| CTRI Number |
CTRI/2010/091/000303 [Registered on: 04/06/2010] |
| Last Modified On: |
04/03/2013 |
| Post Graduate Thesis |
No |
| Type of Trial |
BA/BE |
Type of Study
Modification(s)
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| Study Design |
Randomized, Crossover Trial |
Public Title of Study
Modification(s)
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Azathioprine Bioequivalence study in Rheumatoid Arthritis |
Scientific Title of Study
Modification(s)
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An Open label, balanced, randomized, multicentre, multiple-dose, two-period, two-treatment, two-sequence, steady state, crossover comparative
bioequivalence study of two formulations of Azathioprine in adult
patients with Rheumatoid Arthritis (RA)
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| Trial Acronym |
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Secondary IDs if Any
Modification(s)
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| Secondary ID |
Identifier |
| Sponsor Protocol Number: 1356002, Study Code: ARL/CT/09/002 |
Other |
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)
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| Name |
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| Designation |
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| Affiliation |
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| Address |
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| Phone |
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| Fax |
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| Email |
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Details of Contact Person
Scientific Query
Modification(s)
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| Name |
Atul Solankar |
| Designation |
Vice President |
| Affiliation |
Regulatory Affairs & Corporate Quality Assurance |
| Address |
Accutest Research Laboratories (I) Pvt. Ltd
A-31, MIDC, TTC Industrial Area
Mumbai
MAHARASHTRA
400709
India |
| Phone |
02227780718 |
| Fax |
02227780720 |
| Email |
atul.solankar@accutestindia.com |
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Details of Contact Person
Public Query
Modification(s)
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| Name |
Atul Solankar |
| Designation |
Vice President |
| Affiliation |
Regulatory Affairs & Corporate Quality Affairs |
| Address |
Accutest Research Laboratories (I) Pvt. Ltd
A-31, MIDC, TTC Industrial Area
Mumbai
MAHARASHTRA
400709
India |
| Phone |
02227780718 |
| Fax |
02227780720 |
| Email |
atul.solankar@accutestindia.com |
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Source of Monetary or Material Support
Modification(s)
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| Orion Pharma, Orion Corporation, Finland |
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Primary Sponsor
Modification(s)
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| Name |
Orion Pharma |
| Address |
Orion Corporation, Finland |
| Type of Sponsor |
Pharmaceutical industry-Global |
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Details of Secondary Sponsor
Modification(s)
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Countries of Recruitment
Modification(s)
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India |
Sites of Study
Modification(s)
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| No of Sites = 4 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Kalpesh Trivedi |
AASTHA Arthoscopy & Joint Clinic |
201, Second Floor, Karnavati Hospital,Building, Opp. Town Hall, Ellisbridge,-380006
Ahmadabad
GUJARAT |
07926578558
07926578558
arthroscopist@hotmail.com |
| Dr. Saranjeet Singh |
Dept. of Orthopaedic |
Shree Krishna Hospital & Medical Research center,,Gokal Nagar-388325
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02692228591
02692228591
saranhand@yahoo.com |
| Dr. Rajiv Daveshwar |
HOD Department of orthopedics |
S. S. G. Hospital & Medical Collage,-390 001
Vadodara
GUJARAT |
02652711275
02652711275
dr_rndaveshwar@yahoo.com |
| Dr Nilesh Jagtap |
Royal Hospital |
Pune-Satara Road,Katraj-411046
Pune
MAHARASHTRA |
02024374466
nileshrjagtap@gmail.com |
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Details of Ethics Committee
Modification(s)
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| No of Ethics Committees= 4 |
| Name of Committee |
Approval Status |
| Human Research Ethics Committee |
Approved |
| Institutional Ethics Committee for Human Research (IECHR), Medical College & SSG Hospital, Baroda |
Approved |
| Mahalasa Independent Ethics Committee |
Approved |
| SIDDHANT Independent Ethics Committee |
Approved |
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Regulatory Clearance Status from DCGI
Modification(s)
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Health Condition / Problems Studied
Modification(s)
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| Health Type |
Condition |
| Patients |
Rheumatoid Arthritis , |
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Intervention / Comparator Agent
Modification(s)
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| Type |
Name |
Details |
| Intervention |
Azathioprine 50 mg tablets manufactured by Orion Pharma, Finland |
One tablet twice a daily with 240 ml of water |
| Comparator Agent |
Imuran(R)50 mg Tablet manufactured for Prometheus Laboratories Inc. USA |
One tablet twice daily with 240 ml of water |
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Inclusion Criteria
Modification(s)
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| Age From |
18.00 Year(s) |
| Age To |
55.00 Year(s) |
| Gender |
Both |
| Details |
1. Adult patients, aged between 18 and 55 years (both inclusive) with acceptable BMI
2. RA patients on maintenance therapy with twice daily 50 mg oral Azathioprine with or without a fixed dose (maximum of 30 mg/week) of Methotrexate.
