CTRI

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CTRI Number

CTRI/2016/07/007065 [Registered on: 05/07/2016] Trial Registered Prospectively

Last Modified On:

24/11/2018

Post Graduate Thesis

Type of Trial

BA/BE

Type of Study

Study Design

Randomized, Crossover Trial

Public Title of Study

A bioequivalence study of clozapine tablet 100 mg twice daily (test drug) with ClozarilÂ® 100 mg tablets twice daily (reference drug, Novartis pharmaceuticals corporation, USA) in adult schizophrenic patients under fasting conditions.

Scientific Title of Study

A multicentric open label, balanced, randomized, two treatment, two-period, two-sequence, crossover, steady state bioequivalence evaluation of clozapine tablet 100 mg twice daily (test drug) with ClozarilÂ® 100 mg tablets twice daily (reference drug, Novartis pharmaceuticals corporation, USA) after multiple dose administration in adult schizophrenic patients under fasting conditions

Trial Acronym

Secondary IDs if Any

Secondary ID	Identifier
0207-16, Version: 1.0, Date: 12/04/2016	Protocol Number

Details of Principal Investigator or overall Trial Coordinator (multi-center study)

Name	Mr Srinivasa Rao
Designation	Project Manager
Affiliation	Lambda Therapeutic Research Ltd
Address	Plot No. 38, Near Silver Oak Club S. G. Highway, Gota Ahmadabad GUJARAT 380061 India
Phone	07940202570
Fax	07940202021
Email	srinivasarao@lambda-cro.com

Details of Contact Person
Scientific Query

Name	Dr Dimple Shah
Designation	Assistant General Manager
Affiliation	Lambda Therapeutic Research Ltd
Address	Plot No. 38, Near Silver Oak Club S. G. Highway, Gota Ahmadabad GUJARAT 380061 India
Phone	07940202357
Fax	07940202021
Email	dimpleshah@lambda-cro.com

Details of Contact Person
Public Query

Name	Dr Kaksha Patel
Designation	Asst. Manager
Affiliation	Lambda Therapeutic Research Ltd
Address	Plot No. 38, Near Silver Oak Club S. G. Highway, Gota Ahmadabad GUJARAT 380061 India
Phone	07940202353
Fax	07940202021
Email	kakshajpatel@lambda-cro.com

Source of Monetary or Material Support

Prinston Pharmaceutical Inc. 2002 Eastpark Blvd, Cranbury, NJ 08512, USA. Tel#: 001-609-655-1688 Fax#: 001-609-642-6927

Primary Sponsor

Name	Prinston Pharmaceutical Inc
Address	2002 Eastpark Blvd, Cranbury, NJ 08512, USA. Tel#: 001-609-655-1688 Fax#: 001-609-642-6927
Type of Sponsor	Pharmaceutical industry-Global

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	D.P.M. M.D Phychiatry, Divyam Hospital, Department of Psychiatry, Block No. 84, Palsana Cross Road, National Highway No-8, Surat-394315 Surat GUJARAT	9825137443 divyamhospital@gmail.com
Dr Sam P J	Elite Mission Hospital	P. B. No. - 1414, Division of Psychiatry, Room no. NA (As it is a private hospital), Koorkkenchery P. O., Thrissur - 680007 Thrissur KERALA	07736020004 eliteh.cr@gmail.com
Dr Vemireddy Radhika Reddy	General Hospital, (Associated by Govt. Siddhartha Medical College)	Professor & HOD, Department of Psychiatry, Room no. NA (Only wards are available), Old Govt. General Hospital, (Associated by Govt. Siddhartha Medical College), Hanumanpet, Two Town, Vijayawada-520002 Krishna ANDHRA PRADESH	9848229798 researchsmcggh14@gmail.com
Dr Vipul Singh	GSVM Medical College	Department of Psychiatry, Room no. NA (Only wards are available), GSVM Medical College, Swaroop Nagar, Nagar, Kanpur-208002 Kanpur Nagar UTTAR PRADESH	07052153899 drvipulsingh.research@gmail.com
Dr Bakul Chandrakant Buch	Hatkesh Healthcare Foundation	Opp. Bhutnath Temple, Department of Psychiatry, Room no. NA (As it is a private hospital), Junagadh-362001 Junagadh GUJARAT	9825220330 bakulbuch@gmail.com
Dr Mahesh Chudgar	Mental Illness Treatment Rehabilization (MITR) Foundation	Shantinagar Society, Way to CCD gully, Department of Psychiatry, Room no. NA (As it is a Foundation) Ashram Road, Ahmedabad - 380013 Ahmadabad GUJARAT	9825412109 mahesh_mitr@yahoo.co.in
Dr Vaishal Vora	Ratandeep Multispeciality Hospital	2nd floor, Division of Psychiatry, Room no. NA (As it is a private hospital), Nakshatra Complex, Above HDFC Bank, Maninagar Cross Roads, Maninagar-380008 Ahmadabad GUJARAT	9825440891 vnvora@gmail.com
Dr Kamal Kumar Verma	S P. Medical College & AG of Hospitals	DIMHANS, Department of Psychiatry, Room no. NA (Only wards available), S P. Medical College & AG of Hospitals-334003 Bikaner RAJASTHAN	9782300231 shekhar@sairamresearch.com
Dr Anoop Vincent	Sree Narayana Institute of Medical Sciences	Division of Psychiatry, Sree Narayana Institute of Medical Sciences, Room no. NA (As it is a private hospital), Chalakka, North Kuthiyathodu P.O, Ernakulam - 683594 Ernakulam KERALA	9717477417 research.snims@gmail.com
Dr Umesh Sureshrao Nagapurkar	Sujata Birla Hospital & Medical Research Center	Department of Psychiatry, 3rd Floor, Room No. NA (Only wards are available), Opp. BYTCO College, Nasik Road, Nasik - 422101 Nashik MAHARASHTRA	9823146088 umeshanjali@gmail.com

