Efficacy and Safety of Pimavanserin as Adjunctive Treatment for the Negative Symptoms of Schizophrenia (ADVANCE-2)

August 6, 2025 updated by: ACADIA Pharmaceuticals Inc.

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

454

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina
        • 610-Clinica Privada Banfield S.A.
      • Ciudad Autonoma Buenos Aires, Argentina, 1058 AAJ
        • 601-CENydET- Centro Neurobiologico y de Estres Traumatico-Biopsychomedical Research Group SRL
      • Ciudad Autonoma Buenos Aires, Argentina, C1405BOA
        • 602-FunDamoS
      • Ciudad Autonoma de Buenos Aires, Argentina, C1133AAH
        • 603-Fundación para el Estudio y Tratamiento de las Enfermedades Mentales - FETEM
      • Ciudad Autonoma de Buenos Aires, Argentina
        • 625-NOVAIN Neurociencias Group
      • Ciudad de Mendoza, Argentina, 5502
        • 607-Resolution Psicopharmacology Research Institute
      • Cordoba, Argentina
        • 624-Centro Especializado en Neurociencias CEN
      • Córdoba, Argentina
        • 622-Instituto Medico Damic Srl
      • Córdoba, Argentina
        • 626-Sanatorio Prof. Leon S. Morra S.A.
      • La Plata, Argentina
        • 617-INSA Instituto de Neurociencias San Agustin S.A.
      • La Plata, Argentina
        • 623-Clinica Privada de Salud Mental Santa Teresa de Avila
  • Bulgaria
      • Burgas, Bulgaria, 8000
        • 454-Mental Health Center Prof. Dr. Ivan Temkov - Burgas EO Burgas; Department for Treatment of Emergency Psychiatric Conditions
      • Kardzhali, Bulgaria, 6600
        • 533-State Psychiatric Hospital - Kardzhali, EOOD
      • Lovech, Bulgaria, 5500
        • 569-State Psychiatric Hospital - Lovech
      • Pleven, Bulgaria, 5800
        • 535-UMHAT 'Dr. Georgi Stranski', EAD
      • Plovdiv, Bulgaria, 4004
        • 586-Medical Center Mentalcare OOD
      • Plovdiv, Bulgaria, 4028
        • 563-MC-Hipokrat-N E00D
      • Plovdiv, Bulgaria
        • 592-Medical center Spectar - Plovdiv EOOD
      • Sofia, Bulgaria, 1113
        • 570-Medical Centre "Sveti Naum"
      • Sofia, Bulgaria, 1408
        • 526-DCC "Sv. Vrach and Sv. Sv. Kuzma and Damyan", OOD
      • Sofia, Bulgaria, 1431
        • 405-"UMHAT Alexandrovska EAD, Sofia; Clinic of Psychiatry, First Department of Psychiatry "
      • Sofia, Bulgaria, 1510
        • 568-Medical Center Hera EOOD
      • Sofia, Bulgaria, 1680
        • 528-Medical Center Intermedica, OOD
      • Tsarev Brod, Bulgaria
        • 590-State Psychiatric Hospital - Tzarev Brod
      • Varna, Bulgaria, 9020
        • 498-DCC "Mladost M" - Varna, OOD
      • Veliko Tarnovo, Bulgaria, 5000
        • 455-Mental Health Center - Veliko Tarnovo EOOD,
      • Vratsa, Bulgaria, 3000
        • 401-Mental Health Center - Vratsa EOOD, Vratsa; Department of Psychiatry
    • Stara Zagora
      • Kazanlak, Stara Zagora, Bulgaria, 6100
        • 532-MHAT "Dr. Hristo Stambolski", EOOD
  • Croatia
      • Zagreb, Croatia, 10090
        • 536-Clinic for psychiatry Vrapce
      • Zagreb, Croatia, 10090
        • 537-Clinic for psychiatry Vrapce
      • Zagreb, Croatia, 10090
        • 550-Clinic for psychiatry Vrapce
      • Zagreb, Croatia, 10090
        • 557-Clinic for psychiatry Vrapce
      • Zagreb, Croatia
        • 594-Klinika za psihijatriju Sveti Ivan, n/p Igor Filipčić or Marija Zelenika
  • Czechia
      • Hradec Králové, Czechia, 503 41
        • 512-NeuropsychiatrieHK s.r.o.
      • Klecany, Czechia, 25067
        • 583-Narodni ustav dusevniho zdravi
      • Plzen, Czechia, 31200
        • 519-A-SHINE s.r.o.
      • Praha 10, Czechia, 100 00
        • 513-CLINTRIAL s.r.o.
      • Praha 10, Czechia, 106 00
        • 499-MUDr. Tibor Miklos
  • Hungary
      • Budapest, Hungary, 1083
        • 456-Semmelweis University Department of Psychiatry and Psychotherapy
      • Budapest, Hungary, 1135
        • 520-Nyiro Gyula Korhaz - Orszagos Pszichiatriai es Addiktologiai Intezet
      • Pecs, Hungary, 7633
        • 440-PsychoTech Kft.
    • Bacs
      • Kalocsa, Bacs, Hungary, 6300
        • 410-Mathe es Tarsa Bt.
  • Italy
      • Bari, Italy
        • 580-AOU Consorziale Policlinico di Bari
      • Milano, Italy, 20122
        • 539-"Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico U.O.C. Psichiatria - Padiglione Alfieri, primo piano"
      • Milano, Italy, 20127
        • 566-Ospedale San Raffaele (San Raffaele Turro)
      • Torino, Italy
        • 553-AO Città della Salute e della Scienza di Torino
  • Lithuania
      • Kaunas, Lithuania, 50185
        • 516-Neuromeda, JSC
      • Kaunas, Lithuania, LT-44279
        • 483-Romuvos klinika, UAB
      • Kaunas, Lithuania, LT-48259
        • 518-Kaunas City Outpatient Clinic, Public Institution
      • Silute, Lithuania
        • 484-Medical Center Puriena JSC
  • Poland
      • Bialystok, Poland, 15-756
        • 525-Podlaskie Centrum Psychogeriatrii
      • Bydgoszcz, Poland, 85-080
        • 502-Przychodnia Srodmiescie Sp. z o. o.
      • Gdańsk, Poland, 80-546
        • 579-Centrum Badan Klinicznych P.I. House Sp. z o.o.
      • Katowice, Poland, 40-568
        • 541-Care Clinic centrum Medyczne
      • Lublin, Poland, 20-582
        • 501-Specjalistyczna Praktyka Lekarska Marek Domański
      • Pruszków, Poland, 05-802
        • 578-MSCZ im. Prof. J. Mazurkiewicza
      • Torun, Poland, 87-100
        • 540-Ośr. Badań Klin. CLINSANTE S.C.
  • Russian Federation
      • Lipetsk, Russian Federation, 398007
        • 505-GUZ Lipetsk Regional psychoneurological Hospital #1
      • Moscow, Russian Federation, 107076
