible person (e.g., family member, social worker, caseworker, or nurse) considered reliable by the Investigator in providing support to the subject to help ensure compliance with study treatment, study visits, and protocol procedures, and who is also able to provide input helpful for completing study rating scales
* Diagnosis of schizophrenia made ≥1 year prior to Screening
* Is being treated must be one of the antipsychotics listed below:

  * Aripiprazole

    * Aripiprazole long-acting injectables
    * Abilify Maintena®
  * Aristada®
  * Asenapine
  * Brexpiprazole
  * Cariprazine
  * Lurasidone
  * Olanzapine
  * Paliperidone extended release (ER) (≤9 mg)
  * Paliperidone palmitate

    * Invega Sustenna® (≤156 mg)
    * Invega Trinza® (≤546 mg)
    * Trevicta® (≤350 mg)
    * Xeplion® (≤100 mg)
  * Risperidone
  * Risperidone long-acting injection
* Must be medically stable (including no recent hospitalization for exacerbation of psychiatric disorder) and has been medically stable for at least 12 weeks prior to Screening, in the opinion of the Investigator

Exclusion Criteria:

* Has a current comorbid psychiatric disorder other than schizophrenia or a disorder that would interfere with the ability to complete study assessments
* Is at a significant risk of suicide, in the opinion of the Investigator
* Has a significant risk of violent behavior in the opinion of the Investigator
* A confirmed urine drug screen (UDS) result at Baseline that indicates the presence of any tested prohibited substance of potential abuse, including marijuana
* Is taking a medication or drug or other substance that is prohibited according to this protocol, including medications that prolong the QT interval, strong cytochrome P450 (CYP) 3A4 enzyme (CYP3A4) inhibitors and inducers
* Known family or personal history or symptoms of long QT syndrome or risk factors for torsade de pointes and/or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia, and the presence of congenital prolongation of the QT interval
* Current evidence, or history within the previous 12 weeks prior to Screening, of a serious and/or unstable psychiatric, neurologic, 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
* Has moderate to severe congestive heart failure
* Has a history of myocardial infarction within 6 months prior to enrollment
* Has a body mass index (BMI) \<19 or ≥35 at Screening

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 condition do not meet all prespecified entry criteria).

