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

NCT01192880 | Completed Phase 3

• 2 other identifiers: WN253082010-020470-42
• Study Type: interventional
• Target: 625
• Locations: 7 countries
• Sites: 103

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.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (8)

• Mean Change from Baseline in the Personal and Social Performance (PSP) Total Score at Week 24

  Baseline, Week 24

• Mean Change from Baseline in the PANSS Total Score 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 PANSS Subscale Scores at Week 24

  Baseline, Week 24

• Percentage of Participants With Response, as Assessed by PANSS Negative Symptom Factor Score

  Week 24

Study Arms (3)

Bitopertin 10 mg + Antipsychotics

EXPERIMENTAL

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.

Drug: Bitopertin; Drug: Antipsychotics

Bitopertin 20 mg + Antipsychotics

EXPERIMENTAL

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.

Drug: Bitopertin; Drug: Antipsychotics

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo; Drug: Antipsychotics

Interventions

Placebo DRUG

Participants will receive bitopertin matching placebo once daily for 56 weeks.

Placebo

Bitopertin DRUG

Participants will receive 10 mg or 20 mg of bitopertin.

Also known as: RO4917838

Bitopertin 10 mg + Antipsychotics; Bitopertin 20 mg + Antipsychotics

Antipsychotics DRUG

Participants will continue to receive their stable antipsychotic regiment throughout the study. Study protocol does not specify any particular antipsychotic drug and regimen.

Bitopertin 10 mg + Antipsychotics; Bitopertin 20 mg + Antipsychotics; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (103)

Clinical Innovtions Inc

Costa Mesa, California, 92626, United States

Location

Synergy Clinical Research of Escondido

Escondido, California, 92025, United States

Location

San Fernando Mental Health Center

Granada Hills, California, 91344, United States

Location

University of California San Diego

La Jolla, California, 92093, United States

Location

Excell Research

Oceanside, California, 92056, United States

Location

Artemis Institute for Clinical Research, LLC

San Diego, California, 92103, United States

Location

Collaborative Neuroscience Network Inc.

Torrance, California, 90502, United States

Location

Behavioral Clinical Research Inc.

Lauderhill, Florida, 33319, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Medical Research Group of Central Florida

Orange City, Florida, 3273, United States

Location

Berma Research Group

Plantation, Florida, 33317, United States

Location

Atlanta Center For Medical Research

Atlanta, Georgia, 30308, United States

Location

Indiana University; LaRue Carter Memorial Hospital-Research Unit

Indianapolis, Indiana, 46222, United States

Location

Clinical Insights, Inc.

Glen Burnie, Maryland, 21061, United States

Location

Precise Research Centers

Flowood, Mississippi, 39232, United States

Location

Altea Research Institute

Las Vegas, Nevada, 89102, United States

Location

Ocean Rheumatology

Toms River, New Jersey, 08775, United States

Location

State University of New York at Buffalo; Department of Psychiatry

Buffalo, New York, 14215, United States

Location

New York State Psychiatric Institute; Psychiatry Dept of Columbia University

New York, New York, 10032, United States

Location

Finger Lakes Clinical Research

Rochester, New York, 14618, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

Keystone Clinical Studies, LLC

Norristown, Pennsylvania, 19403, United States

Location

Scranton Medical Institutes Llc.

Scranton, Pennsylvania, 18503, United States

Location

Community Clinical Research Inc.

Austin, Texas, 78754, United States

Location

University Hills Clinical Research

Irving, Texas, 75062, United States

Location

Lifetree Clinical Research

Salt Lake City, Utah, 84106, United States

Location

Eastside Therapeutic Resource

Kirkland, Washington, 98033, United States

Location

DDPDS Prof Dr Ivan Temkov EOOD

Burgas, 8000, Bulgaria

Location

MHAT Dr.Hristo Stambolski EOOD; Psychiatry Ward of Acute Psychotic Disiorders in Severe Stage

Kazanlak, 6100, Bulgaria

Location

State Psychiatric Hospital Sv. Ivan Rilski Novi Iskar; First Man Dept. and First Woman Dept.

