Clinical trial NCT01192880: A Study to Evaluate Efficacy and Safety of Bitopertin in Participants With Persistent, Predominant Negative Symptoms of Schizophrenia
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: 625
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 Phase 3, multi-center, randomized, double blind, parallel-group, placebo-controlled study will evaluate the efficacy and safety of RO4917838 (bitopertin) 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 52 weeks, followed by an optional treatment extension for up to 3 years.


Eligibility criteria: Inclusion Criteria:

* Based on the screening Structured Clinical Interview for and Statistical Manual of Mental Disorders, 4th Edition (DSM IV) - Clinical Trial (SCID CT), a DSM-IV- Text Revision (DSM-IV-TR) diagnosis of schizophrenia, paranoid, disorganized, residual, undifferentiated or catatonic subtype
* A score of 40 or greater on the sum of the 14 PANSS negative and disorganized thought factor items (items scored 1-7 for a maximum possible score of 98)
* A score of 22 or less on the sum of the 8 PANSS positive symptom factor items. The score of the items of P1 (delusions), P3 (hallucinatory behavior), P6 (suspiciousness) and G9 (unusual thought content) meet the following requirements: no more than 2 of the above items have a score of 4; all of the above items score less than 5
* Clinical stability for 6 months prior to randomization as well as antipsychotic treatment stability for the past 8 weeks at the time of randomization
* Are at least moderately ill, as defined by Clinical Global Impression - Severity (CGI S) of negative symptoms score more than or equal to (\>/=) 4
* Stable doses of anticholinergic, antidepressive medication for at least 8 weeks prior to randomization is allowed as long as the respective scales cut-off entry criteria are met
* With the exception of clozapine, participants are on any of the available marketed atypical or typical antipsychotics (treatment with a maximum of 2 antipsychotics)
* Have a caregiver considered reliable by the investigator
* Female participants who are not either surgically sterile or post-menopausal must agree to use at least one effective forms of contraception from agree to remain sexually abstinent from screening until 90 days after the completion of the study medication

Exclusion Criteria:

* Evidence that participant has clinically significant, uncontrolled and unstable disorder (for example, cardiovascular, renal, hepatic disorder)
* Body Mass Index (BMI) of less than (\<) 17 or more 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 on the Parkinsonism item of the Extrapyramidal Symptoms Rating Scale - Abbreviated (ESRS-A) (Clinical Global Impression, Parkinsonism)
* Positive result on the serum pregnancy test or are breast feeding at screening, or intend to become pregnant during the course of the trial.
* History of neuroleptic malignant syndrome (NMS)
* Based on the DSM-IV-TR criteria and screening SCID-CT have: other current DSM-IV-TR Axis I diagnosis; alcohol or substance dependence within 12 months or abuse within 3 months with the exception of nicotine; dementia, delirium and other amnestic disorder per DSM-IV-TR
* Treated with electroconvulsive therapy (ECT) within 6 months prior to randomization
* Ever received RO4917838 or another glycine transporter 1 (GLYT 1) inhibitor
* Require high doses of benzodiazepines (\> 4 mg per day lorazepam or equivalent)
* Have a positive urine drug screen for amphetamines (including 3,4-Methylenedioxymethamphetamine \[MDMA\]/ecstasy), cocaine, barbiturate, cannabis and/or opiates

