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CTRI Number  CTRI/2022/09/045447 [Registered on: 12/09/2022] Trial Registered Prospectively
Last Modified On: 15/03/2023
Post Graduate Thesis  No 
Type of Trial  BA/BE 
Type of Study    
Study Design  Other 
Public Title of Study   Two treatment Bioequivalence study of Methotrexate 2.5 mg in patients with Rheumatoid Arthritis (RA). 
Scientific Title of Study   A multicenter, randomized, open label, two treatment, two period, two sequence, single-dose, crossover, bioequivalence study of Methotrexate Tablets 2.5 mg (manufactured by Elite Pharmaceuticals) with Methotrexate Tablets 2.5 mg (Distributed by West-Ward Pharmaceuticals Corp. Eatontown, NJ 07724) in patients with Rheumatoid Arthritis (RA), who are already on established regimens of 2.5 mg every 12 hours under fasting condition. 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
21-VIN-0292 Version 3 dated 25 May 2022  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Sumit Arora 
Designation  Vice President Clinical Operations 
Affiliation  Veeda Clinical Research Ltd 
Address  Veeda Clinical Research Ltd., Shivalik Plaza, Near I.I.M., Ambawadi, Ahmedabad – 380 015, India

Ahmadabad
GUJARAT
380015
India 
Phone  07930013000  
Fax    
Email  Sumit.arora@veedacr.com  
 
Details of Contact Person
Scientific Query  
Name  Dr Ravi Alamchandani 
Designation  General Manager 
Affiliation  Veeda Clinical Research Ltd 
Address  Veeda Clinical Research Ltd., Shivalik Plaza, Near I.I.M., Ambawadi, Ahmedabad – 380 015, India

Ahmadabad
GUJARAT
380015
India 
Phone  07930013000  
Fax    
Email  Ravi.A1950@veedacr.com  
 
Details of Contact Person
Public Query  
Name  Dr Ravi Alamchandani 
Designation  General Manager 
Affiliation  Veeda Clinical Research Ltd 
Address  Veeda Clinical Research Ltd., Shivalik Plaza, Near I.I.M., Ambawadi, Ahmedabad – 380 015, India

Ahmadabad
GUJARAT
380015
India 
Phone  07930013000  
Fax    
Email  Ravi.A1950@veedacr.com  
 
Source of Monetary or Material Support  
Elite Pharmaceuticals 165 Ludlow Ave. Northvale, NJ 07647. Tel. No.: 201-367-7879 Fax No.: 201-750-2755  
 
Primary Sponsor  
Name  Elite Pharmaceuticals 
Address  165 Ludlow Ave. Northvale, NJ 07647 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
Veeda Clinical Research Limited  Shivalik Plaza, Near IIM, Aambawadi, Ahmedabad 380015, Gujarat , India 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 4  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Sunil Maheshwari  Amena Khatun Multi Specialty Hospital  Sarkhej Road, Ahmedabad-380055.
Ahmadabad
GUJARAT 		 9898983555

drsunilmaheshwari10@gmail.com 
Dr Neelana Gowda VP Patil  K R Hospital, Mysore Medical college and Research Institute  Dept. of Orthopedics,Irwin road, Mysore 570001 Karnataka India
Mysore
KARNATAKA 		 9886701888

drneelanpatil@gmail.com 
Dr Neel Bhavsar  Netaji Polyclinic  Block #50, Meghaninagar last bus stop, meghaninagar, Ahemdabad-382475
Ahmadabad
GUJARAT 		 9638040954

neelbhavsarpi@gmail.com 
Dr Liyakat Ali Gauri  S P Medical College and AG of Hospitals  Bikaner Rajasthan 334003
Bikaner
RAJASTHAN 		 01512226300

