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SchizophreniaPhase 3ADVANCE-2NCT04531982

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

A Phase 3 study testing Pimavanserin in people with Schizophrenia, run by ACADIA Pharmaceuticals Inc. at 102 sites in 12 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

To evaluate the efficacy and safety of adjunctive pimavanserin compared with adjunctive placebo in the treatment of negative symptoms of schizophrenia Read more about this study

Who is it for?
Ages 18 to 55 years
Conditions the study is for
Schizophrenia
What is being tested?
Pimavanserin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
454 participants
Where
102 sitesin 12 countries
Study dates
5 Aug 2020to 19 Feb 2024
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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
Show all 22Show fewer
  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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).

Trial locations and contacts

102 sites in 12 countries.

102 sites in 12 countries

Russia18 sites

  • 505-GUZ Lipetsk Regional psychoneurological Hospital #1

    Lipetsk, 398007

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

    Moscow, 107076

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

    Moscow, 117152

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

    Saint Petersburg, 190121

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

    Saint Petersburg, 190121

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

    Saint Petersburg, 192019

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

    Saint Petersburg, 192019

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

    Saint Petersburg, 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, 192019

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

    Saint Petersburg, 193167

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

    Saint Petersburg, 197341

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

    Saint Petersburg, 197341

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

    Saint Petersburg, 197341

  • 458-State Budget Healthcare Institution "Samara Psychiatric Hospital

    Samara, 443016

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

    Smolensk, 214019

  • 572-Klinika StoLet" Ltd.

    Tomsk, 634009

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

    Tonnel’nyy, Stavropol Kray, 357034

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

    Yaroslavl, 150003

Other trials in Russia

Bulgaria17 sites

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

    Burgas, 8000

  • 533-State Psychiatric Hospital - Kardzhali, EOOD

    Kardzhali, 6600

  • 532-MHAT "Dr. Hristo Stambolski", EOOD

    Kazanlak, Stara Zagora, 6100

  • 569-State Psychiatric Hospital - Lovech

    Lovech, 5500

  • 535-UMHAT 'Dr. Georgi Stranski', EAD

    Pleven, 5800

  • 586-Medical Center Mentalcare OOD

    Plovdiv, 4004

  • 563-MC-Hipokrat-N E00D

    Plovdiv, 4028

  • 592-Medical center Spectar - Plovdiv EOOD

    Plovdiv

  • 570-Medical Centre "Sveti Naum"

    Sofia, 1113

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

    Sofia, 1408

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

    Sofia, 1431

  • 568-Medical Center Hera EOOD

    Sofia, 1510

  • 528-Medical Center Intermedica, OOD

    Sofia, 1680

  • 590-State Psychiatric Hospital - Tzarev Brod

    Tsarev Brod

  • 498-DCC "Mladost M" - Varna, OOD

    Varna, 9020

  • 455-Mental Health Center - Veliko Tarnovo EOOD,

    Veliko Tarnovo, 5000

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

    Vratsa, 3000

Other trials in Bulgaria

Argentina11 sites

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

    Buenos Aires, C1133AAH

  • 610-Clinica Privada Banfield S.A.

    Buenos Aires

  • 625-NOVAIN Neurociencias Group

    Buenos Aires

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

    Ciudad Autonoma Buenos Aires, 1058 AAJ

  • 602-FunDamoS

    Ciudad Autonoma Buenos Aires, C1405BOA

  • 622-Instituto Medico Damic Srl

    Córdoba

  • 624-Centro Especializado en Neurociencias CEN

    Córdoba

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

    Córdoba

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

    La Plata

  • 623-Clinica Privada de Salud Mental Santa Teresa de Avila

    La Plata

  • 607-Resolution Psicopharmacology Research Institute

    Mendoza, 5502

Other trials in Argentina

Serbia10 sites

  • 424-Institute of Mental health

    Belgrade, 11000

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

    Belgrade, 11000

  • 584-Clinic for Psychiatry, Clinical Canter of Serbia

    Belgrade

  • 587-Institute of Mental health

    Belgrade

  • 472-Special Neuropsychiatric Hospital Kovin

    Kovin

  • 430-Psychiatric Clinic, Clinical Center Kragujevac

    Kragujevac, 34000

  • 423-Clinical Center Kragujevac, Clinic of Psychiatry

    Kragujevac

  • 427-Clinical Center Nis, Mental Health Protection Clinic

    Niš, 18000

  • 585-Special Hospital for Psychiatric Diseases "Gornja Toponica"

    Niš

  • 593-Specialized Hospital for Neuropsychiatric Diseases "Sveti Vracevi"

