Bioequivalence study in adult schizophrenic patients already receiving stable daily dose of Clozapine 25 mg tablet twice daily under fasting conditions.
- Conditions
- Health Condition 1: null- Schizophrenia
- Registration Number
- CTRI/2017/06/008857
- Lead Sponsor
- Changzhou Pharmaceutical Factory
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- Sex
- Not specified
- Target Recruitment
- 0
1.Men and women aged 18-65 years (both inclusive) having clinical diagnosis of schizophrenia (DSM IV-TR).
2.Patients have a diagnosis of treatment-resistant schizophrenia {Treatment resistance is defined as an inadequate response to at least two antipsychotic drugs at the maximally tolerated dose within the recommended therapeutic range in treatment lasting six weeks or more. Termination of a medication due to adverse events before reaching the appropriate dose and duration should not be regarded as a failed treatment due to non response to the medication.
3.Schizophrenic patients who are on stable dose of Clozapine 25 mg for at least 3 months prior to randomization and receiving Clozapine 25 mg twice daily.
4.Patients should be otherwise healthy as determined by physical examination, medical history, and routine hematologic and biochemical tests.
5.Willing and able to comply with housing, restrictions and other protocol requirements as indicated by signed written informed consent witnessed by a legally acceptable representative.
6.Females of childbearing potential (sexually active women who have not completed 1 year after menopause & have not gone through hysterectomy or bilateral tubal ligation) must have a negative pregnancy test (at screening and prior to check-in in Period I) as well as must be non-lactating at screening and must agree to use an effective contraceptive method during study.
7.No participation in any clinical study within the past 90 days.
1.A history of allergic reactions to Clozapine / any of the component of study drug or other chemically related psychotropic drugs
2.Concurrent primary psychiatric disorder other than schizophrenia or neurological diagnosis, including organic mental disorder, neuroleptic malignant syndrome, severe tardive dyskinesia, or idiopathic Parkinsonâ??s disease and dementia related psychosis, a history of epilepsy or other predisposing risk factors for seizures, history of multiple syncopal attacks or any other clinically significant CNS disorder.
3.Patients with the following cardiac conditions:
•Recent myocardial infarction ( <12 months)
•QTc prolongation (screening electrocardiogram with QTc >450 msec for men, QTc >470 msec for women)
•History of QTc prolongation or using concomitant medications which prolong QTc interval.
•Sustained cardiac arrhythmia or history of sustained cardiac arrhythmia
•Uncompensated congestive heart failure, myocarditis, cardiomyopathy
•Complete left bundle branch block
•First-degree heart block with PR interval > 0.22 seconds
4.Patients with significant renal or hepatic impairment in which dose reduction is necessary as per the clinical evaluation of the patient by the Investigator.
5.Patients with narrow-angle glaucoma, concomitant anticholinergic medications, prostatic hypertrophy, or other conditions in which anticholinergic medications are required for the treatment, paralytic ileus, intestinal obstruction etc.
6.Patients with known history of CYP2D6 poor metabolizers.
7.A history of granulocytopenia/ agranulocytosis or myeloproliferative disorders (drug-induced or idiopathic)
8.Patient with the history or presence of 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) at the time of screening.
9.Concurrent use of antihypertensive medication or any medication that might pre¬dispose to orthostatic hypotension
10.A medical or surgical condition that might interfere with the absorption, metabolism, or excretion of Clozapine
11.Any of the following hematological abnormality at screening
•Total white blood cell count < 4000/c.mm
•Absolute neutrophil count < 2000/c.mm
•Absolute eosinophil count > 700 / c.mm
•Patients with poor glycemic control as defined by HbA1c >=7% and/or fasting blood glucose >160 mg/dL at screening
•Patients with total cholesterol >300 mg/dL and triglycerides level > 300 mg/dL at screening
12.Concurrent use of other drugs known to suppress bone marrow function
13.Expected changes in concomitant medications during the period of study.
14.Positive tests for drug or alcohol abuse at screening or baseline.
15.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.
16.History of multiple syncopal episodes.
17.Patients have a history of narrow-angle glaucoma
18.Use of any of the following medications within14 days or at least five half lives have not been passed between last dose of the previous medication and first dose of the study medication, preceding enrolment including but not limited to:
Study & Design
- Study Type
- BA/BE
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To demonstrate the bioequivalence at steady state of Clozapine tablets 25 mg of Changzhou Pharmaceutical Factory, China vs. Clozaril® 25 mg Tablets, distributed by: Novartis Pharma Corporation East Hanover, NJ 07936 in adult schizophrenic patients already receiving stable daily dose of Clozapine 25 mg tablet twice daily under fasting conditions.Timepoint: A total of 34 blood samples will be collected during the study for PK analysis. The pre-dose blood sample of 4.0 mL (00.00) will be scheduled to be collected within 5 minutes before morning dosing on days 8, 9, 10 and days 18, 19, 20 of the study. On day 10 & day 20, the post-dose blood samples of 4.0 mL each will be drawn at 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0 hrs following morning drug administration.
- Secondary Outcome Measures
Name Time Method ILTimepoint: NA