Clinical trial NCT01192867: A Study of RO4917838 in Participants With Persistent, Predominant Negative Symptoms of Schizophrenia (NN25310)
Official title: A Phase III, Multi-Center, Randomized, 24 Week, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate Efficacy and Safety of RO4917838 in Stable Patients With Persistent, Predominant Negative Symptoms of Schizophrenia Treated With Antipsychotics Followed by a 28 Week, Double-Blind Treatment Period
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2010-09-01
Enrollment: 629
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This multi-center, randomized, double-blind, parallel-group, placebo-controlled study will evaluate the efficacy and safety of RO4917838 in participants with persistent, predominant negative symptoms of schizophrenia. Participants, on stable treatment with antipsychotics, will be randomized to receive daily oral doses of RO4917838 or matching placebo for 56 weeks (treatment period 1 of 24 weeks and treatment period 2 of 32 weeks), followed by an optional treatment extension for up to 3 years. After 52 weeks, participants who were originally randomized to an active treatment will be randomly assigned to receive either placebo or continue on the originally assigned study treatment for 4 weeks washout period (Week 52 to Week 56) for the assessment of potential withdrawal effects in a blinded manner using participants staying on active treatment as a control. Participants initially randomized to placebo will remain on placebo. After 56 weeks, participants who were switched to placebo in the washout period will return to their blinded, active treatment arm.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of schizophrenia of paranoid, disorganized, residual, undifferentiated or catatonic subtype
* Predominant negative symptoms
* With the exception of clozapine, participants are on any of the available marketed atypical or typical antipsychotics (treatment with a maximum of two antipsychotics)

Exclusion Criteria:

* Evidence that participant has clinically significant, uncontrolled and unstable disorder (e.g. cardiovascular, renal, hepatic disorder)
* Body Mass Index (BMI) of less than (\<) 17 or greater than (\>) 40 kilograms per meter square (kg/m\^2)
* Depressive symptoms, defined as a score of 9 or greater on the Calgary Depression Rating Scale for Schizophrenia (CDSS)
* A severity score of 3 or greater on the Parkinsonism item of the Exrapyramidal Symptoms Rating Scale-Abbreviated (ESRS-A) (Clinical Global Impression, Parkinsonism)

Primary outcomes:
measure: Change From Baseline in the Positive and Negative Symptoms Scales (PANSS) Negative Symptoms Factor Score at Week 24 (All-Participant Population)
timeFrame: Baseline, Week 24
measure: Percentage of Participants With Adverse Events (All-Participant Population)
timeFrame: Week 24
Secondary outcomes:
measure: Change From Baseline in the PANSS Negative Symptoms Factor Score at Week 24 (Complement Factor H Related Protein 1 High [CFHR1-High] Subgroup Population)
timeFrame: Baseline, Week 24
measure: Change From Baseline in the Personal and Social Performance (PSP) Total Score at Week 24 (All-Participant Population)
timeFrame: Baseline, Week 24
measure: Change From Baseline in the PSP Total Score at Week 24 (CFHR1-High Subgroup Population)
timeFrame: Baseline, Week 24
measure: Change From Baseline in the PANSS Total Score at Week 24 (All-Participant Population)
timeFrame: Baseline, Week 24
measure: Change From Baseline in the PANSS Total Score at Week 24 (CFHR1-High Subgroup Population)
timeFrame: Baseline, Week 24
measure: Change From Baseline in the PANSS Factor Score at Week 24 (All-Participant Population)
timeFrame: Baseline, Week 24
measure: Change From Baseline in the PANSS Factor Score at Week 24 (CFHR1-High Subgroup Population)
timeFrame: Baseline, Week 24
measure: Change From Baseline in the PANSS Subscale Scores at Week 24 (All-Participant Population)
timeFrame: Baseline, Week 24
measure: Change From Baseline in the PANSS Subscale Scores at Week 24 (CFHR1-High Subgroup Population)
timeFrame: Baseline, Week 24
measure: Percentage of Participants Who Have at least 20 Percent (%) Improvement From Baseline in the PANSS Negative Symptom Factor Score at Week 24 (All-Participant Population)
