A Clinical Trial to study the clinical bioequivalence of Clozapine 100 mg tablet of Aurobindo in comparison to Clozaril® (Clozapine) 100 mg tablet of Novartis in patients suffering from Schizophrenia

Completed

• Conditions: Schizophrenia

• Registration Number: CTRI/2013/06/003745
• Lead Sponsor: Aurobindo Pharma Limited

Brief Summary

This study is a randomized, Multicenter, Open-Label, Two-Treatment, Two Sequence, Two-Period, cross over, steady state Clinical Bio-equivalence study to determine multiple oral doses clinical bioequivalence of Clozapine 100 mg tablet of Aurobindo with Clozaril® (Clozapine) 100 mg tablet of Novartis in schizophrenic patient’s already receiving Clozapine 100 mg in stable regimen patients with schizophrenia and this study will be conducted in two centers in India. xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /

 The Primary objective will be to determine clinical bioequivalence of test drug with the active comparator (reference drug). The secondary objective of the study is to monitor the adverse events, to ensure safety and tolerability as assessed by reported adverse events, laboratory, clinical investigations and vital signs in the schizophrenic patients.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-06-20
• Last Update Posted: 2015-09-18

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

• 1)Patients have a diagnosis of a) treatment-resistant schizophrenia or; b)schizophrenia, chronic (all types) and in a residual phase or in remission, or schizoaffective disorder according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria 2)Body mass index between 18 and 35kg/m2 aged between 18 and 60 years 3)Patients should be appropriate candidates for Clozapine therapy (as stated in product labeling) and have been taking a stable dose of Clozapine for at least three months.
• 4. Patients who are already receiving/ stabilized on Clozapine daily dose of 100mg twice daily (100 mg Q12h).
• 5)Patients should be otherwise healthy as determined by physical examination, medical history, and no significant abnormality in any of the laboratory parameters including ECG and Chest X-ray.
• 6)Ability to comprehend the full nature and purpose of the study, including possible risks and adverse events; ability to co-operate with the Investigator and to comply with the requirements of the entire study.
• 7)Patients/Legal Representative has given written consent after being advised of the nature and risks of the study.
• 8)Patients must have adequate hematologic reserve I.Hemoglobin ≥10gm/dL II.WBC (white blood cells) >4000/mm3 III.Platelets ≥100,000/mm3 IV.ANC (absolute neutrophils count) >2000/mm3 9) Adequate and stable hepatic function at screening as defined by: I.Bilirubin <1.5 X ULN (upper limit of normal) II.AST/ ALT <1.5 X ULN III.Total Triglycerides <1.5 X ULN IV.Total Cholesterol <1.5 X ULN 10) Adequate renal function at screening as defined by: I.Creatinine <1.5 X ULN for the clinical laboratory 11) Female subjects of childbearing potential must have a negative serum pregnancy test at enrolment.

Exclusion Criteria

• 1)History of suicidal tendencies (e.g. suicidal attempts) within the past 3 months prior to screening or immediate risk of harm to self or other at the time of Screening, as judged by the investigator.
• 2)Absolute neutrophil count ≤ 2000/mm3 and WBC count ≤ 4000/mm3.
• 4)Patients have a medical or surgical condition that might interfere with the absorption, metabolism, or excretion of Clozapine or other study medications.
• 5)Patients have a history of granulocytopenia or myeloproliferative disorder, either drug-induced or idiopathic.
• 6)Patients have a history of clinically significant cardiovascular, renal, hepatic,respiratory, endocrine (except noninsulin-dependent diabetes mellitus), or gastrointestinal disease.
• 7)Patients have a known history of human immunodeficiency virus infection.
• 8)Patients have a history of epilepsy or seizures or are comatose or experiencing severe central nervous system depression.
• 9)Patients are unable to communicate with the investigator.
• 10)Patients have a history of allergic reactions to Clozapine or chemically related psychotropic drugs.
• 11)Patients have a concurrent primary psychiatric or neurological diagnosis, including organic mental disorder (DSM-IV criteria), mental retardation, severe tardive dyskinesia, or idiopathic Parkinson’s disease.
• 12)Patients have had electroconvulsive therapy within the past one month.
• 13)Patients have demonstrated clinically significant homicidal behavior within the past 12 months.
• 14. Patients have received an investigational drug within the past 90 days.
• 15. Patients have a history of narrow-angle glaucoma.
• 16. Patients require treatment with drugs that are known to interact with Clozapine (e.g., agents having a well-known potential to suppress bone-marrow functioning, drugs that are highly protein-bound, cimetidine, or phenytoin).
• Clozapine may also potentiate the effects of antihypertensive and anticholinergics; therefore, caution should be taken if patients receiving these drugs are enrolled in the study.
• 17. Patients have a known history of phenylketonuria.
• 18. Significant orthostatic hypotension (i.e., a drop in systolic blood pressure of 30 mm hg or more and / or a drop in diastolic blood pressure of 20 mm Hg or more on standing) 19) Concurrent use of antihypertensive medication or any medication that might predispose to orthostatic hypotension.
• 20)Concurrent use of other drugs known to suppress bone marrow function.
• 21)Positive tests for drug or alcohol abuse at screening or baseline.
• 22)A history of alcohol or drug dependence by Diagnostic and statistical manual of Mental Disorders IV (DSM-IV) criteria during the 6-month period immediately prior to study entry.
• 23)History of multiple syncopal episodes.
• 24)Patients who smokes.

Study & Design

• Study Type: BA/BE
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
2)Cmax-ss: Maximum concentration over the steady state dosing interval.	Day 7, 8, 9, 10 and Day 17,18,19,20
1)AUC0- : Area under the plasma concentration – time curve over the steady state dosing interval.	Day 7, 8, 9, 10 and Day 17,18,19,20
3)Cmin-ss: Minimum concentration over the steady state dosing interval	Day 7, 8, 9, 10 and Day 17,18,19,20

Secondary Outcome Measures

Name	Time	Method
1. Css-avg: Average concentration over the steady state dosing interval	2.Percentage fluctuation

Trial Locations

Locations (2)

Asha Hospital; 🇮🇳 Hyderabad, ANDHRA PRADESH, India

SNEH Clinic; 🇮🇳 Ahmadabad, GUJARAT, India

Asha Hospital

🇮🇳Hyderabad, ANDHRA PRADESH, India

Dr G Prasad Rao

Principal investigator

914027568979

prasad40@gmail.com