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History of Changes for Study: NCT04531982
Efficacy and Safety of Pimavanserin as Adjunctive Treatment for the Negative Symptoms of Schizophrenia (ADVANCE-2)
Latest version (submitted August 15, 2023) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 August 26, 2020 None (earliest Version on record)
2 November 2, 2020 Study Status and Contacts/Locations
3 December 17, 2020 Study Status and Contacts/Locations
4 December 23, 2020 Study Status, Eligibility and Study Design
5 January 22, 2021 Contacts/Locations and Study Status
6 February 19, 2021 Contacts/Locations and Study Status
7 April 1, 2021 Contacts/Locations and Study Status
8 April 30, 2021 Contacts/Locations and Study Status
9 July 9, 2021 Contacts/Locations and Study Status
10 July 19, 2021 Contacts/Locations and Study Status
11 October 14, 2021 Contacts/Locations and Study Status
12 August 26, 2022 Contacts/Locations and Study Status
13 November 15, 2022 Study Status and Eligibility
14 December 12, 2022 Contacts/Locations and Study Status
15 February 28, 2023 Contacts/Locations and Study Status
16 March 30, 2023 Contacts/Locations and Study Status
17 April 18, 2023 Study Status
18 June 7, 2023 Study Status
19 June 15, 2023 Study Status and Contacts/Locations
20 July 6, 2023 Study Status and Contacts/Locations
21 August 15, 2023 Recruitment Status, Contacts/Locations, Study Status and Study Design
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Study NCT04531982
Submitted Date:  November 15, 2022 (v13)

Open or close this module Study Identification
Unique Protocol ID: ACP-103-064
Brief Title: Efficacy and Safety of Pimavanserin as Adjunctive Treatment for the Negative Symptoms of Schizophrenia (ADVANCE-2)
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
Secondary IDs:
Open or close this module Study Status
Record Verification: November 2022
Overall Status: Recruiting
Study Start: August 5, 2020
Primary Completion: March 2023 [Anticipated]
Study Completion: March 2023 [Anticipated]
First Submitted: August 26, 2020
First Submitted that
Met QC Criteria:
August 26, 2020
First Posted: August 31, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
November 15, 2022
Last Update Posted: November 17, 2022 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: ACADIA Pharmaceuticals Inc.
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: To evaluate the efficacy and safety of adjunctive pimavanserin compared with adjunctive placebo in the treatment of negative symptoms of schizophrenia
Detailed Description:
Open or close this module Conditions
Conditions: Schizophrenia
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 426 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
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
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 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 16-item scale that can be completed in approximately 15 to 20 minutes. The NSA-16 has been validated for the assessment of the negative symptoms of schizophrenia and assesses 5 domains of negative symptoms: (1) communication, (2) emotion/affect, (3) social involvement, (4) motivation, and (5) retardation.
Secondary Outcome Measures:
1. 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 CGI-SCH-S is a clinician-rated, 7-point scale that is designed to evaluate positive, negative, depressive, cognitive symptoms, and overall severity in schizophrenia. For the purposes of this study, only the negative symptoms will be evaluated.
2. Clinical Global Impression of Schizophrenia Scale-Improvement (CGI-SCH-I) of negative symptoms score at Week 26
[ Time Frame: 26 Weeks Treatment Duration ]

The CGI-SCH-I is a clinician-rated, 7-point scale that is designed to evaluate change in positive, negative, depressive, cognitive symptoms, and overall severity in schizophrenia. For the purposes of this study, only the negative symptoms will be evaluated.
3. Proportion of CGI-SCH-I of negative symptoms responders (CGI-SCH-I of negative symptoms score of 1 or 2) at Week 26
[ Time Frame: 26 Weeks Treatment Duration ]

The CGI-SCH-I is a clinician-rated, 7-point scale that is designed to evaluate change in positive, negative, depressive, cognitive symptoms, and overall severity in schizophrenia. For the purposes of this study, only the negative symptoms will be evaluated.
4. Personal and Social Performance (PSP) scale score - change from Baseline to Week 26
[ Time Frame: 26 Weeks Treatment Duration ]

The PSP is a validated, 100-point, single-item rating scale to assess the psychosocial functioning of subjects with schizophrenia. Ratings are based on the assessment of subject functioning across four domains of socially useful activities (e.g., work and study, personal and social relationships, self-care, and disturbing and aggressive behavior).
5. Proportion of NSA-16 responders (≥20%and ≥30% reduction in NSA-16 total score) at Week 26
[ Time Frame: 26 Weeks Treatment Duration ]