OR
Having moderate to aggressive disease stage, as per American Rheumatism Association defined by the presence of at least 3 of the following criteria:
(a) tenderness of more than 6 joints
(b) swelling of more than 3 joints
(c) morning stiffness longer than 45 minutes
(d) articular index greater than 20
(e) ESR greater than 28 mm/h.
3. As per discretion of Principal Investigator, CRP, ANTI-CCP antibodies
& RA factor done within 6 months of screening or at screening
suggestive of active Rheumatoid arthritis
4. Is subject off corticosteroids or on a stable dose of corticosteroid for at least 2 weeks prior to enrollment. The maximal daily dose of corticosteroid at Baseline must not exceed the equivalent of 10 mg of prednisone.
5. Is subject free of any clinically significant condition or situation, other than RA that, in the opinion of the investigator, would interfere with the study evaluations or optimal participation in the study.
6. Are the Liver and kidney function (ALT /AST/ AP / creatinine < 2 x upper normal limit).
7. Are the Subject?s Screening and Baseline clinical laboratory tests (complete blood count [CBC] and blood chemistries) within acceptable ranges.
8. Subjects are willing and able to adhere to the study visit schedule and other protocol requirements as evidenced by a written informed consent.
9. If the subject is a woman of child-bearing potential or a man, is he/she agreeing to use a medically accepted method of contraception prior to screening, while receiving protocol-specified medication, and for 6 months after stopping the medication.
10. For female subjects of childbearing potential is serum pregnancy test (beta-HCG) negative.
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| ExclusionCriteria |
| Details |
1. Is the subject on therapy with any other agent apart from twice daily dose of Azathioprine alone or alongwith use of NSAIDs, fixed low-dose glucocorticoids and/or fixed dose of Methotrexate Anemia (hemoglobin < 08 gm %).
2. Does the subject have Anemia (hemoglobin < 08 gm %).
3. Does the patient have with low or absent TPMT activity (<5.5 unit)
4. Does the patient have bone marrow suppression (platelets / leucocytes < 1 x lower normal level).
5. Did the patient have any small bowel surgery interfering significantly with resorptive area.
6. Is subject concomitantly using allopurinol, ACE-inhibitors or furosemide.
7. Is the patient pregnanct or expecting pregnancy or lactation within 6 months.
8. Does the subject have a history of a known allergy/sensitivity to study drug or its excipients
9. Did subject have serious infections (eg, active hepatitis, pneumonia, or pyelonephritis) within 2 months of screening. (Less serious infections (such as acute upper respiratory tract infection [colds] or a simple urinary tract infection) need not be considered as an exclusion at the discretion of the investigator)
10. Did subjects have a nontuberculous mycobacterial infection or opportunistic infection (eg, cytomegalovirus, Pneumocystis carinii, aspergillosis) within 6 months prior to Screening
11. Subjects who have a known infection with human immunodeficiency virus (HIV) and/or hepatitis B or hepatitis C
12. Does the subject have current signs and symptoms of systemic lupus erythematosus, or severe, progressive, or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac, neurologic, or cerebral diseases.
13. Does the subject have a known history of demyelinating disease suggestive of multiple sclerosis or optic neuritis.
14. Does the subject have presence of a transplanted organ (with the exception of a corneal transplant >3 months prior to screening).
