Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder

Study Overview
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Brief Summary
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The purposes of this study are to assess the efficacy, safety, and side effects among doses approved by the Food and Drug Administration and higher (not FDA approved) doses of olanzapine in patients with schizophrenia or schizoaffective disorder.

Official Title
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Efficacy of High Dose Olanzapine in a Controlled Fixed Dose-Response Trial for the Treatment of Schizophrenia and Schizoaffective Disorder

Conditions
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Schizophrenia, Schizoaffective Disorder

Intervention / Treatment
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* Drug: Olanzapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: You must be 18 to 60 years old You must have been diagnosed with schizophrenia or schizoaffective disorder You must be able to visit the doctor's office 8 times over a 9 week period You must agree to participate with all tests and examinations that are required for this study Exclusion Criteria: You are a woman and are pregnant or breastfeeding You presently have an acute or unstable medical illness You have a history of an allergic reaction to olanzapine You are taking medications that are not permitted in this study. Your physician will discuss these with you You have taken part in another clinical research trial within the last 30 days or you have received treatment with a drug in the last 30 days that has not received regulatory approval.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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

| Intervention/Treatment |
| --- |
|Drug: Olanzapine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary objective of this study is to assess the fixed dose response relationship for efficacy between standard and higher doses of olanzapine (10, 20, and 40 mg/day) in patients with schizophrenia or schizoaffective disorder. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the dose response efficacy of olanzapine in improving psychopathology of schizophrenia as measured by a mean change from baseline on the PANSS subscores and Clinical Global Impression-Severity(CGI-S) Scale as well as by the absolute score |  |  | 
| of CGI-I (Improvement) Scale |  |  | 
| To assess the efficacy of olanzapine doses between treatment arms (e.g. 10 mg/day versus 40 mg/day ) in improving the psychopathology of schizophrenia as measured by mean changed from baseline on the PANSS total and subscores and Clinical Global |  |  | 
| Impression-Severity (CGI-S) Scale as well as by absolute score of CGI-I (Improvement) Scale |  |  | 
| To assess the efficacy of olanzapine doses as measured by efficacy scales in patients who have successfully completed the 2 week titration period |  |  | 
| To assess the efficacy of olanzapine doses within the standard range of 10 and 20 mg/day versus high dose 40 mg/day in improving the psychopathology of schizophrenia as measured by mean change from baseline on the PANSS total |  |  | 
| To assess the response rate of olanzapine doses in improving the psychopathology of schizophrenia. Clinical response is defined as an improvement (reduction) of =>20% from baseline in the PANSS total score |  |  | 
| To compare the time to response among all olanzapine treatment arms. Clinical response is defined as an improvement (reduction) of =>20% from baseline in the PANSS total score. In addition, the cumulative frequency distribution of differential |  |  | 
| rates of response reduction in PANSS total score will be assessed at 8 weeks |  |  | 
| To compare the dose response efficacy between all olanzapine treatment arms in improving depressive symptoms as measured by a mean change from baseline on the Montgomery-Asberg Depression Rating Scale (MADRS) |  |  | 
| To assess the efficacy between all olanzapine treatment arms in improving patients' overall level of functioning and health-related quality of life as measured by the Global assessment of Functioning (GAF) and the Heinrich Carpenter |  |  | 
| Quality of Life Scale (QLS) |  |  | 
| To analyze steady-state olanzapine plasma concentrations following 10, 20, and 40 mg daily dosing and examine the associations between state plasma levels, efficacy, and safety measures |  |  | 
| To assess the safety between treatment arms and the safety dose-response relationship between the olanzapine treatment groups as determined by: |  |  | 
| Treatment-emergent adverse events, |  |  | 
| ECG |  |  | 
| Vital signs and fasting laboratory analytes (clinical chemistry, hematology, lipid panel, and prolactin) |  |  | 
| Appetite as measured by the Eating Behavior Assessment |  |  | 
| Extrapyramidal symptoms as measured by the Modified Simpson-Angus Scale, The Barnes Akathisia Rating Scale, and the Abnormal Involuntary Movement Scale (AIMS) |  |  |