The NSA-16 is a 16-item scale that can be completed in approximately 15 to 20 minutes. The NSA-16 has been validated for the assessment of the negative symptoms of schizophrenia and assesses 5 domains of negative symptoms: (1) communication, (2) emotion/affect, (3) social involvement, (4) motivation, and (5) retardation.
6. Positive and Negative Syndrome Scale (PANSS) total score - change from Baseline to Week 26
[ Time Frame: 26 Weeks Treatment Duration ]

The PANSS is a 30-item scale used to evaluate the presence, absence, and severity of schizophrenia symptoms. The 30 items are arranged as 7 positive symptom items, 7 negative symptom items, and 16 general psychopathology symptom items. The PANSS total score can range from a minimum of 30 to a maximum of 210.
7. PANSS negative subscores - change from Baseline to Week 26
[ Time Frame: 26 Weeks Treatment Duration ]

The PANSS is a 30-item scale used to evaluate the presence, absence, and severity of schizophrenia symptoms. The 30 items are arranged as 7 positive symptom items, 7 negative symptom items, and 16 general psychopathology symptom items. The PANSS total score can range from a minimum of 30 to a maximum of 210.
8. PANSS Marder factor (negative symptoms) score - change from Baseline to Week 26
[ Time Frame: 26 Weeks Treatment Duration ]

The PANSS is a 30-item scale used to evaluate the presence, absence, and severity of schizophrenia symptoms. The 30 items are arranged as 7 positive symptom items, 7 negative symptom items, and 16 general psychopathology symptom items. The PANSS total score can range from a minimum of 30 to a maximum of 210.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 55 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
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).

