A Multicentric, Double-blind, Randomized, Two-Treatment, Two-sequence, Two-period, Cross-over, Steady-state Clinical Bioequivalence Study of Clozapine 100 mg Tablets of Aurobindo Pharma Limited, India (Test) with Clozaril® (Clozapine) 100 mg tablets of Novartis Pharmaceuticals Canada INC., Canada (Reference) in Schizophrenic Patients Already Receiving/ Stabilized With Clozapine Under Fasting Conditions.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 28
- 试验地点
- 2
- 主要终点
- state dosing interval.
研究概览
简要总结
This is a multicentre study and primary objective is to to determine clinical bioequivalence of multiple oral doses of Clozapine 100 mg tablets of Aurobindo Pharma Limited, India with Clozaril® (Clozapine) 100 mg tablets of Novartis Pharmaceuticals Canada Inc., Canada in schizophrenic patient‟s already receiving Clozapine 100 mg in stable regimen at steady state and secondary objective of this study is to assess the safety and tolerability of
Clozapine
研究设计
- 研究类型
- Interventional
- 分配方式
- Stratified block randomization
- 盲法
- Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 60.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Patients diagnosed with 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.
- •Patients with Body mass index between 18 and 35kg/m2 and aged between 18 and 60 years.
- •Patients who are appropriate candidates for Clozapine therapy (as stated in product labeling) and have been taking a stable dose of Clozapine 100 mg twice daily for at least three months before enrolment in the study.
- •Patients who are healthy as determined by physical examination, medical history, and no significant abnormality in any of the laboratory parameters including ECG and Chest X-ray.
- •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.
- •Patients/Legally Acceptable Representative has given written consent after being advised of the nature and risks of the study.
- •Patients must have adequate hematologic reserve i.
- •Hemoglobin ≥10gm/dL ii.
- •WBC (white blood cells) >4000 /mm3 or /μL iii.
- •Platelets ≥100,000 mm3 or /μL iv.
- •ANC (absolute neutrophils count) >2000/mm3 or /μL
- •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 Cholesterol <1.5 X ULN
- •Adequate renal function at screening as defined by: a.
- •Creatinine <1.5 X ULN for the clinical laboratory 10.Female patients of childbearing potential must have a negative serum pregnancy test at screening.
排除标准
- •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.
- •Absolute neutrophil count ≤ 2000 /mm3 or /μL and WBC count ≤ 4000 /mm3 or /μL.
- •Elderly patients with diagnosed dementia related psychosis.
- •Patients with medical or surgical condition that might interfere with the absorption, metabolism, or excretion of Clozapine or other study medications.
- •Patients with history of granulocytopenia or myeloproliferative disorder, either drug-induced or idiopathic.
- •Patients with history of clinically significant cardiovascular, renal, hepatic, respiratory, endocrine (except noninsulin-dependent diabetes mellitus), or gastrointestinal disease.
- •Patient‟s positive for HIV, HBs (Ag) or HCV.
- •Patients with history of epilepsy or seizures or are comatose or experiencing severe central nervous system depression.
- •Patients are unable to communicate with the investigator.
- •Patients with history of allergic reactions to Clozapine or chemically related psychotropic drugs.
- •Patients having concurrent primary psychiatric or neurological diagnosis, including organic mental disorder (DSM-IV criteria), mental retardation, severe tardive dyskinesia, or idiopathic Parkinson‟s disease.
- •Patients who had undergone electroconvulsive therapy within the past one month.
- •Patients have demonstrated clinically significant homicidal behavior within the past 12 months.
- •Patients have received an investigational drug within the past 90 days.
- •Patients having a history of narrow-angle glaucoma.
- •Patients requiring treatment with drugs that are known to interact with Clozapine (e.g., agents having a well-known potential to suppress bonemarrow 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.
- •Patients with known history of phenylketonuria.
- •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)
- •Concurrent use of antihypertensive medication or any medication that might pre-dispose to orthostatic hypotension.
- •Concurrent use of other drugs known to suppress bone marrow function.
- •Positive tests for drug or alcohol abuse at screening or baseline.
- •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.
- •History of multiple syncopal episodes.
- •Patients who smoke.
- •Expected changes in concomitant medication during the period of study.
结局指标
主要结局
state dosing interval.
时间窗: Predose will be collected within 10 minutes prior to dosing on Day 7 8 and 9 in Period I Day 17 18 and 19 in Period II. On Day 10 and Day 20, pre dose sample will be collected within 10 minutes prior to morning dosing and 0.25, 0.50, 1.00, 1.50, 2.00, 2.50, 3.00, 3.50, 4.00, 5.00, 6.00, 8.00, 10.00 and 12.00 hrs post morning dose
AUC0-Ï„ Area under the plasma concentration time curve over the steady
时间窗: Predose will be collected within 10 minutes prior to dosing on Day 7 8 and 9 in Period I Day 17 18 and 19 in Period II. On Day 10 and Day 20, pre dose sample will be collected within 10 minutes prior to morning dosing and 0.25, 0.50, 1.00, 1.50, 2.00, 2.50, 3.00, 3.50, 4.00, 5.00, 6.00, 8.00, 10.00 and 12.00 hrs post morning dose
Cmaxss Maximum concentration over the steady state dosing interval.
时间窗: Predose will be collected within 10 minutes prior to dosing on Day 7 8 and 9 in Period I Day 17 18 and 19 in Period II. On Day 10 and Day 20, pre dose sample will be collected within 10 minutes prior to morning dosing and 0.25, 0.50, 1.00, 1.50, 2.00, 2.50, 3.00, 3.50, 4.00, 5.00, 6.00, 8.00, 10.00 and 12.00 hrs post morning dose
Cminss Minimum concentration over the steady state dosing interval
时间窗: Predose will be collected within 10 minutes prior to dosing on Day 7 8 and 9 in Period I Day 17 18 and 19 in Period II. On Day 10 and Day 20, pre dose sample will be collected within 10 minutes prior to morning dosing and 0.25, 0.50, 1.00, 1.50, 2.00, 2.50, 3.00, 3.50, 4.00, 5.00, 6.00, 8.00, 10.00 and 12.00 hrs post morning dose
次要结局
- Cssavg Average concentration over the steady state dosing interval(Percentage fluctuation)