Efficacy Study of Early Onset of Antipsychotic Drug Action in Schizophrenia

Study Overview
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Brief Summary
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The current study has been designed to address the significance of early onset of response prospectively in patients treated with an atypical antipsychotic.

Official Title
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Predicting Response to Risperidone Treatment Through Identification of Early-onset of Antipsychotic Drug Action in Schizophrenia.

Conditions
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Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder

Intervention / Treatment
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* Drug: olanzapine
* Drug: risperidone
* Drug: risperidone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must demonstrate acute psychopathologic severity criteria and be at least moderately ill. Patients must have experienced an exacerbation of their illness within the previous 2 weeks. Patients in whom a switch to another antipsychotic medication is acutely indicated. Exclusion Criteria: Patients who are deemed nonresponsive to risperidone or olanzapine. Patients who have been hospitalized for greater than 2 weeks immediately prior to Visit 1. Patients having received olanzapine or risperidone in the past 30 days. Treatment with clozapine within 1 year prior to Visit 1. Diagnosis of substance-induced psychosis by Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria within 7 days of Visit 1 (or at any time during the study), or confirmed on clinical grounds within 72 hours subsequent to Visit 1 (or at any time during the study). A diagnosis of Parkinson's disease, dementia-related psychosis, or related disorders.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Olanzapine for Not Early Onset response (NEO) patients | Drug: olanzapine<br>* 10-20 milligrams (mg), oral, daily, 10 weeks.<br>* Other names: Zyprexa;|
| Active Comparator: 2<br>Risperidone for Not Early Onset response (NEO) patients | Drug: risperidone<br>* 2-6 mg, oral, daily, for 10 weeks.<br>|
| Active Comparator: 3<br>Risperidone for Early Onset response (EO) patients | Drug: risperidone<br>* 2-6 mg, oral, daily, 10 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes From Study Period II Baseline (Week 0) to Weeks 3, 4, 6, 8, and 12 in Positive and Negative Syndrome Scale (PANSS) Total Score in Early Onset Response and Not Early Onset Response-Risperidone Patients | Assesses positive symptoms, negative symptoms, and general psychopathology specifically associated with schizophrenia. Scale consists of 30 items. Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). Sum of 30 items is PANSS total score and ranges from 30 to 210. Change = time point - single-blind baseline (Week 0). | Weeks 0, 3, 4, 6, 8, 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes From Study Period III Baseline (Week 2) to Weeks 3, 4, 6, 8, and 12 in Positive and Negative Syndrome Scale Total Score in Not Early Onset Response-Risperidone and Not Early Onset Response-Olanzapine Patients | Assesses positive symptoms, negative symptoms, and general psychopathology specifically associated with schizophrenia. Scale consists of 30 items. Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). Sum of 30 items is PANSS total score and ranges from 30 to 210. Change = time point - double-blind baseline (Week 2). | Weeks 2, 3, 4, 6, 8, 12 | 
| The Number of Participants in the Early Onset (EO) and Not Early Onset-Risperidone (NEO-RIS) Groups Who Show a 20% or Greater Reduction in Positive and Negative Syndrome Scale (PANSS) Total Score | The number of participants who experienced a 20% or greater reduction in their PANSS Total score during the 12 weeks they were on risperidone. | Week 0 to Week 12 | 
| The Number of Participants in the Not Early Onset-Risperidone (NEO-RIS) and Not Early Onset-Olanzapine (NEO-OLZ) Groups Who Show a 20% or Greater Reduction in Positive and Negative Syndrome Scale (PANSS) Total Score | The number of not early onset participants who experienced a 20% or greater reduction in PANSS Total Score at any time during the 12 weeks of combined Study Period II and Study Period III. | Week 0 to Week 12 | 
| Number of Participants in the Early Onset and Not Early Onset-Risperidone Groups Who Show a 50% or Greater Reduction in Positive and Negative Syndrome Scale (PANSS) Total Score From Baseline or Meet 'a Priori' Specified Criteria for Remission | 'a priori' specified criteria for remission defined as a score of 3 (mild), 2 (minimal), or 1 (absent) on all of the following 8 PANSS items: delusions, conceptual disorganization, hallucinatory behavior, unusual thought content, mannerisms and posturing, blunted effect, passive/apathetic withdrawal, lack of spontaneity and flow of conversation. | Week 0 to Week 12 | 