timeFrame: Baseline, Week 24
measure: Percentage of Participants Who Have at least 20% Improvement From Baseline in the PANSS Negative Symptom Factor Score at Week 24 (CFHR1-High Subgroup Population)
timeFrame: Baseline, Week 24
measure: Percentage of Participants Who Have at least 20% Improvement From Baseline in the PANSS Negative Symptom Factor Score for Two out of Three Assessments During 24 Weeks (All-Participant Population)
timeFrame: Baseline up to Week 24
measure: Percentage of Participants Who Have at least 20% Improvement From Baseline in the PANSS Negative Symptom Factor Score for Two out of Three Assessments During 24 Weeks (CFHR1-High Subgroup Population)
timeFrame: Baseline up to Week 24
measure: Percentage of Participants With Improvement From Baseline in the Overall Clinical Status Based on Clinical Global Impression - Improvement (CGI-I) Score (All-Participant Population)
timeFrame: Baseline, Week 24
measure: Percentage of Participants With Improvement From Baseline in the Overall Clinical Status Based on CGI-I Score (CFHR1 Subgroup Population)
timeFrame: Baseline, Week 24
measure: Percentage of Participants With Improvement From Baseline in the Overall Clinical Status Based on CGI-I Score for Two out of Three Assessments During 24 Weeks (All-Participant Population)
timeFrame: Baseline up to Week 24
measure: Percentage of Participants With Improvement From Baseline in the Overall Clinical Status Based on CGI-I Score for Two out of Three Assessments During 24 Weeks (CFHR1 Subgroup Population)
timeFrame: Baseline up to Week 24
measure: Percentage of Participants With Improvement From Baseline in the Negative Symptoms Based on CGI-I Negative Symptoms Score (All-Participant Population)
timeFrame: Baseline, Week 24
measure: Percentage of Participants With Improvement From Baseline in the Negative Symptoms Based on CGI-I Negative Symptoms Score (CFHR1 Subgroup Population)
timeFrame: Baseline, Week 24
measure: Percentage of Participants With Improvement From Baseline in the Negative Symptoms Based on CGI-I Negative Symptoms Score for Two out of Three Assessments During 24 Weeks (All-Participant Population)
timeFrame: Baseline up to Week 24
measure: Percentage of Participants With Improvement From Baseline in the Negative Symptoms Based on CGI-I Negative Symptoms Score for Two out of Three Assessments During 24 Weeks (CFHR1 Subgroup Population)
timeFrame: Baseline up to Week 24
measure: Percentage of Participants Who Have at least 20% Improvement From Baseline in the PANSS Negative Symptom Factor Score at Week 24 and Improvement in the Negative Symptoms Based on CGI-I Negative Symptoms Score (All-Participant Population)
timeFrame: Baseline, Week 24
measure: Percentage of Participants Who Have at least 20% Improvement From Baseline in the PANSS Negative Symptom Factor Score at Week 24 and Improvement in the Negative Symptoms Based on CGI-I Negative Symptoms Score (CFHR1 Subgroup Population)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Severity of Illness Based on Clinical Global Impression - Severity (CGI-S) Overall Score (All-Participant Population)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Severity of Illness Based on CGI-S Overall Score (CFHR1 Subgroup Population)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Severity of Illness Based on CGI-S Negative Symptoms Score (All-Participant Population)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Severity of Illness Based on CGI-S Negative Symptoms Score (CFHR1 Subgroup Population)
timeFrame: Baseline, Week 24
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: K&S Professional Research Services LLC
state: Arkansas
city: Anaheim
country: United States
facility: Advanced Research Center Inc.
state: California
city: Cerritos
country: United States
facility: Comprehensive Clinical Development- Cerritos CA
state: California
city: Downey
country: United States
facility: Diligent Clinical Trials Inc
state: California
city: La Palma
country: United States
facility: Care Research Center
state: California
city: Pasadena
country: United States
facility: Pasadena Research Institute
state: California
city: Pico Rivera
country: United States
facility: CNRI - Los Angeles, LLC
state: California
city: Miami
country: United States
facility: Pharmax Research Clinic Inc.