Open or close this module Contacts/Locations
Central Contact Person: Sandra Filosi
Telephone: 6092506920
Email: sfilosi@acadia-pharm.com
Locations: Argentina
CENydET- Centro Neurobiologico y de Estres Traumatico-Biopsychomedical Research Group SRL
[Recruiting]
Ciudad Autonoma Buenos Aires, Argentina, 1058 AAJ
FunDamoS
[Recruiting]
Ciudad Autonoma Buenos Aires, Argentina, C1405BOA
Fundación para el Estudio y Tratamiento de las Enfermedades Mentales - FETEM
[Recruiting]
Ciudad Autonoma de Buenos Aires, Argentina, C1133AAH
Resolution Psicopharmacology Research Institute
[Recruiting]
Ciudad de Mendoza, Argentina, 5502
Bulgaria
Mental Health Center Prof. Dr. Ivan Temkov - Burgas EO Burgas; Department for Treatment of Emergency Psychiatric Conditions
[Recruiting]
Burgas, Bulgaria, 8000
State Psychiatric Hospital - Kardzhali, EOOD
[Recruiting]
Kardzhali, Bulgaria, 6600
State Psychiatric Hospital - Lovech
[Recruiting]
Lovech, Bulgaria, 5500
UMHAT 'Dr. Georgi Stranski', EAD
[Recruiting]
Pleven, Bulgaria, 5800
Medical Center Mentalcare OOD
[Recruiting]
Plovdiv, Bulgaria, 4004
MC-Hipokrat-N E00D
[Completed]
Plovdiv, Bulgaria, 4028
Medical Centre "Sveti Naum"
[Recruiting]
Sofia, Bulgaria, 1113
DCC "Sv. Vrach and Sv. Sv. Kuzma and Damyan", OOD
[Recruiting]
Sofia, Bulgaria, 1408
"UMHAT Alexandrovska EAD, Sofia; Clinic of Psychiatry, First Department of Psychiatry "
[Recruiting]
Sofia, Bulgaria, 1431
Medical Center Hera EOOD
[Recruiting]
Sofia, Bulgaria, 1510
Medical Center Intermedica, OOD
[Recruiting]
Sofia, Bulgaria, 1680
DCC "Mladost M" - Varna, OOD
[Recruiting]
Varna, Bulgaria, 9020
Mental Health Center - Veliko Tarnovo EOOD,
[Recruiting]
Veliko Tarnovo, Bulgaria, 5000
Mental Health Center - Vratsa EOOD, Vratsa; Department of Psychiatry
[Recruiting]
Vratsa, Bulgaria, 3000
Bulgaria, Stara Zagora
MHAT "Dr. Hristo Stambolski", EOOD
[Recruiting]
Kazanlak, Stara Zagora, Bulgaria, 6100
Croatia
Clinic for psychiatry Vrapce 536
[Recruiting]
Zagreb, Croatia, 10090
Clinic for psychiatry Vrapce 537
[Recruiting]
Zagreb, Croatia, 10090
Clinic for psychiatry Vrapce 550
[Recruiting]
Zagreb, Croatia, 10090
Clinic for psychiatry Vrapce 557
[Recruiting]
Zagreb, Croatia, 10090
Czechia
NeuropsychiatrieHK s.r.o.
[Recruiting]
Hradec Králové, Czechia, 503 41
Narodni ustav dusevniho zdravi
[Recruiting]
Klecany, Czechia, 25067
A-SHINE s.r.o.
[Recruiting]
Plzen, Czechia, 31200
CLINTRIAL s.r.o.
[Completed]
Praha 10, Czechia, 100 00
MUDr. Tibor Miklos
[Completed]
Praha 10, Czechia, 106 00
Hungary
Semmelweis University Department of Psychiatry and Psychotherapy
[Recruiting]
Budapest, Hungary, 1083
Nyiro Gyula Korhaz - Orszagos Pszichiatriai es Addiktologiai Intezet
[Completed]
Budapest, Hungary, 1135
PsychoTech Kft.
[Recruiting]
Pecs, Hungary, 7633
Hungary, Bacs
Mathe es Tarsa Bt.
[Recruiting]
Kalocsa, Bacs, Hungary, 6300
Italy
"Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico U.O.C. Psichiatria - Padiglione Alfieri, primo piano"
[Recruiting]
Milano, Italy, 20122
Ospedale San Raffaele (San Raffaele Turro)
[Recruiting]
Milano, Italy, 20127
Lithuania
Neuromeda, JSC
[Completed]
Kaunas, Lithuania, 50185
Romuvos klinika, UAB
[Completed]
Kaunas, Lithuania, LT-44279
Kaunas City Outpatient Clinic, Public Institution
[Withdrawn]
Kaunas, Lithuania, LT-48259
Silutes Mental Health and Psychotherapy Center, JSC
[Withdrawn]
Silute, Lithuania, 99142
Poland
Podlaskie Centrum Psychogeriatrii
[Recruiting]
Bialystok, Poland, 15-756
Przychodnia Srodmiescie Sp. z o. o.
[Withdrawn]
Bydgoszcz, Poland, 85-080
Centrum Badan Klinicznych P.I. House Sp. z o.o.
[Recruiting]
Gdańsk, Poland, 80-546
Care Clinic centrum Medyczne
[Withdrawn]
Katowice, Poland, 40-568
Specjalistyczna Praktyka Lekarska Marek Domański
[Recruiting]
Lublin, Poland, 20-582
MSCZ im. prof. J. Mazurkiewicza
[Withdrawn]
Pruszków, Poland, 05-802
Ośr. Badań Klin. CLINSANTE S.C.
[Completed]
Torun, Poland, 87-100
Russian Federation
GUZ Lipetsk Regional psychoneurological Hospital #1
[Completed]
Lipetsk, Russian Federation, 398007
"SBIH of Moscow ""Psychiatric Clinical Hospital # 4 n.a. P.B. Gannushkin"" Short name: PCH N4 n.a. P.B.Gannushkin"
[Recruiting]
Moscow, Russian Federation, 107076
SBIH of Moscow "Psych Clinical Hospital #1 N.A. Alekseev"
[Recruiting]
Moscow, Russian Federation, 117152
Saint-Petersburg state healthcare institution "Saint Nicolas wonderworker psychiatric hospital"
[Recruiting]
Saint Petersburg, Russian Federation, 190121