drliyakatgauri@rediffmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 4  
Name of Committee  Approval Status 
Amena Khatun Hospital Ethics Committee  Approved 
ETHICS COMMITTEE, S P MEDICAL College  Approved 
IEC- Mysore Medical College and Research Institute and Associated Hospital  Approved 
Parth Hospital Institutional Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI
Modification(s)  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: M069||Rheumatoid arthritis, unspecified,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Methotrexate Tablets 2.5 mg of West-Ward Pharmaceuticals Corp. Eatontown, NJ 07724  Single dose of Methotrexate 2.5 mg tablet as per randomization schedule 
Intervention  Methotrexate Tablets 2.5 mg of Elite Pharmaceuticals, USA  Single dose of Methotrexate 2.5 mg tablet as per randomization schedule. 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  65.00 Year(s)
Gender  Both 
Details  1. Male and female patient with age of 18-65 years (both inclusive)
2. Body mass index (BMI) between 18.5 and 30 kg/m² (both inclusive)
3. Patients with active rheumatoid arthritis diagnosed according to the revised 2010 American College of Rheumatology (ACR) criteria for the classification of rheumatoid arthritis who are receiving methotrexate therapy.
4. Patients must be on an established dose of methotrexate 2.5 mg 12 hourly for 3 doses per week for ≥ 28 Days prior to screening
5. Patient meets the ACR 1991 revised criteria for RA Global Functional Status I or II.
6. Patient on other medications (excluding MTX) for the treatment of RA should have discontinued these medications at least 28 Days or 5 half-lives of the drug (whichever is longer) before screening.
7. No history of addiction to any recreational drug or drug dependence
8. Patient must be able to give informed consent for participation in the trial.
9. Male patients must agree to use a male condom throughout the study and for a minimum of 3 months after the end of therapy.
10. Serum pregnancy test at screening and urine pregnancy test at check-in must be negative for female patients
11. Women of child bearing potential, unless surgically sterile (with documented evidence of hysterectomy / bilateral salpingectomy / bilateral oophorectomy at least 6 months prior to Study drug administration) or postmenopausal for at least 12 consecutive months, must have negative pregnancy test at screening visit and before randomization and must agree to 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 the study and up to 6 months after the last dose of study drug. Cessation of birth control after this point should be discussed with a responsible physician.
 
 
ExclusionCriteria 
Details  1. A history of allergic or adverse reactions to Methotrexate Sodium or any related drug or any excipient of methotrexate tablets
2. Patients with presence of any neoplasm or with past history of any neoplasm
3. Patients who have pre-existing hematopoietic impairment/ blood dyscrasias, such as bone marrow hypoplasia, aplastic anemia, pancytopenia, leukopenia, neutropenia, thrombocytopenia and or significant anemia
4. History of peptic ulcer disease or ulcerative colitis, or any other gastrointestinal disorder or defect that would interfere with the absorption of the study drug and/or predispose the subject to an increased risk of gastrointestinal toxicity.
5. Patient with lymphadenopathy and lymphoproliferative disorders
6. Patients suffering from any acute infection within two weeks prior to randomization
7. Patients with history of tumor lysis syndrome.
8. Patient had major surgery within 4 weeks prior to study entry, or who have not recovered from prior major surgery
9. History of difficulty with donating blood or difficulty in accessibility of veins
10. Patient with liver enzyme test abnormalities, aspartate aminotransferase (AST), alanine aminotransferase (ALT) or total bilirubin > 2 times the upper limit of normal (ULN)
11. Patient positive on Breath alcohol analyzer test at the time of baseline visit.
12. Positive for drugs of abuse prior to receiving the first dose of investigational medicinal product in the study.
13. Patients with presence or previous history of clinically significant systemic disease which might confound the results of the study or pose an additional risk in administering study drug(s) to the patient at the discretion of investigator. This may include, but not be limited to, a history of drug or food allergies, uncompensated heart failure, uncontrolled diabetes mellitus, severe hepatic failure, severe pulmonary disease, or history of mental disease and patients with alcoholic liver disease or other chronic liver disease.
14. Patients for whom oral administration of drug is not possible.
15. Patients who have overt or laboratory evidence of immunodeficiency syndromes.
16. Patients found positive for HIV, Syphilis, Hepatitis B surface antigen or Hepatitis C antibody at screening.
17. Pregnant or lactating females.
18. Donation of blood (1 unit or 350 ml) within 90 Days prior to receiving the first dose of investigational medicinal product for the current study.
19. Expected changes in concomitant medications during the period of study
20. Have ongoing clinically significant adverse event(s) due to prior treatments administered, as determined by the investigator.
21. In the opinion of the Investigator, the patient will not be compliant with the requirements of the study procedures.
22. Receipt of an investigational medicinal product or participation in an other drug research study within 30 Days (or 5 half-lives, whichever is longer) prior to receiving the first dose of investigational medicinal product for the current study.
Note: Elimination half-life of the study drug should be taken in to consideration for inclusion of the patient in the study.
23. Any surgical/medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drug, or which may jeopardize the patient in case of participation in the study.
24. Patients with any uncontrolled medical condition or active infection, etc or any abnormal laboratory findings
25. Patients with creatinine clearance < 60 mL/min (calculated based on Cockcroft-Gault formula).
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Not Applicable 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
To assess the pharmacokinetics and establish bioequivalence of the sponsor’s Test Product.  In each period total 22 venous blood samples of 04 ml will be withdrawn at Pre-dose (0.0 hour) & at 0.167,0.250,0.500, 0.750,1.0,1.250,1.5, 1.750,2.0,2.333,2.667, 3.0,3.5,4.0,4.5,5.0,6.0,7.0,8.0,10.0 and 12.00 hours post-dose after first-dose administration in each period.
Pre-dose sample will be collected within 5 minutes prior to drug administration
 
