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

Phase 3

Completed

Conditions: Schizophrenia

Interventions: Drug: Placebo
Drug: Pimavanserin

Registration Number: NCT04531982

Lead Sponsor: ACADIA Pharmaceuticals Inc.

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: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 454

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo + background antipsychotic, taken as two tablets, once daily by mouth
Drug - Pimavanserin	Pimavanserin	Pimavanserin 34 mg taken as two tablets + background antipsychotic, once daily by mouth

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (102): 623-Clinica Privada de Salud Mental Santa Teresa de Avila
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La Plata, Argentina
586-Medical Center Mentalcare OOD
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Plovdiv, Bulgaria
583-Narodni ustav dusevniho zdravi
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Klecany, Czechia
410-Mathe es Tarsa Bt.
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Kalocsa, Bacs, Hungary
518-Kaunas City Outpatient Clinic, Public Institution
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Kaunas, Lithuania
526-DCC "Sv. Vrach and Sv. Sv. Kuzma and Damyan", OOD
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Sofia, Bulgaria
536-Clinic for psychiatry Vrapce
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Zagreb, Croatia
537-Clinic for psychiatry Vrapce
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Zagreb, Croatia
472-Special Neuropsychiatric Hospital Kovin
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Kovin, Serbia
610-Clinica Privada Banfield S.A.
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Buenos Aires, Argentina
622-Instituto Medico Damic Srl
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Córdoba, Argentina
617-INSA Instituto de Neurociencias San Agustin S.A.
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La Plata, Argentina
603-Fundación para el Estudio y Tratamiento de las Enfermedades Mentales - FETEM
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Ciudad Autonoma de Buenos Aires, Argentina
602-FunDamoS
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Ciudad Autonoma Buenos Aires, Argentina
455-Mental Health Center - Veliko Tarnovo EOOD,
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Veliko Tarnovo, Bulgaria
571-St. Petersburg SHI "Psychoneurological Dispensary #10"
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Saint-Petersburg, Russian Federation
453-"Saint-Petersburg Scientific Research Psychoneurological Institute n.a. V.M. Bekhterev"
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Saint-Petersburg, Russian Federation
580-AOU Consorziale Policlinico di Bari
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Bari, Italy
539-"Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico U.O.C. Psichiatria - Padiglione Alfieri, primo piano"
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Milano, Italy
483-Romuvos klinika, UAB
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Kaunas, Lithuania
525-Podlaskie Centrum Psychogeriatrii
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Bialystok, Poland
541-Care Clinic centrum Medyczne
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Katowice, Poland
565-"Kyiv CH on Railway Transport #2 of Branch Center of Healthcare Public Company Ukr Railway Short site name: Kyiv Railway Clinical Hospital № 2"
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Kyiv, Ukraine
588-Institucion Hospitalaria Hestia Palau - Ensayos clinicos
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Barcelona, Spain
424-Institute of Mental health
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Belgrade, Serbia
460-Kyiv City Psychoneurological Hospital #3 General Psychiatry Department No. 2
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Kyiv, Vasylkiv District Kyiv Region, Ukraine
509-CI Odesa Regional Medical Centre of Mental Health
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Odesa, Ukraine
475-Hospital Gregorio Marañon
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Madrid, Spain
579-Centrum Badan Klinicznych P.I. House Sp. z o.o.
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Gdańsk, Poland
540-Ośr. Badań Klin. CLINSANTE S.C.
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Torun, Poland
581-SBIH of Moscow "Psych Clinical Hospital #1 N.A. Alekseev"
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Moscow, Russian Federation
465-"Saint-Petersburg Scientific Research Psychoneurological Institute n.a. V.M. Bekhterev
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Saint Petersburg, Russian Federation
444-SPHI "City Mental Hospital #3 n.a. I.I.Skvortsov-Stepanov"
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Saint-Petersburg, Russian Federation
452-Saint Petersburg State Public Institution of Healthcare "City Psychiatric Hospital #3 n.a. I. I. Skvortsov-Stepanov",
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Saint Petersburg, Russian Federation
458-State Budget Healthcare Institution "Samara Psychiatric Hospital
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Samara, Russian Federation
416-FSBEI HE "Smolensk State Medical University" of the MoH of the RF (Clinical Research Centre of diagnostics and medicines)
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Smolensk, Russian Federation
494-CSM La Corredoria
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Oviedo, Spain
431-Hospital Psiquiátrico Provincial Doctor Villacian
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Valladolid, Spain
422-State Budget healthcare Institution of Yaroslavl region "Yaroslavl region clinical psychiatric hospital"
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Yaroslavl, Russian Federation
425-Clinical Hospital Center "Dr. Dragisa Misovic-Dedinje", Clinic of Psychiatry
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Belgrade, Serbia
584-Clinic for Psychiatry, Clinical Canter of Serbia
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Belgrade, Serbia
587-Institute of Mental health
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Belgrade, Serbia
508-CI Cherkasy Regional Psychiatric Hospital of ChRC
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Smila, Cherkas'ka Oblast, Ukraine
564-Regional Clinical Psychiatric Hospital
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Kropyvnytskyi, Kirovograd Region, Ukraine
434-State Institution "Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine", Department of Urgent Psychiatry and Narcology
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Kharkiv, Ukraine
574-Hospital Clinic de Barcelona
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Barcelona, Spain
576-Hospital Universitari Vall d'Hebron
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Barcelona, Spain
427-Clinical Center Nis, Mental Health Protection Clinic
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Nis, Serbia