state: Florida
city: Marietta
country: United States
facility: Northwest Behavioral Research Center
state: Georgia
city: Oak Brook
country: United States
facility: American Medical Research, Inc
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa College of Medicine; Psychiatry Research
state: Iowa
city: Glen Burnie
country: United States
facility: Clinical Insights, Inc.
state: Maryland
city: Saint Louis
country: United States
facility: St Louis Clinical Trials
state: Missouri
city: Toms River
country: United States
facility: Ocean Rheumatology
state: New Jersey
city: Willingboro
country: United States
facility: CRI Worldwide LLC
state: New Jersey
city: Albuquerque
country: United States
facility: Raymond G. Murphy VA Medical Center
state: New Mexico
city: Brooklyn
country: United States
facility: Behavioral Medical Research of Brooklyn
state: New York
city: Fresh Meadows
country: United States
facility: Comprehensive NeuroScience
state: New York
city: Raleigh
country: United States
facility: North Carolina Psychiatric Research Center
state: North Carolina
city: Cincinnati
country: United States
facility: UC Health Clinical Trials Office
state: Ohio
city: Philadelphia
country: United States
facility: Belmont Center for Comprehensive Treatment; Research
state: Pennsylvania
city: Bellaire
country: United States
facility: Claghorn-Lesem Research Clinic, Inc.
state: Texas
city: Dallas
country: United States
facility: FutureSearch Clinical Trials, LP
state: Texas
city: Dallas
country: United States
facility: Pillar Clinical Research LLC
state: Texas
city: The Woodlands
country: United States
facility: Family Psychiatry of the Woodlands P.A.
state: Texas
city: Bothell
country: United States
facility: Pacific Institute of Medical Sciences
state: Washington
city: Kirkland
country: United States
facility: Eastside Therapeutic Resource
state: Washington
city: Buenos Aires
country: Argentina
facility: Centro SERES
city: Buenos Aires
country: Argentina
facility: Fundacion para el Estudio y Tratamiento des las Enfi Mentales
city: Caba
country: Argentina
facility: Mulieris
city: Ciudad Autonoma Bs As
country: Argentina
facility: Facene Fund.Argentina Contra Enferm.Neur.Del Envejecimiento
city: Ciudad Autonoma Bs As
country: Argentina
facility: Instituto Nacional de Psicopatologia
city: Ciudad de Mendoza
country: Argentina
facility: Resolution Psicopharmacology Research Institute
city: Cordoba
country: Argentina
facility: Instituto DAMIC - Fundación Rusculleda
city: Cordoba
country: Argentina
facility: Sanatorio Prof.Leon.S.Morra S.A
city: La Plata
country: Argentina
facility: Instituto de Neurociencias San Agustín S.A.
city: Mendoza
country: Argentina
facility: Centro de Psiquiatria Biologica Professor Julio J. Herrera; Psiquiatria
city: Mendoza
country: Argentina
facility: Centro de Asistencia e Investigación en Neurociencias
city: Rosario
country: Argentina
facility: CIAP - Centro de Investigacion y Asistencia en Psiquiatria
city: Santiago del Estero
country: Argentina
facility: Centro de Investigacion Clinica Farmacologica en Psiquiatria
city: Westmead
country: Australia
facility: Westmead Hospital; Department of Psychiatry
state: New South Wales
city: Clayton
country: Australia
facility: Monash Medical Centre-Clayton Campus; School of Psychology and Psychiatry
state: Victoria
city: Frankston
country: Australia
facility: Frankston Hospital; Mental Health Service
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital; Monash Alfred Psychiatry Research Centre (MAP-RC)
state: Victoria
city: Barranquilla
country: Colombia
facility: Centro de Investigaciones y Proyectos en Neurociencias CIPNA
city: Bello
country: Colombia
facility: E.S.E. Hospital Mental de Antioquia
city: Bogota
country: Colombia
facility: Centro de Investigaciones del Sistema Nervioso Limitada - Gr
city: Kuopio
country: Finland
facility: Privater
city: Caen
country: France
facility: Centre Hospitalier Universitaire Caen; Pôle Psychiatrie - Addictologie
city: Clermont-ferrand
country: France
facility: CHU Gabriel Montpied; Service de Psychiatrie
city: Dole
country: France
facility: Centre Hospitalier Specialise du Jura
city: Elancourt
country: France
facility: Cabinet Médical Ambroise Paré
city: Marseille
country: France
facility: Hôpital de la Conception; Pôle Psychiatrique Centre
city: Strasbourg
country: France
facility: CHU Strasbourg Nouvel Hôpital Civil;Service de Psychiatrie I
city: Toulon
country: France
facility: Hopital Chalucet; Unite de Psychiatrie
city: Balassagyarmat
country: Hungary
facility: Dr. Kenessey Albert Hospital; Psychiatry I.