| Number of Participants in the Not Early Onset-Risperidone and Not Early Onset-Olanzapine Groups Who Show a 50% or Greater Reduction in Positive and Negative Syndrome Scale Total Score From Baseline or Meet 'a Priori' Specified Criteria for Remission | 'a priori' specified criteria for remission defined as a score of 3 (mild), 2 (minimal), or 1 (absent) on all of the following 8 PANSS items: delusions, conceptual disorganization, hallucinatory behavior, unusual thought content, mannerisms and posturing, blunted effect, passive/apathetic withdrawal, lack of spontaneity and flow of conversation. | Week 2 to Week 12 | 
| Number of Participants With Psychiatric Hospitalizations in the Early Onset and Not Early Onset-Risperidone Groups | Psychiatric Hospitalizations were measured by the Modified Schizophrenia Care and Assessment Program Health Questionnaire (SCAP-HQ) from which it could be determined the number of patients with a psychiatric episode that required an overnight stay in a hospital. | Week 2 to Week 12 | 
| Vital Signs - Mean Change From Baseline to 10 Week Endpoint in Body Mass Index | Body mass index is an estimate of body fat based on body weight divided by height squared. Change = Endpoint minus baseline. | Week 2 to Week 12 | 
| Number of Participants With Treatment-Emergent Abnormal Fasting Laboratory Analytes Reported in >=2% of All Participants | Number of participants who experienced abnormal fasting laboratory values at any time during Study Period III. Laboratory reference ranges are dependent on the patient's gender, origin, and age. | Week 2 to Week 12 | 
| Mean Change From Baseline to 10 Week Endpoint in Extrapyramidal Symptoms as Measured by the Modified Simpson-Angus Scale | Measures neuroleptic-induced parkinsonism. Total score consists of the sum of 10 items: 7 items (items 1, 3, 4, 7, 8, 9, 10) rated on a 4-point severity scale where 0=normal and 4=extreme, and 3 items (items 2, 5, 6) rated on a 2-point severity scale where 0=normal and 2=definitely abnormal/present. The total score ranges from 0 to 34. | Week 2 to Week 12 | 
| Mean Change From Baseline to 10 Week Endpoint in Extrapyramidal Symptoms as Measured by the Barnes Akathisia Rating Scale - Total Score | Evaluates akathisia associated with use of antipsychotic medications, includes objective and subjective component plus global impression rating for overall disorder. Components rated on scale of 0 to 3 for objective and subjective items and 0 to 5 for global clinical assessment, for total score of 0 (absence of akathisia) to 11 (severe akathisia). | Week 2 to Week 12 | 
| Mean Change From Baseline to 10 Week Endpoint in Extrapyramidal Symptoms as Measured by the Abnormal Involuntary Movement Scale (AIMS)- Non-Global Total Score | A 12-item instrument assesses observed abnormal movements in different parts of body. Ten items are scored in a 5-point scale (0 = none/normal, 4 = severe) which evaluates abnormal movements in three main anatomic areas (orofacial area, extremities, and trunk). Two items are yes/no questions regarding dentures. Total scores range from 0 to 42. | Week 2 to Week 12 | 
| Vital Signs - Mean Change From Baseline to 10 Week Endpoint in Sitting Pulse Rate | Changes from Study Period III baseline to endpoint in sitting pulse rate. Change = Endpoint minus baseline. | Week 2 and Week 12 | 
| Vital Signs - Change From Baseline to 10 Week Endpoint in Standing Diastolic Blood Pressure | Change from Study Period III baseline to endpoint in standing blood pressure. Change = Endpoint minus baseline. | Week 2 and Week 12 | 
| Vital Signs - Change From Baseline to 10 Week Endpoint in Standing Mean Arterial Pressure | Change from Study Period III baseline to endpoint in standing mean arterial pressure. Change = Endpoint minus baseline. | Week 2 and Week 12 | 
| Vital Signs - Mean Change From Baseline to 10 Week Endpoint in Standing Pulse Rate | Change from Study Period III baseline to endpoint in standing pulse rate. Change = Endpoint minus baseline. | Week 2 and Week 12 | 
| Vital Signs - Mean Change From Baseline to 10 Week Endpoint in Standing Systolic Blood Pressure | Change from Study Period III baseline to endpoint in standing systolic blood pressure. Change = Endpoint minus baseline. | Week 2 and Week 12 | 
| Vital Signs - Mean Change From Baseline to 10 Week Endpoint in Body Weight | Change from Study Period III baseline to endpoint in body weight. Change = Endpoint minus baseline. | Week 2 and Week 12 |