Primary outcomes:
measure: Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Negative Symptom Factor Score at Week 24
timeFrame: Baseline, Week 24
measure: Percentage of Participants with Adverse Events
timeFrame: From baseline up to 24 weeks
Secondary outcomes:
measure: Mean Change from Baseline in the Personal and Social Performance (PSP) Total Score at Week 24
timeFrame: Baseline, Week 24
measure: Mean Change from Baseline in the PANSS Total Score at Week 24
timeFrame: Baseline, Week 24
measure: Mean Change from Baseline in the PANSS Factor Scores at Week 24
timeFrame: Baseline, Week 24
measure: Mean Change from Baseline in the PANSS Subscale Scores at Week 24
timeFrame: Baseline, Week 24
measure: Percentage of Participants With Response, as Assessed by PANSS Negative Symptom Factor Score
timeFrame: Week 24
measure: Percentage of Participants with Response, as Assessed by CGI-I Overall and Negative Symptoms Rating Score
timeFrame: Week 24
measure: Percentage of Participants with Both At Least 20% Improvement from Baseline in the PANSS Negative Symptom Factor Score and with a CGI-I Negative Symptoms Rating of Either Much or Very Much Improvement
timeFrame: Week 24
measure: Mean Change from Baseline in the CGI-S Overall and Negative Symptoms Rating Score
timeFrame: Baseline, Week 24
Other outcomes:
Locations:
city: Costa Mesa
country: United States
facility: Clinical Innovtions Inc
state: California
city: Escondido
country: United States
facility: Synergy Clinical Research of Escondido
state: California
city: Granada Hills
country: United States
facility: San Fernando Mental Health Center
state: California
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Oceanside
country: United States
facility: Excell Research
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research, LLC
state: California
city: Torrance
country: United States
facility: Collaborative Neuroscience Network Inc.
state: California
city: Lauderhill
country: United States
facility: Behavioral Clinical Research Inc.
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Orange City
country: United States
facility: Medical Research Group of Central Florida
state: Florida
city: Plantation
country: United States
facility: Berma Research Group
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center For Medical Research
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University; LaRue Carter Memorial Hospital-Research Unit
state: Indiana
city: Glen Burnie
country: United States
facility: Clinical Insights, Inc.
state: Maryland
city: Flowood
country: United States
facility: Precise Research Centers
state: Mississippi
city: Las Vegas
country: United States
facility: Altea Research Institute
state: Nevada
city: Toms River
country: United States
facility: Ocean Rheumatology
state: New Jersey
city: Buffalo
country: United States
facility: State University of New York at Buffalo; Department of Psychiatry
state: New York
city: New York
country: United States
facility: New York State Psychiatric Institute; Psychiatry Dept of Columbia University
state: New York
city: Rochester
country: United States
facility: Finger Lakes Clinical Research
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Norristown
country: United States
facility: Keystone Clinical Studies, LLC
state: Pennsylvania
city: Scranton
country: United States
facility: Scranton Medical Institutes Llc.
state: Pennsylvania
city: Austin
country: United States
facility: Community Clinical Research Inc.
state: Texas
city: Irving
country: United States
facility: University Hills Clinical Research
state: Texas
city: Salt Lake City
country: United States
facility: Lifetree Clinical Research
state: Utah
city: Kirkland
country: United States
facility: Eastside Therapeutic Resource
state: Washington
city: Bourgas
country: Bulgaria
facility: DDPDS Prof Dr Ivan Temkov EOOD
city: Kazanlak
country: Bulgaria
facility: MHAT Dr.Hristo Stambolski EOOD; Psychiatry Ward of Acute Psychotic Disiorders in Severe Stage
city: Novi Iskar
country: Bulgaria
facility: State Psychiatric Hospital Sv. Ivan Rilski Novi Iskar; First Man Dept. and First Woman Dept.
city: Pazardzhik
country: Bulgaria
facility: State Psychiatric Hospital - Pazardzhik AD; Department for active treatment of men and for women
city: Plovdiv
country: Bulgaria
facility: UMHAT Dr Georgi Stranski; EAD; Psychiatry
city: Radnevo
country: Bulgaria
facility: State Psychiatric Hospital Dr. G. Kissiov; 3-d Women Ward 1-st Men Ward
city: Rousse
country: Bulgaria
facility: DDPDIU-Ruse; Men acute department Women acute department
city: Sofia
country: Bulgaria
facility: Military Medical Academy- MHAT
city: Baoding
country: China
facility: Hebei Mental Health Centre
city: Beijing
country: China
facility: Beijing Huilongguan Hospital; Department of Psychiatric
city: Beijing
country: China
facility: Peking University Sixth Hospital; Department of Psychiatry
city: Beijing
country: China
facility: Beijing An Ding Hosp.Capital Medical University; 5th Clinical Dept Depression Centre
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: GuangzhouGuangdong
country: China