city: Budapest
country: Hungary
facility: Fov.Onk.Szt Janos Korh. E-Budai Egyesitett Korhazai; Pszichiatriaci rehabilitacio
city: Budapest
country: Hungary
facility: Semmelweis Egyetem AOK; Pszichiatriai es Pszichoterapias Klinika
city: Budapest
country: Hungary
facility: Fovarosi Onkormanyzat Nyiro Gyula Korhaza; Pszichatria II
city: Budapest
country: Hungary
facility: Fovarosi Onkormanyzat Nyiro Gyula Korhaza; Pszichiatria I.
city: Budapest
country: Hungary
facility: UNO Medical Trials Kft.
city: Gyor
country: Hungary
facility: Petz Aladar Megyei Oktato Korhaz; Pszichiatria I.
city: Gyula
country: Hungary
facility: Békés Megyei Pándy Kálmán Kórház; Onkologiai tanszek
city: Ahmedabad
country: India
facility: Samvedna Hospitals; Samvedana Psychiatry and Sex Therapy Hospital
city: Ahmedabad
country: India
facility: Sneh Clinic
city: Ahmedabad
country: India
facility: Gujarat Institute of Psychological Research (GIPS)
city: Jaipur
country: India
facility: Mental Health Care & Research
city: Jaipur
country: India
facility: R. K.Yadav Memorial Mental Health & De-Addiction Hospital
city: Kalyan
country: India
facility: Manav Neuropsychiatric Hospital Pvt. Ltd.
city: Mangalore
country: India
facility: Kasturba Medical College & Hospital
city: Mangalore
country: India
facility: K. S. Hegde Medical Academy
city: Pune
country: India
facility: Poona Hospital and Research Centre
city: Vadodara
country: India
facility: Brij Psychiatry Hospital & Muskaan Research Centre; Maanav Health Foundation
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Korea University Ansan Hospital
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
city: Incheon
country: Korea, Republic of
facility: Gil Hospital. Gachon University
city: Jeollabuk-do
country: Korea, Republic of
facility: Chonbuk National Uni Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea St.Mary's Hospital
city: Mexico
country: Mexico
facility: Arete Proycectos y Administracion S.C
city: Monterrey
country: Mexico
facility: Centro de Investigacion Medica S.C; Hospital Santa Cecilia de Monterrey S.A. de C.V.