Novi Iskar, 1282, Bulgaria

Location

State Psychiatric Hospital - Pazardzhik AD; Department for active treatment of men and for women

Pazardzhik, 4400, Bulgaria

Location

UMHAT Dr Georgi Stranski; EAD; Psychiatry

Plovdiv, 4002, Bulgaria

Location

State Psychiatric Hospital Dr. G. Kissiov; 3-d Women Ward 1-st Men Ward

Radnevo, 6260, Bulgaria

Location

DDPDIU-Ruse; Men acute department Women acute department

Rousse, 7003, Bulgaria

Location

Military Medical Academy- MHAT

Sofia, 1606, Bulgaria

Location

Hebei Mental Health Centre

Baoding, 071000, China

Location

Beijing Huilongguan Hospital; Department of Psychiatric

Beijing, 071000, China

Location

Peking University Sixth Hospital; Department of Psychiatry

Beijing, 100083, China

Location

Beijing An Ding Hosp.Capital Medical University; 5th Clinical Dept Depression Centre

Beijing, 100088, China

Location

The Second Xiangya Hospital of Central South University

Changsha, 410011, China

Location

West China Hospital, Sichuan University

Chengdu, 610041, China

Location

Guangzhou Brain Hospital

GuangzhouGuangdong, 510370, China

Location

The First Affiliated Hospital of College of Medicine, Zhejiang University(First Hospital of Zhejiang

Hangzhou, 310003, China

Location

The Second Affiliated Hospital of Zhejiang University College

Hangzhou, 310009, China

Location

The First Affilliated Hospital of Kunming Medical College

Kunming, 650032, China

Location

Nanjing Brain Hospital

Nanjing, 210029, China

Location

Shanghai Mental Health Center

Shanghai, 200030, China

Location

Tongji Hospital of Tongji University

Shanghai, 200065, China

Location

Renmin Hospital of Wuhan University

Wuhan, 430060, China

Location

Wuxi Mental Health Center

Wuxi, 214151, China

Location

The First Affiliated Hospital of The Fourth Military Medical University (Xijing Hospital)

Xi'an, 710032, China

Location

First Affiliated Hospital of Medical College of Xi'an Jiaotong University

Xi'an, 710061, China

Location

Xi'an Mental Health Center

Xi'an, 710061, China

Location

Saint Anne s.r.o.

Brno, 602 00, Czechia

Location

Krajska nemocnice Liberec a.s.

Liberec, 460 63, Czechia

Location

Psychiatricka ambulance

Mělník, 276 01, Czechia

Location

A-Shine s.r.o.

Pilsen, 312 00, Czechia

Location

Clintrial,s.r.o.

Prague, 100 00, Czechia

Location

Medical Services Prague s.r.o.

Prague, 160 00, Czechia

Location

Psychiatricke Centrum Praha

Praha 8 - Bohnice, 181 03, Czechia

Location

CTCenter MaVe s.r.o.

Sternberk, 785 01, Czechia

Location

Azienda Ospedaliero-Universitaria Consorziale Pol. di Bari; Neuroscienze e Organi di Senso

Bari, Apulia, 70124, Italy

Location

Azienda Ospedaliera Universitaria Federico II

Napoli, Campania, 80131, Italy

Location

Asst Degli Spedali Civili Di Brescia; Servizio di farmacia

Brescia, Lombardy, 25123, Italy

Location

Clinica Mangiagalli

Milan, Lombardy, 20122, Italy

Location

ASST FATEBENEFRATELLI SACCO; Psichiatria (Fatebenefratelli)

