Efficacy and Safety of Pimavanserin as Adjunctive Treatment for the Negative Symptoms of Schizophrenia

NCT ID: NCT04531982

Last Updated: 2025-08-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 454 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-05
• Study Completion Date: 2024-02-19

Brief Summary

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

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Drug - Pimavanserin

Pimavanserin 34 mg taken as two tablets + background antipsychotic, once daily by mouth

Group Type: EXPERIMENTAL

Pimavanserin

Intervention Type: DRUG

Pimavanserin 34 mg, taken as two blinded 17 mg tablets once daily by mouth

Placebo

Placebo + background antipsychotic, taken as two tablets, once daily by mouth

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo, taken as two blinded tablets once daily by mouth

Interventions

Pimavanserin

Pimavanserin 34 mg, taken as two blinded 17 mg tablets once daily by mouth

Intervention Type: DRUG

Placebo

Placebo, taken as two blinded tablets once daily by mouth

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ACADIA Pharmaceuticals Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

603-Fundación para el Estudio y Tratamiento de las Enfermedades Mentales - FETEM

Buenos Aires, , Argentina

610-Clinica Privada Banfield S.A.

Buenos Aires, , Argentina

625-NOVAIN Neurociencias Group

Buenos Aires, , Argentina

601-CENydET- Centro Neurobiologico y de Estres Traumatico-Biopsychomedical Research Group SRL

Ciudad Autonoma Buenos Aires, , Argentina

602-FunDamoS

Ciudad Autonoma Buenos Aires, , Argentina

622-Instituto Medico Damic Srl

Córdoba, , Argentina

624-Centro Especializado en Neurociencias CEN

Córdoba, , Argentina

626-Sanatorio Prof. Leon S. Morra S.A.

Córdoba, , Argentina

617-INSA Instituto de Neurociencias San Agustin S.A.

La Plata, , Argentina

623-Clinica Privada de Salud Mental Santa Teresa de Avila

La Plata, , Argentina

607-Resolution Psicopharmacology Research Institute

Mendoza, , Argentina

532-MHAT "Dr. Hristo Stambolski", EOOD

Kazanlak, Stara Zagora, Bulgaria

454-Mental Health Center Prof. Dr. Ivan Temkov - Burgas EO Burgas; Department for Treatment of Emergency Psychiatric Conditions

Burgas, , Bulgaria

533-State Psychiatric Hospital - Kardzhali, EOOD

Kardzhali, , Bulgaria

569-State Psychiatric Hospital - Lovech

Lovech, , Bulgaria

535-UMHAT 'Dr. Georgi Stranski', EAD

Pleven, , Bulgaria

586-Medical Center Mentalcare OOD

Plovdiv, , Bulgaria

563-MC-Hipokrat-N E00D

Plovdiv, , Bulgaria

592-Medical center Spectar - Plovdiv EOOD

Plovdiv, , Bulgaria

570-Medical Centre "Sveti Naum"

Sofia, , Bulgaria

526-DCC "Sv. Vrach and Sv. Sv. Kuzma and Damyan", OOD

Sofia, , Bulgaria

405-"UMHAT Alexandrovska EAD, Sofia; Clinic of Psychiatry, First Department of Psychiatry "

Sofia, , Bulgaria

568-Medical Center Hera EOOD

Sofia, , Bulgaria

528-Medical Center Intermedica, OOD

Sofia, , Bulgaria

590-State Psychiatric Hospital - Tzarev Brod

Tsarev Brod, , Bulgaria

498-DCC "Mladost M" - Varna, OOD

Varna, , Bulgaria

455-Mental Health Center - Veliko Tarnovo EOOD,

Veliko Tarnovo, , Bulgaria

401-Mental Health Center - Vratsa EOOD, Vratsa; Department of Psychiatry

Vratsa, , Bulgaria

536-Clinic for psychiatry Vrapce

Zagreb, , Croatia

537-Clinic for psychiatry Vrapce

Zagreb, , Croatia

550-Clinic for psychiatry Vrapce

Zagreb, , Croatia

557-Clinic for psychiatry Vrapce

Zagreb, , Croatia

594-klinika za psihijatriju Sveti Ivan, n/p Igor Filipčić or Marija Zelenika

Zagreb, , Croatia

512-NeuropsychiatrieHK s.r.o.

