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

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

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Placebo; Drug: Standard Antipsychotic Therapy; Drug: RO4917838

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Orangeburg, New York, United States, 10962

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Orally daily for 6 weeks; Drug: Standard Antipsychotic Therapy; 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.
Experimental: RO4917838	Drug: Standard Antipsychotic Therapy; 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.; Drug: RO4917838; 10 mg daily orally for 6 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Kantrowitz JT, Epstein ML, Lee M, Lehrfeld N, Nolan KA, Shope C, Petkova E, Silipo G, Javitt DC. Improvement in mismatch negativity generation during d-serine treatment in schizophrenia: Correlation with symptoms. Schizophr Res. 2018 Jan;191:70-79. doi: 10.1016/j.schres.2017.02.027. Epub 2017 Mar 18.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: May 4, 2010
• First Submitted That Met QC Criteria: May 4, 2010
• First Posted (Estimate): May 5, 2010

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Cognition Disorders; Schizophrenia; Psychotic Disorders; Cognitive Dysfunction; Physiological Effects of Drugs; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Antipsychotic Agents
• Other Study ID Numbers: BP22445