CTRI/2019/11/022073 [Registered on: 20/11/2019] Trial Registered Prospectively
Last Modified On:
24/12/2020
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
A Study of Clozapine Extended Release Capsule 200 mg Once Daily in Adult Schizophrenic Patients.
Scientific Title of Study
A Multicentric, Open Label, Balanced, Randomized, Two-Period, Two Sequence, Crossover, Steady State, Food Effect Study of Clozapine Extended Release Capsule 200 mg Once Daily (Test drug, Intas Pharmaceuticals Limited, India) After Multiple Dose Administration in Adult Schizophrenic Patients Under Fasting and Fed Condition.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
0567-18, Version no. 2.1, Date: 13 June 2019
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Mr Prashant Modi
Designation
General Manager
Affiliation
Lambda Therapeutic Research Ltd
Address
Lambda House, Department of Project Management & Regulatory Affairs, Plot No. 38, Survey No. 388 Near Silver Oak Club, S. G.
Highway, Gota Ahmadabad GUJARAT 382481 India
Phone
07940202375
Fax
07940202021
Email
prashantmodi@lambda-cro.com
Details of Contact Person Scientific Query
Name
Dr Naman Shah
Designation
General Manager
Affiliation
Lambda Therapeutic Research Ltd.
Address
Lambda House, Department of CTM Medical Services, Plot No. 38, Survey No. 388 Near Silver Oak Club, S. G. Highway, Gota Ahmadabad GUJARAT 382481 India
Phone
07940202389
Fax
07940202021
Email
namanshah@lambda-cro.com
Details of Contact Person Public Query
Name
Mr Prashant Modi
Designation
General Manager
Affiliation
Lambda Therapeutic Research Ltd
Address
Lambda House, Department of Project Management & Regulatory Affairs, Plot No. 38, Survey No. 388 Near Silver Oak Club, S. G.
Highway, Gota Ahmadabad GUJARAT 382481 India
Phone
07940202375
Fax
07940202021
Email
prashantmodi@lambda-cro.com
Source of Monetary or Material Support
Intas Pharmaceuticals Limited, Corporate House, Nr. Sola Bridge, S.G. Highway, Thaltej, Ahmedabad – 380054, Gujarat, India.
Primary Sponsor
Name
Intas Pharmaceuticals Limited
Address
Corporate House, Nr. Sola Bridge, S.G. Highway, Thaltej, Ahmedabad– 380054
Gujarat, India.
Type of Sponsor
Pharmaceutical industry-Indian
Details of Secondary Sponsor
Name
Address
NA
NA
Countries of Recruitment
India
Sites of Study
No of Sites = 10
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Timir Shah
Divyam Hospital
Block No. 84, Department of Clinical Research, Room No. NA, Palsana Cross Road, N. H No. 8, Palsana - 394315, Surat GUJARAT
09825137443
drtcshah@gmail.com
Dr Pradeep Kumar Saha
Institute of Psychiatry, Centre of Excellence
7, Department of Clinical Research, Room No. NA, D. L. Khan Road - 700025 Kolkata WEST BENGAL
9830277607
pradeepnimhan@gmail.com
Dr T S Sathyanarayana Rao
JSS Medical College Hospital,
Department of Clinical Research, Room No. NA, M G Road- 570004 Mysore KARNATAKA
9845282399
tssrao19@yahoo.com
Dr Vasudeo Paralikar
KEM Hospital Research Centre
489, Department of Clinical Research, Room No. NA, Sardar Moodliar Road, Rasta Peth - 411011, Pune MAHARASHTRA
09922010959
research@kemhrcpune.org
Dr Vaishal Vora
Ratandeep Multispeciality Hospital
5th Floor, Department of Clinical Research, Room No. NA, Nakshtra Complex, above HDFC Bank, Maninagar, - 380008 Ahmadabad GUJARAT
9825440891
vnvora@gmail.com
Dr Ramashanker Yadav
Shivam Hospital
Jashoda Nagar Cross Road, Department of Clinical Research, Room No. NA, Maninagar - 380008 Ahmadabad GUJARAT
8264049261
investigator.research1@gmail.com
Dr Rajesh Ram
Shree Giriraj Multispeciality Hospital
Department of Clinical Research, Room No. NA, 27-Navjyot Park- 360005 Rajkot GUJARAT
9429484064
drramrajesh78@gmail.com
Dr Bakul Buch
Shri Hatkesh Healthcare Foundation
Saraswati Mandir Complex, Department of Clinical Research, Room No. NA, Near Bhutnath Temple, College Road, -362001 Junagadh GUJARAT
9825220330
bakulbuch@gmail.com
Dr Umesh Nagapurkar
Sujata Birla Hospital & Medical Research Centre
Opp. Bytco College, Department of Clinical Research, Room No. NA, Nashik Pune Highway, Nashik Road - 422101 Nashik MAHARASHTRA
9823146088
umeshanjali@gmail.com
Dr Lakhan Kataria
Sumandeep Vidhyapeeth & Dhiraj General Hospital
at & PO Piparia, Department of Clinical Research, Room No. NA, Waghodia, - 391760 Vadodara GUJARAT
Clozapine Extended Release capsule 200 mg of Intas
Pharmaceuticals Limited, India
Dose: 200 mg; Frequency: once daily under fasting condition; Mode of Administration: Per oral ; Duration of treatment:
10 days
Intervention
Clozapine Extended Release capsule 200 mg of Intas Pharmaceuticals Limited, India
Dose: 200 mg; Frequency: once daily under fed condition; Mode of Administration: Per oral ; Duration of treatment: 10 days
Comparator Agent
NA
NA
Inclusion Criteria
Age From
18.00 Year(s)
Age To
60.00 Year(s)
Gender
Both
Details
1. Written informed consent for participation in the study by the patient and Patient 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 atleast six weeks).
