A Study to Evaluate Efficacy and Safety of Bitopertin in Participants With Persistent, Predominant Negative Symptoms of Schizophrenia
- Conditions
- Schizophrenia
- Interventions
- Registration Number
- NCT01192880
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 625
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Bitopertin 10 mg + Antipsychotics Antipsychotics Treatment Period 1: Participants will receive bitopertin 10 milligrams (mg) tablet orally once daily for 24 weeks. Treatment Period 2: Participants will receive bitopertin 10 mg tablet orally once daily for 28 weeks (up to Study Week 52). After Week 52 there will be a 4-week washout period for at least 50 percent (%) of participants (up to Week 56). Long-Term Extension: After Week 56, participants will enter the long term extension period and continue to receive bitopertin 10 mg tablet orally once daily up to 3 years. In addition, throughout the study, participants will continue their same stable antipsychotic treatment as they were receiving prior to entry in the study. Placebo Antipsychotics Treatment Period 1: Participants will receive bitopertin matching placebo tablet orally once daily for 24 weeks. Treatment Period 2: Participants will receive bitopertin matching placebo tablet orally once daily for 32 weeks (up to Study Week 56). Long-Term Extension: After Week 56, participants will enter the long term extension period and will be switched to (in blinded manner) bitopertin 10 mg tablet orally once daily up to 3 years. In addition, throughout the study, participants will continue their same stable antipsychotic treatment as they were receiving prior to entry in the study. Bitopertin 20 mg + Antipsychotics Antipsychotics Treatment Period 1: Participants will receive bitopertin 20 mg tablet orally once daily for 24 weeks. Treatment Period 2: Participants will receive bitopertin 20 mg tablet orally once daily for 28 weeks (up to Study Week 52). After Week 52 there will be a 4-week washout period for at least 50% of participants (up to Week 56). Long-Term Extension: After Week 56, participants will enter the long term extension period and continue to receive bitopertin 20 mg tablet orally once daily up to 3 years. In addition, throughout the study, participants will continue their same stable antipsychotic treatment as they were receiving prior to entry in the study. Placebo Placebo Treatment Period 1: Participants will receive bitopertin matching placebo tablet orally once daily for 24 weeks. Treatment Period 2: Participants will receive bitopertin matching placebo tablet orally once daily for 32 weeks (up to Study Week 56). Long-Term Extension: After Week 56, participants will enter the long term extension period and will be switched to (in blinded manner) bitopertin 10 mg tablet orally once daily up to 3 years. In addition, throughout the study, participants will continue their same stable antipsychotic treatment as they were receiving prior to entry in the study. Bitopertin 10 mg + Antipsychotics Bitopertin Treatment Period 1: Participants will receive bitopertin 10 milligrams (mg) tablet orally once daily for 24 weeks. Treatment Period 2: Participants will receive bitopertin 10 mg tablet orally once daily for 28 weeks (up to Study Week 52). After Week 52 there will be a 4-week washout period for at least 50 percent (%) of participants (up to Week 56). Long-Term Extension: After Week 56, participants will enter the long term extension period and continue to receive bitopertin 10 mg tablet orally once daily up to 3 years. In addition, throughout the study, participants will continue their same stable antipsychotic treatment as they were receiving prior to entry in the study. Bitopertin 20 mg + Antipsychotics Bitopertin Treatment Period 1: Participants will receive bitopertin 20 mg tablet orally once daily for 24 weeks. Treatment Period 2: Participants will receive bitopertin 20 mg tablet orally once daily for 28 weeks (up to Study Week 52). After Week 52 there will be a 4-week washout period for at least 50% of participants (up to Week 56). Long-Term Extension: After Week 56, participants will enter the long term extension period and continue to receive bitopertin 20 mg tablet orally once daily up to 3 years. In addition, throughout the study, participants will continue their same stable antipsychotic treatment as they were receiving prior to entry in the study.
- Primary Outcome Measures
Name Time Method Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Negative Symptom Factor Score at Week 24 Baseline, Week 24 Percentage of Participants with Adverse Events From baseline up to 24 weeks
- Secondary Outcome Measures
Name Time Method Mean Change from Baseline in the PANSS Total Score at Week 24 Baseline, Week 24 Mean Change from Baseline in the PANSS Subscale Scores at Week 24 Baseline, Week 24 Mean Change from Baseline in the PANSS Factor Scores at Week 24 Baseline, Week 24 Mean Change from Baseline in the Personal and Social Performance (PSP) Total Score at Week 24 Baseline, Week 24 Percentage of Participants with Response, as Assessed by CGI-I Overall and Negative Symptoms Rating Score Week 24 Percentage of Participants With Response, as Assessed by PANSS Negative Symptom Factor Score Week 24 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 Week 24 Mean Change from Baseline in the CGI-S Overall and Negative Symptoms Rating Score Baseline, Week 24
Trial Locations
- Locations (103)
Synergy Clinical Research of Escondido
🇺🇸Escondido, California, United States
Excell Research
🇺🇸Oceanside, California, United States
Behavioral Clinical Research Inc.
