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

Schizophrenia Clinical Trial

— 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04531982
• Other study ID #: ACP-103-064
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 5, 2020
• Est. completion date: January 2024

Study information

• Verified date: August 2023
• Source: ACADIA Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 454
• Est. completion date: January 2024
• Est. primary completion date: January 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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).

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• Pimavanserin
Pimavanserin 34 mg, taken as two blinded 17 mg tablets once daily by mouth
• Placebo
Placebo, taken as two blinded tablets once daily by mouth

Locations

Country	Name	City	State
Argentina	610-Clinica Privada Banfield S.A.	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	603-Fundación para el Estudio y Tratamiento de las Enfermedades Mentales - FETEM	Ciudad Autonoma de Buenos Aires
Argentina	625-NOVAIN Neurociencias Group	Ciudad Autonoma de Buenos Aires
Argentina	607-Resolution Psicopharmacology Research Institute	Ciudad de Mendoza
Argentina	624-Centro Especializado en Neurociencias CEN	Cordoba
Argentina	622-Instituto Medico Damic Srl	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
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	532-MHAT "Dr. Hristo Stambolski", EOOD	Kazanlak	Stara Zagora
Bulgaria	569-State Psychiatric Hospital - Lovech	Lovech
Bulgaria	535-UMHAT 'Dr. Georgi Stranski', EAD	Pleven
Bulgaria	563-MC-Hipokrat-N E00D	Plovdiv
Bulgaria	586-Medical Center Mentalcare OOD	Plovdiv
Bulgaria	592-Medical center Spectar - Plovdiv EOOD	Plovdiv
Bulgaria	405-"UMHAT Alexandrovska EAD, Sofia; Clinic of Psychiatry, First Department of Psychiatry "	Sofia
Bulgaria	526-DCC "Sv. Vrach and Sv. Sv. Kuzma and Damyan", OOD	Sofia
Bulgaria	528-Medical Center Intermedica, OOD	Sofia
Bulgaria	568-Medical Center Hera EOOD	Sofia
Bulgaria	570-Medical Centre "Sveti Naum"	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
Croatia	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 Filipcic or Marija Zelenika	Zagreb
Czechia	512-NeuropsychiatrieHK s.r.o.	Hradec Králové
Czechia	583-Narodni ustav dusevniho zdravi	Klecany
Czechia	519-A-SHINE s.r.o.	Plzen
Czechia	499-MUDr. Tibor Miklos	Praha 10
Czechia	513-CLINTRIAL s.r.o.	Praha 10
Hungary	456-Semmelweis University Department of Psychiatry and Psychotherapy	Budapest
Hungary	520-Nyiro Gyula Korhaz - Orszagos Pszichiatriai es Addiktologiai Intezet	Budapest
Hungary	410-Mathe es Tarsa Bt.	Kalocsa	Bacs
Hungary	440-PsychoTech Kft.	Pecs
Italy	580-AOU Consorziale Policlinico di Bari	Bari
Italy	539-"Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico U.O.C. Psichiatria - Padiglione Alfieri, primo piano"	Milano
Italy	566-Ospedale San Raffaele (San Raffaele Turro)	Milano
Italy	553-AO Città della Salute e della Scienza di Torino	Torino
Lithuania	483-Romuvos klinika, UAB	Kaunas
Lithuania	516-Neuromeda, JSC	Kaunas
Lithuania	518-Kaunas City Outpatient Clinic, Public Institution	Kaunas
Lithuania	484-Medical Center Puriena JSC	Silute
Poland	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 Domanski	Lublin
Poland	578-MSCZ im. prof. J. Mazurkiewicza	Pruszków
Poland	540-Osr. Badan Klin. CLINSANTE S.C.	Torun
Russian Federation	505-GUZ Lipetsk Regional psychoneurological Hospital #1	Lipetsk
Russian Federation	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	581-SBIH of Moscow "Psych Clinical Hospital #1 N.A. Alekseev"	Moscow
Russian Federation	415-Saint-Petersburg state healthcare institution "Saint Nicolas wonderworker psychiatric hospital"	Saint Petersburg
Russian Federation	451-V. M. Bekhterev National Research Medical Center For Psychiatry and Neurology	Saint Petersburg
Russian Federation	452-Saint Petersburg State Public Institution of Healthcare "City Psychiatric Hospital #3 n.a. I. I. Skvortsov-Stepanov",	Saint Petersburg
Russian Federation	464-Saint Petersburg State Budget Healthcare Institution "City Psychiatric Hospital No. 6 (Inpatient Department with Treatment Center)	Saint Petersburg
Russian Federation	465-"Saint-Petersburg Scientific Research Psychoneurological Institute n.a. V.M. Bekhterev	Saint Petersburg
Russian Federation	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	444-SPHI "City Mental Hospital #3 n.a. I.I.Skvortsov-Stepanov"	Saint-Petersburg
Russian Federation	453-"Saint-Petersburg Scientific Research Psychoneurological Institute n.a. V.M. Bekhterev"	Saint-Petersburg
Russian Federation	496-SPHI "City Mental Hospital #3 n.a. I.I.Skvortsov-Stepanov"	Saint-Petersburg
Russian Federation	571-St. Petersburg SHI "Psychoneurological Dispensary #10"	Saint-Petersburg
Russian Federation	458-State Budget Healthcare Institution "Samara Psychiatric Hospital	Samara
Russian Federation	416-FSBEI HE "Smolensk State Medical University" of the MoH of the RF (Clinical Research Centre of diagnostics and medicines)	Smolensk
Russian Federation	572-Klinika StoLet" Ltd.	Tomsk
Russian Federation	417-State budget healthcare Institution of Stavropol region "Regional specialized psychiatric hospital #2".	Tonnel'nyy	Stavropol Region
Russian Federation	422-State Budget healthcare Institution of Yaroslavl region "Yaroslavl region clinical psychiatric hospital"	Yaroslavl
Serbia	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	423-Clinical Center Kragujevac, Clinic of Psychiatry	Kragujevac
Serbia	430-Psychiatric Clinic, Clinical Center Kragujevac	Kragujevac
Serbia	585-Special Hospital for Psychiatric Diseases "Gornja Toponica"	Niš
Serbia	427-Clinical Center Nis, Mental Health Protection Clinic	Nis
Serbia	593-Specialized Hospital for Neuropsychiatric Diseases "Sveti Vracevi"	Novi Kneževac
Spain	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
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	564-Regional Clinical Psychiatric Hospital	Kropyvnytskyi	Kirovograd Region
Ukraine	435-Kyiv Regional Medical Incorporation "Psychiatry". Center of Novel Treatment and Rehabilitation of Psychotic disorders, build 5, Department #30	Kyiv
Ukraine	460-Kyiv City Psychoneurological Hospital #3 General Psychiatry Department No. 2	Kyiv	Vasylkiv District Kyiv Region
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	508-CI Cherkasy Regional Psychiatric Hospital of ChRC	Smila	Cherkas'ka Oblast

