A Phase 1, Open Label Study Of The Pharmacokinetics Of Multiple Doses Of Oral CP-690,550 And Single Doses Of Oral Methotrexate In Rheumatoid Arthritis Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] for CP-690,550
研究概览
简要总结
This study was designed to estimate the effects of methotrexate (MTX) on the pharmacokinetics (PK) of CP-690,550 when administered to subjects with rheumatoid arthritis (RA), to estimate the effects of CP-690,550 on the PK of MTX and to evaluate the short-term safety and tolerability of co-administration of CP-690,550 and MTX.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults diagnosed with moderate to severe RA (Rheumatoid Arthritis)
- •Diagnosis of RA based on the American College of Rheumatology 1987 revised criteria.
- •Treatment with an oral stable weekly dose of Methotrexate (MTX) (15-25 mg/week, administered as a single dose [SD]) for a minimum of 4 doses (4 weeks)
排除标准
- •Blood dyscrasias including confirmed: Hemoglobin <9 g/dL or Hematocrit <30%; White blood cell count <3.0 x 109/L; Absolute neutrophil count <1.2 x 109/L; Platelet count <100 x 109/L
- •Evidence or history of clinically significant infections within the past 6 months (eg, those requiring hospitalization, requiring parenteral antimicrobial therapy, or those with recurrent oral or genital herpes, recurrent herpes zoster, or any infection otherwise judged by the investigator to have the potential for exacerbation by participation in the trial.
- •Total bilirubin, AST (aspartate aminotransferase) or ALT (alanine aminotransferase) more than 1.2 times the upper limit of normal at the Screening visit, or a history of clinically significant elevated liver function tests (LFTs) while on current MTX dose or chronic liver disease, recent or active hepatitis.
研究组 & 干预措施
CP-690,550 (tofacitinib) 30 mg q12h
Individual dose of methotrexate with the addition of CP-690,550 30 mg q12h
干预措施: CP-690,550 (tofacitinib) (Drug)
CP-690,550 (tofacitinib) 30 mg q12h
Individual dose of methotrexate with the addition of CP-690,550 30 mg q12h
干预措施: Methotrexate (MTX) (Drug)
结局指标
主要结局
Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] for CP-690,550
时间窗: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7
AUC (0-12)= area under the plasma concentration time-curve from time zero (pre-dose) to 12 hours (0-12).
Maximum Observed Plasma Concentration (Cmax) for CP-690,550
时间窗: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Methotrexate (MTX)
时间窗: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 and 48 hours post-dose on Day 1 and Day 7
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Maximum Observed Plasma Concentration (Cmax) for Methotrexate (MTX)
时间窗: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12, 24 and 48 hours post-dose on Day 1 and Day 7
次要结局
- Time to Reach Maximum Observed Plasma Concentration (Tmax) for CP-690,550(0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7)
- Plasma Decay Half-Life (t1/2) for CP-690,550(0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7)
- Apparent Oral Clearance (CL/F) for CP-690,550(0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) for Methotrexate (MTX)(0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 ,12, 24 and 48 hours post-dose on Day 1 and Day 7)
- Plasma Decay Half-Life (t1/2) for Methotrexate (MTX)(0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 , 12, 24 and 48 hours post-dose on Day 1 and Day 7)
- Apparent Oral Clearance (CL/F) for Methotrexate (MTX)(0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 , 12, 24 and 48 hours post-dose on Day 1 and Day 7)
- Total Amount of Unchanged Drug Excreted in the Urine From Time Zero to 12 Hours (Ae[0-12]) for CP-690,550(0 (pre-dose) through 12 hours post-dose on Day 6 and Day 7)
- Renal Clearance (CL R) for CP-690,550(0 (pre-dose) through 24 hours post-dose on Day 6 and Day 7)
- Total Amount of Unchanged Drug Excreted in the Urine From Time Zero to 24 Hours (Ae[0-24]) for Methotrexate (MTX)(0 (pre-dose) through 24 hours post-dose on Day 1 and Day 7)
- Renal Clearance (CL R) for Methotrexate (MTX)(0 (pre-dose) through 24 hours post-dose on Day 1 and Day 7)