Hradec Králové, , Czechia

583-Narodni ustav dusevniho zdravi

Klecany, , Czechia

519-A-SHINE s.r.o.

Pilsen, , Czechia

513-CLINTRIAL s.r.o.

Prague, , Czechia

499-MUDr. Tibor Miklos

Prague, , Czechia

410-Mathe es Tarsa Bt.

Kalocsa, Bacs, Hungary

456-Semmelweis University Department of Psychiatry and Psychotherapy

Budapest, , Hungary

520-Nyiro Gyula Korhaz - Orszagos Pszichiatriai es Addiktologiai Intezet

Budapest, , Hungary

440-PsychoTech Kft.

Pécs, , Hungary

580-AOU Consorziale Policlinico di Bari

Bari, , Italy

539-"Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico U.O.C. Psichiatria - Padiglione Alfieri, primo piano"

Milan, , Italy

566-Ospedale San Raffaele (San Raffaele Turro)

Milan, , Italy

553-AO Città della Salute e della Scienza di Torino

Torino, , Italy

516-Neuromeda, JSC

Kaunas, , Lithuania

483-Romuvos klinika, UAB

Kaunas, , Lithuania

518-Kaunas City Outpatient Clinic, Public Institution

Kaunas, , Lithuania

484-Medical Center Puriena JSC

Šilutė, , Lithuania

525-Podlaskie Centrum Psychogeriatrii

Bialystok, , Poland

502-Przychodnia Srodmiescie Sp. z o. o.

Bydgoszcz, , Poland

579-Centrum Badan Klinicznych P.I. House Sp. z o.o.

Gdansk, , Poland

541-Care Clinic centrum Medyczne

Katowice, , Poland

501-Specjalistyczna Praktyka Lekarska Marek Domański

Lublin, , Poland

578-MSCZ im. prof. J. Mazurkiewicza

Pruszków, , Poland

540-Ośr. Badań Klin. CLINSANTE S.C.

Torun, , Poland

417-State budget healthcare Institution of Stavropol region "Regional specialized psychiatric hospital #2".

Tonnel’nyy, Stavropol Kray, Russia

505-GUZ Lipetsk Regional psychoneurological Hospital #1

Lipetsk, , Russia

573-"SBIH of Moscow ""Psychiatric Clinical Hospital # 4 n.a. P.B. Gannushkin"" Short name: PCH N4 n.a. P.B.Gannushkin"

Moscow, , Russia

581-SBIH of Moscow "Psych Clinical Hospital #1 N.A. Alekseev"

Moscow, , Russia

415-Saint-Petersburg state healthcare institution "Saint Nicolas wonderworker psychiatric hospital"

Saint Petersburg, , Russia

571-St. Petersburg SHI "Psychoneurological Dispensary #10"

Saint Petersburg, , Russia

451-V. M. Bekhterev National Research Medical Center For Psychiatry and Neurology

Saint Petersburg, , Russia

453-"Saint-Petersburg Scientific Research Psychoneurological Institute n.a. V.M. Bekhterev"

Saint Petersburg, , Russia

465-"Saint-Petersburg Scientific Research Psychoneurological Institute n.a. V.M. Bekhterev

Saint Petersburg, , Russia

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."