🇺🇸Lauderhill, Florida, United States
Artemis Institute for Clinical Research, LLC
🇺🇸San Diego, California, United States
Collaborative Neuroscience Network Inc.
🇺🇸Torrance, California, United States
University of Miami Miller School of Medicine
🇺🇸Miami, Florida, United States
Atlanta Center For Medical Research
🇺🇸Atlanta, Georgia, United States
Medical Research Group of Central Florida
🇺🇸Orange City, Florida, United States
Berma Research Group
🇺🇸Plantation, Florida, United States
Indiana University; LaRue Carter Memorial Hospital-Research Unit
🇺🇸Indianapolis, Indiana, United States
Clinical Insights, Inc.
🇺🇸Glen Burnie, Maryland, United States
Ocean Rheumatology
🇺🇸Toms River, New Jersey, United States
State University of New York at Buffalo; Department of Psychiatry
🇺🇸Buffalo, New York, United States
Finger Lakes Clinical Research
🇺🇸Rochester, New York, United States
Keystone Clinical Studies, LLC
🇺🇸Norristown, Pennsylvania, United States
New York State Psychiatric Institute; Psychiatry Dept of Columbia University
🇺🇸New York, New York, United States
Community Clinical Research Inc.
🇺🇸Austin, Texas, United States
University Hills Clinical Research
🇺🇸Irving, Texas, United States
Scranton Medical Institutes Llc.
🇺🇸Scranton, Pennsylvania, United States
Eastside Therapeutic Resource
🇺🇸Kirkland, Washington, United States
DDPDS Prof Dr Ivan Temkov EOOD
🇧🇬Bourgas, Bulgaria
Lifetree Clinical Research
🇺🇸Salt Lake City, Utah, United States
MHAT Dr.Hristo Stambolski EOOD; Psychiatry Ward of Acute Psychotic Disiorders in Severe Stage
🇧🇬Kazanlak, Bulgaria
UMHAT Dr Georgi Stranski; EAD; Psychiatry
🇧🇬Plovdiv, Bulgaria
State Psychiatric Hospital - Pazardzhik AD; Department for active treatment of men and for women
🇧🇬Pazardzhik, Bulgaria
Beijing Huilongguan Hospital; Department of Psychiatric
🇨🇳Beijing, China
Clinical Innovtions Inc
🇺🇸Costa Mesa, California, United States
Azienda Ospedaliera Universitaria Federico II
🇮🇹Napoli, Campania, Italy
The First Affilliated Hospital of Kunming Medical College
🇨🇳Kunming, China
Saint Anne s.r.o.
🇨🇿Brno, Czech Republic
Krajska nemocnice Liberec a.s.
🇨🇿Liberec, Czech Republic
Psychiatricka ambulance
🇨🇿Melnik, Czech Republic
Medical Services Prague s.r.o.
🇨🇿Praha 6, Czech Republic
A-Shine s.r.o.
🇨🇿Plzen, Czech Republic
Clintrial,s.r.o.
🇨🇿Praha 10, Czech Republic
CTCenter MaVe s.r.o.
🇨🇿Sternberk, Czech Republic
Azienda Ospedaliera di Padova
🇮🇹Padova, Veneto, Italy
Kohnodai Hp., National Center for Global Health and Medicine
🇯🇵Chiba, Japan
Koseikai Kusatsu Hospital
🇯🇵Hiroshima-shi, Japan
Daiwakai Seimou Hospital
🇯🇵Gunma, Japan
NHO Hizen Psychiatric Medical Center
🇯🇵Kanzaki-gun, Japan
Fukkokai Soubu Hospital
🇯🇵Funabashi-shi, Japan
Hokkaido University Hospital
🇯🇵Hokkaido, Japan
NHO Higashiowari Hospital
🇯🇵Nagoya-Shi, Japan
Sankeikai Nishigahara Hospital
🇯🇵Kita-Ku, Japan
Jinseikai Hosogi Unity Hospital
🇯🇵Kochi-shi, Japan
NHO Kikuchi National Hospital
🇯🇵Koshi-shi, Japan
Hospital of the University of Occupational and Environmental Health,Japan
🇯🇵Kitakyushu-shi, Japan
Shinkokai Shiranui Hospital
🇯🇵Omuta-shi, Japan
Sawayamakai Teine Hospital
🇯🇵Sapporo-shi, Japan
Asakayama General Hospital
🇯🇵Sakai-shi, Japan
Tonankai Ashirbetsu Hospital
🇯🇵Sapporo-shi, Japan
National Center Of Neurology And Psychiatry Hospital
🇯🇵Tokyo, Japan
Tohoku Seishin Hokenkai Aoba Hospital
🇯🇵Sendai-shi, Japan
Jisenkai Nanko Psychiatric Institute
🇯🇵Shirakawa-shi, Japan
Tokyo Women's Medical University Hospital
