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

NCT04531982 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: ACP-103-064
• Study Type: interventional
• Target: 454
• Locations: 12 countries
• Sites: 102

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

Outcome Measures

Primary Outcomes (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.

  26 Weeks Treatment Duration

Secondary Outcomes (1)

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

  26 Weeks Treatment Duration

Study Arms (2)

Drug - Pimavanserin

EXPERIMENTAL

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

Drug: Pimavanserin

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Pimavanserin DRUG

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

Drug - Pimavanserin

Placebo DRUG

Placebo, taken as two blinded tablets once daily by mouth

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ACADIA Pharmaceuticals Inc.: lead

Study Sites (102)

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

Buenos Aires, C1133AAH, Argentina

Location

610-Clinica Privada Banfield S.A.

Buenos Aires, Argentina

Location

625-NOVAIN Neurociencias Group

Buenos Aires, Argentina

Location

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

Ciudad Autonoma Buenos Aires, 1058 AAJ, Argentina

Location

602-FunDamoS

Ciudad Autonoma Buenos Aires, C1405BOA, Argentina

Location

622-Instituto Medico Damic Srl

Córdoba, Argentina

Location

624-Centro Especializado en Neurociencias CEN

Córdoba, Argentina

Location

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

Córdoba, Argentina

Location

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

La Plata, Argentina

Location

623-Clinica Privada de Salud Mental Santa Teresa de Avila

La Plata, Argentina

Location

607-Resolution Psicopharmacology Research Institute

Mendoza, 5502, Argentina

Location

532-MHAT "Dr. Hristo Stambolski", EOOD

Kazanlak, Stara Zagora, 6100, Bulgaria

Location

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

Burgas, 8000, Bulgaria

Location

533-State Psychiatric Hospital - Kardzhali, EOOD

Kardzhali, 6600, Bulgaria

Location

569-State Psychiatric Hospital - Lovech

Lovech, 5500, Bulgaria

Location

535-UMHAT 'Dr. Georgi Stranski', EAD

Pleven, 5800, Bulgaria

Location

586-Medical Center Mentalcare OOD

Plovdiv, 4004, Bulgaria

Location

563-MC-Hipokrat-N E00D

Plovdiv, 4028, Bulgaria

Location

592-Medical center Spectar - Plovdiv EOOD

Plovdiv, Bulgaria

Location

570-Medical Centre "Sveti Naum"

Sofia, 1113, Bulgaria

Location

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

Sofia, 1408, Bulgaria

Location

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

Sofia, 1431, Bulgaria

Location

568-Medical Center Hera EOOD

Sofia, 1510, Bulgaria

Location

528-Medical Center Intermedica, OOD

Sofia, 1680, Bulgaria

Location

590-State Psychiatric Hospital - Tzarev Brod

Tsarev Brod, Bulgaria

Location

498-DCC "Mladost M" - Varna, OOD

Varna, 9020, Bulgaria

Location

455-Mental Health Center - Veliko Tarnovo EOOD,

Veliko Tarnovo, 5000, Bulgaria

Location

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

Vratsa, 3000, Bulgaria

Location

536-Clinic for psychiatry Vrapce

Zagreb, 10090, Croatia

Location

537-Clinic for psychiatry Vrapce

Zagreb, 10090, Croatia

Location

550-Clinic for psychiatry Vrapce

Zagreb, 10090, Croatia

Location

557-Clinic for psychiatry Vrapce

Zagreb, 10090, Croatia

Location

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

Zagreb, Croatia

Location

512-NeuropsychiatrieHK s.r.o.

Hradec Králové, 503 41, Czechia

Location

583-Narodni ustav dusevniho zdravi

Klecany, 25067, Czechia

Location

519-A-SHINE s.r.o.

Pilsen, 31200, Czechia

Location

513-CLINTRIAL s.r.o.

Prague, 100 00, Czechia

Location

499-MUDr. Tibor Miklos

Prague, 106 00, Czechia

Location

410-Mathe es Tarsa Bt.

Kalocsa, Bacs, 6300, Hungary

Location

456-Semmelweis University Department of Psychiatry and Psychotherapy

Budapest, 1083, Hungary

Location

520-Nyiro Gyula Korhaz - Orszagos Pszichiatriai es Addiktologiai Intezet

Budapest, 1135, Hungary

Location

440-PsychoTech Kft.

Pécs, 7633, Hungary

Location

580-AOU Consorziale Policlinico di Bari

Bari, Italy

Location

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

Milan, 20122, Italy

Location

566-Ospedale San Raffaele (San Raffaele Turro)

Milan, 20127, Italy

Location

553-AO Città della Salute e della Scienza di Torino

Torino, Italy

Location

516-Neuromeda, JSC

Kaunas, 50185, Lithuania

Location

483-Romuvos klinika, UAB

Kaunas, LT-44279, Lithuania

Location

518-Kaunas City Outpatient Clinic, Public Institution

Kaunas, LT-48259, Lithuania

Location

484-Medical Center Puriena JSC

Šilutė, Lithuania

Location

525-Podlaskie Centrum Psychogeriatrii

Bialystok, 15-756, Poland

Location

502-Przychodnia Srodmiescie Sp. z o. o.

