| CTRI Number |
CTRI/2018/04/013054 [Registered on: 05/04/2018] Trial Registered Prospectively |
| Last Modified On: |
20/09/2023 |
| Post Graduate Thesis |
No |
| Type of Trial |
BA/BE |
|
Type of Study
|
Clinical endpoint bio equivalent study |
| Study Design |
Randomized, Crossover Trial |
|
Public Title of Study
|
BA/BE study of clozapine 100 mg tablets in Patients with Schizophrenia under Fasting conditions. |
|
Scientific Title of Study
|
A Multicentric, Open Label, Randomized, Two-Treatment, Two-sequence, Two-period, Cross-over, Multiple dose, Steady-state Clinical Bioequivalence Study of Clozapine Tablets USP 100 mg of Alkem Laboratories Limited, India (Test) with CLOPINE® 100 mg (Clozapine) tablets, Hospira Australia Pty Ltd (Reference) in Patients with Schizophrenia under Fasting conditions. |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| CR181-17, Version 1.0, Amendment-01, Dated 26.02.2018 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Subhra Lahiri |
| Designation |
Associate Vice President |
| Affiliation |
AXIS Clinicals Ltd |
| Address |
AXIS Clinicals Ltd
1-121/1 Miyapur Hyderabad 500049
Telengana INDIA
AXIS Clinicals Ltd
1-121/1 Miyapur Hyderabad 500049
Telengana INDIA
Hyderabad
ANDHRA PRADESH
500049
India |
| Phone |
4040408060 |
| Fax |
4040408060 |
| Email |
Subhra.L@axisclinicals.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Subhra Lahiri |
| Designation |
Associate Vice President |
| Affiliation |
AXIS Clinicals Ltd |
| Address |
AXIS Clinicals Ltd
1-121/1 Miyapur Hyderabad 500049
Telengana INDIA
AXIS Clinicals Ltd
1-121/1 Miyapur Hyderabad 500049
Telengana INDIA
Hyderabad
ANDHRA PRADESH
500049
India |
| Phone |
4040408060 |
| Fax |
4040408060 |
| Email |
Subhra.L@axisclinicals.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Subhra Lahiri |
| Designation |
Associate Vice President |
| Affiliation |
AXIS Clinicals Ltd |
| Address |
AXIS Clinicals Ltd
1-121/1 Miyapur Hyderabad 500049
Telengana INDIA
AXIS Clinicals Ltd
1-121/1 Miyapur Hyderabad 500049
Telengana INDIA
Hyderabad
ANDHRA PRADESH
500049
India |
| Phone |
4040408060 |
| Fax |
4040408060 |
| Email |
Subhra.L@axisclinicals.com |
|
|
Source of Monetary or Material Support
|
|
|
Primary Sponsor
|
| Name |
Alkem Laboratories Ltd |
| Address |
C61 C62 MIDC Industrial Estate Taloja
Dist Raigad 410 208
Maharashtra India
Tel 91 22 2741 2731 2741 2732
|
| Type of Sponsor |
Pharmaceutical industry-Indian |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| AXIS Clinicals Ltd |
1 121/1 Miyapur Hyderabad 500049
Telangana INDIA
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 3 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Timir Shah |
Divyam Hospital |
block no. 84, Palsana
Cross Roads, National
Highway no-8, Surat- 394315,
Gujarat, India
Surat
GUJARAT |
9825137443
drtcshah@gmail.com |
| Dr Bakul Buch |
Hatkesh Healthcare Foundation |
Clinical Research Department,
opp, Bhutnath Temple,
College Road, Junagadh 362001,
Gujarat, India.
Junagadh
GUJARAT |
9825220330
bakulbuch@gmail.com |
| Dr Vaishal Vora |
Ratandeep Multispecialty Hospital |
Nakshatra,Complex,
above HDFC bank, Maninagar
Cross Roads, Maninagar- 380008,
Ahmedabad, Gujarat, India.
Ahmadabad
GUJARAT |
9825440891
ratandeepmsh@yahoo.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 3 |
| Name of Committee |
Approval Status |
| Divyam Hospital Ethical Review Board |
Approved |
| Ethics Committee Ratnadeep Multispecialty Hospital |
Approved |
| Hatkesh Healthcare Foundation Ethics Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
Schizophrenia, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
CLOPINE® 100 mg Clozapine tablets |
The study will consist of two period. Each eligible patient will receive either test or reference drug for 20 consecutive days under fasting condition |
| Intervention |
Clozapine Tablets USP 100 mg |
The study will consist of two period Each eligible patient will receive either test or reference drug for 20 consecutive days under fasting condition |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
55.00 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 55 years (both inclusive).
3.Patient is on for Clozapine therapy and has been taking a stable dose of Clozapine Tablets 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 ≤ 2000 /mm3 or /µL and WBC count ≤ 4000 /mm3 or /µL.
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, HBsAg 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. Patient with known history of 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.
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
AUC0Ï„ Area under the plasma concentration time curve over the steady state dosing interval.
Cmaxss Maximum concentration over the steady state dosing interval.
|
Venous blood samples 5 mL will be withdrawn within 5 minutes prior to dosing on Day 7 8 9 17 18 19 confirm steady state condition.
On Day 10 and Day 20 venous blood samples 5mL will be collected at 0.00 5 minutes prior to morning dose and 0.25 0.50 1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50 5.00 5.50 6.00 7.00 8.00 10.00 and 12.00
|
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
Cminss Minimum concentration over the steady state dosing interval.
Cavgss Average concentration over the steady state dosing interval.
Percentage fluctuation Cmaxss Cminss Cavgss 100
Tmaxss Time of maximum measured plasma concentration over the steady state dosing interval.
Cpd predose concentration Predose concentrations determined before a dose at steady state.
Safety and tolerability
|
Venous blood samples 5 mL will be withdrawn within 5 minutes prior to dosing on Day 7 8 9 17 18 19 confirm steady state condition.
On Day 10 and Day 20 venous blood samples 5mL will be collected at 0.00 5 minutes prior to morning dose and 0.25 0.50 1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50 5.00 5.50 6.00 7.00 8.00 10.00 and 12.00 |
|
|
Target Sample Size
|
Total Sample Size="48"
Sample Size from India="48"
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
|
Phase 1/ Phase 2 |
|
Date of First Enrollment (India)
|
16/04/2018 |
| 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="3"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
NONE YET |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
Brief Summary
Modification(s)
|
A Multicentric, Open Label, Randomized, Two-Treatment, Two-sequence, Two-period, Cross-over, Multiple dose, Steady-state Clinical Bioequivalence Study of Clozapine Tablets USP 100 mg of Alkem Laboratories Limited, India (Test) with CLOPINE® 100 mg (Clozapine) tablets, Hospira Australia Pty Ltd (Reference) in Patients with Schizophrenia under Fasting conditions. AUC0-τ: Area under the plasma concentration – time curve over the steady state dosing interval. Cmax-ss: Maximum concentration over the steady state dosing interval. Cmin-ss: Minimum concentration over the steady state dosing interval. Cavg-ss: Average concentration over the steady state dosing interval. Percentage fluctuation: [Cmax-ss – Cmin-ss / Cavg-ss] *100 Tmax-ss: Time of maximum measured plasma concentration over the steady state dosing interval. Cpd (pre-dose concentration)-Pre-dose concentrations determined before a dose at steady state. Safety and tolerability as assessed by reported adverse events, laboratory and clinical investigations, and vital signs |