Milan, Lombardy, 20124, Italy

Location

Azienda Ospedaliero Universitaria Molinette San Giovanni Bat

Turin, Piedmont, 10126, Italy

Location

A.O. Universitaria Pisana; Psichiatria

Pisa, Tuscany, 56126, Italy

Location

Azienda Ospedaliera di Padova

Padua, Veneto, 35128, Italy

Location

Kohnodai Hp., National Center for Global Health and Medicine

Chiba, 272-8516, Japan

Location

Fukkokai Soubu Hospital

Funabashi-shi, 273-8540, Japan

Location

Daiwakai Seimou Hospital

Gunma, 370-2455, Japan

Location

Koseikai Kusatsu Hospital

Hiroshima, 733-0864, Japan

Location

Hokkaido University Hospital

Hokkaido, 060-8648, Japan

Location

NHO Hizen Psychiatric Medical Center

Kanzaki-gun, 842-0192, Japan

Location

Sankeikai Nishigahara Hospital

Kita-ku, 114-0024, Japan

Location

Hospital of the University of Occupational and Environmental Health,Japan

Kitakyushu-shi, 807-8556, Japan

Location

Jinseikai Hosogi Unity Hospital

Kochi, 780-8535, Japan

Location

NHO Kikuchi National Hospital

Koshi-shi, 861-1116, Japan

Location

Yuge Hospital

Kumamoto, 861-8002, Japan

Location

Jinkokai Kurayoshi Hospital

Kurayoshi-shi, 682-0023, Japan

Location

NHO Higashiowari Hospital

Nagoya, 463-0802, Japan

Location

Shinkokai Shiranui Hospital

Omuta-shi, 836-0004, Japan

Location

Asakayama General Hospital

Sakaishi, 590-0018, Japan

Location

Tonankai Ashirbetsu Hospital

Sapporo, 004-0841, Japan

Location

Sawayamakai Teine Hospital

Sapporo, 006-0816, Japan

Location

Tohoku Seishin Hokenkai Aoba Hospital

Sendai, 983-0836, Japan

Location

Jisenkai Nanko Psychiatric Institute

Shirakawa-shi, 961-0021, Japan

Location

Tokyo Women's Medical University Hospital

Tokyo, 162-8666, Japan

Location

National Center Of Neurology And Psychiatry Hospital

Tokyo, 187-8551, Japan

Location

Korenkai Minamitoyama Nakagawa Hospital

Toyama, 939-8073, Japan

Location

Fujita Health University Hospital

Toyoake-shi, 470-1192, Japan

Location

Deep Intention Hiyoshi Hospital

Yokohama, 223-0062, Japan

Location

Kanagawa Prefectural Psychiatric Center Kinko Hospital

Yokohama, 233-0006, Japan

Location

Yokohama Aihara Hospital

Yokohama, 246-0026, Japan

Location

Kemerovo Regional Clinical Psychiatric Hospital

Kemerovo, 650036, Russia

Location

GUZ Lipetsk Regional psychoneurological Hospital #1; Dispansary Department

Lipetsk, 399313, Russia

Location

Institution of RAMS (Mental Health Research Center of RAMS); Psychopharmacology laboratory

Moscow, 115522, Russia

Location

Central Moscow Regional Clinical Psychiatric Hospital

Moscow, 127083, Russia

Location

City Psychiatric Hospital #2 of St. Nikolay Chudotvorets

Saint Petersburg, 190121, Russia

Location

StP SR Psychoneurological Institute n.a.V.M.Bekhterev of MoH

Saint Petersburg, 192019, Russia

Location

MHI City Clinical Hospital #2 named after V.I. Razumovsky; Psychiatric

Sartatov, 410028, Russia

Location

Arkhangelsk Regional Clinical Psychiatric Hospital

Talagi, 163530, Russia

Location

Related Publications (2)

• 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.

  PMID: 28433500 DERIVED

• 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.

  PMID: 28117049 DERIVED

MeSH Terms

Conditions

Schizophrenia

Interventions

(4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl)(5-methanesulfonyl-2-(2,2,2-trifluoro-1-methylethoxy)phenyl)methanone; Antipsychotic Agents

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Tranquilizing Agents; Central Nervous System Depressants; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Central Nervous System Agents; Therapeutic Uses; Psychotropic Drugs

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2010
• First Posted: September 1, 2010
• Study Start: November 1, 2010
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: February 15, 2017

Record last verified: 2017-02

Locations

US (27); JP (26); RU (8); CN (18); IT (8); CZ (8); BU (8)