Phase 1, Placebo-controlled, Randomized, Sequential, Parallel-group, Dose Escalation Study to Evaluate 28-day Multiple Dose Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of CP-690,550 in Stable Renal Allograft Recipients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Mycophenolic Acid (MPA) Plasma Trough Concentration at Baseline
研究概览
简要总结
This was a Phase 1 dose escalation study to evaluate the safety, tolerability and pharmacokinetics of 28-day treatment of CP-690,550 in stable renal allograft recipients. In Stage 1, ascending doses of CP-690,550 were to be administered sequentially to 3-4 cohorts of subjects. After Stage 1, one dose level was to be selected for dosing in an expanded cohort in Stage 2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
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
- •Medically stable kidney transplant patients 6 or more months after transplantation.
- •Subjects must be on mycophenolate mofetil 1-2 gm daily
- •In Cohort 3 (and 4, if conducted) in Stage 1 and the expanded cohort in Stage 2, subjects must be on a calcineurin inhibitor-free regimen.
排除标准
- •Any rejection episodes in the preceding 3 months.
- •Treated with Thymoglobulin or OKT3 for acute rejection in the past 6 months.
研究组 & 干预措施
Placebo
干预措施: Placebo (Drug)
CP-690,550 5 mg BID
干预措施: CP-690,550 5 mg BID (Drug)
CP-690,550 15 mg BID
干预措施: CP-690,550 15 mg BID (Drug)
CP-690,550 30 mg BID
干预措施: CP-690,550 30 mg BID (Drug)
结局指标
主要结局
Mycophenolic Acid (MPA) Plasma Trough Concentration at Baseline
时间窗: Screening, 0 hour (pre-dose) on Day 1
Pro-drug MMF was metabolically converted to active form MPA in the liver. The baseline for MPA trough concentrations was defined as the average of the values obtained at Screening and on Day 1 (pre-dose). MPA levels were assessed at different visits to assess change in MPA trough levels due to CP-690,550 exposure.
Cyclosporine (CsA) Plasma Trough Concentration at Day 15
时间窗: 0 hour (pre-dose) on Day 15
CsA levels were assessed at different visits to assess change in CsA trough levels due to CP-690,550 exposure.
Accumulation Ratio (Rac) For CP-690,550
时间窗: 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12 hours post-dose on Day 1 and 29
Rac obtained from AUC(0-12) (Day 29) divided by AUC(0-12) (Day 1).
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) at Steady State For CP-690,550
时间窗: 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12, 24 hours post-dose on Day 29
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) at steady state.
Area Under the Curve From Time Zero to 12 Hour Concentration [AUC(0-12)] at Steady State For CP-690,550
时间窗: 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12 hours post-dose on Day 29
Area under the plasma concentration time-curve from zero to 12 hour concentration \[AUC(0-12)\] at steady state.
Maximum Observed Plasma Concentration (Cmax) For CP-690,550
时间窗: 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12 hours post-dose on Day 1
Time to Reach Maximum Observed Plasma Concentration (Tmax) For CP-690,550
时间窗: 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12 hours post-dose on Day 1
Time to Reach Maximum Observed Plasma Concentration (Tmax) at Steady State For CP-690,550
时间窗: 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12, 24 hours post-dose on Day 29
Plasma Decay Half-Life (t1/2) For CP-690,550
时间窗: 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12 hours post-dose on Day 1
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Mycophenolic Acid (MPA) Plasma Trough Concentration at Day 15
时间窗: 0 hour (pre-dose) on Day 15
Pro-drug MMF was metabolically converted to active form MPA in the liver. MPA levels were assessed at different visits to assess change in MPA trough levels due to CP-690,550 exposure.
Mycophenolic Acid (MPA) Plasma Trough Concentration at Day 29
时间窗: 0 hour (pre-dose) on Day 29
Pro-drug MMF was metabolically converted to active form MPA in the liver. MPA levels were assessed at different visits to assess change in MPA trough levels due to CP-690,550 exposure.
Cyclosporine (CsA) Plasma Trough Concentration at Baseline
时间窗: Screening, 0 hour (pre-dose) on Day 1
The baseline for CsA trough concentrations was defined as the average of the values obtained at Screening and on Day 1 (pre-dose). CsA levels were assessed at different visits to assess change in CsA trough levels due to CP-690,550 exposure.
Cyclosporine (CsA) Plasma Trough Concentration at Day 57
时间窗: 0 hour (pre-dose) on Day 57
CsA levels were assessed at different visits to assess change in CsA trough levels due to CP-690,550 exposure.
Mycophenolic Acid (MPA) Plasma Trough Concentration at Day 8
时间窗: 0 hour (pre-dose) on Day 8
Pro-drug MMF was metabolically converted to active form MPA in the liver. MPA levels were assessed at different visits to assess change in MPA trough levels due to CP-690,550 exposure.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) For CP-690,550
时间窗: 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12 hours post-dose on Day 1
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Maximum Observed Plasma Concentration (Cmax) at Steady State For CP-690,550
时间窗: 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12, 24 hours post-dose on Day 29
Plasma Decay Half-Life (t1/2) at Steady State For CP-690,550
时间窗: 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12, 24 hours post-dose on Day 29
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half at steady state.
Mycophenolic Acid (MPA) Plasma Trough Concentration at Day 57
时间窗: 0 hour (pre-dose) on Day 57
Pro-drug MMF was metabolically converted to active form MPA in the liver. MPA levels were assessed at different visits to assess change in MPA trough levels due to CP-690,550 exposure.
Cyclosporine (CsA) Plasma Trough Concentration at Day 8
时间窗: 0 hour (pre-dose) on Day 8
CsA levels were assessed at different visits to assess change in CsA trough levels due to CP-690,550 exposure.
Cyclosporine (CsA) Plasma Trough Concentration at Day 29
时间窗: 0 hour (pre-dose) on Day 29
CsA levels were assessed at different visits to assess change in CsA trough levels due to CP-690,550 exposure.
Tacrolimus (TAC) Plasma Trough Concentration at Baseline
时间窗: Screening, 0 hour (pre-dose) on Day 1
The baseline for TAC trough concentrations was defined as the average of the values obtained at Screening and on Day 1 (pre-dose). TAC levels were assessed at different visits to assess change in TAC trough levels due to CP-690,550 exposure.
Tacrolimus (TAC) Plasma Trough Concentration at Day 15
时间窗: 0 hour (pre-dose) on Day 15
TAC levels were assessed at different visits to assess change in TAC trough levels due to CP-690,550 exposure.
Tacrolimus (TAC) Plasma Trough Concentration at Day 29
时间窗: 0 hour (pre-dose) on Day 29
TAC levels were assessed at different visits to assess change in TAC trough levels due to CP-690,550 exposure.
Tacrolimus (TAC) Plasma Trough Concentration at Day 57
时间窗: 0 hour (pre-dose) on Day 57
TAC levels were assessed at different visits to assess change in TAC trough levels due to CP-690,550 exposure.
Tacrolimus (TAC) Plasma Trough Concentration at Day 8
时间窗: 0 hour (pre-dose) on Day 8
TAC levels were assessed at different visits to assess change in TAC trough levels due to CP-690,550 exposure.
次要结局
未报告次要终点