Bioequivalence Study of Two Formulations of Azathioprine USP 50 mg tablet in Adult Rheumatoid Arthritis Patients Under Fasting Condition.
- Conditions
- Health Condition 1: null- Rheumatoid ArthritisHealth Condition 2: M059- Rheumatoid arthritis with rheumatoid factor, unspecified
- Registration Number
- CTRI/2017/10/009982
- Lead Sponsor
- RPG Life Sciences Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Yet Recruiting
- Sex
- Not specified
- Target Recruitment
- 0
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. Patientâ??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.
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 carcinom
Study & Design
- Study Type
- BA/BE
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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.Timepoint: 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 Measures
Name Time Method 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.Timepoint: Throughout the Study