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Completed

NCT Number: NCT01192880

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

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.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

DDPDS Prof Dr Ivan Temkov EOOD, Burgas, Bulgaria

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Placebo

Drug

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

bitopertin

Drug

Participants will receive 10 mg or 20 mg of bitopertin.

Other names: RO4917838

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.

Primary outcomes

  1. Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Negative Symptom Factor Score at Week 24

    Time frame: Baseline, Week 24

  2. Percentage of Participants with Adverse Events

    Time frame: From baseline up to 24 weeks

Secondary outcomes

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

    Time frame: Baseline, Week 24

  2. Mean Change from Baseline in the PANSS Total Score at Week 24

    Time frame: Baseline, Week 24

  3. Mean Change from Baseline in the PANSS Factor Scores at Week 24

    Time frame: Baseline, Week 24

  4. Mean Change from Baseline in the PANSS Subscale Scores at Week 24

    Time frame: Baseline, Week 24

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

    Time frame: Week 24

  6. Percentage of Participants with Response, as Assessed by CGI-I Overall and Negative Symptoms Rating Score

    Time frame: Week 24

  7. 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

    Time frame: Week 24

  8. Mean Change from Baseline in the CGI-S Overall and Negative Symptoms Rating Score

    Time frame: Baseline, Week 24

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study 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

Important dates

Study start
2010
Primary completion
2014
Study completion
2014
First posted
Sep 1, 2010
Registry last updated
Feb 15, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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