| CTRI Number |
CTRI/2017/10/009982 [Registered on: 03/10/2017] Trial Registered Prospectively |
| Last Modified On: |
17/11/2018 |
| Post Graduate Thesis |
No |
| Type of Trial |
BA/BE |
|
Type of Study
|
Bioequivalence Study in Patients |
| Study Design |
Randomized, Crossover Trial |
|
Public Title of Study
|
Bioequivalence Study of Two Formulations of Azathioprine USP 50 mg tablet in Adult Rheumatoid Arthritis Patients Under Fasting Condition. |
|
Scientific Title of Study
|
A Multicenter, Randomized, Open Label, Two Treatment, Two Period, Two Sequence, Single-Dose, Two-way, Crossover, Bioequivalence, Pilot Study to Evaluate the Bioequivalence of Azathioprine Tablets USP 50mg of RPG Life Sciences Compared to Imuran® 50 mg Tablets of Prometheus Laboratories Inc., USA in Adult Rheumatoid Arthritis Patients Under Fasting Condition |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| ARL/CT/ 17 /004 Version 01 Dated 28 June 2017 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Ajaykumar B Malle |
| Designation |
General Manager Clinical Development Services |
| Affiliation |
Accutest Research Laboratories (I) Pvt. Ltd. |
| Address |
Clinical Development Services Department
A-77, Khairne MIDC, TTC Industrial Area,
Khairne, Navi Mumbai
Mumbai
MAHARASHTRA
400709
India |
| Phone |
02227780718 |
| Fax |
02227780720 |
| Email |
ajay.malle@accutestglobal.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Ajaykumar B Malle |
| Designation |
General Manager Clinical Development Services |
| Affiliation |
Accutest Research Laboratories (I) Pvt. Ltd. |
| Address |
Clinical Development Services Department,
A-77, Khairne MIDC, TTC Industrial Area,
Khairne, Navi Mumbai
Mumbai
MAHARASHTRA
400709
India |
| Phone |
02227780718 |
| Fax |
02227780720 |
| Email |
ajay.malle@accutestglobal.com |
|
Details of Contact Person
Public Query
|
| Name |
Siddhesh Garge |
| Designation |
Clinical Project Manager |
| Affiliation |
Accutest Research Laboratories (I) Pvt. Ltd. |
| Address |
Clinical Development Services Department,
A-77, Khairne MIDC, TTC Industrial Area,
Khairne, Navi Mumbai
Mumbai
MAHARASHTRA
400709
India |
| Phone |
02227780718 |
| Fax |
02227780720 |
| Email |
Siddhesh.garge@accutestglobal.com |
|
|
Source of Monetary or Material Support
|
| RPG Life Sciences Ltd
463, 4th Floor, RPG HOUSE,
Dr. Annie Besant Road, Worli, Mumbai-400 030.
Maharashtra, INDIA
|
|
|
Primary Sponsor
|
| Name |
RPG Life Sciences Ltd |
| Address |
463, 4th Floor, RPG HOUSE,
Dr. Annie Besant Road, Worli, Mumbai-400 030.
Maharashtra, INDIA
|
| Type of Sponsor |
Pharmaceutical industry-Indian |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| Accutest Research Laboratories I Pvt Ltd |
A-77, Khairne MIDC, TTC Industrial Area,
Khairne, Navi Mumbai-400 709
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 2 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Gururaj Pramod |
Srikara Hospital |
Plot No. 50, LB Nagar, Ring Road, Hyderabad- 500074, Telangana
Hyderabad
ANDHRA PRADESH |
919908649700
drkgururaj@gmail.com |
| Dr Bharat Mody |
Wellcare Hospital |
Ground Floor,Near Mercedes Show Room, Atladara-Vadsar Ring Road, Atladara, Vadodara-390012
Vadodara
GUJARAT |
919824036065
912652309888
centreforkneesurgery@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 2 |
| Name of Committee |
Approval Status |
| Ethics Committee Centre For Knee Surgery |
Approved |
| SNR Galaxy Hospital Ethics Committee |
Submittted/Under Review |
|
|
Regulatory Clearance Status from DCGI
|
|
Health Condition / Problems Studied
Modification(s)
|
| Health Type |
Condition |
| Patients |
Rheumatoid Arthritis, (1) ICD-10 Condition: M059||Rheumatoid arthritis with rheumatoid factor, unspecified, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Azathioprine tablets USP 50 mg of RPG Life Sciences Ltd. |
One Tablet 50 mg once a day. Single Oral dose Study |
| Comparator Agent |
Imuran® 50 mg tablets of Prometheus Laboratories Inc., USA |
One Tablet 50 mg once a day. Single Oral dose Study |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
1.Men or Women, between 18 to 65 years of age (both inclusive) at the first time of signing of the informed consent.
2.Subject has understood and signed the informed consent form to participate in the study.
3.Confirmed diagnosis of rheumatoid arthritis according to American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) criteria 2010 set at least 6 months prior to screening Patients on maintenance therapy with single fixed dose of Azathioprine 50 mg per day with or without a fixed dose (maximum of 30 mg/week) of Methotrexate for at least 1 month.
4.Patients on maintenance therapy with single fixed dose of Azathioprine 50 mg per day with or without a fixed dose (maximum of 30 mg/week) of Methotrexate for at least 1 month.
5.Patients with prior/current use of corticosteroids usage can be enrolled provided they should be on/off 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. Patient’s screening laboratory assessment (complete blood count [CBC] and blood chemistries) are clinically non-significant as per the discretion of the Investigator.
6.Patients without 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.
