Pharmacokinetic study of two formulations of Azathioprine Tablets 50 mg in Adult Subjects with Rheumatoid Arthritis.
Completed
- Conditions
- Rheumatoid Arthritis under Fasting Conditions.
- Registration Number
- CTRI/2018/07/014995
- Lead Sponsor
- Alkem Laboratories Ltd
- Brief Summary
A Randomized, Open-Label, Two-Period, Two-Treatment, TwoSequence, Crossover, Multicenter, Single-Dose, Bioequivalence Study of Azathioprine Scored Tablets 50 mg of Alkem Laboratories Limited and ‘IMURAN®’ (Azathioprine) Scored Tablets 50 mg of Prometheus Laboratories Inc., USA in Adult Subjects with Rheumatoid Arthritis under Fasting Conditions.
64 subjects will be required to be enrolled (randomized) in the study for approx. 60 days that includes screening period and treatment period.
The end of the study will be the date of the last study visit for the last subject in the study.
The study will commence only after the approval from the Local Regulatory Approval (DCGI).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 64
Inclusion Criteria
- Subjects who qualify for the study should meet the following inclusion criteria: 1.
- Males or non-pregnant or non-lactating females between 18-65 years of age (both inclusive).
- All males and females of childbearing potential must practice an acceptable method of contraception.
- RA subjects on maintenance therapy with single fixed dose of Azathioprine 50 mg/100 mg per day with or without a fixed dose (maximum of 30 mg/week) of Methotrexate.
- Subjects with prior/current use of corticosteroids usage can be enrolled provided that they should be on or off maintenance 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 and subjects willing to not change their concurrent medications during the study.
- All subjects should have a Body Mass Index (BMI) less than or equal to 30 but greater than or equal to 18.
- BMI values should be rounded to the nearest integer.
- (e.g. 30.4 rounds down to 30, while 17.5 rounds up to 18).
- Able to provide written informed consent to participate in the study.
- Able to comply with study requirements and assessments.
Exclusion Criteria
- Subjects with any of the following criteria should be excluded: 1.
- History of allergic responses to Azathioprine, or other related drugs and any of its formulation ingredients.
- Institutionalized subjects.
- Subjects receiving Disease Modifying Anti-Rheumatic Drugs (DMARDs) other than allowed in the study.
- Subjects who have changed their dose or regimen of Azathioprine in the last 4 weeks.
- Subjects with presence of TPMT mutation and/or presence of NUDT15 mutation who are at increased risk of drug toxicity.
- Subjects with Hemoglobin level less than 10 gm%.
- Subjects with inadequate hepatic, renal and bone marrow function.
- Hepatic function: Alanine Transaminase (ALT) / Aspartate Transaminase (AST) / Alkaline Phosphatase / Bilirubin > 2 x upper limit of normal.
- Renal function: Serum Creatinine> 2 x upper limit of normal.
- Bone marrow function: ANC less than or equal to 1500/mm3 and WBC less than or equal to 4000/mm3 (should meet both), total platelet count less than 1 x lower limit of normal range.
- Subjects who are receiving xanthine oxidase inhibitor (e.g. allopurinol, oxipurinol and thiopurinol), aminosalicylate derivatives (e.g., olsalazine, mesalazine, or sulphasalazine), drugs affecting leucocyte production e.g. cotrimoxazole, ACE inhibitors, warfarin, ribavirin or similar drugs.
- Subjects undergoing concomitant chemotherapy.
- Received live attenuated vaccine with in last 3 months.
- History of or currently receiving doxorubicin.
- Subjects with severe infections (e.g. active hepatitis, pneumonia, or pyelonephritis) within 2 months of screening.
- Less severe infections (such as acute upper respiratory tract infection [colds] or a simple urinary tract infection) need not be considered as exclusion and should be kept at the discretion of the investigator.
- Subjects with a non-tuberculous mycobacterial infection or opportunistic infection (e.g. cytomegalovirus, pneumocystis carinii, aspergillosis) within 6 months prior to screening.
- Subjects who have a known history of demyelinating disease suggestive of multiple sclerosis or optic neuritis.
- Subjects who have presence of a transplanted organ (with the exception of a corneal transplant more than 3 months prior to screening).
- Subjects 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 (e.g. nodes in the posterior triangle of the neck, infra-clavicular, epitrochlear, or periaortic areas), or splenomegaly.
- Subjects who 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).
- Subjects who have other inflammatory diseases i.e. Systemic Lupus Erythematosus (SLE), Multiple sclerosis, Ankylosing spondylitis etc.
- Subjects who have a history of latent or active granulomatous infection, including tuberculosis (TB), histoplasmosis, or coccidioidomycosis.
- Use of prohibited medications (listed in Section 9.0) within 30 days prior to enrollment in the study.
- 21.Consumption of grapefruit, grapefruit-like or grapefruit containing products within 7 days of drug administration.
- Ingestion of any alcoholic, caffeine or xanthine containing food or beverage within the 48 hours prior to randomization.
- Major surgery to the gastrointestinal tract, the liver or kidney within 4 weeks of study entry (Check-in day) which may impact on the pharmacokinetics of Azathioprine.
- History of drug dependence, history of alcoholism in the past 2 years prior to screening.
- History of difficulty in swallowing, or any gastrointestinal disease which could affect drug absorption.
- History of difficulty with donating blood or difficulty in accessibility of veins or intolerance to venipuncture.
- History of allergic response to heparin.
- A positive hepatitis screen (includes subtypes B and C).
- A positive test result for HIV antibody or syphilis (RPR/VDRL).
- Any significant ECG changes.
- Any significant disease or condition which might compromise the haemopoeitic, gastrointestinal (e.g. pancreatitis), renal, hepatic, cardiovascular, respiratory, central nervous system, diabetes, psychosis, or any other body system.
- Any food allergy, intolerance, restriction or special diet that, in the opinion of the Principal Investigator or Sub-Investigator, could contraindicate the subject’s participation in this study .
- Any other condition 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.
Study & Design
- Study Type
- BA/BE
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Pharmacokinetic parameters Cmax, AUCt, AUCi, Tmax, Kel, tHalf and AUC_%Extrap_obs In each period, total 15 venous blood samples (06 mL each) will be collected, at pre-dose (0.0 hour) and at 0.167, 0.333, 0.5, 0.667, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0 and 8.0 hours
- Secondary Outcome Measures
Name Time Method To evaluate the safety of Investigational Products. NA
Trial Locations
- Locations (6)
Aman Hospital and Research Center
🇮🇳Vadodara, GUJARAT, India
DrJivraj Mehta Smarak Health Foundation
🇮🇳Ahmadabad, GUJARAT, India
Medilink Hospital Research Center
🇮🇳Ahmadabad, GUJARAT, India
Meditrina Institute of Medical Sciences
🇮🇳Nagpur, MAHARASHTRA, India
Shree Hospital & Critical Care Centre
🇮🇳Nagpur, MAHARASHTRA, India
Sushruta Multispeciality Hospital And Research Centre
🇮🇳Dharwad, KARNATAKA, India
Aman Hospital and Research Center🇮🇳Vadodara, GUJARAT, IndiaDr Pankaj PatniPrincipal investigator919924637374drpankajpatni@yahoo.com