435-Kyiv Regional Medical Incorporation "Psychiatry". Center of Novel Treatment and Rehabilitation of Psychotic disorders, build 5, Department #30
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Kyiv, Ukraine
575-Hospital Universitario 12 de Octubre
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Madrid, Spain
607-Resolution Psicopharmacology Research Institute
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Ciudad de Mendoza, Argentina
625-NOVAIN Neurociencias Group
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Ciudad Autonoma de Buenos Aires, Argentina
532-MHAT "Dr. Hristo Stambolski", EOOD
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Kazanlak, Stara Zagora, Bulgaria
533-State Psychiatric Hospital - Kardzhali, EOOD
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Kardzhali, Bulgaria
569-State Psychiatric Hospital - Lovech
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Lovech, Bulgaria
592-Medical center Spectar - Plovdiv EOOD
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Plovdiv, Bulgaria
570-Medical Centre "Sveti Naum"
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Sofia, Bulgaria
405-"UMHAT Alexandrovska EAD, Sofia; Clinic of Psychiatry, First Department of Psychiatry "
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Sofia, Bulgaria
568-Medical Center Hera EOOD
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Sofia, Bulgaria
528-Medical Center Intermedica, OOD
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Sofia, Bulgaria
590-State Psychiatric Hospital - Tzarev Brod
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Tsarev Brod, Bulgaria
550-Clinic for psychiatry Vrapce
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Zagreb, Croatia
498-DCC "Mladost M" - Varna, OOD
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Varna, Bulgaria
512-NeuropsychiatrieHK s.r.o.
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Hradec Králové, Czechia
557-Clinic for psychiatry Vrapce
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Zagreb, Croatia
519-A-SHINE s.r.o.
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Plzen, Czechia
520-Nyiro Gyula Korhaz - Orszagos Pszichiatriai es Addiktologiai Intezet
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Budapest, Hungary
513-CLINTRIAL s.r.o.
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Praha 10, Czechia
499-MUDr. Tibor Miklos
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Praha 10, Czechia
456-Semmelweis University Department of Psychiatry and Psychotherapy
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Budapest, Hungary
440-PsychoTech Kft.
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Pecs, Hungary
566-Ospedale San Raffaele (San Raffaele Turro)
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Milano, Italy
553-AO Città della Salute e della Scienza di Torino
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Torino, Italy
516-Neuromeda, JSC
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Kaunas, Lithuania
502-Przychodnia Srodmiescie Sp. z o. o.
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Bydgoszcz, Poland
484-Medical Center Puriena JSC
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Silute, Lithuania
501-Specjalistyczna Praktyka Lekarska Marek Domański
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Lublin, Poland
505-GUZ Lipetsk Regional psychoneurological Hospital #1
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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"
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Moscow, Russian Federation
578-MSCZ im. prof. J. Mazurkiewicza
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Pruszków, Poland
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."
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Saint Petersburg, Russian Federation
417-State budget healthcare Institution of Stavropol region "Regional specialized psychiatric hospital #2".
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Tonnel'nyy, Stavropol Region, Russian Federation
464-Saint Petersburg State Budget Healthcare Institution "City Psychiatric Hospital No. 6 (Inpatient Department with Treatment Center)
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Saint Petersburg, Russian Federation
529-Hospital Provincial de Zamora
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Zamora, Spain
563-MC-Hipokrat-N E00D
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Plovdiv, Bulgaria
601-CENydET- Centro Neurobiologico y de Estres Traumatico-Biopsychomedical Research Group SRL
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Ciudad Autonoma Buenos Aires, Argentina
624-Centro Especializado en Neurociencias CEN
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Cordoba, Argentina
626-Sanatorio Prof. Leon S. Morra S.A.
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Córdoba, Argentina
454-Mental Health Center Prof. Dr. Ivan Temkov - Burgas EO Burgas; Department for Treatment of Emergency Psychiatric Conditions
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Burgas, Bulgaria
535-UMHAT 'Dr. Georgi Stranski', EAD
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Pleven, Bulgaria
401-Mental Health Center - Vratsa EOOD, Vratsa; Department of Psychiatry
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Vratsa, Bulgaria
594-klinika za psihijatriju Sveti Ivan, n/p Igor Filipčić or Marija Zelenika
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Zagreb, Croatia
415-Saint-Petersburg state healthcare institution "Saint Nicolas wonderworker psychiatric hospital"
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Saint Petersburg, Russian Federation
451-V. M. Bekhterev National Research Medical Center For Psychiatry and Neurology
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Saint Petersburg, Russian Federation
496-SPHI "City Mental Hospital #3 n.a. I.I.Skvortsov-Stepanov"
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Saint-Petersburg, Russian Federation
572-Klinika StoLet" Ltd.
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Tomsk, Russian Federation
430-Psychiatric Clinic, Clinical Center Kragujevac
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Kragujevac, Serbia
423-Clinical Center Kragujevac, Clinic of Psychiatry
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Kragujevac, Serbia
585-Special Hospital for Psychiatric Diseases "Gornja Toponica"
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Niš, Serbia
593-Specialized Hospital for Neuropsychiatric Diseases "Sveti Vracevi"
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Novi Kneževac, Serbia
567-"CIH Kharkiv Regional Clinical Psychiatric Hospital #3 Psychiatric Department of Primary Psychotic Episod Short Site name: CIH KRCPH #3 PD of PPE "
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Kharkiv, Ukraine
582-SI Institute of Neurology,Psychiatry&Narcology of NAMSU
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Kharkiv, Ukraine