4. Male and female patients between 18 and 60 years of age (both inclusive).
5. Non-smokers.
6. Male patients with weight ≥ 50 kg and female patients with weight ≥ 45 kg.
7. Not having any significant diseases or clinically significant abnormal findings except schizophrenia during screening-including medical history, physical examination, laboratory evaluations, 12-lead ECG and X-ray chest (posteroanterior view) recording, ophthalmic examination etc. which is likely to
adversely affect patient safety by participating in the study or study objectives
in investigator opinion.
8. The investigator must ensure that the respective hepatic, renal, haematopoietic,
cardiac and respiratory functions are appropriate to include the patient in the
study.
9. Patients have been on a daily stable dose of 200 mg clozapine formulation for at least 3 month prior to screening visit.
10. Able to comply with study procedures in the opinion of the investigator.
11. 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. Cessation of birth control after this point should be discussed with a responsible physician.
12. Sexually active women, unless surgically sterile (at least 6 months prior to study
drug administration) or postmenopausal for at least 12 consecutive months, must use an effective method of avoiding pregnancy (including oral, transdermal, or implanted contraceptives [any hormonal method in conjunction with a secondary method], intrauterine device, female condom with spermicide, diaphragm with spermicide, absolute sexual abstinence, use of condom with spermicide by sexual partner or sterile [at least 6 months prior to Study drug administration] sexual partner) for at least 4 weeks prior to study drug administration, during study and up to 30 days after the last dose of study drug. Cessation of birth control after this point should be discussed with a responsible physician.
ExclusionCriteria
Details
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 predispose 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 0.
5. Concurrent primary psychiatric or neurological diagnosis (except schizophrenia),
including organic mental disorder, severe tardive dyskinesia, or idiopathic Parkinson disease.
6. An absolute neutrophil count <1500/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 epilepsy or risk for seizures, 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, or who have smoked within last six months prior to start of the study.
13. Positive tests for drug or alcohol abuse at screening and baseline.
14. A history of alcohol or drug dependence by Diagnostic and Statistical Manual of
Mental Disorders V (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.
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.
17. A known case of or positive test for HIV infection or hepatitis B or HCV.
18. Known history of hereditary problems of galactose intolerance, the Lapp lactase
deficiency or glucose galactose malabsorption.
19. Psychosis judged to be the direct physiological effect of an abused medication or
substance.
20. Hospitalisation for an exacerbation of schizophrenia within two months prior to screening and during the screening period.
21. Patients who, in the opinion of the investigator, pose an imminent risk of suicide
or a danger to self or others.
22. Patients with the following cardiac conditions are excluded:
a. Recent myocardial infarction (<12 months).
b. QTc prolongation (screening electrocardiogram with QTc>450 msec).
c. History of QTc prolongation or using concomitant medications which prolong QTc interval.
d. First-degree heart block with PR interval > 0.22 seconds.
e. Sustained cardiac arrhythmia or history of sustained cardiac arrhythmia.
f. Uncompensated congestive heart failure, myocarditis, cardiomyopathy.
g. Complete left bundle branch block.
23. Presence of narrow angle glaucoma assessed by tonometry.
24. Patient with hypokalemia and / or hypomagnesemia.
25. Patients with uncontrolled diabetes mellitus or fasting blood glucose ≥ 126 mg/dl
at screening visit.
26. Patient with hyperprolactinemia at screening visit which as judged by Investigator could lead to safety risk to the patient upon participation in the trial or could interfere with the conduct of the trial.
27. Dementia related psychosis.
28. Concurrent use of other drugs known to suppress bone marrow function.
29. Pregnant or lactating females.
30. A history of risk for seizures.
31. Compliance with outpatient medication schedule not expected.
32. Expected changes in concomitant medications during the period of study.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Characterization and Comparision of the Pharmacokinetic Profile of Clozapine Extended
Release Capsule 200 mg When Administered Once Daily Under Fasting and Fed Condition.
Pre-dose blood sample
Day 07, Day 08, Day 09, Day 10, Day 17, Day 18, Day 19 and Day 20
Total Sample Size="92" Sample Size from India="92" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
N/A
Date of First Enrollment (India)
21/01/2020
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="0" Months="10" Days="0"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
None Yet
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
Clozapine, a dibenzodiazepine derivative with potent antipsychotic properties, is indicated for the management of patients with severe schizophrenia who fail to respond adequately to at least two different antipsychotic drug treatments. In this study, the steady state pharmacokinetics and food effect of clozapine ER capsules of Intas Pharmaceuticals Limited, India (test formulation) will be assessed after multiple dose administration to adult, schizophrenic patient in a crossover design study. The Sponsor has developed an extended release formulation of clozapine. This formulation being extended release formulation, it is expected to improve the compliance, reduce drug free interval and reduce side effects which is very important considering schizophrenic population. This study is being conducted to characterize and compare the pharmacokinetic profile of the Sponsor’s formulation clozapine extended release capsule 200 mg (Test drug, Intas Pharmaceuticals Ltd., India) when administered once daily under fasting and fed condition. As a high number of healthy Patients experienced serious adverse effects after administration of antipsychotics such as hypotension, tachycardia etc., hence, regulatory authorities are recommending that studies should be conducted on Schizophrenic patients. The study is being conducted on schizophrenic patients, who are on a stable dose of clozapine, and the patients cannot be deprived of the clozapine while on treatment, the study has been planned to be a continuous administration of the test formulation without any intervening washout period.