A Randomized, Double Blind, Double-Dummy, Multi Center, Parallel, Phase III Study to Evaluate theEfficacy and Safety of Tacrolimus Lipid Tablets (Manufactured by Intas Pharmaceuticals Ltd) Comparedto Prograf (Tacrolimus Immediate Release Capsules-Astellas Pharma Canada, Inc) in Adult Patients withActive Rheumatoid Arthritis Who Have Resistance OR Intolerance to DMARDs
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 364
- 试验地点
- 23
- 主要终点
- Comparision of the efficacy of Tacrolimus lipid tablets versus Prograf in patients
研究概览
简要总结
Rheumatoid arthritis (RA) is a chronic progressive inflammatory disease characterized by swelling and pain in multiple joints. The primary lesion of RA is considered to be in synovial membranes. Synovial cell proliferation gradually affects surrounding cartilage and bone, frequently leading to the disruption or deformation of joints. Physical symptoms other than those of joints include subcutaneous nodules or vascular inflammation, skin ulcers, and pulmonary fibrosis. RA is therefore considered not a joint disease but a systemic disease. Immune abnormalities underlie the pathology of RA, and the correction of these abnormalities is currently considered optimal therapy for RA. The outlook for patients with rheumatoid arthritis has improved significantly over the last three decades with the use of disease-modifying antirheumatic drugs. However, despite the use of methotrexate, cytokine inhibitors, and molecules targeting T and B cells, a percentage of patients do not respond or lose their response over time. Because of the known role of T cell activation in disease pathogenesis, the observed immunomodulating actions of tacrolimus, and the encouraging results of many clinical trials led us to develop Tacrolimus in RA. This is a Phase III, randomized, double blind, parallel study to compare the efficacy and safety of tacrolimus lipid tablets in adult patients with active rheumatoid arthritis (RA) resistance or intolerance to DMARDs. Patients will be permitted to remain on a stable dose of NSAIDs for at least 4 weeks prior to screening and a stable dose of oral glucocorticoid up to 10 mg (Prednisolone equivalent) for at least 4 weeks prior study drug administration and to be maintained throughout the study. The study will commence only after a written approval is obtained from the Independent/Institutional Ethics Committee and applicable regulatory authorities.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Double Blind Double Dummy
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Patients willing to give written informed consent for participation in the study before initiating any study related procedure..
- •Adult patients of age 18 years or older who should meet the criteria for Rheumatoid Arthritis as per American College of Rheumatology at least for last 6 months with ACR functional class I–III.
- •Patients should have documented evidence of, either resistance or intolerance to 1 or more DMARDs -DMARD resistance is defined as continued active RA despite receiving a therapeutic dosage of a specific DMARD for a duration of time typically sufficient to elicit therapeutic response. Methotrexate dose should be greater than or equal to 20 mg per week for last 6 months and on stable doses for 4 weeks prior to enrolment in the study to define resistance. -DMARD intolerance is defined as the inability or unwillingness of the patient to continue therapy due to an adverse drug experience.
- •Patient with Moderate to severe diseases i.e. DAS
- •CRP score more than 3.2 (calculated as per Appendix III) at screening.
- •Washout of any previous DMARDs given before randomization and if there is documented previous use of hydroxychloroquine then it should be at least 3 months before randomization
- •Sexually active women, unless surgically sterile (at least 6 months prior to study drug administration) or postmenopausal for at least 12 consecutive months, must 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 study and up to 30 days after the last dose of study drug
- •In case of Male patients: Either patient partners or patients themselves must use an effective method of avoiding pregnancy for at least 4 weeks prior to study drug administration, during study and up to 30 days after the last dose of study drug
- •No other serious illness including cardiac disease (ischemic heart disease, treatment-requiring arrhythmia, heart failure) that according to investigator might jeopardize the well-being, the safety of patients, the compliance to study medications and validity of data generated during the study.
排除标准
- •Known hypersensitivity to Tacrolimus or any of its components
- •Patients who had received biological products (e.g. Infliximab, etanercept, etc.) or agents (e.g. leflunomide) with an inhibitory effect on the progression of joint destruction within 12 weeks before administration of the study drug.
- •Patients whose daily oral glucocorticoid dose exceeded 10 mg (Prednisolone equivalent) within 4 weeks before administration of the study drug.
- •Intra- or periarticular steroids or tacrolimus in any dosage form administered within 4 weeks prior to screening.
- •Patients who had been previously treated with Tacrolimus and found resistant for current disease.
- •Pregnant or breast-feeding female.
- •Clinically significant Liver disease (defined by levels of Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, or Total bilirubin greater than or equal to 2 times the upper limit of normal).
- •Clinically significant renal disease (defined by value of either serum creatinine, serum urea or serum uric acid value above the upper limit of normal).
- •Clinically significant Bone marrow suppression defined as haemoglobin level less than 9 gm per dl, white blood cell count less than 3,000/mm3, platelet count <100,000/mm
- •Patients with HIV or Hepatitis B or C infection.
- •Have active dysphagia, swallowing disorders, bowel obstruction, or severe gastrointestinal motility disorders.
- •Have any evidence of active malignancy except for basal cell carcinoma of the skin.
- •A history of malignancy is not an exclusion
- •Have participated in a study of an investigational drug during the 30 days preceding randomization.
结局指标
主要结局
Comparision of the efficacy of Tacrolimus lipid tablets versus Prograf in patients
时间窗: Day 14, Day 28, Day 56, Day 84, Day 112
with active rheumatoid arthritis who have resistance or intolerance to
时间窗: Day 14, Day 28, Day 56, Day 84, Day 112
DMARDs.
时间窗: Day 14, Day 28, Day 56, Day 84, Day 112
次要结局
- Evaluation and comparision of the safety of patients exposed to the investigational medicinal products.(Evaluation of the Pharmacokinetic parameters in patients with active)