    Novi Kneževac

Other trials in Serbia

Ukraine9 sites

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

    Kharkiv, 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, 61068

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

    Kharkiv, 61068

  • 564-Regional Clinical Psychiatric Hospital

    Kropyvnytskyi, Kirovohrad Oblast, 25491

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

    Kyiv, Vasylkiv District Kyiv Region, 08631

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

    Kyiv, 04080

  • 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, 3049

  • 509-CI Odesa Regional Medical Centre of Mental Health

    Odesa, 65014

  • 508-CI Cherkasy Regional Psychiatric Hospital of ChRC

    Smila, Cherkasy Oblast, 20708

Other trials in Ukraine

Spain8 sites

  • 574-Hospital Clinic de Barcelona

    Barcelona, 08036

  • 576-Hospital Universitari Vall d'Hebron

    Barcelona, 8035

  • 588-Institucion Hospitalaria Hestia Palau - Ensayos clinicos

    Barcelona

  • 475-Hospital Gregorio Marañon

    Madrid, 28007

  • 575-Hospital Universitario 12 de Octubre

    Madrid, 28041

  • 494-CSM La Corredoria

    Oviedo, 33011

  • 431-Hospital Psiquiátrico Provincial Doctor Villacian

    Valladolid, 47016

  • 529-Hospital Provincial de Zamora

    Zamora, 49021

Other trials in Spain

Poland7 sites

  • 525-Podlaskie Centrum Psychogeriatrii

    Bialystok, 15-756

  • 502-Przychodnia Srodmiescie Sp. z o. o.

    Bydgoszcz, 85-080

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

    Gdansk, 80-546

  • 541-Care Clinic centrum Medyczne

    Katowice, 40-568

  • 501-Specjalistyczna Praktyka Lekarska Marek Domański

    Lublin, 20-582

  • 578-MSCZ im. prof. J. Mazurkiewicza

    Pruszków, 05-802

  • 540-Ośr. Badań Klin. CLINSANTE S.C.

    Torun, 87-100

Other trials in Poland

Croatia5 sites

  • 536-Clinic for psychiatry Vrapce

    Zagreb, 10090

  • 537-Clinic for psychiatry Vrapce

    Zagreb, 10090

  • 550-Clinic for psychiatry Vrapce

    Zagreb, 10090

  • 557-Clinic for psychiatry Vrapce

    Zagreb, 10090

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

    Zagreb

Other trials in Croatia

Czechia5 sites

  • 512-NeuropsychiatrieHK s.r.o.

    Hradec Králové, 503 41

  • 583-Narodni ustav dusevniho zdravi

    Klecany, 25067

  • 519-A-SHINE s.r.o.

    Pilsen, 31200

  • 513-CLINTRIAL s.r.o.

    Prague, 100 00

  • 499-MUDr. Tibor Miklos

    Prague, 106 00

Other trials in Czechia

Hungary4 sites

  • 456-Semmelweis University Department of Psychiatry and Psychotherapy

    Budapest, 1083

  • 520-Nyiro Gyula Korhaz - Orszagos Pszichiatriai es Addiktologiai Intezet

    Budapest, 1135

  • 410-Mathe es Tarsa Bt.

    Kalocsa, Bacs, 6300

  • 440-PsychoTech Kft.

    Pécs, 7633

Other trials in Hungary

Italy4 sites

  • 580-AOU Consorziale Policlinico di Bari

    Bari

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

    Milan, 20122

  • 566-Ospedale San Raffaele (San Raffaele Turro)

    Milan, 20127

  • 553-AO Città della Salute e della Scienza di Torino

    Torino

Other trials in Italy

Lithuania4 sites

  • 516-Neuromeda, JSC

    Kaunas, 50185

  • 483-Romuvos klinika, UAB

    Kaunas, LT-44279

  • 518-Kaunas City Outpatient Clinic, Public Institution

    Kaunas, LT-48259

  • 484-Medical Center Puriena JSC

    Šilutė

Other trials in Lithuania

About this study

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

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

Conditions
Schizophrenia
Being tested
Pimavanserin, Placebo
Medical subject headings
Schizophrenia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PimavanserinDrug

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

  • PlaceboDrug

    Placebo, taken as two blinded tablets once daily by mouth

Study groups in NCT04531982
Study groupRoleWhat they receive
Drug - PimavanserinExperimentalPimavanserin 34 mg taken as two tablets + background antipsychotic, once daily by mouth
Receives: Drug: Pimavanserin
PlaceboPlacebo comparatorPlacebo + background antipsychotic, taken as two tablets, once daily by mouth
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Negative Symptom Assessment-16 (NSA-16) Total Score - Change From Baseline to Week 26

    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.

    Measured: 26 Weeks Treatment Duration

Secondary outcomes (1)

  1. Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH-S) of Negative Symptoms Score - Change From Baseline to Week 26

    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).

    Measured: 26 Weeks Treatment Duration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2020
  2. Study start5 Aug 2020
  3. Primary completion25 Jan 2024
  4. Study completion19 Feb 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
454 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04531982
Sponsor's protocol ID
ACP-103-064
Acronym
ADVANCE-2
Status last verified
Mar 2025
First submitted
26 Aug 2020
Last updated
22 Aug 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 36190440

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pimavanserin in people with Schizophrenia, run by ACADIA Pharmaceuticals Inc. at 102 sites in 12 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 102 sites in Russia, Bulgaria, Argentina, Serbia, Ukraine and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Negative Symptom Assessment-16 (NSA-16) Total Score - Change From Baseline to Week 26 (time frame: 26 Weeks Treatment Duration). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04531982, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2025.

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