A multicenter, randomized, open label, two treatment, two period,two sequence, single-dose, crossover, bioequivalence study ofMethotrexate Tablets 2.5 mg (manufactured for Actavis LLC) withMethotrexate Tablets USP 2.5 mg (DAVA Pharmaceuticals, Inc.,Fort Lee, NJ 07024 USA) in patients with mild to severe psoriasisor rheumatoid arthritis (RA), who are already on establishedregimens of 2.5 mg every 12 hours under fasting condition.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- Actavis LLC
- 入组人数
- 42
- 试验地点
- 16
- 主要终点
- The objective of this pivotal study is to compare the
研究概览
简要总结
To compare and evaluate the bioequivalence study of Methotrexate Tablets 2.5 mg (manufactured for Actavis LLC) with Methotrexate Tablets USP 2.5 mg (DAVA Pharmaceuticals, Inc.,Fort Lee, NJ 07024 USA) in patients with mild to severe psoriasis or rheumatoid arthritis (RA), who are already on established regimens of 2.5 mg every 12 hours under fasting condition. Total expected duration of the study will be of at least 8 days from the day of admission of the first period till the end of study sample collection in period II. There will be at least 7 days duration between the IMP administrations in two study periods. After IMP administration in each period (on day 1), patients will be advised to receive their scheduled dose of 2.5 mg Methotrexate tablet 12 hours apart for additional 2 doses using locally approved drug. A total of 22 PK samples will be collected during each period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Men or Women, in between 18 to 65 years of age (both inclusive).
- •2.Ability to provide informed consent prior to participation in the study
- •Patients with mild to severe psoriasis or rheumatoid arthritis, who are already on established regimens of 2.5 mgevery 12 hours (7.5 mg per week in three divided doses).
- •4.Confirmed diagnosis of psoriasis by clinical examination.or Confirmed diagnosis of mild to severe rheumatoid arthritis based on at least 1 of the following: i.
- •Documented history of positive rheumatoid factor ii.
- •Current presence of rheumatoid factor iii.
- •Radiographic erosion within 12 months prior to enrolment iv.
- •Presence of serum anti-cyclic citrullinated peptideantibodies (anti-CCP).
- •Women of childbearing potential must have a negative serum or urine pregnancy test, must be using an adequate method of contraception.
- •No history of addiction to any recreational drug or drug dependence.
- •No participation in any clinical study within the past 60 days.
排除标准
- •1.A history of allergic or adverse reactions to Methotraxate Sodium or any comparable or similar product
- •Patients with alcoholism, alcoholic liver disease or other chronic liver disease.
- •3.Patients who have overt or laboratory evidence of immunodeficiency syndromes.
- •4.Patients who have pre-existing blood dyscrasias, such as bone marrow hypoplasia, leukopenia, thrombocytopenia or significant anemia
- •Expected changes in concomitant medications during the period of study 6.Tested positive for Alcohol breath or Urine drug of abuse.
- •7.Patients who are:pregnant, breast feeding,Of childbearing potential without a negative pregnancy test at baseline, Male or female of childbearing potential unwilling to use barrier contraceptive precautions throughout the trial and at least for 3 months (for males) and for at least one ovulatory cycle (for females) after last dose of study medication, Patient had major surgery within 4 weeks prior to study entry, or who have not recovered from prior major surgery,Patients with known positivity for human immunodeficiency virus (HIV), HBsAg and HCV, Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent.
- •8.History of difficulty with donating blood or difficulty in accessibility of veins.
- •Oral Administration of Drug is not possible.
- •10.An unusual or abnormal diet, for whatever reason e.g.religious fasting.
- •11.Donation of blood (1 unit or 350 ml) within 90 days prior to receiving the first dose of investigational medicinal product for the current study.
- •12.Evidence of any significant uncontrolled concomitant disease which in the investigators opinion would exclude the patient participation.
- •Patients with any evidence of organ dysfunction or any clinically significant deviation from normal in their physical or clinical evaluation including ECG and X-ray results except study indication.
- •Any treatment which could affect the pharmacokinetic of methotrexate (salicylates, hypoglycaemics, diuretics,sulphonamides, diphenylhydantoins, tetracyclines,chloramphenicol and p-aminobenzoic acid, probenecid,penicillins, Chloroquine, omeprazole, etretinate, cotrimoxazole and trimethoprim etc.) administered within 1 month of starting of study.
- •15.Patients who are diagnosed to be HIV 1 and 2 or Hepatitis B(HBsAg) or Hepatitis C (HCV) virus reactive/positive.
- •Patients with clinically significant abnormal haemoglobin(Hb), total white blood cells count (WBC), differential WBC count, platelet count and hematocrite.
- •Patients who, have clinically significant abnormal laboratory values.
- •18.Patients with a clinically significant past history or current medical condition of:Pulmonary disorders (COPD and asthma),Cardiovascular disorders (especially cardiac blocks), Neurological disorders, GIT disorders including history or presence of significant gastric and duodenal ulceration, Renal and/or hepatic disorder coagulation disorders.
- •19.Endocrine disorders (especially diabetes mellitus).
- •20.History or presence of cancer.
结局指标
主要结局
The objective of this pivotal study is to compare the
时间窗: predose sample of 3.5 mL will be collected within 5 minutes before dosing on day 1 of each period. Post dose sample of 3.5 mL each will be drawn at 0.167,0.250,0.500,0.750,1.000,1.250,1.500,1.750,2.000,2.333,2.667, 3.000, 3.500, 4.000, 4.500, 5.000, 6.000, 7.000, 8.000, 10.000, & 12.000
bioavailability of methotrexate from Methotrexate Tablets 2.5
时间窗: predose sample of 3.5 mL will be collected within 5 minutes before dosing on day 1 of each period. Post dose sample of 3.5 mL each will be drawn at 0.167,0.250,0.500,0.750,1.000,1.250,1.500,1.750,2.000,2.333,2.667, 3.000, 3.500, 4.000, 4.500, 5.000, 6.000, 7.000, 8.000, 10.000, & 12.000
mg (manufactured for Actavis LLC) and Methotrexate Tablets
时间窗: predose sample of 3.5 mL will be collected within 5 minutes before dosing on day 1 of each period. Post dose sample of 3.5 mL each will be drawn at 0.167,0.250,0.500,0.750,1.000,1.250,1.500,1.750,2.000,2.333,2.667, 3.000, 3.500, 4.000, 4.500, 5.000, 6.000, 7.000, 8.000, 10.000, & 12.000
USP 2.5 mg (DAVA Pharmaceuticals,USA) in patients with mild to severe psoriasis or rheumatoid
时间窗: predose sample of 3.5 mL will be collected within 5 minutes before dosing on day 1 of each period. Post dose sample of 3.5 mL each will be drawn at 0.167,0.250,0.500,0.750,1.000,1.250,1.500,1.750,2.000,2.333,2.667, 3.000, 3.500, 4.000, 4.500, 5.000, 6.000, 7.000, 8.000, 10.000, & 12.000
arthritis (RA), who are already on established regimens of 2.5 mg every 12 hours under fasting condition.
时间窗: predose sample of 3.5 mL will be collected within 5 minutes before dosing on day 1 of each period. Post dose sample of 3.5 mL each will be drawn at 0.167,0.250,0.500,0.750,1.000,1.250,1.500,1.750,2.000,2.333,2.667, 3.000, 3.500, 4.000, 4.500, 5.000, 6.000, 7.000, 8.000, 10.000, & 12.000
次要结局
- To monitor the adverse events and to ensure the safety of Patient(NA)