city: Monterrey
country: Mexico
facility: Medikalink
city: Monterrey
country: Mexico
facility: Instituto de informacion e investigacion en salud mental AC
city: San Luis Potosi
country: Mexico
facility: Hospital Lomas de San Luis Internacional
city: Arad
country: Romania
facility: Spitalul Clinic Judetean Arad; Departamentul de Psihiatrie
city: Bucuresti
country: Romania
facility: Spit Univ Urgenta Militar Dr. Carol Davila; Sectia Psihiatrie
city: Bucuresti
country: Romania
facility: Spitalul Clinic de Psihiatrie Prof. Dr. Alexandru Obregia; Clinical III Psihiatrie
city: Bucuresti
country: Romania
facility: Spitalul Clinic de Psihiatrie Prof. Dr. Alexandru Obregia; Comunitara si Reintegrare Psihosociala
city: Bucuresti
country: Romania
facility: Spitalul Clinic de Psihiatrie Prof. Dr. Alexandru Obregia; Sectia Clinica XIII Psihiatrie
city: Cluj-Napoca
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Cluj; Sectia Clinica de Psihiatrie III
city: Lasi
country: Romania
facility: Spitalul Universitar de Psihiatrie Socola
city: Oradea
country: Romania
facility: Spitalul Clinic Municipal Dr. Gavril Curteanu; Sectia Clinica Psihiatrie I
city: Sibiu
country: Romania
facility: Spitalul de Psihiatrie Dr. Gh. Preda Sibiu;CSM Adulti Sibiu
city: Targouiste
country: Romania
facility: Cabinet Medical S.C. Lorentina 2102 S.R.L.; Psihiatrie
city: Kemerovo
country: Russian Federation
facility: Kemerovo Regional Clinical Psychiatric Hospital
city: Lipetsk
country: Russian Federation
facility: GUZ Lipetsk Regional psychoneurological Hospital #1; Dispansary Department
city: Moscow Region
country: Russian Federation
facility: Moscow Region Psychiatric Hospital #5
city: Moscow
country: Russian Federation
facility: Scientifically Research Institute of Psychiatry of Ministry of Health of the Russian Federation
city: Moscow
country: Russian Federation
facility: Institution of RAMS (Mental Health Research Center of RAMS)
city: Moscow
country: Russian Federation
facility: Federal State Institution Moscow SRI of Psychiatry of Minzdravsocrazvitia
city: Moscow
country: Russian Federation
facility: Central Moscow Regional Clinical Psychiatric Hospital
city: Nizhny Novgorod
country: Russian Federation
facility: City Clinical Psychiatry Hospital #1
city: Saint Petersburg
country: Russian Federation
facility: Military Medical Academy
city: Samara
country: Russian Federation
facility: Samara Psychiatric Hospital
city: Sartatov
country: Russian Federation
facility: Mhi City Clinical Hospital #2 Named After v.i. Razumousky
city: St Petersbourg
country: Russian Federation
facility: St. Petersburg State Healthcare Institution
city: St Petersburg
country: Russian Federation
facility: St. Petersburg GUZ City Psychiatric Hospital #6
city: St Petersburg
country: Russian Federation
facility: St. Petersburg State Healthcare Institution "City Mental Hospital #3; I.I. Skvortsov-Stepanov
city: St. Petersburg
country: Russian Federation
facility: City Psychiatric Hospital #2 of St. Nikolay Chudotvorets
city: St. Petersburg
country: Russian Federation
facility: Saint Petersburg Psychoneurological Research Institute of Roszdrav n.a. Bekhterev
city: Talagi
country: Russian Federation
facility: Arkhangelsk Regional Clinical Psychiatric Hospital
city: Tomsk
country: Russian Federation
facility: Tomsk Clinical Psychiatric Hospital
city: Malmö
country: Sweden
facility: Integrerad Närsjukvård i Malmö
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Huddinge, Psykiatri Sydväst
city: Stockholm
country: Sweden
facility: Danderyds Sjukhus AB; PRIMA Vuxenpsykiatri
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset; Psykosvård och rättspsykiatrisk vård
city: Edinburgh
country: United Kingdom
facility: Royal Edinburgh Hospital; Psychiatry
city: London
country: United Kingdom
facility: Institute of Pyschiatry
city: Oxford
country: United Kingdom
facility: Wareneford Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Georgiades A, Davis VG, Atkins AS, Khan A, Walker TW, Loebel A, Haig G, Hilt DC, Dunayevich E, Umbricht D, Sand M, Keefe RSE. Psychometric characteristics of the MATRICS Consensus Cognitive Battery in a large pooled cohort of stable schizophrenia patients. Schizophr Res. 2017 Dec;190:172-179. doi: 10.1016/j.schres.2017.03.040. Epub 2017 Apr 20.
citation: Bugarski-Kirola D, Blaettler T, Arango C, Fleischhacker WW, Garibaldi G, Wang A, Dixon M, Bressan RA, Nasrallah H, Lawrie S, Napieralski J, Ochi-Lohmann T, Reid C, Marder SR. Bitopertin in Negative Symptoms of Schizophrenia-Results From the Phase III FlashLyte and DayLyte Studies. Biol Psychiatry. 2017 Jul 1;82(1):8-16. doi: 10.1016/j.biopsych.2016.11.014. Epub 2016 Dec 15.