Therapeutic Drug Monitoring for Individualized Clozapine Therapy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the factors affecting the occurrence of adverse drug reactions (glucose and lipid metabolism abnormality, changes in liver function index and sleeping tendency) and clinical effects in schizophrenia patients with clozapine treatment

Detailed Description
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The baseline tests (sleeping tendency assessment, clinical symptom and cognitive assessments, clinical laboratory tests, genotyping, exploratory biomarker tests, etc.) are conducted to the schizophrenia patients before initiation of the clozapine dosing. On day 15 and 57, the changes from baseline clinical symptom and cognitive function are assessed after clozapine treatment. Also, the occurrence of adverse drug reactions are evaluated. In addition, blood sample collections are performed for the assessment of clozapine and its metabolite levels.

Official Title
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A Clinical Trial to Investigate the Factors Affecting Adverse Drug Reactions and Clinical Efficacy of Clozapine in Korean

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Clozapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who are diagnosed with schizophrenia spectrum disorder and are expected to use clozapine for more than 57 days to treat or prevent recurrence of schizophrenia Patients who are 19 years or older Patient who understands the contents of the clinical research and provide their written informed consent forms Exclusion Criteria: Patients taking a drug that the researcher deems inappropriate before clozapine administration Patients who can not use an appropriate contraceptive method during the study period Patients whom the researcher deemed inappropriate for clinical research participation

Ages Eligible for Study
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Minimum Age: 19 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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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Clozapine|Clozapine is administered orally according to individual prescribed dosing regimens.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose and lipid metabolism abnormality | Change from baseline glucose and lipid profiles after clozapine administration | Change from baseline glucose and lipid profiles on Day 15, and 57 | 
| Liver function abnormality | Change from baseline liver function test | Change from baseline liver function test on Day 15, and 57 | 
| Sleeping tendency assessment | Epworth sleepiness scale (ESS). ESS is comprised of eight questions, each asking about the subject's likelihood of dozing off or falling asleep in a particular situation that is commonly met in daily life. Each ESS item score measures a particular situational sleep propensity, and respondents use a four-point scale from 0 (no chance of dozing/falling asleep) to 3 (high chance of dozing/falling asleep) for each of the eight questions. The sum of eight item scores (the total ESS score) measures the subject's average sleep propensity across those different situations in daily life. A total ESS score of 16-24 points indicates severe excessive daytime sleepiness. | Change from baseline sleeping tendency assessment on Day 15, and 57 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive function assessment | MCCB (MATRICS Consensus Cognitive Battery). | Change from baseline MCCB on Day 57, and 127 | 
| Clinical symptom assessment | Brief Psychiatric Rating Scale (BPRS). BPRS is a 24-item scale that measures psychiatric symptoms such as depression, anxiety, hallucinations and unusual behaviour. Each symptom is rated on a scale from 1(not present) to 7(extremely severe). The sum of all 24 items is then calculated to a maximum score of 168. The higher the score, the more psychiatrically impaired the patient is. | Change from baseline BPRS on Day 15, and 57 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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genetic polymorphism, pharmacodynamic variability, personalized pharmacotherapy, adverse drug reaction, quality of life