Bioavailability study of Clozapine tablets 100 mg of, Inc. in adult schizophrenic patients already receiving stable daily dose of Clozapine
- Conditions
- Health Condition 1: F01-F99- Mental, Behavioral and Neurodevelopmental disorders
- Registration Number
- CTRI/2020/10/028190
- Lead Sponsor
- Mankind Pharma Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 17
1.Men and women aged 18-65 years (both inclusive) having clinical diagnosis of schizophrenia (DSM V-TR) with BMI 18.5-30 kg/m2 (both inclusive).
2.Patients have a diagnosis of treatment-resistant schizophrenia {Treatment resistance is defined as a lack of satisfactory clinical improvement despite the use of adequate doses of at least two different antipsychotic agents, including an atypical antipsychotic agent, prescribed for adequate duration. (Atleast 15 days for each antipsychotic agent.)}, or have severe, untreatable neurological adverse reactions to other antipsychotic agents, including atypical antipsychotics.
3.Schizophrenic patients who are on stable dose of Clozapine for at least 3 months prior to randomization and receiving Clozapine in multiples of 100 mg every 12 hours.
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.Willing to comply with the study requirements as per protocol and with the outpatient dosing schedule.
7.Females of childbearing potential (who has not completed 1 year after menopause or have not gone through hysterectomy or bilateral tubal ligation) must have a negative pregnancy test (at screening, before randomization) as well as must be non-lactating at screening and must agree to use an effective contraceptive method during study.
8.No participation in any clinical study within the past 90 days.
9.The investigator must ensure that the respective hepatic, renal, haematopoietic, cardiac and respiratory functions are appropriate to include the patient in the study.
1.A history of allergic reactions to Clozapine or other chemically related psychotropic drugs
2.Concurrent primary psychiatric or neurological diagnosis, including organic mental disorder, severe tardive dyskinesia, or idiopathic Parkinsonââ?¬•s disease.
3.History of severe renal or cardiac disorders (e.g. myocarditis, cardiomyopathy, bradycardia, mitral valve incompetence and pulmonary embolism), paralytic ileus, prostatic enlargement, colonic disease or lower abdominal surgery, active liver disease associated with nausea, anorexia or jaundice; progressive liver disease, hepatic failure.
4.A history of granulocytopenia/ agranulocytosis or myeloproliferative disorders (drug-induced or idiopathic)
5.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)
6.Concurrent use of antihypertensive medication or any medication that might pre�¬dispose to orthostatic hypotension
7.A medical or surgical condition that might interfere with the absorption, metabolism, or excretion of Clozapine
8.A history of epilepsy or risk for seizures.
9.Any of the following investigational abnormality in screening
�Total white blood cell count < 4000/c.mm
�Absolute neutrophil count < 2000/c.mm
�Absolute eosinophil count > 700 / c.mm
�HbA1c > 9%
�QTc > 450 milliseconds
10.Concurrent use of other drugs known to suppress bone marrow function
11.Expected changes in concomitant medications during the period of study.
12.Positive tests for drug or alcohol abuse at screening or baseline.
13.A history of alcohol or drug dependence by Diagnostic and Statistical Manual of Mental Disorders V (DSM-V) criteria during the 6-month period immediately prior to study entry.
14.History of multiple syncopal episodes.
15.Patients have a history of narrow-angle glaucoma
16.Use of any of the following in the 14 days preceding enrolment including but not limited to:
�Drugs significantly influencing CYP1A2 activity.
�Drugs significantly inducing and inhibiting CYP3A4 activity
�Drugs significantly inhibiting CYP2D6 activity.
�Medications known to prolong the QTc interval
�Substances known to have a substantial potential for causing agranulocytosis
�Phenytoin, lithium
�highly protein bound substances
�Antihypertensive and other drugs known to cause postural hypotension.
�Alcohol, MAOIs, CNS depressants including narcotics and benzodiazepines
�Antimuscarinic
17.Patient had major surgery within 4 weeks prior to study entry, or who have not recovered from prior major surgery.
18.Patients with known positivity for human immunodeficiency virus (HIV), HBsAg or HCV.
19.Chronic Smokers who smokes greater than or equal to 10 cigarettes or equivalent per day or inability to abstain from smoking during the study.
20.History of difficulty with donating blood or difficulty in accessibility of veins.
21.Compliance with outpatient medication schedule not expected as per Principal investigatorââ?¬•s opinion.
Study & Design
- Study Type
- BA/BE
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To assess the bioavailability at steady state of Clozapine tablets 100 mg of Mankind Pharma Ltd, India vs. CLOZARIL�® (Clozapine) tablets 100 mg of HLS Therapeutics (USA), Inc. in adult schizophrenic patients already receiving stable daily dose of Clozapine administered in equally divided doses at 12-hour intervals.Timepoint: To assess the bioavailability at steady state of Clozapine tablets 100 mg of Mankind Pharma Ltd, India vs. CLOZARIL�® (Clozapine) tablets 100 mg of HLS Therapeutics (USA), Inc. in adult schizophrenic patients already receiving stable daily dose of Clozapine administered in equally divided doses at 12-hour intervals.
- Secondary Outcome Measures
Name Time Method To monitor the safety and tolerability profile of the study formulations.Timepoint: Physical examination,vital signs,ECG,laboratory <br/ ><br>evaluations and adverse event monitoring <br/ ><br>PK samples will be collected through cannula placed in a forearm vein. The pre-dose blood sample of 3.0 mL (00.00 hrs) will be collected within 5 minutes prior to dosing time on day 7, 8, 9 & 10 in period I and on day 17, 18, 19 & 20 in period II of study