A bioequivalence study of Clozapine capsule 200 mg once daily (test drug, Intas pharmaceuticals limited, India) with Clozaril® 100 mg tablets twice daily (reference drug, Novartis pharmaceuticals corporation, USA) in adult schizophrenic patients under fasting conditions.
- Conditions
- Health Condition 1: F209- Schizophrenia, unspecified
- Registration Number
- CTRI/2016/12/007553
- Lead Sponsor
- INTAS PHARMACEUTICALS LIMITED
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 14
1. Written informed consent for participation in the study by the patient and Patientâ??s Legally Acceptable Representative (LAR).
2. Patient has a documented clinical diagnosis of schizophrenia according to DSM 5 at least six months prior to screening.
3. Patients have a diagnosis of treatment-resistant schizophrenia (Treatment resistance is the failure to respond to two or more antipsychotic medications given in therapeutic dose for more than six weeks or more).
4. Male and female patients between 18 and 60 years of age (both inclusive).
5. Having a Body Mass Index (BMI) between 18 and 30 (both inclusive), calculated as weight in kg / height in m2.
6. Not having any significant diseases or clinically significant abnormal findings except schizophrenia during screening
7. The investigator must ensure that the respective hepatic, renal, haematopoietic, cardiac and respiratory functions are appropriate to include the patient in the study.
8. Patients have been on a daily stable dose of 200 mg clozapine formulation for at least 3 month prior to screening visit.
9. Able to comply with study procedures in the opinion of the investigator.
10. In case of Male patients: Either partner or patient must use an effective method of avoiding pregnancy for at least 4 weeks prior to study drug administration, during study and up to 30 days after the last dose of study drug.
11. Sexually active women, unless surgically sterile (at least 6 months prior to study drug administration) or postmenopausal for at least
twelve consecutive months, must use an effective method of avoiding pregnancy (including oral, transdermal, or implanted contraceptives, intrauterine device, female condom with spermicide, diaphragm with spermicide, absolute sexual abstinence, use of condom with spermicide by sexual partner or sterile for at least 4 weeks prior to study drug administration, during study and up to 30 days after the last dose of study drug.
1. Patient with known hypersensitivity/ intolerance to clozapine or any other component of the drug.
2. Clinically symptomatic orthostatic hypotension
Note: Orthostatic hypotension is defined as a drop in systolic blood pressure of 20 mm Hg or more and/or a drop in diastolic blood pressure of 10 mm Hg or more on standing
3. Concurrent use of antihypertensive medication or any medication that might pre-dispose to orthostatic hypotension.
4. Supine blood pressure less than 110/70 mm Hg or pulse rate less than 60 or more than 100 beat per minute at screening and Day 1.
5. Concurrent primary psychiatric or neurological diagnosis (except schizophrenia), including organic mental disorder, severe tardive dyskinesia, or idiopathic Parkinsonâ??s disease
6. A total white blood cell count below 3500/µL, or an absolute neutrophil count <2000/µL performed at the screening and a day prior to randomization.
7. A history of granulocytopenia, agranulocytosis or myeloproliferative disorders (drug-induced or idiopathic).
8. A history of uncontrolled epilepsy, paralytic ileus, or multiple syncopal episodes.
9. A medical or surgical condition that might interfere with the absorption, metabolism, or excretion of clozapine.
10. Known case of poor metabolizer individuals with reduced activity of cytochrome P450 enzymes particularly, 1A2, 2D6 and 3A4.
11. Ingestion of any restricted medication at any time within 07 days before the first study drug administration.
12. Smokers who smoke 10 or more than 10 cigarette/day or inability to abstain from smoking during the study.
13. Positive tests for drug or alcohol abuse at screening or baseline.
14. A history of alcohol or drug dependence by Diagnostic and Statistical Manual of Mental Disorders IV (DSM 5) criteria during the 6-month period immediately prior to study entry.
15. Donation of blood (1 unit or 350 ml) within 90 days prior to receiving the first dose of study medication or during the study.
Note: In case the blood loss is less than or equal to 200 ml; Patient may be dosed 60 days after blood loss.
16. Receipt of an investigational medicinal product or participation in a drug research study within 90 days prior to receiving the first dose of study medication or during the study.
Note: Elimination half-life of the study drug should be taken in to consideration for inclusion of the patient in the study.
17. A positive hepatitis screen including hepatitis B surface antigen, HCV.
18. Known case of HIV infection.
19. Known history of hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose galactose malabsorption.
20. Psychosis judged to be the direct physiological effect of an abused medication or substance.
21. Hospitalisation for an exacerbation of schizophrenia within two months prior to screening and during the screening period.
22. Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others.
23. Presence of narrow angle glaucoma assessed by tonometry.
24.Patients with uncontrolled Diabetes mellitus or fasting blood glucose >= 126 mg/dl at screening visit. <b
Study & Design
- Study Type
- BA/BE
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method comparision of the bioavailability and characterize the pharmacokinetic profileTimepoint: Day 10 and Day 20
- Secondary Outcome Measures
Name Time Method To monitor the safety of the patients who are exposed to the investigational medicinal productTimepoint: Day 1 to Day 20