Saint Petersburg, , Russia

464-Saint Petersburg State Budget Healthcare Institution "City Psychiatric Hospital No. 6 (Inpatient Department with Treatment Center)

Saint Petersburg, , Russia

444-SPHI "City Mental Hospital #3 n.a. I.I.Skvortsov-Stepanov"

Saint Petersburg, , Russia

452-Saint Petersburg State Public Institution of Healthcare "City Psychiatric Hospital #3 n.a. I. I. Skvortsov-Stepanov",

Saint Petersburg, , Russia

496-SPHI "City Mental Hospital #3 n.a. I.I.Skvortsov-Stepanov"

Saint Petersburg, , Russia

458-State Budget Healthcare Institution "Samara Psychiatric Hospital

Samara, , Russia

416-FSBEI HE "Smolensk State Medical University" of the MoH of the RF (Clinical Research Centre of diagnostics and medicines)

Smolensk, , Russia

572-Klinika StoLet" Ltd.

Tomsk, , Russia

422-State Budget healthcare Institution of Yaroslavl region "Yaroslavl region clinical psychiatric hospital"

Yaroslavl, , Russia

424-Institute of Mental health

Belgrade, , Serbia

425-Clinical Hospital Center "Dr. Dragisa Misovic-Dedinje", Clinic of Psychiatry

Belgrade, , Serbia

584-Clinic for Psychiatry, Clinical Canter of Serbia

Belgrade, , Serbia

587-Institute of Mental health

Belgrade, , Serbia

472-Special Neuropsychiatric Hospital Kovin

Kovin, , Serbia

430-Psychiatric Clinic, Clinical Center Kragujevac

Kragujevac, , Serbia

423-Clinical Center Kragujevac, Clinic of Psychiatry

Kragujevac, , Serbia

427-Clinical Center Nis, Mental Health Protection Clinic

Niš, , Serbia

585-Special Hospital for Psychiatric Diseases "Gornja Toponica"

Niš, , Serbia

593-Specialized Hospital for Neuropsychiatric Diseases "Sveti Vracevi"

Novi Kneževac, , Serbia

574-Hospital Clinic de Barcelona

Barcelona, , Spain

576-Hospital Universitari Vall d'Hebron

Barcelona, , Spain

588-Institucion Hospitalaria Hestia Palau - Ensayos clinicos

Barcelona, , Spain

475-Hospital Gregorio Marañon

Madrid, , Spain

575-Hospital Universitario 12 de Octubre

Madrid, , Spain

494-CSM La Corredoria

Oviedo, , Spain

431-Hospital Psiquiátrico Provincial Doctor Villacian

Valladolid, , Spain

529-Hospital Provincial de Zamora

Zamora, , Spain

508-CI Cherkasy Regional Psychiatric Hospital of ChRC

Smila, Cherkasy Oblast, Ukraine

564-Regional Clinical Psychiatric Hospital

Kropyvnytskyi, Kirovograd Region, Ukraine

460-Kyiv City Psychoneurological Hospital #3 General Psychiatry Department No. 2

Kyiv, Vasylkiv District Kyiv Region, Ukraine

434-State Institution "Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine", Department of Urgent Psychiatry and Narcology

Kharkiv, , Ukraine

567-"CIH Kharkiv Regional Clinical Psychiatric Hospital #3 Psychiatric Department of Primary Psychotic Episod Short Site name: CIH KRCPH #3 PD of PPE "

Kharkiv, , Ukraine

582-SI Institute of Neurology,Psychiatry&Narcology of NAMSU

Kharkiv, , Ukraine

435-Kyiv Regional Medical Incorporation "Psychiatry". Center of Novel Treatment and Rehabilitation of Psychotic disorders, build 5, Department #30

Kyiv, , Ukraine

565-"Kyiv CH on Railway Transport #2 of Branch Center of Healthcare Public Company Ukr Railway Short site name: Kyiv Railway Clinical Hospital № 2"

Kyiv, , Ukraine

509-CI Odesa Regional Medical Centre of Mental Health

Odesa, , Ukraine

Countries

Argentina; Bulgaria; Croatia; Czechia; Hungary; Italy; Lithuania; Poland; Russia; Serbia; Spain; Ukraine

References

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.

Reference Type: DERIVED

PMID: 36190440 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ACP-103-064

Identifier Type: -

Identifier Source: org_study_id