Official Title: “A 6-Week, Multicenter, Rater-blind, Randomized, Risperidone-controlled Study to Evaluate the Efficacy and Safety of Seroquel (Quetiapine Fumarate) in the Treatment of Chinese Han Patients With Schizophrenia”

The primary objective of this study is to evaluate the efficacy of seroquel in the treatment of patients with acute schizophrenia compared with risperidone by evaluating the change of PANSS total score from the baseline to week 6.

Study Type: Interventional

Study Design: Allocation: Randomized, Control: Active Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Study Primary Completion Date: May 2010

This is a rater- blind, parallel assignment, randomized and active controlled study. The subjects investigated are outpatients or inpatient with schizophrenia from the Chinese Han race. The screening phase lasts for 1 week. The eligible patients enter the next randomized treatment phase. The titration duration is 1 week. After the first week, the patients are administered with a flexible dose regimen. In this study, the effective doses range of seroquel and risperidone are 600-750mg/d and 3-6mg/d respectively and the treatment duration lasts for 6 weeks.

The efficacy and safety of seroquel in the treatment of patients with schizophrenia have been confirmed by multiple double blind studies. This study is designed to evaluate the efficacy and safety of seroquel in the treatment of Chinese Han patients with schizophrenia.

Therefore, the single blind and active control design should be selected for this study. The drug titration method and dose are within the range specified in the instruction and patients with schizophrenia are tolerant to the drug in clinical treatment.

The purpose of schizophrenic patient treatment is to improve the core symptoms, prevent suicide and other aggressive behavior, alleviate the side reactions caused by the drug, and recover the life functions of patients. Generally, the treatment in the acute phase lasts for 6 to 8 weeks. In this study, the treatment in the acute phase lasts for 6 weeks.

The rating scales used in this study are standard psychiatric rating scales with good validity and are widely used in the study of antischizophrenia drugs and in the treatment of patients with schizophrenia in China. The PANSS is developed from two early rating scales, namely the brief psychiatric rating scale (BPRS) and the psychiatric rating scale. The high inter-investigator reliability and repeated measurement reliability of these scales have been proved by multiple studies. The clinical global impression (CGI) is a simple but convenient global impression scale. It is applicable to any patients treated and studied by the psychiatric department. The Carlgary depression scale for schizophrenia (CDSS) is used to evaluate the depressive symptoms of patients with schizophrenia. It has good reliability and validity. The abnormal involuntary movement scale (AIMS) is another evaluation tool consisting of 12 items. The AIMS is used to evaluate the abnormal involuntary movements related to antischizophrenia drugs. The AIMS is nearly the most frequently used multi-item rating scale evaluating of tardive dyskinesia. The Simpson and Angus scale (SAS) is also a rating scale commonly used since its release in 1970. The validity of SAS has been verified in the double blind and placebo-controlled study involving two haloperidol doses.

Intervention(s) in this Clinical Trial

• Drug: Quetiapine
  • Quetiapine fumarate, 25mg/200 mg, the dose titration is carried in week 1. flexible doses(600-750 mg/d) from week 2 to week 6. If a patient is intolerant, the doses can be adjusted as judged by investigator.
• Drug: risperidone
  • risperidone, 1mg/tablet, the dose titration is carried in week 1. flexible doses(3-6 mg/d) from week 2 to week 6. If a patient is intolerant, the doses can be adjusted as judged by investigator.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Quetiapine fumarate, flexible doses(600-750 mg/d)
• Active Comparator: 2
  • risperidone, flexible doses(3-6 mg/d)

Primary Measures

• the change of PANSS total score
  • Time Frame: from the baseline to week 6
    Safety Issue?: No

Secondary Measures

• The Carlgary depression scale for schizophrenia (CDSS)
  • Time Frame: from the baseline to week 6
    Safety Issue?: No
• The abnormal involuntary movement scale (AIMS)
  • Time Frame: from the baseline to Week 6
    Safety Issue?: Yes
• The Simpson and Angus scale (SAS)
  • Time Frame: from the baseline to week 6
    Safety Issue?: Yes
• The clinical global impression (CGI),including CGI-I and CGI-S
  • Time Frame: from the baseline to week 6
    Safety Issue?: No

Inclusion Criteria:

• 1. Written informed consent provided by legal guardians or patients.
• 2. Patients who met DSM-IV criteria for schizophrenia: 295.20 (Schizophrenia, Catatonic
• Type), 295.10 (Schizophrenia, Disorganized Type), 295.30 (Schizophrenia, Paranoid
• Type), 295.60 (Schizophrenia, Residual Type), and 296.90 (Mood Disorder NOS).
• 3. Age from 18-65 years old, male or female, Han nationality.
• 4. PANSS total score at least 70 at baseline.
• 5. Female patients of childbearing potential must be using a reliable method of contraception and have a negative urine human chorionic gonadotropin (HCG) test at enrolment.
• 6. Able to understand and comply with the requirements of the study. -

Exclusion Criteria:

• 1. Pregnancy or lactation.
• 2. A diagnosis of any DSM-IV Axis I disorders that is not defined in the inclusion criteria, except schizophrenia.
• 3. Patients who have an imminent risk of suicide or a danger to self or others as judged by investigator.
• 4. Known intolerance or lack of efficacy to seroquel and/or risperidone, as judged by the investigator.
• 5. Use of seroquel and/or risperidone within 28 days prior to enrolment.
• 6. Use of any of the following cytochrome P450 3A4 inhibitors in the 14 days preceding enrolment including but not limited to: ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, troleandomycin, indinavir, nelfinavir, ritonavir, fluvoxamine and saquinavir.
• 7. Use of any of the following cytochrome P450 inducers in the 14 days preceding enrollment including but not limited to: phenytoin, carbamazepine, barbiturates, rifampin, St. John's Wort, and glucocorticoids.
• 8. Use of a long acting antipsychotics Within one dosing interval
• 9. Substance or alcohol dependence at enrolment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria.
• 10. Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse as defined by DSM-IV criteria within 28 days prior to enrolment.
• 11. Medical conditions that would affect the absorption, distribution, metabolism, or excretion of study treatment.
• 12. Unstable or inadequately treated medical illness (e.g. CHF - congestive heart failure, angina pectoris, hypertension) as judged by the investigator.
• 13. Involvement in the planning and conduct of the study.
• 14. Participation in another drug trial within 28 days prior enrolment into this study.
• 15. Patient with diabetes mellitus.
• 16. The patient's absolute neutrophil count (ANC) ≤ 1.5 x 109/L and the ALT and AST values in the liver function test exceeding two times of the upper limits of normal values.
• 17. Use of Electroconvulsive therapy within 28 days prior to randomization.
• 18. Use of clozapine within 28 days prior to randomization.
• 19. Previous enrolment in the present study -

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Shanghai Mental Health Center

Overall Clinical Trial Officials and Contacts

Huafang LI, MD,PhD Principal Investigator Drug Clinical Trial Office, Shanghai Mental Health Center  

Information obtained from ClinicalTrials.gov on September 01, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00817648

Study ID Number: D1443L00071

ClinicalTrials.gov Identifier: NCT00817648

Health Authority: China: State Food and Drug Administration