facility: Guangzhou Brain Hospital
city: Hangzhou
country: China
facility: The First Affiliated Hospital of College of Medicine, Zhejiang University(First Hospital of Zhejiang
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University College
city: Kunming
country: China
facility: The First Affilliated Hospital of Kunming Medical College
city: Nanjing
country: China
facility: Nanjing Brain Hospital
city: Shanghai
country: China
facility: Shanghai Mental Health Center
city: Shanghai
country: China
facility: Tongji Hospital of Tongji University
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
city: Wuxi
country: China
facility: Wuxi Mental Health Center
city: Xi'an
country: China
facility: The First Affiliated Hospital of The Fourth Military Medical University (Xijing Hospital)
city: Xi'an
country: China
facility: First Affiliated Hospital of Medical College of Xi'an Jiaotong University
city: Xi'an
country: China
facility: Xi'an Mental Health Center
city: Brno
country: Czech Republic
facility: Saint Anne s.r.o.
city: Liberec
country: Czech Republic
facility: Krajska nemocnice Liberec a.s.
city: Melnik
country: Czech Republic
facility: Psychiatricka ambulance
city: Plzen
country: Czech Republic
facility: A-Shine s.r.o.
city: Praha 10
country: Czech Republic
facility: Clintrial,s.r.o.
city: Praha 6
country: Czech Republic
facility: Medical Services Prague s.r.o.
city: Praha 8 - Bohnice
country: Czech Republic
facility: Psychiatricke Centrum Praha
city: Sternberk
country: Czech Republic
facility: CTCenter MaVe s.r.o.
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
state: Campania
city: Brescia
country: Italy
facility: Asst Degli Spedali Civili Di Brescia; Servizio di farmacia
state: Lombardia
city: Milano
country: Italy
facility: Clinica Mangiagalli
state: Lombardia
city: Milano
country: Italy
facility: ASST FATEBENEFRATELLI SACCO; Psichiatria (Fatebenefratelli)
state: Lombardia
city: Torino
country: Italy
facility: Azienda Ospedaliero Universitaria Molinette San Giovanni Bat
state: Piemonte
city: Bari
country: Italy
facility: Azienda Ospedaliero-Universitaria Consorziale Pol. di Bari; Neuroscienze e Organi di Senso
state: Puglia
city: Pisa
country: Italy
facility: A.O. Universitaria Pisana; Psichiatria
state: Toscana
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
state: Veneto
city: Chiba
country: Japan
facility: Kohnodai Hp., National Center for Global Health and Medicine
city: Funabashi-shi
country: Japan
facility: Fukkokai Soubu Hospital
city: Gunma
country: Japan
facility: Daiwakai Seimou Hospital
city: Hiroshima-shi
country: Japan
facility: Koseikai Kusatsu Hospital
city: Hokkaido
country: Japan
facility: Hokkaido University Hospital
city: Kanzaki-gun
country: Japan
facility: NHO Hizen Psychiatric Medical Center
city: Kita-Ku
country: Japan
facility: Sankeikai Nishigahara Hospital
city: Kitakyushu-shi
country: Japan
facility: Hospital of the University of Occupational and Environmental Health,Japan
city: Kochi-shi
country: Japan
facility: Jinseikai Hosogi Unity Hospital
city: Koshi-shi
country: Japan
facility: NHO Kikuchi National Hospital
city: Kumamoto-shi
country: Japan
facility: Yuge Hospital
city: Kurayoshi-shi
country: Japan
facility: Jinkokai Kurayoshi Hospital
city: Nagoya-Shi
country: Japan
facility: NHO Higashiowari Hospital
city: Omuta-shi
country: Japan
facility: Shinkokai Shiranui Hospital
city: Sakai-shi
country: Japan
facility: Asakayama General Hospital
city: Sapporo-shi
country: Japan
facility: Tonankai Ashirbetsu Hospital
city: Sapporo-shi
country: Japan
facility: Sawayamakai Teine Hospital
city: Sendai-shi
country: Japan
facility: Tohoku Seishin Hokenkai Aoba Hospital
city: Shirakawa-shi
country: Japan
facility: Jisenkai Nanko Psychiatric Institute
city: Tokyo
country: Japan
facility: Tokyo Women's Medical University Hospital
city: Tokyo
country: Japan
facility: National Center Of Neurology And Psychiatry Hospital
city: Toyama-shi
country: Japan
facility: Korenkai Minamitoyama Nakagawa Hospital
city: Toyoake-shi
country: Japan
facility: Fujita Health University Hospital
city: Yokohama-shi
country: Japan
facility: Deep Intention Hiyoshi Hospital
city: Yokohama-shi
country: Japan
facility: Kanagawa Prefectural Psychiatric Center Kinko Hospital
city: Yokohama-shi
country: Japan
facility: Yokohama Aihara Hospital
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
country: Russian Federation
facility: Institution of RAMS (Mental Health Research Center of RAMS); Psychopharmacology laboratory
city: Moscow
country: Russian Federation
facility: Central Moscow Regional Clinical Psychiatric Hospital
city: Sartatov
country: Russian Federation
facility: MHI City Clinical Hospital #2 named after V.I. Razumovsky; Psychiatric
city: St. Petersburg
country: Russian Federation
facility: City Psychiatric Hospital #2 of St. Nikolay Chudotvorets
city: St. Petersburg
country: Russian Federation
facility: StP SR Psychoneurological Institute n.a.V.M.Bekhterev of MoH
city: Talagi
country: Russian Federation
facility: Arkhangelsk Regional Clinical Psychiatric 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.