Primary outcomes:
measure: Negative Symptom Assessment-16 (NSA-16) Total Score - Change From Baseline to Week 26
timeFrame: 26 Weeks Treatment Duration
Secondary outcomes:
measure: Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH-S) of Negative Symptoms Score - Change From Baseline to Week 26
timeFrame: 26 Weeks Treatment Duration
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: 610-Clinica Privada Banfield S.A.
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: 601-CENydET- Centro Neurobiologico y de Estres Traumatico-Biopsychomedical Research Group SRL
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: 602-FunDamoS
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: 603-Fundación para el Estudio y Tratamiento de las Enfermedades Mentales - FETEM
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: 625-NOVAIN Neurociencias Group
city: Ciudad de Mendoza
country: Argentina
facility: 607-Resolution Psicopharmacology Research Institute
city: Cordoba
country: Argentina
facility: 624-Centro Especializado en Neurociencias CEN
city: Córdoba
country: Argentina
facility: 622-Instituto Medico Damic Srl
city: Córdoba
country: Argentina
facility: 626-Sanatorio Prof. Leon S. Morra S.A.
city: La Plata
country: Argentina
facility: 617-INSA Instituto de Neurociencias San Agustin S.A.
city: La Plata
country: Argentina
facility: 623-Clinica Privada de Salud Mental Santa Teresa de Avila
city: Kazanlak
country: Bulgaria
facility: 532-MHAT "Dr. Hristo Stambolski", EOOD
state: Stara Zagora
city: Burgas
country: Bulgaria
facility: 454-Mental Health Center Prof. Dr. Ivan Temkov - Burgas EO Burgas; Department for Treatment of Emergency Psychiatric Conditions
city: Kardzhali
country: Bulgaria
facility: 533-State Psychiatric Hospital - Kardzhali, EOOD
city: Lovech
country: Bulgaria
facility: 569-State Psychiatric Hospital - Lovech
city: Pleven
country: Bulgaria
facility: 535-UMHAT 'Dr. Georgi Stranski', EAD
city: Plovdiv
country: Bulgaria
facility: 586-Medical Center Mentalcare OOD
city: Plovdiv
country: Bulgaria
facility: 563-MC-Hipokrat-N E00D
city: Plovdiv
country: Bulgaria
facility: 592-Medical center Spectar - Plovdiv EOOD
city: Sofia
country: Bulgaria
facility: 570-Medical Centre "Sveti Naum"
city: Sofia
country: Bulgaria
facility: 526-DCC "Sv. Vrach and Sv. Sv. Kuzma and Damyan", OOD
city: Sofia
country: Bulgaria
facility: 405-"UMHAT Alexandrovska EAD, Sofia; Clinic of Psychiatry, First Department of Psychiatry "
city: Sofia
country: Bulgaria
facility: 568-Medical Center Hera EOOD
city: Sofia
country: Bulgaria
facility: 528-Medical Center Intermedica, OOD
city: Tsarev Brod
country: Bulgaria
facility: 590-State Psychiatric Hospital - Tzarev Brod
city: Varna
country: Bulgaria
facility: 498-DCC "Mladost M" - Varna, OOD
city: Veliko Tarnovo
country: Bulgaria
facility: 455-Mental Health Center - Veliko Tarnovo EOOD,
city: Vratsa
country: Bulgaria
facility: 401-Mental Health Center - Vratsa EOOD, Vratsa; Department of Psychiatry
city: Zagreb
country: Croatia
facility: 536-Clinic for psychiatry Vrapce
city: Zagreb
country: Croatia
facility: 537-Clinic for psychiatry Vrapce
city: Zagreb
country: Croatia
facility: 550-Clinic for psychiatry Vrapce
city: Zagreb
country: Croatia
facility: 557-Clinic for psychiatry Vrapce
city: Zagreb
country: Croatia
facility: 594-klinika za psihijatriju Sveti Ivan, n/p Igor Filipčić or Marija Zelenika
city: Hradec Králové
country: Czechia
facility: 512-NeuropsychiatrieHK s.r.o.
city: Klecany
country: Czechia
facility: 583-Narodni ustav dusevniho zdravi
city: Plzen
country: Czechia
facility: 519-A-SHINE s.r.o.
city: Praha 10
country: Czechia
facility: 513-CLINTRIAL s.r.o.
city: Praha 10
country: Czechia
facility: 499-MUDr. Tibor Miklos
city: Kalocsa
country: Hungary
facility: 410-Mathe es Tarsa Bt.
state: Bacs
city: Budapest
country: Hungary
facility: 456-Semmelweis University Department of Psychiatry and Psychotherapy
city: Budapest
country: Hungary
facility: 520-Nyiro Gyula Korhaz - Orszagos Pszichiatriai es Addiktologiai Intezet
city: Pecs
country: Hungary
facility: 440-PsychoTech Kft.
city: Bari
country: Italy
facility: 580-AOU Consorziale Policlinico di Bari
city: Milano
country: Italy
facility: 539-"Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico U.O.C. Psichiatria - Padiglione Alfieri, primo piano"
city: Milano
country: Italy
facility: 566-Ospedale San Raffaele (San Raffaele Turro)
city: Torino
country: Italy
facility: 553-AO Città della Salute e della Scienza di Torino
city: Kaunas
country: Lithuania
facility: 516-Neuromeda, JSC
city: Kaunas
country: Lithuania
facility: 483-Romuvos klinika, UAB
city: Kaunas
country: Lithuania
facility: 518-Kaunas City Outpatient Clinic, Public Institution
city: Silute
country: Lithuania
facility: 484-Medical Center Puriena JSC
city: Bialystok
country: Poland
facility: 525-Podlaskie Centrum Psychogeriatrii
city: Bydgoszcz
country: Poland
facility: 502-Przychodnia Srodmiescie Sp. z o. o.
city: Gdańsk
country: Poland
facility: 579-Centrum Badan Klinicznych P.I. House Sp. z o.o.
city: Katowice
country: Poland
facility: 541-Care Clinic centrum Medyczne
city: Lublin
country: Poland
facility: 501-Specjalistyczna Praktyka Lekarska Marek Domański
city: Pruszków
country: Poland
facility: 578-MSCZ im. prof. J. Mazurkiewicza
city: Torun
country: Poland
facility: 540-Ośr. Badań Klin. CLINSANTE S.C.
city: Tonnel'nyy
country: Russian Federation
facility: 417-State budget healthcare Institution of Stavropol region "Regional specialized psychiatric hospital #2".
state: Stavropol Region
city: Lipetsk
country: Russian Federation
