| CTRI Number |
CTRI/2015/05/005824 [Registered on: 29/05/2015] Trial Registered Retrospectively |
| Last Modified On: |
18/09/2015 |
| Post Graduate Thesis |
No |
| Type of Trial |
BA/BE |
|
Type of Study
|
|
| Study Design |
Randomized, Crossover Trial |
|
Public Title of Study
|
BA/BE study of Clozapine 100 mg tablets in Schizoprenia patients |
|
Scientific Title of Study
|
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. |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| CR03513, Version 1.0 Dated 20.12.2013 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
DrSubhraLahiri |
| Designation |
AssociateVicePresident |
| Affiliation |
AxisClinicalsLimited |
| Address |
1-121/1MiyapurSerlingampally, Hyderabad
1-121/1MiyapurSerlingampally, Hyderabad
Hyderabad
ANDHRA PRADESH
500049
India |
| Phone |
914040408064 |
| Fax |
914040408003 |
| Email |
subhra.L@axisclinicals.com |
|
Details of Contact Person
Scientific Query
|
| Name |
DrSubhraLahiri |
| Designation |
AssociateVicePresident |
| Affiliation |
AxisClinicalsLimited |
| Address |
1-121/1MiyapurSerlingampally, Hyderabad
1-121/1MiyapurSerlingampally, Hyderabad
Hyderabad
ANDHRA PRADESH
500049
India |
| Phone |
914040408064 |
| Fax |
914040408003 |
| Email |
subhra.L@axisclinicals.com |
|
Details of Contact Person
Public Query
|
| Name |
DrSubhraLahiri |
| Designation |
AssociateVicePresident |
| Affiliation |
AxisClinicalsLimited |
| Address |
1-121/1MiyapurSerlingampally, Hyderabad
1-121/1MiyapurSerlingampally, Hyderabad
Hyderabad
ANDHRA PRADESH
500049
India |
| Phone |
914040408064 |
| Fax |
914040408003 |
| Email |
subhra.L@axisclinicals.com |
|
|
Source of Monetary or Material Support
|
|
|
Primary Sponsor
|
| Name |
AurobindoPharmaLimited |
| Address |
Survey No 313 Bachupally Village Quthubullapur mandal Hyderabad 500090 |
| Type of Sponsor |
Pharmaceutical industry-Indian |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 2 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr TimirShah |
Divyam Hospital |
B No 84 Palsana crossroad National highway number 8 Surat 394315
Surat
GUJARAT |
9199825137443
drtcshah@gmail.com |
| Dr ViashalNVora |
Ratandeep Multispeciality Hospital |
2ndfloor Nakshatra Complex Above HDFC bank Maninagarcrossroad Maninagar Ahmedabad
Ahmadabad
GUJARAT |
919825440891
917922124022
vnvora@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 2 |
| Name of Committee |
Approval Status |
| Divyam Hospital Ethical Review Board |
Approved |
| Ratandeep Institutional Ethics Committee |
Approved |
|
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Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
Schizoprenia, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Clozapine Tablets 100 mg Aurobindo Pharma Limited India |
This study will consists of two periods and is multiple dose study. Eligible patients will be administered with test or reference twice daily orally for every 12 hours for 10 consecutive days in each period crossed over without washout. |
| Comparator Agent |
Clozaril(Clozapine)Novartis PharmaceuticalsCanadaInc |
This study will consists of two periods and is multiple dose study. Eligible patients will be administered with test or reference twice daily orally for every 12 hours for 10 consecutive days in each period crossed over without washout. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
60.00 Year(s) |
| Gender |
Both |
| Details |
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.
2. Patients with Body mass index between 18 and 35kg/m2 and aged
between 18 and 60 years.
3. 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.
4. 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.
5. 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.
6. Patients/Legally Acceptable Representative has given written consent
after being advised of the nature and risks of the study.
7. 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
8. 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 Triglycerides <1.5 X ULN
iv. Total Cholesterol <1.5 X ULN
9. 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
|
|
| ExclusionCriteria |
| Details |
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.
2. Absolute neutrophil count ≤ 2000 /mm3 or /μL and WBC count ≤ 4000
/mm3 or /μL.
3. Elderly patients with diagnosed dementia related psychosis.
4. Patients with medical or surgical condition that might interfere with the
absorption, metabolism, or excretion of Clozapine or other study
medications.
5. Patients with history of granulocytopenia or myeloproliferative disorder,
either drug-induced or idiopathic.
6. Patients with history of clinically significant cardiovascular, renal,
hepatic, respiratory, endocrine (except noninsulin-dependent diabetes
mellitus), or gastrointestinal disease.
7. Patient‟s positive for HIV, HBs (Ag) or HCV.
8. Patients with history of epilepsy or seizures or are comatose or
experiencing severe central nervous system depression.
9. Patients are unable to communicate with the investigator.
10. Patients with history of allergic reactions to Clozapine or chemically
related psychotropic drugs.
11. 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.
12. Patients who had undergone electroconvulsive therapy within the past one
month.
13. Patients have demonstrated clinically significant homicidal behavior
within the past 12 months.
14. Patients have received an investigational drug within the past 90 days.
15. Patients having a history of narrow-angle glaucoma.
16. 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.
17. Patients with known history of phenylketonuria.
18. 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)
19. Concurrent use of antihypertensive medication or any medication that
might pre-dispose to orthostatic hypotension.
20. Concurrent use of other drugs known to suppress bone marrow function.
21. Positive tests for drug or alcohol abuse at screening or baseline.
22. 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.
23. History of multiple syncopal episodes.
24. Patients who smoke.
25. Expected changes in concomitant medication during the period of study.
|
|
|
Method of Generating Random Sequence
|
Stratified block randomization |
|
Method of Concealment
|
Pharmacy-controlled Randomization |
|
Blinding/Masking
|
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
AUC0-Ï„ Area under the plasma concentration time curve over the steady
state dosing interval.
Cmaxss Maximum concentration over the steady state dosing interval.
Cminss Minimum concentration over the steady state dosing interval |
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 |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
Cssavg Average concentration over the steady state dosing interval
Percentage fluctuation
Tmax Time of maximum measured plasma concentration over the steady
state dosing interval
Cpd Predose concentrations determined before a
dose at steady state
Safety and tolerability |
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 |
|
|
Target Sample Size
|
Total Sample Size="28"
Sample Size from India="28"
Final Enrollment numbers achieved (Total)= ""
Final Enrollment numbers achieved (India)="" |
|
Phase of Trial
|
N/A |
|
Date of First Enrollment (India)
|
30/04/2015 |
| Date of Study Completion (India) |
Date Missing |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="1"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
Nil |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
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 |