Details of Ethics Committee
Modification(s)

No of Ethics Committees= 5
Name of Committee	Approval Status
Divyam Hospital Ethical Review Board, Dr. Timir Shah	Approved
Ethics Committee, S P. Medical College & AG of Hospitals, Dr. Kamal Kumar Verma	Approved
Institutional Ethics Commiittee, Mental Illness Treatment Rehabilization (MITR) Foundation, Dr. Mahesh Chudgar	Approved
Institutional Ethics Commiittee, Siddhartha Medical College & Govt. General Hospital, Dr. Vemireddy Radhika Reddy	Approved
Yash Society Institutional Ethics Commiittee, Dr. Umesh Sureshrao Nagapurkar	Approved

Regulatory Clearance Status from DCGI

Status

Approved/Obtained

Health Condition / Problems Studied
Modification(s)

Health Type	Condition
Patients	(1) ICD-10 Condition: F209\|\|Schizophrenia, unspecified,

Intervention / Comparator Agent

Type	Name	Details
Intervention	Clozapine 100 mg tablet of Prinston Pharmaceutical Inc., USA	Dose: 100 mg; Frequency: twice daily; Mode of Administration: Per oral; Duration of treatment: 10 days
Comparator Agent	ClozarilÂ® of Novartis Pharmaceuticals Corporation, USA	Dose: 100 mg; Frequency: twice daily; Mode of Administration: Per oral; Duration of treatment: 10 days

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 Patientâ€™s Legally Acceptable Representative (LAR). 2. Patient has a documented clinical diagnosis of schizophrenia according to DSM IV-TR 3. Patients have a diagnosis of treatment-resistant schizophrenia 4. Male or female patients between 18 and 60 years of age 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. Patients have been on a daily stable dose of 200 mg clozapine formulation 8. Able to comply with study procedures in the opinion of the investigator. 9. Both male and female patients of child bearing potential must be practicing adequate contraception.Female patients of child-bearing potential must not be orlikely to be pregnant or lactating and must have a negative serum pregnancy test at screening and negative urine pregnancy test at randomization.

ExclusionCriteria

Details

1. Patient with known hypersensitivity/ intolerance to clozapine or any other component of the drug.

2. Clinically symptomatic orthostatic hypotension

3. Concurrent use of antihypertensive medication or any medication that might pre-dispose to orthostatic hypotension.

4. Concurrent primary psychiatric or neurological diagnosis (except schizophrenia), including organic mental disorder, severe tardive dyskinesia, or idiopathic Parkinsonâ€™s disease.

5. A history of granulocytopenia or myeloproliferative disorders (drug-induced or idiopathic).

6. A medical or surgical condition that might interfere with the absorption, metabolism, or excretion of clozapine.

7. Known case of poor metabolizer individuals with reduced activity of cytochrome P450 enzymes particularly, 1A2, 2D6 and 3A4.

8. Smokers who smoke 10 or more than 10 cigarette/day or inability to abstain from smoking during the study.

9. Positive tests for drug or alcohol abuse

10. A history of alcohol or drug dependence during the 6-month period immediately prior to study entry

11. Donation of blood (1 unit or 350 ml) within 90 days prior to receiving the first dose of study medication or during the study.

12. 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.

13. A positive hepatitis screen including hepatitis B surface antigen, HCV.

14. Known case of HIV infection.

15. Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others.

16. Presence of glaucoma

17. History of clozapine induced agranulocytosis or severe granulocytopenia

18. Patient with hyperprolactinemia

19. Concurrent use of other drugs known to suppress bone marrow function

Method of Generating Random Sequence

Computer generated randomization

Method of Concealment

Not Applicable

Blinding/Masking

Open Label

Primary Outcome

Outcome	TimePoints
Cmax,ss and AUC0-T,ss	Day 10 and Day 20

Secondary Outcome

Outcome	TimePoints
Incidence of drug related Adverse Events as assessed by clinical examination, vitals and/or laboratory parameters for both the treatments	Day 1 to Day 20

Target Sample Size

Total Sample Size="38"
Sample Size from India="38"
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)

12/07/2016

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="0"
Months="6"
Days="0"

Recruitment Status of Trial (Global)

Not Applicable

Recruitment Status of Trial (India)

Not Yet Recruiting

Publication Details

Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?

Brief Summary

The Sponsor has developed tablet formulation of clozapine. As a high number of healthy subjects experienced serious adverse effects after administration of antipsychotics such as hypotension, tachycardia etc., regulatory authorities recommend that pharmacokinetic study of clozapine should be conducted on schizophrenic patients. The objective of the present study is to assess and compare the bioavailability and to characterize the pharmacokinetic profile of the Sponsorâ€™s formulation (Clozapine tablet 100 mg, twice daily) with respect to the reference formulation (ClozarilPrinston Pharmaceutical Inc., USA or Clozaril^Â®of Novartis Pharmaceuticals Corporation, USA, 100 mg tablets twice daily) in schizophrenic patients stabilized on clozapine 200 mg per day under fasting condition. Through this study, we will prospectively collect the data from adult schizophrenic patients who will be randomly assigned to receive either clozapine 100 mg tablet of ^Â®(Novartis Pharmaceuticals Corporation, USA) for the pharmacokinetic profiling.