A Study Comparing the Efficacy and Tolerability of Ziprasidone vs. Clozapine for the Treatment of Schizophrenia in Patients Who Continue to Have Symptoms on or Cannot Tolerate Other Antipsychotic Drugs

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy and safety of ziprasidone and clozapine in schizophrenic patients who are resistant and/or intolerant to antipsychotic treatment

Official Title
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Double Blind, Double-Dummy Multicenter, Parallel Group Comparison Of The Efficacy And The Tolerability Of Ziprasidone Vs. Clozapine In Schizophrenic Patients Who Are Refractory And/Or Intolerant To Antipsychotic Therapy

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Clozapine
* Drug: Ziprasidone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CGI - S ≥4 PANSS ≥ 80 Inpatients or outpatients Exclusion Criteria: Patients with a history of myeloproliferative diseases, history of granulocytopenia, agranulocytosis due to a drug Diagnosis of substance dependence within previous 3 months using DSM-IV criteria History of seizure Organic mental disease, including mental retardation or epilepsy

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Active Comparator: A<br> | Drug: Clozapine<br>* Clozapine 25 or 100 mg tablets. Patients were initially titrated over the first 10 days to 300 mg/day and remained at this dose for 1 week. Thereafter, the dose could be varied between 250 and 600 mg/day based on response and tolerability for a total treatment duration of 18 weeks<br>|
| Experimental: B<br> | Drug: Ziprasidone<br>* Ziprasidone 40, 60, or 80 mg capsules. Patients were initially titrated over the first 3 days to 80 mg/day, which could subsequently be increased to between 80 and 160 mg/day based on response and tolerability for a total treatment duration of 18 weeks<br>* Other names: Geodon, Zeldox;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to endpoint in Positive and Negative Syndrome Scale (PANSS) total scores |  | Until Final Visit (within 18 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of responders, based on change from baseline to endpoint in PANSS total score |  | Until Final Visit (within 18 weeks) | 
| Change from baseline to endpoint in Clinical Global Impressions-Severity (CGI-S) scores |  | Baseline and weekly from Weeks 1-18 | 
| Time to discontinuation |  | Up to 18 weeks | 
| Change from baseline to endpoint in cognitive function assessments, including Rey serial verbal learning test, Stroop Color Word test, and Trail Making Test |  | Baseline and Weeks 12 and 18 | 
| Change from baseline to endpoint in Global Assessment of Functioning (GAF) scores |  | Baseline and Week 8, 12, and 18 | 
| Change from baseline in Modified Resource Utilization Questionnaire (RUQ) scores |  | Baseline and Weeks 4, 8, 12, and 18 | 
| Change from baseline to endpoint in Drug Attitude Inventory (DAI) scores |  | Screening and Weeks 1, 8, 12, and 18 | 
| Change from baseline to endpoint in PANSS subscale scores |  | Baseline and weekly from Weeks 1-18 | 
| Adverse events |  | Weekly from Weeks 1-18 | 
| Change from baseline to endpoint in Calgary Depression Scale (CDSS) scores |  | Baseline and Weeks 8, 12, and 18 | 
| Change from baseline in Caregiver Activity Survey (CAS) |  | Screening and Weeks 1, 8, 12, and 18 | 
| Change from baseline in laboratory tests |  | Screening and weekly from Weeks 1-18 | 
| Change from baseline in electrocardiogram |  | Screening and Weeks 1, 8, 12, and 18 | 
| Change from baseline in movement disorder rating scales, including Barnes Akathisia Rating Scale, Abnormal Involuntary Movement Scale, and Simpson-Angus Scale |  | Baseline and Weeks 1, 8, 12, and 18 | 
| Change from baseline to endpoint in Clinical Global Impressions-Improvement (CGI-I) scores |  | Baseline and weekly from Weeks 1-18 | 
| Change from baseline to endpoint in Patient Preference Scale (PPS) scores |  | Screening and Weeks 1, 8, 12, and 18 |