"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."
[Recruiting]
Saint Petersburg, Russian Federation, 192019
"Saint-Petersburg Scientific Research Psychoneurological Institute n.a. V.M. Bekhterev - 465"
[Recruiting]
Saint Petersburg, Russian Federation, 192019
V. M. Bekhterev National Research Medical Center For Psychiatry and Neurology
[Recruiting]
Saint Petersburg, Russian Federation, 192019
Saint Petersburg State Budget Healthcare Institution "City Psychiatric Hospital No. 6 (Inpatient Department with Treatment Center)
[Recruiting]
Saint Petersburg, Russian Federation, 193167
Saint Petersburg State Public Institution of Healthcare "City Psychiatric Hospital #3 n.a. I. I. Skvortsov-Stepanov",
[Recruiting]
Saint Petersburg, Russian Federation, 197341
St. Petersburg SHI "Psychoneurological Dispensary #10"
[Recruiting]
Saint-Petersburg, Russian Federation, 190121
"Saint-Petersburg Scientific Research Psychoneurological Institute n.a. V.M. Bekhterev - 453"
[Recruiting]
Saint-Petersburg, Russian Federation, 192019
SPHI "City Mental Hospital #3 n.a. I.I.Skvortsov-Stepanov - 496"
[Recruiting]
Saint-Petersburg, Russian Federation, 197341
SPHI "City Mental Hospital #3 n.a. I.I.Skvortsov-Stepanov"-444
[Recruiting]
Saint-Petersburg, Russian Federation, 197341
State Budget Healthcare Institution "Samara Psychiatric Hospital
[Recruiting]
Samara, Russian Federation, 443016
FSBEI HE "Smolensk State Medical University" of the MoH of the RF (Clinical Research Centre of diagnostics and medicines)
[Recruiting]
Smolensk, Russian Federation, 214019
Klinika StoLet" Ltd.
[Recruiting]
Tomsk, Russian Federation, 634009
State Budget healthcare Institution of Yaroslavl region "Yaroslavl region clinical psychiatric hospital"
[Recruiting]
Yaroslavl, Russian Federation, 150003
Russian Federation, Stavropol Region
State budget healthcare Institution of Stavropol region "Regional specialized psychiatric hospital #2".
[Recruiting]
Tonnel'nyy, Stavropol Region, Russian Federation, 357034
Serbia
Clinical Hospital Center "Dr. Dragisa Misovic-Dedinje", Clinic of Psychiatry
[Recruiting]
Belgrade, Serbia, 11000
Institute of Mental health
[Recruiting]
Belgrade, Serbia, 11000
Clinical Center Kragujevac, Clinic of Psychiatry
[Recruiting]
Kragujevac, Serbia, 34000
Psychiatric Clinic, Clinical Center Kragujevac
[Recruiting]
Kragujevac, Serbia, 34000
Clinical Center Nis, Mental Health Protection Clinic
[Recruiting]
Nis, Serbia, 18000
Spain
Hospital Clinic de Barcelona
[Recruiting]
Barcelona, Spain, 08036
Hospital Universitari Vall d'Hebron
[Withdrawn]
Barcelona, Spain, 8035
Hospital Gregorio Marañon
[Recruiting]
Madrid, Spain, 28007
Hospital Universitario 12 de Octubre
[Recruiting]
Madrid, Spain, 28041
CSM La Corredoria
[Recruiting]
Oviedo, Spain, 33011
Centro de Salud Parquesol, 2ª planta - Servicio de Psiquiatria
[Recruiting]
Valladolid, Spain, 47016
Hospital Provincial de Zamora
[Recruiting]
Zamora, Spain, 49021
Ukraine
"CIH Kharkiv Regional Clinical Psychiatric Hospital #3 Psychiatric Department of Primary Psychotic Episod Short Site name: CIH KRCPH #3 PD of PPE "
[Recruiting]
Kharkiv, Ukraine, 61068
SI Institute of Neurology,Psychiatry&Narcology of NAMSU
[Recruiting]
Kharkiv, Ukraine, 61068
State Institution "Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine", Department of Urgent Psychiatry and Narcology
[Recruiting]
Kharkiv, Ukraine, 61068
Kyiv Regional Medical Incorporation "Psychiatry". Center of Novel Treatment and Rehabilitation of Psychotic disorders, build 5, Department #30
[Recruiting]
Kyiv, Ukraine, 04080
"Kyiv CH on Railway Transport #2 of Branch Center of Healthcare Public Company Ukr Railway Short site name: Kyiv Railway Clinical Hospital № 2"
[Recruiting]
Kyiv, Ukraine, 3049
CI Odesa Regional Medical Centre of Mental Health
[Recruiting]
Odesa, Ukraine, 65014
Ukraine, Cherkas'ka Oblast
CI Cherkasy Regional Psychiatric Hospital of ChRC
[Recruiting]
Smila, Cherkas'ka Oblast, Ukraine, 20708
Ukraine, Kirovograd Region
Regional Clinical Psychiatric Hospital
[Recruiting]
Kropyvnytskyi, Kirovograd Region, Ukraine, 25491
Ukraine, Vasylkiv District Kyiv Region
Kyiv City Psychoneurological Hospital #3 General Psychiatry Department No. 2
[Withdrawn]
Kyiv, Vasylkiv District Kyiv Region, Ukraine, 08631
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Links:
Available IPD/Information:

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