A Study of RO4917838 (Bitopertin) in Patients With Acute Exacerbation of Schizophrenia

Study Overview
=================
Brief Summary
-----------------
This randomized, double-blind, placebo- and active-controlled, parallel group study will evaluate the safety and efficacy of RO4917838 (bitopertin) in patients with acute exacerbation of schizophrenia. Patients will be randomized to receive either RO4917838 10 mg or RO4917838 30 mg or olanzapine 15 mg or placebo orally daily for 4 weeks as inpatients, with a 4-week follow-up period.

Official Title
-----------------
A Phase II, Multi-center, Randomized, 4-week, Double-blind, Parallel Group, Placebo and Active-controlled Trial of the Safety and Efficacy of RO4917838 vs. Placebo in Patients With an Acute Exacerbation of Schizophrenia

Conditions
-----------------
Schizophrenia

Intervention / Treatment
-----------------
* Drug: bitopertin [RO4917838]
* Drug: bitopertin [RO4917838]
* Drug: olanzapine
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult patients, 18-65 years of age Diagnosis of schizophrenia (Diagnostic and Statistical Manual of Mental Disorders DSM IV-TR) Acute exacerbation which began within the prior 8 weeks Female patients must be surgically sterile or post-menopausal, or agree to use effective contraception for the duration of the study Exclusion Criteria: Current psychiatric diagnosis other than schizophrenia Alcohol or substance dependence within 3 months or abuse within 1 month (except for nicotine) Electro-convulsive therapy (ECT) within the prior 6 months Previous treatment with RO4917838 or another GLYT inhibitor Current treatment with olanzapine, or previous treatment with intolerability or lack of response Treatment with long-acting injectable antipsychotic within 2 dosing intervals Treatment with > 2 antipsychotics within 3 months History of neuroleptic malignant syndrome Have treatment-resistant schizophrenia as judged by treating physician or have failed two trials according to criteria in protocol

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: bitopertin [RO4917838]<br>* 10 mg orally daily, 4 weeks<br>|
| Experimental: B<br> | Drug: bitopertin [RO4917838]<br>* 30 mg orally daily, 4 weeks<br>|
| Active Comparator: C<br> | Drug: olanzapine<br>* 15 mg orally daily, 4 weeks<br>|
| Placebo Comparator: D<br> | Drug: placebo<br>* orally daily, 4 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Positive and Negative Syndrome Scale (PANSS) total score |  | from baseline to Day 28 | 
| Safety: Incidence adverse events |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response, defined as at least 30% or 50% improvement from baseline PANSS total score |  | from baseline to Day 28 | 
| Change in symptomatology as measured by the PANSS factor and subscale scores |  | from baseline to Day 28 | 
| Global improvement as measured by the Clinical Global Impressions-Severity (CGI-S) scale |  | from baseline to Day 28 | 
| Global improvement as measured by the Clinical Global Impressions-Change (CGI-C) rating scale |  | from baseline to Day 28 | 
| Observable behavioural change as determined by the Nurses' Observation Scale For Inpatient Evaluation (NOSIE) |  | from baseline to Day 28 | 
| Time to readiness for discharge from inpatient unit as assessed by the Readiness For Hospital Discharge Questionnaire (RDQ) |  | from baseline to Day 28 |