7.Women of childbearing potential (include girls who have entered puberty and all women who have a uterus and ovaries and have not completed menopause wherein menopause is the permanent end of menstruation and fertility. Females who have 12 consecutive months of spontaneous amenorrhea (not induced by a medical condition or medical therapy) or have bilateral absence of ovaries (surgical or congenital) have completed menopause must have a negative serum pregnancy test at screening and negative urine pregnancy test on check in to housing, and must agree to use an adequate method of contraception.
8.Body mass index (BMI) between 18.0 kg/m2 to 30.0 kg/m2, both inclusive calculated as (weight in kg) / (height in m)2 and body weight of not more than 130 kg.
|
|
| ExclusionCriteria |
| Details |
1.Adult patients with RA on therapy with any other agent apart from twice daily dose of Azathioprine alone or along with use of NSAIDs, fixed low-dose glucocorticoids and/or fixed dose of Methotrexate
2.Patient with known low or absent TPMT activity.
3.Anemia with hemoglobin < 08 gm% (except when principal investigator feels it is secondary to disease activity/Methotrexate induced and in the best judgment of subject who is fit for phlebotomy blood loss as per protocol).
4.Females of childbearing potential unwilling to use adequate contraception (as defined in the protocol) throughout the trial and for one month after the last dose of study medication.
5.Males unwilling to use a male condom throughout the trial and for three months after the last dose of study medication
6.Pregnancy or expecting pregnancy or lactation within 6 months.
7.Patients with inadequate hepatic, renal and bone marrow function,
Bone marrow function ANC ≤ 1500/mm3 and WBC ≤ 4000/mm3 (should meet both)
Platelet count ≤ 100,000/mm3
Renal function Serum Creatinine ≥ 2 times ULN
Hepatic function Total Bilirubin ≥ 1.5 times ULN
ALT/AST ≥ 2 times ULN
Alkaline phosphatase ≥ 2 times ULN
8. Patients who have had 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 exclusion at the discretion of the investigator.
9.Patients who have had a non tuberculous mycobacterial infection or opportunistic infection (eg, cytomegalovirus, Pneumocystis carinii, aspergillosis) within 6 months prior to Screening.
10.Patients who have current signs and symptoms of systemic lupus erythematosus, or severe, progressive, or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac, neurologic, or cerebral diseases.
11.Patients who have a known history of demyelinating disease suggestive of multiple sclerosis or optic neuritis.
12.Patients who 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.
13.Patients with small bowel injury interfering significantly with resorptive area.
14.Patients with bone marrow suppression (platelets / leucocytes < 1 x lower normal level).
15.Patients with history of a known allergy/sensitivity to study drug or its excipients
16.Ongoing treatment with allopurinol, oxipurinol and thiopurinol and other xanthine oxidase inhibitors, thioguanineoraminosalicylate derivatives (e.g., olsalazine, mesalazine, or sulphasalazine), Infliximab, ACE-inhibitors, furosemide and ribavirin at the time of screening (> 7 days before first IP dosing) which cannot be stopped for study period.
17.Patients with other inflammatory diseases that might interfere with the evaluation of the RA.
18.Patients have presence of a transplanted organ (with the exception of a corneal transplant >3 months prior to screening).
19.Patients with 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).
20.Patients with any concomitant chemotherapy and prior exposure to doxorubicin.
21.Patients participating in any other clinical study or has received treatment with any investigational drug or device within 3 months prior to screening.
22.Use of any recreational drugs or history of drug addiction.
23.Patients with alcoholism, alcoholic liver disease or other chronic liver disease.
24.Patients who are diagnosed to be HIV or Hepatitis B (HBsAg) or Hepatitis C (HCV) virus reactive/positive.
25.Any other condition or abnormal findings that, in the investigator’s judgment, might increase the risk to the subject or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study.
26.Blood donation/ loss exceeding 200 mL within last 60 days prior to receiving the first dose of investigational product for the current study.
27.Demonstrates, in the opinion of study staff, veins unsuitable for repeated venipuncture (e.g. veins difficult to locate, access, or puncture; veins with a tendency to rupture during or after puncture).
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| To characterize the pharmacokinetic profiles of azathioprine and its metabolite 6-MP following a single dose of azathioprine 50 mg tablets under fasting condition and to assess the bioequivalence of azathioprine 50 mg tablets between the Test product and Reference product. |
The pre-dose blood sample (00.00) will be collected within 10 minutes before dosing on Day 1 and day 2. On day 1 & day 2, the post-dose blood samples will be drawn at 0.167, 0.333, 0.500, 0.666, 0.83,1.000, 1.500, 2.000, 2.500, 3.000, 3.500, 4.000, 5.000, 6.000, 8.000 & 12.000 hours following drug administration in each period |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| To monitor the safety and tolerability of azathioprine 50 mg tablets in adult patients, who are diagnosed to have RA and are presently receiving oral azathioprine 50 mg. |
Throughout the Study |
|
|
Target Sample Size
|
Total Sample Size="12"
Sample Size from India="12"
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)
|
16/10/2017 |
| 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)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
Not Applicable |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
RPG Life sciences Ltd has developed generic version of azathioprine 50 mg tablets. The present study aims to evaluate bioequivalence of Azathioprine tablets USP 50 mg, a test formulation against corresponding reference product, Imuran ® 50 mg tablets of Prometheus Laboratories Inc., USA, in adult patients, who are diagnosed to have rheumatoid arthritis (RA) and are presently being treated with azathioprine oral tablets.
Primary objective: To characterize the pharmacokinetic profiles of azathioprine and its metabolite 6-MP following a single dose of azathioprine 50 mg tablets under fasting condition and to assess the bioequivalence of azathioprine 50 mg tablets between the Test product and Reference product.
Secondary objective: To monitor the safety and tolerability of azathioprine 50 mg tablets in adult patients, who are diagnosed to have RA and are presently receiving oral azathioprine 50 mg. |