A Study to Evaluate Efficacy and Safety of Bitopertin in Participants With Persistent, Predominant Negative Symptoms of Schizophrenia

Schizophrenia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01192880
• Other study ID #: WN25308
• Secondary ID: 2010-020470-42
• Status: Completed
• Phase: Phase 3
• First received: August 30, 2010
• Last updated: February 14, 2017
• Start date: November 2010
• Est. completion date: July 2014

Study information

• Verified date: February 2017
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 625
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• Placebo
Participants will receive bitopertin matching placebo once daily for 56 weeks.
• Bitopertin
Participants will receive 10 mg or 20 mg of bitopertin.
• Antipsychotics
Participants will continue to receive their stable antipsychotic regiment throughout the study. Study protocol does not specify any particular antipsychotic drug and regimen.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Bulgaria,  China,  Czech Republic,  Italy,  Japan,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Negative Symptom Factor Score at Week 24		Baseline, Week 24
Primary	Percentage of Participants with Adverse Events		From baseline up to 24 weeks
Secondary	Mean Change from Baseline in the Personal and Social Performance (PSP) Total Score at Week 24		Baseline, Week 24
Secondary	Mean Change from Baseline in the PANSS Total Score at Week 24		Baseline, Week 24
Secondary	Mean Change from Baseline in the PANSS Factor Scores at Week 24		Baseline, Week 24
Secondary	Mean Change from Baseline in the PANSS Subscale Scores at Week 24		Baseline, Week 24
Secondary	Percentage of Participants With Response, as Assessed by PANSS Negative Symptom Factor Score		Week 24
Secondary	Percentage of Participants with Response, as Assessed by CGI-I Overall and Negative Symptoms Rating Score		Week 24
Secondary	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
Secondary	Mean Change from Baseline in the CGI-S Overall and Negative Symptoms Rating Score		Baseline, Week 24