| CTRI Number |
CTRI/2016/08/007151 [Registered on: 05/08/2016] Trial Registered Prospectively |
| Last Modified On: |
05/08/2016 |
| 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, Open Label, 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 Leponex (Clozapine) 100 mg tablets of Novartis Pharma GmbH 90327 Nürnberg (Reference) in Schizophrenic Patients Already Receiving/ Stabilized With Clozapine Under Fasting Conditions. |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| CR104-15, Version 1.0, Dated 09.06.2015 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Subhra Lahiri |
| Designation |
AVP - CR and CDM |
| Affiliation |
Axis Clinicals Limited |
| Address |
AXIS Clinicals Ltd Clinical Research Department 1-121/1, Miyapur,Hyderabad, Telangana
Rangareddi
ANDHRA PRADESH
500049
India |
| Phone |
04040408064 |
| Fax |
04040408060 |
| Email |
subhra.l@axisclinicals.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Subhra Lahiri |
| Designation |
AVP - CR and CDM |
| Affiliation |
Axis Clinicals Limited |
| Address |
AXIS Clinicals Ltd Clinical Research Department 1-121/1, Miyapur,Hyderabad, Telangana
ANDHRA PRADESH
500049
India |
| Phone |
04040408064 |
| Fax |
04040408060 |
| Email |
subhra.l@axisclinicals.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Subhra Lahiri |
| Designation |
AVP - CR and CDM |
| Affiliation |
Axis Clinicals Limited |
| Address |
AXIS Clinicals Ltd Clinical Research Department 1-121/1, Miyapur,Hyderabad, Telangana
ANDHRA PRADESH
500049
India |
| Phone |
04040408064 |
| Fax |
04040408060 |
| Email |
subhra.l@axisclinicals.com |
|
|
Source of Monetary or Material Support
|
| APL Research Center
Aurobindo Pharma Limited
Survey No -313, Bachupally Village,
Qutubullapur Mandal,
Hyderabad -500 090, India, |
|
|
Primary Sponsor
|
| Name |
APL Research Center |
| Address |
APL Research Center
Aurobindo Pharma Limited
Survey No -313, Bachupally Village,
Qutubullapur Mandal,
Hyderabad -500 090, India, |
| 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 Timir Shah |
Divyam Hospital. |
Divyam Hospital.
Department of psychiatry, Room Number 1, Block No.84, Palsana Cross Roads,
National Highway No – 8,
Surat – 394315, Gujarat,
India.
Surat
GUJARAT |
9825137443
drtcshah@gmail.com |
| Dr Vaishal N Vora |
Ratandeep Multispeciality Hospital |
Ratandeep Multispecialty Hospital, Department of psychiatry, Room number 1, 2nd Floor Nakshatra Complex,
Above HDFC Bank,
Maninagar Cross Roads, Maninagar,
Ahmedabad- 380008, Gujarat,
India.
Ahmadabad
GUJARAT |
9825440891
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 |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
Schizophrenia, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Clozapine Tablets 100 mg
Manufactured by: Aurobindo Pharma Limited |
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 |
Leponex (Clozapine) 100 mg tablets
Manufactured by: Novartis Pharma GmbH 90327 Nürnberg |
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. Patient 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, Fifth Edition (DSM-V) criteria.
2. Patient with Body mass index between 18.5 to 30 kg/m2 (both inclusive) and aged between 18 to 60 years (both inclusive).
3. Patient is on for Clozapine therapy and has been taking a stable dose of Clozapine 100 mg twice daily for at least three months before enrolment in the study.
4. Patient having adequate hematologic reserve at screening as per principal investigator assessment.
5. Patient having adequate and stable hepatic function and renal function at screening as per principal investigator assessment.
6. Patient should have no clinically significant abnormality in any of the laboratory parameters including ECG and Chest X-ray as per the discretion of Principal Investigator.
7. Patient and Legally Acceptable Representative had given consent after being advised of the nature and risks of the study.
8. Female patient of childbearing potential must have a negative serum pregnancy test at screening.
9. Patient agreed to use acceptable methods of birth control as directed by study team. |
|
| 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 less than or equal to 2000 /mm3 or /microliter and WBC count less than or equal to 4000 /mm3 or /microliter.
3. Elderly patient with diagnosed dementia related psychosis.
4. Patient with medical or surgical condition that might interfere with the absorption, metabolism, or excretion of Clozapine or other study medications.
5. Patient with history of granulocytopenia or myeloproliferative disorder, either drug-induced or idiopathic.
6. Patient with history of clinically significant cardiovascular, renal, hepatic, respiratory, endocrine (except noninsulin-dependent diabetes mellitus), or gastrointestinal disease.
7. Patient found to be positive for HIV, HBs (Ag) or HCV.
8. Patient with history of epilepsy or seizures or are comatose or experiencing severe central nervous system depression.
9. Patient is unable to communicate with the investigator.
10. Patients with history of allergic reactions to Clozapine or chemically related psychotropic drugs.
11. Patients having concurrent neurological diagnosis, including mental retardation, severe tardive dyskinesia, or idiopathic Parkinson’s disease.
12. Patients who had undergone electroconvulsive therapy within the past one month.
13. Patient had demonstrated clinically significant homicidal behavior within the past 12 months.
14. Patient had received any investigational drug within the past 90 days.
15. Patient had history of narrow-angle glaucoma.
16. Patient with known history of phenylketonuria.
17. 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)
18. Patient with uncontrolled hypertension as per the discretion of PI
19. Patient is on concurrent use of other drugs known to suppress bone marrow function.
20. Patient had history of multiple syncopal episodes.
21. Patient is smoker and alcoholic.
22. Patient consumed grape fruit (mosumbi/sweet lime) juice within the 48 hours prior to study check-in.
23. Patient had history of difficulty with donating blood or difficulty in accessibility of veins |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
AUC0-τ: Area under the plasma concentration – time curve over the steadystate dosing interval.
Cmax-ss: Maximum concentration over the steady state dosing interval. |
Predose will be collected within 5 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 5 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 |
| Cmin-ss, Cavg-ss, Percentage fluctuation, Tmax-ss, Cpd (pre-dose concentration), Safety and tolerability |
Predose will be collected within 5 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 5 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 and safety assessment |
|
|
Target Sample Size
|
Total Sample Size="28"
Sample Size from India="28"
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)
|
08/09/2016 |
| 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="1"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
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 multicentric, open-label, 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 Leponex (Clozapine) 100 mg tablets of Novartis Pharma GmbH 90327 Nürnberg (Reference) in schizophrenic patients |