 
Secondary Outcome  
Outcome  TimePoints 
To monitor the adverse events and to ensure the safety of the patients.  Vital, ECG, Physical Examinations, Laboratory evaluations, and adverse event monitoring. 
 
Target Sample Size   Total Sample Size="48"
Sample Size from India="48" 
Final Enrollment numbers achieved (Total)= "48"
Final Enrollment numbers achieved (India)="48" 
Phase of Trial   N/A 
Date of First Enrollment (India)   12/09/2022 
Date of Study Completion (India) 19/11/2022 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="0"
Months="7"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Completed 
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)?  

Response - NO
Brief Summary   The study consist of 2 period, each patient will receive either a Test or Reference product (Methotrexate 2.5  mg- IMP) in crossover manner based on randomization schedule.

The dosing schedule as follow;

Period 1 (Day 1): 

On Day 0, patient will be asked to reach the site atleast 12 hours prior to schedule dosing on Day 1. Patient will be administered IMP on Day 1 under supervision of trained study staff. The patient will be advised to take two subsequent doses of the locally approved drug as per institutional practice at 12 hours (±10 minutes) of interval after the administration of study drug on Day 1. Patient will be discharged after administering the third dose (Non-IMP product) on Day 2.

There will be a washout period of at least 7 Days between first dosing (IMP administration) in both the period.

In period II:

Patient will be crossed over to other investigational product (allocated as per randomization schedule) on Day 8 and will be asked to reach the site at least 12 hours prior to schedule dosing on Day 8. Patient will be discharged after administering the third dose (Non-IMP product) on Day 9.

In both period,

A total of 44 blood samples each of 04 mL will be collected from each patient for PK assessment during the study.

The venous blood samples will be withdrawn at Pre-dose (0.000 hour) and at 0.167, 0.250, 0.500, 0.750, 1.000, 1.250, 1.500, 1.750, 2.000, 2.333, 2.667, 3.000, 3.500, 4.000, 4.500, 5.000, 6.000, 7.000, 8.000, 10.000 and 12.000 hours post-dose after first-dose administration in each period.

Pre-dose sample will be collected within 5 minutes prior to drug administration.
 
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