15. Does the subject have a history of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (eg, nodes in the posterior triangle of the neck, infra-clavicular, epitrochlear, or periaortic areas), or splenomegaly.
16. Does the subject have any current known malignancy or malignancy within 5 years prior to screening (except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence).
17. Does the subject have poor tolerability of venipuncture or lack of adequate venous access for required blood sampling during the study period.
18. Does the subject have a known substance abuse or dependency (drug or alcohol) within 3 years of Screening
19. Does the subject have other inflammatory diseases that might interfere with the evaluation of the Rheumatoid Arthritis.
20. Does the subject have a history of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis, prior to Screening.
21. Has the subject received any specified prohibited treatment more recently than the indicated washout period prior to Screening
22. Is the subject participating in any other clinical study or has received treatment with any investigational drug or device within 3 months prior Screening
23. Is the subject part of the staff or a family member of the staff personnel directly involved with this study.
24. Does the subject have any other condition that, in the investigator?s judgment, might increase the risk to the patient or decrease the chance of obtaining satisfactory information needed to achieve the objectives of the study
25. Does the subject have any abnormal baseline findings considered by the investigator to indicate conditions that might affect study endpoints.
Note: If the patient has participated in a study in which blood loss is ≥ 200 mL, patient can be dosed only after completion of 60 days from the previous study.
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Method of Generating Random Sequence
Modification(s)
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Computer generated randomization |
Method of Concealment
Modification(s)
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Not Applicable |
Blinding/Masking
Modification(s)
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Open Label |
Primary Outcome
Modification(s)
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| Outcome |
TimePoints |
| Bioequivalence will be established if the estimated 90% confidence intervals of the ratio (test/reference) of AUCtau and Cmaxss will be within the acceptance range. The acceptance range for bioequivalence is 80-125%, unless the intra-subject CV turns out to be more than 30% (i.e., Azathioprine and 6 Mercaptopurine highly variable) then the acceptance range for Cmaxss is 75-133%. |
pre-dose, 10 min, 20 min, 30 min, 40 min, 50 min, 1 hr, 1 hr 15 min, 1 hr 30 min, 1 hr 45 min, 2 hr, 3 hr, 5 hr, 8 hr and 12 hr |
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Secondary Outcome
Modification(s)
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| Outcome |
TimePoints |
| To assess the safety of Azathioprine in the adult patients with Rheumatoid Arthritis (RA) |
Safety parameters like Physical examination, ECG (screening and post study) adverse events, vital signs, will be recorded in the study |
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Target Sample Size
Modification(s)
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Total Sample Size="40"
Sample Size from India="40"
Final Enrollment numbers achieved (Total)= ""
Final Enrollment numbers achieved (India)="" |
Phase of Trial
Modification(s)
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Phase 1 |
Date of First Enrollment (India)
Modification(s)
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07/04/2010 |
| Date of Study Completion (India) |
Date Missing |
| Date of First Enrollment (Global) |
07/04/2010 |
| Date of Study Completion (Global) |
Date Missing |
Estimated Duration of Trial
Modification(s)
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Years="0"
Months="7"
Days="11" |
Recruitment Status of Trial (Global)
Modification(s)
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Completed |
| Recruitment Status of Trial (India) |
Completed |
Publication Details
Modification(s)
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Nil |
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Individual Participant Data (IPD) Sharing Statement
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Will individual participant data (IPD) be shared publicly (including data dictionaries)?
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Brief Summary
Modification(s)
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This study is An Open label, balanced, randomized, multicentre, multiple-dose, two-period, two-treatment, two-sequence, steady state, crossover comparative bioequivalence study of two formulations of Azathioprine in adult patients with Rheumatoid Arthritis (RA) To assess and compare the steady-state pharmacokinetics of an oral formulations of Azathioprine (test product) in comparison with oral formulations of Azathioprine (reference product) in adult patients with Rheumatoid Arthritis (RA). To assess the safety of Azathioprine in the adult patients with Rheumatoid Arthritis (RA). Total 40 patients will be enrolled in the study. |