        • 573-"SBIH of Moscow ""Psychiatric Clinical Hospital # 4 n.a. P.B. Gannushkin"" Short name: PCH N4 n.a. P.B.Gannushkin"
      • Moscow, Russian Federation, 117152
        • 581-SBIH of Moscow "Psych Clinical Hospital #1 N.A. Alekseev"
      • Saint Petersburg, Russian Federation, 190121
        • 415-Saint-Petersburg State Healthcare Institution "Saint Nicolas Wonderworker Psychiatric Hospital"
      • Saint Petersburg, Russian Federation, 192019
        • 451-V. M. Bekhterev National Research Medical Center For Psychiatry and Neurology
      • Saint Petersburg, Russian Federation, 192019
        • 465-"Saint-Petersburg Scientific Research Psychoneurological Institute n.a. V.M. Bekhterev
      • Saint Petersburg, Russian Federation, 192019
        • 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, Russian Federation, 193167
        • 464-Saint Petersburg State Budget Healthcare Institution "City Psychiatric Hospital No. 6 (Inpatient Department with Treatment Center)
      • Saint Petersburg, Russian Federation, 197341
        • 452-Saint Petersburg State Public Institution of Healthcare "City Psychiatric Hospital #3 n.a. I. I. Skvortsov-Stepanov",
      • Saint-Petersburg, Russian Federation, 190121
        • 571-St. Petersburg SHI "Psychoneurological Dispensary #10"
      • Saint-Petersburg, Russian Federation, 192019
        • 453-"Saint-Petersburg Scientific Research Psychoneurological Institute n.a. V.M. Bekhterev"
      • Saint-Petersburg, Russian Federation, 197341
        • 444-SPHI "City Mental Hospital #3 n.a. I.I.Skvortsov-Stepanov"
      • Saint-Petersburg, Russian Federation, 197341
        • 496-SPHI "City Mental Hospital #3 n.a. I.I.Skvortsov-Stepanov"
      • Samara, Russian Federation, 443016
        • 458-State Budget Healthcare Institution "Samara Psychiatric Hospital
      • Smolensk, Russian Federation, 214019
        • 416-FSBEI HE "Smolensk State Medical University" of the MoH of the RF (Clinical Research Centre of diagnostics and medicines)
      • Tomsk, Russian Federation, 634009
        • 572-Klinika StoLet" Ltd.
      • Yaroslavl, Russian Federation, 150003
        • 422-State Budget Healthcare Institution of Yaroslavl Region "Yaroslavl Region Clinical Psychiatric Hospital"
    • Stavropol Region
      • Tonnel'nyy, Stavropol Region, Russian Federation, 357034
        • 417-State budget healthcare Institution of Stavropol region "Regional specialized psychiatric hospital #2".
  • Serbia
      • Belgrade, Serbia, 11000
        • 424-Institute of Mental health
      • Belgrade, Serbia, 11000
        • 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
      • Kovin, Serbia
        • 472-Special Neuropsychiatric Hospital Kovin
      • Kragujevac, Serbia, 34000
        • 430-Psychiatric Clinic, Clinical Center Kragujevac
      • Kragujevac, Serbia
        • 423-Clinical Center Kragujevac, Clinic of Psychiatry
      • Nis, Serbia, 18000
        • 427-Clinical Center Nis, Mental Health Protection Clinic
      • Niš, Serbia
        • 585-Special Hospital for Psychiatric Diseases "Gornja Toponica"
      • Novi Kneževac, Serbia
        • 593-Specialized Hospital for Neuropsychiatric Diseases "Sveti Vracevi"
  • Spain
      • Barcelona, Spain, 08036
        • 574-Hospital Clinic de Barcelona
      • Barcelona, Spain, 8035
        • 576-Hospital Universitari Vall d'Hebron
      • Barcelona, Spain
        • 588-Institucion Hospitalaria Hestia Palau - Ensayos clinicos
      • Madrid, Spain, 28007
        • 475-Hospital Gregorio Marañon
      • Madrid, Spain, 28041
        • 575-Hospital Universitario 12 de Octubre
      • Oviedo, Spain, 33011
        • 494-CSM La Corredoria
      • Valladolid, Spain, 47016
        • 431-Hospital Psiquiátrico Provincial Doctor Villacian
      • Zamora, Spain, 49021
        • 529-Hospital Provincial de Zamora
  • Ukraine
      • Kharkiv, Ukraine, 61068
        • 434-State Institution "Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine", Department of Urgent Psychiatry and Narcology
      • Kharkiv, Ukraine, 61068
        • 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, 61068
        • 582-SI Institute of Neurology,Psychiatry&Narcology of NAMSU
      • Kyiv, Ukraine, 04080
        • 435-Kyiv Regional Medical Incorporation "Psychiatry". Center of Novel Treatment and Rehabilitation of Psychotic disorders, build 5, Department #30
      • Kyiv, Ukraine, 3049
        • 565-"Kyiv CH on Railway Transport #2 of Branch Center of Healthcare Public Company Ukr Railway Short site name: Kyiv Railway Clinical Hospital № 2"
      • Odesa, Ukraine, 65014
        • 509-CI Odesa Regional Medical Centre of Mental Health
    • Cherkas'ka Oblast
      • Smila, Cherkas'ka Oblast, Ukraine, 20708
        • 508-CI Cherkasy Regional Psychiatric Hospital of ChRC
    • Kirovograd Region
      • Kropyvnytskyi, Kirovograd Region, Ukraine, 25491
        • 564-Regional Clinical Psychiatric Hospital
    • Vasylkiv District Kyiv Region
      • Kyiv, Vasylkiv District Kyiv Region, Ukraine, 08631
        • 460-Kyiv City Psychoneurological Hospital #3 General Psychiatry Department No. 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Drug - Pimavanserin
Pimavanserin 34 mg taken as two tablets + background antipsychotic, once daily by mouth
Drug: Pimavanserin
Pimavanserin 34 mg, taken as two blinded 17 mg tablets once daily by mouth
Placebo Comparator: Placebo
Placebo + background antipsychotic, taken as two tablets, once daily by mouth
Drug: Placebo
Placebo, taken as two blinded tablets once daily by mouth