Sponsors (1)

Lead Sponsor	Collaborator
ACADIA Pharmaceuticals Inc.

Countries where clinical trial is conducted

Argentina,  Bulgaria,  Croatia,  Czechia,  Hungary,  Italy,  Lithuania,  Poland,  Russian Federation,  Serbia,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Negative Symptom Assessment-16 (NSA-16) total score - change from Baseline to Week 26	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.	26 Weeks Treatment Duration
Secondary	Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH-S) of negative symptoms score - change from Baseline to Week 26	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.	26 Weeks Treatment Duration
Secondary	Clinical Global Impression of Schizophrenia Scale-Improvement (CGI-SCH-I) of negative symptoms score at Week 26	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.	26 Weeks Treatment Duration
Secondary	Proportion of CGI-SCH-I of negative symptoms responders (CGI-SCH-I of negative symptoms score of 1 or 2) at Week 26	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.	26 Weeks Treatment Duration
Secondary	Personal and Social Performance (PSP) scale score - change from Baseline to Week 26	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).	26 Weeks Treatment Duration
Secondary	Proportion of NSA-16 responders (=20%and =30% reduction in NSA-16 total score) at Week 26	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.	26 Weeks Treatment Duration
Secondary	Positive and Negative Syndrome Scale (PANSS) total score - change from Baseline to Week 26	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.	26 Weeks Treatment Duration
Secondary	PANSS negative subscores - change from Baseline to Week 26	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.	26 Weeks Treatment Duration
Secondary	PANSS Marder factor (negative symptoms) score - change from Baseline to Week 26	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.	26 Weeks Treatment Duration