🇯🇵Tokyo, Japan
Yokohama Aihara Hospital
🇯🇵Yokohama-shi, Japan
Deep Intention Hiyoshi Hospital
🇯🇵Yokohama-shi, Japan
Institution of RAMS (Mental Health Research Center of RAMS); Psychopharmacology laboratory
🇷🇺Moscow, Russian Federation
Kanagawa Prefectural Psychiatric Center Kinko Hospital
🇯🇵Yokohama-shi, Japan
Kemerovo Regional Clinical Psychiatric Hospital
🇷🇺Kemerovo, Russian Federation
GUZ Lipetsk Regional psychoneurological Hospital #1; Dispansary Department
🇷🇺Lipetsk, Russian Federation
MHI City Clinical Hospital #2 named after V.I. Razumovsky; Psychiatric
🇷🇺Sartatov, Russian Federation
Central Moscow Regional Clinical Psychiatric Hospital
🇷🇺Moscow, Russian Federation
City Psychiatric Hospital #2 of St. Nikolay Chudotvorets
🇷🇺St. Petersburg, Russian Federation
StP SR Psychoneurological Institute n.a.V.M.Bekhterev of MoH
🇷🇺St. Petersburg, Russian Federation
Arkhangelsk Regional Clinical Psychiatric Hospital
🇷🇺Talagi, Russian Federation
Hebei Mental Health Centre
🇨🇳Baoding, China
The Second Xiangya Hospital of Central South University
🇨🇳Changsha, China
West China Hospital, Sichuan University
🇨🇳Chengdu, China
Guangzhou Brain Hospital
🇨🇳GuangzhouGuangdong, China
The First Affiliated Hospital of College of Medicine, Zhejiang University(First Hospital of Zhejiang
🇨🇳Hangzhou, China
The Second Affiliated Hospital of Zhejiang University College
🇨🇳Hangzhou, China
Tongji Hospital of Tongji University
🇨🇳Shanghai, China
Renmin Hospital of Wuhan University
🇨🇳Wuhan, China
Wuxi Mental Health Center
🇨🇳Wuxi, China
Peking University Sixth Hospital; Department of Psychiatry
🇨🇳Beijing, China
Beijing An Ding Hosp.Capital Medical University; 5th Clinical Dept Depression Centre
🇨🇳Beijing, China
Shanghai Mental Health Center
🇨🇳Shanghai, China
The First Affiliated Hospital of The Fourth Military Medical University (Xijing Hospital)
🇨🇳Xi'an, China
First Affiliated Hospital of Medical College of Xi'an Jiaotong University
🇨🇳Xi'an, China
Xi'an Mental Health Center
🇨🇳Xi'an, China
Asst Degli Spedali Civili Di Brescia; Servizio di farmacia
🇮🇹Brescia, Lombardia, Italy
Clinica Mangiagalli
🇮🇹Milano, Lombardia, Italy
ASST FATEBENEFRATELLI SACCO; Psichiatria (Fatebenefratelli)
🇮🇹Milano, Lombardia, Italy
Azienda Ospedaliero Universitaria Molinette San Giovanni Bat
🇮🇹Torino, Piemonte, Italy
Azienda Ospedaliero-Universitaria Consorziale Pol. di Bari; Neuroscienze e Organi di Senso
🇮🇹Bari, Puglia, Italy
A.O. Universitaria Pisana; Psichiatria
🇮🇹Pisa, Toscana, Italy
San Fernando Mental Health Center
🇺🇸Granada Hills, California, United States
Psychiatricke Centrum Praha
🇨🇿Praha 8 - Bohnice, Czech Republic
Fujita Health University Hospital
🇯🇵Toyoake-shi, Japan
Duke University
🇺🇸Durham, North Carolina, United States
State Psychiatric Hospital Dr. G. Kissiov; 3-d Women Ward 1-st Men Ward
🇧🇬Radnevo, Bulgaria
Military Medical Academy- MHAT
🇧🇬Sofia, Bulgaria
Precise Research Centers
🇺🇸Flowood, Mississippi, United States
State Psychiatric Hospital Sv. Ivan Rilski Novi Iskar; First Man Dept. and First Woman Dept.
🇧🇬Novi Iskar, Bulgaria
University of California San Diego
🇺🇸La Jolla, California, United States
DDPDIU-Ruse; Men acute department Women acute department
🇧🇬Rousse, Bulgaria
Yuge Hospital
🇯🇵Kumamoto-shi, Japan
Jinkokai Kurayoshi Hospital
🇯🇵Kurayoshi-shi, Japan
Korenkai Minamitoyama Nakagawa Hospital
🇯🇵Toyama-shi, Japan
Altea Research Institute
🇺🇸Las Vegas, Nevada, United States
Nanjing Brain Hospital
🇨🇳Nanjing, China