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Negative Symptom Assessment-16 (NSA-16) Total Score - Change From Baseline to Week 26
Time Frame: 26 Weeks Treatment Duration
The NSA-16 is a semi-structured interview and a validated scale containing 16 items for evaluating negative symptoms of schizophrenia, i.e. the reduction or absence of emotional expression and volitional behaviors normally present in a healthy person. Items are scored based on behaviors during the interview (items 1-4, 6, 7, 9, 11, 15, 16) or previous 7 days (items 5, 8, 10, 12-14) on a 6-point scale from 1 to 6. The NSA-16 total score is the sum of item scores. It can range from 16 to a maximum of 96, with higher scores denoting more severe negative symptoms in schizophrenia.
26 Weeks Treatment Duration

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH-S) of Negative Symptoms Score - Change From Baseline to Week 26
Time Frame: 26 Weeks Treatment Duration
The Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH S) is a clinician-rated, 7-point scale to evaluate positive, negative, depressive, cognitive symptoms and overall severity in schizophrenia. For the purpose of this study, only the negative symptoms were evaluated. The score could range from 1 (normal, not ill) to 7 (among the most severely ill).
26 Weeks Treatment Duration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ACADIA Pharmaceuticals Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 5, 2020

Primary Completion (Actual)

January 25, 2024

Study Completion (Actual)

February 19, 2024

Study Registration Dates

First Submitted

August 26, 2020

First Submitted That Met QC Criteria

August 26, 2020

First Posted (Actual)

August 31, 2020

Study Record Updates

Last Update Posted (Actual)

August 22, 2025

Last Update Submitted That Met QC Criteria

August 6, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACP-103-064

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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