facility: 505-GUZ Lipetsk Regional psychoneurological Hospital #1
city: Moscow
country: Russian Federation
facility: 573-"SBIH of Moscow ""Psychiatric Clinical Hospital # 4 n.a. P.B. Gannushkin"" Short name: PCH N4 n.a. P.B.Gannushkin"
city: Moscow
country: Russian Federation
facility: 581-SBIH of Moscow "Psych Clinical Hospital #1 N.A. Alekseev"
city: Saint Petersburg
country: Russian Federation
facility: 415-Saint-Petersburg state healthcare institution "Saint Nicolas wonderworker psychiatric hospital"
city: Saint Petersburg
country: Russian Federation
facility: 451-V. M. Bekhterev National Research Medical Center For Psychiatry and Neurology
city: Saint Petersburg
country: Russian Federation
facility: 465-"Saint-Petersburg Scientific Research Psychoneurological Institute n.a. V.M. Bekhterev
city: Saint Petersburg
country: Russian Federation
facility: 495-"FSBI "National medical scientific center of psychiatry and neurology n.a. V.M. Bekhterev" MoH Short name: NMSC of Psy&Neuro n.a. Bekhterev, 12 dep."
city: Saint Petersburg
country: Russian Federation
facility: 464-Saint Petersburg State Budget Healthcare Institution "City Psychiatric Hospital No. 6 (Inpatient Department with Treatment Center)
city: Saint Petersburg
country: Russian Federation
facility: 452-Saint Petersburg State Public Institution of Healthcare "City Psychiatric Hospital #3 n.a. I. I. Skvortsov-Stepanov",
city: Saint-Petersburg
country: Russian Federation
facility: 571-St. Petersburg SHI "Psychoneurological Dispensary #10"
city: Saint-Petersburg
country: Russian Federation
facility: 453-"Saint-Petersburg Scientific Research Psychoneurological Institute n.a. V.M. Bekhterev"
city: Saint-Petersburg
country: Russian Federation
facility: 444-SPHI "City Mental Hospital #3 n.a. I.I.Skvortsov-Stepanov"
city: Saint-Petersburg
country: Russian Federation
facility: 496-SPHI "City Mental Hospital #3 n.a. I.I.Skvortsov-Stepanov"
city: Samara
country: Russian Federation
facility: 458-State Budget Healthcare Institution "Samara Psychiatric Hospital
city: Smolensk
country: Russian Federation
facility: 416-FSBEI HE "Smolensk State Medical University" of the MoH of the RF (Clinical Research Centre of diagnostics and medicines)
city: Tomsk
country: Russian Federation
facility: 572-Klinika StoLet" Ltd.
city: Yaroslavl
country: Russian Federation
facility: 422-State Budget healthcare Institution of Yaroslavl region "Yaroslavl region clinical psychiatric hospital"
city: Belgrade
country: Serbia
facility: 424-Institute of Mental health
city: Belgrade
country: Serbia
facility: 425-Clinical Hospital Center "Dr. Dragisa Misovic-Dedinje", Clinic of Psychiatry
city: Belgrade
country: Serbia
facility: 584-Clinic for Psychiatry, Clinical Canter of Serbia
city: Belgrade
country: Serbia
facility: 587-Institute of Mental health
city: Kovin
country: Serbia
facility: 472-Special Neuropsychiatric Hospital Kovin
city: Kragujevac
country: Serbia
facility: 430-Psychiatric Clinic, Clinical Center Kragujevac
city: Kragujevac
country: Serbia
facility: 423-Clinical Center Kragujevac, Clinic of Psychiatry
city: Nis
country: Serbia
facility: 427-Clinical Center Nis, Mental Health Protection Clinic
city: Niš
country: Serbia
facility: 585-Special Hospital for Psychiatric Diseases "Gornja Toponica"
city: Novi Kneževac
country: Serbia
facility: 593-Specialized Hospital for Neuropsychiatric Diseases "Sveti Vracevi"
city: Barcelona
country: Spain
facility: 574-Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: 576-Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: 588-Institucion Hospitalaria Hestia Palau - Ensayos clinicos
city: Madrid
country: Spain
facility: 475-Hospital Gregorio Marañon
city: Madrid
country: Spain
facility: 575-Hospital Universitario 12 de Octubre
city: Oviedo
country: Spain
facility: 494-CSM La Corredoria
city: Valladolid
country: Spain
facility: 431-Hospital Psiquiátrico Provincial Doctor Villacian
city: Zamora
country: Spain
facility: 529-Hospital Provincial de Zamora
city: Smila
country: Ukraine
facility: 508-CI Cherkasy Regional Psychiatric Hospital of ChRC
state: Cherkas'ka Oblast
city: Kropyvnytskyi
country: Ukraine
facility: 564-Regional Clinical Psychiatric Hospital
state: Kirovograd Region
city: Kyiv
country: Ukraine
facility: 460-Kyiv City Psychoneurological Hospital #3 General Psychiatry Department No. 2
state: Vasylkiv District Kyiv Region
city: Kharkiv
country: Ukraine
facility: 434-State Institution "Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine", Department of Urgent Psychiatry and Narcology
city: Kharkiv
country: Ukraine
facility: 567-"CIH Kharkiv Regional Clinical Psychiatric Hospital #3 Psychiatric Department of Primary Psychotic Episod Short Site name: CIH KRCPH #3 PD of PPE "
city: Kharkiv
country: Ukraine
facility: 582-SI Institute of Neurology,Psychiatry&Narcology of NAMSU
city: Kyiv
country: Ukraine
facility: 435-Kyiv Regional Medical Incorporation "Psychiatry". Center of Novel Treatment and Rehabilitation of Psychotic disorders, build 5, Department #30
city: Kyiv
country: Ukraine
facility: 565-"Kyiv CH on Railway Transport #2 of Branch Center of Healthcare Public Company Ukr Railway Short site name: Kyiv Railway Clinical Hospital № 2"
city: Odesa
country: Ukraine
facility: 509-CI Odesa Regional Medical Centre of Mental Health
Study officials:
References:
citation: Darwish M, Bugarski-Kirola D, Passarell J, Owen J, Jaworowicz D, DeKarske D, Stankovic S. Pimavanserin Exposure-Response Analyses in Patients With Schizophrenia: Results From the Phase 2 ADVANCE Study. J Clin Psychopharmacol. 2022 Nov-Dec 01;42(6):544-551. doi: 10.1097/JCP.0000000000001611. Epub 2022 Oct 3.