A Study of the Effect of RO4917838 on Biomarker Measures of Cognitive Dysfunction in Participants With Schizophrenia and Schizoaffective Disorder

Study Overview
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Brief Summary
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This randomized, double-blind, placebo-controlled parallel group study will assess the effect on biomarkers measures of cognitive dysfunction, the clinical efficacy and safety of RO4917838 in participants with schizophrenia and schizoaffective disorder. Participants will be randomized to receive either RO4917838 (10 milligrams [mg] daily orally) or placebo for 6 weeks, in addition to their stable antipsychotic medication. Anticipated time on study treatment is 6 weeks.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Parallel Arm Study of the Effect of RO4917838 on Biomarker Measures of Cognitive Dysfunction in Schizophrenia and Schizoaffective Disorder

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Placebo
* Drug: RO4917838
* Drug: Standard Antipsychotic Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of schizophrenia or schizoaffective disorder (based on screening tests) Medically stable for 1 month and psychiatrically stable without symptom exacerbation for 6 weeks prior to baseline On stable treatment with a maximum of 2 antipsychotics Exclusion Criteria: Change in regimen for any psychotropic or sleep medication within 1 month Treatment with more than (>) 1 mood stabilizer or antidepressant Use of clozapine within 2 months Bipolar disorder, or more than mild anxiety disorder

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Orally daily for 6 weeks<br>Drug: Standard Antipsychotic Therapy<br>* Participants will continue to receive their current antipsychotic treatment (as they are receiving at the time of screening). Protocol does not specify any particular standard antipsychotic therapy.<br>|
| Experimental: RO4917838<br> | Drug: RO4917838<br>* 10 mg daily orally for 6 weeks<br>Drug: Standard Antipsychotic Therapy<br>* Participants will continue to receive their current antipsychotic treatment (as they are receiving at the time of screening). Protocol does not specify any particular standard antipsychotic therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Cognitive Dysfunction Biomarker (Mismatch Negativity) at Week 6, as Measured Using Electroencephalography (EEG) |  | Baseline, Week 6 | 
| Change From Baseline in Cognitive Dysfunction Biomarker (Visual Event-Related Potential [ERP]) at Week 6, as Measured Using EEG |  | Baseline, Week 6 | 
| Change From Baseline in Cognitive Dysfunction Biomarker (N1 Refractoriness) at Week 6, as Measured Using EEG |  | Baseline, Week 6 | 
| Change From Baseline in Cognitive Dysfunction Biomarker (P3 Component) at Week 6, as Measured Using EEG |  | Baseline, Week 6 | 
| Change From Baseline in Cognitive Dysfunction Biomarker (Visual Evoked Potential [VEP]) at Week 6, as Measured Using EEG |  | Baseline, Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Cognitive Dysfunction Biomarker (Mismatch Negativity) at Week 1, as Measured Using EEG |  | Baseline, Week 1 | 
| Change From Baseline in Cognitive Dysfunction Biomarker (Visual Event-Related Potential [ERP]) at Week 1, as Measured Using EEG |  | Baseline, Week 1 | 
| Change From Baseline in Cognitive Dysfunction Biomarker (N1 Refractoriness) at Week 1, as Measured Using EEG |  | Baseline, Week 1 | 
| Change From Baseline in Cognitive Dysfunction Biomarker (P3 Component) at Week 1, as Measured Using EEG |  | Baseline, Week 1 | 
| Positive Predictive Value of Cognitive Dysfunction Biomarkers (Mismatch Negativity, ERP, N1 Refractoriness, P3 Component, and VEP) Change at Week 1 to Predict the Presence of Biomarker Response at Week 6, as Measured Using EEG |  | Baseline, Weeks 1 and 6 | 
| Positive Predictive Value of Cognitive Dysfunction Biomarkers (Mismatch Negativity, ERP, N1 Refractoriness, P3 Component, and VEP) Change at Week 1 to Predict the Change in Symptoms at Week 6, as Measured Using EEG |  | Baseline, Weeks 1 and 6 | 
| Change From Baseline in Positive and Negative Syndrome Scale Score |  | Baseline, Weeks 1, 3, and 6 | 
| Change From Baseline in Negative Symptom Assessment Score |  | Baseline, Weeks 1, 3, and 6 | 
| Change From Baseline in Clinical Global Impression Scale |  | Baseline, Weeks 1, 3, and 6 | 
| Change From Baseline in Calgary Depression Scale Score |  | Baseline, Weeks 1, 3, and 6 | 
| Change From Baseline in Global Assessment of Functioning Score |  | Baseline, Weeks 1, 3, and 6 | 
| Change From Baseline in Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Cognition Battery Score |  | Baseline, Weeks 1, 3, and 6 | 
| Change From Baseline in Cognitive Dysfunction Biomarker (Visual Evoked Potential [VEP]) at Week 1, as Measured Using EEG |  | Baseline, Week 1 |