Bydgoszcz, 85-080, Poland

Location

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

Gdansk, 80-546, Poland

Location

541-Care Clinic centrum Medyczne

Katowice, 40-568, Poland

Location

501-Specjalistyczna Praktyka Lekarska Marek Domański

Lublin, 20-582, Poland

Location

578-MSCZ im. prof. J. Mazurkiewicza

Pruszków, 05-802, Poland

Location

540-Ośr. Badań Klin. CLINSANTE S.C.

Torun, 87-100, Poland

Location

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

Tonnel’nyy, Stavropol Kray, 357034, Russia

Location

505-GUZ Lipetsk Regional psychoneurological Hospital #1

Lipetsk, 398007, Russia

Location

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

Moscow, 107076, Russia

Location

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

Moscow, 117152, Russia

Location

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

Saint Petersburg, 190121, Russia

Location

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

Saint Petersburg, 190121, Russia

Location

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

Saint Petersburg, 192019, Russia

Location

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

Saint Petersburg, 192019, Russia

Location

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

Saint Petersburg, 192019, Russia

Location

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, Russia

Location

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

Saint Petersburg, 193167, Russia

Location

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

Saint Petersburg, 197341, Russia

Location

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

Saint Petersburg, 197341, Russia

Location

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

Saint Petersburg, 197341, Russia

Location

458-State Budget Healthcare Institution "Samara Psychiatric Hospital

Samara, 443016, Russia

Location

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

Smolensk, 214019, Russia

Location

572-Klinika StoLet" Ltd.

Tomsk, 634009, Russia

Location

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

Yaroslavl, 150003, Russia

Location

424-Institute of Mental health

Belgrade, 11000, Serbia

Location

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

Belgrade, 11000, Serbia

Location

584-Clinic for Psychiatry, Clinical Canter of Serbia

Belgrade, Serbia

Location

587-Institute of Mental health

Belgrade, Serbia

Location

472-Special Neuropsychiatric Hospital Kovin

Kovin, Serbia

Location

430-Psychiatric Clinic, Clinical Center Kragujevac

Kragujevac, 34000, Serbia

Location

423-Clinical Center Kragujevac, Clinic of Psychiatry

Kragujevac, Serbia

Location

427-Clinical Center Nis, Mental Health Protection Clinic

Niš, 18000, Serbia

Location

585-Special Hospital for Psychiatric Diseases "Gornja Toponica"

Niš, Serbia

Location

593-Specialized Hospital for Neuropsychiatric Diseases "Sveti Vracevi"

Novi Kneževac, Serbia

Location

574-Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

576-Hospital Universitari Vall d'Hebron

Barcelona, 8035, Spain

Location

588-Institucion Hospitalaria Hestia Palau - Ensayos clinicos

Barcelona, Spain

Location

475-Hospital Gregorio Marañon

Madrid, 28007, Spain

Location

575-Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

494-CSM La Corredoria

Oviedo, 33011, Spain

Location

431-Hospital Psiquiátrico Provincial Doctor Villacian

Valladolid, 47016, Spain

Location

529-Hospital Provincial de Zamora

Zamora, 49021, Spain

Location

508-CI Cherkasy Regional Psychiatric Hospital of ChRC

Smila, Cherkasy Oblast, 20708, Ukraine

Location

564-Regional Clinical Psychiatric Hospital

Kropyvnytskyi, Kirovograd Region, 25491, Ukraine

Location

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

Kyiv, Vasylkiv District Kyiv Region, 08631, Ukraine

Location

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

Kharkiv, 61068, Ukraine

Location

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, Ukraine

Location

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

Kharkiv, 61068, Ukraine

Location

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

Kyiv, 04080, Ukraine

Location

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, Ukraine

Location

509-CI Odesa Regional Medical Centre of Mental Health

Odesa, 65014, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 36190440 DERIVED

MeSH Terms

Conditions

Schizophrenia

Interventions

pimavanserin

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: Senior Director, Medical Information
• Organization: Acadia Pharmaceuticals Inc.

medicalinformation@acadia-pharm.com

8444222342

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2020
• First Posted: August 31, 2020
• Study Start: August 5, 2020
• Primary Completion: January 25, 2024
• Study Completion: February 19, 2024
• Last Updated: August 22, 2025
• Results First Posted: April 1, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CR (5); UA (9); PL (7); BU (17); HU (4); AR (11); LI (4); SE (10); CZ (5); IT (4); ES (8); RU (18)