A Study Of CP-690,550 In Stable Kidney Transplant Patients

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Kidney Transplant

Intervention / Treatment
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* Drug: Placebo
* Drug: CP-690,550 5 mg BID
* Drug: CP-690,550 15 mg BID
* Drug: CP-690,550 30 mg BID


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: Any rejection episodes in the preceding 3 months. Treated with Thymoglobulin or OKT3 for acute rejection in the past 6 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo tables twice daily (BID) for 28 days<br>|
| Experimental: CP-690,550 5 mg BID<br> | Drug: CP-690,550 5 mg BID<br>* CP-690,550 5 mg BID for 28 days<br>|
| Experimental: CP-690,550 15 mg BID<br> | Drug: CP-690,550 15 mg BID<br>* CP-690,550 15 mg BID for 28 days<br>|
| Experimental: CP-690,550 30 mg BID<br> | Drug: CP-690,550 30 mg BID<br>* CP-690,550 30 mg BID for 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) For CP-690,550 | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). | 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12 hours post-dose on Day 1 | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) at Steady State For CP-690,550 | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) at steady state. | 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12, 24 hours post-dose on Day 29 | 
| Area Under the Curve From Time Zero to 12 Hour Concentration [AUC(0-12)] at Steady State For CP-690,550 | Area under the plasma concentration time-curve from zero to 12 hour concentration [AUC(0-12)] at steady state. | 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12 hours post-dose on Day 29 | 
| Maximum Observed Plasma Concentration (Cmax) For CP-690,550 |  | 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12 hours post-dose on Day 1 | 
| Maximum Observed Plasma Concentration (Cmax) at Steady State For CP-690,550 |  | 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12, 24 hours post-dose on Day 29 | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) For CP-690,550 |  | 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 |  | 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12, 24 hours post-dose on Day 29 | 
| Accumulation Ratio (Rac) For CP-690,550 | Rac obtained from AUC(0-12) (Day 29) divided by AUC(0-12) (Day 1). | 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12 hours post-dose on Day 1 and 29 | 
| Plasma Decay Half-Life (t1/2) For CP-690,550 | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12 hours post-dose on Day 1 | 
| Plasma Decay Half-Life (t1/2) at Steady State For CP-690,550 | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half at steady state. | 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12, 24 hours post-dose on Day 29 | 
| Mycophenolic Acid (MPA) Plasma Trough Concentration at Baseline | 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. | Screening, 0 hour (pre-dose) on Day 1 | 
| Mycophenolic Acid (MPA) Plasma Trough Concentration at 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. | 0 hour (pre-dose) on Day 8 | 
| Mycophenolic Acid (MPA) Plasma Trough Concentration at 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. | 0 hour (pre-dose) on Day 15 | 
| Mycophenolic Acid (MPA) Plasma Trough Concentration at 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. | 0 hour (pre-dose) on Day 29 | 
| Mycophenolic Acid (MPA) Plasma Trough Concentration at 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. | 0 hour (pre-dose) on Day 57 | 
| Cyclosporine (CsA) Plasma Trough Concentration at Baseline | 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. | Screening, 0 hour (pre-dose) on Day 1 | 
| Cyclosporine (CsA) Plasma Trough Concentration at Day 8 | CsA levels were assessed at different visits to assess change in CsA trough levels due to CP-690,550 exposure. | 0 hour (pre-dose) on Day 8 | 
| Cyclosporine (CsA) Plasma Trough Concentration at Day 15 | CsA levels were assessed at different visits to assess change in CsA trough levels due to CP-690,550 exposure. | 0 hour (pre-dose) on Day 15 | 
| Cyclosporine (CsA) Plasma Trough Concentration at Day 29 | CsA levels were assessed at different visits to assess change in CsA trough levels due to CP-690,550 exposure. | 0 hour (pre-dose) on Day 29 | 
| Cyclosporine (CsA) Plasma Trough Concentration at Day 57 | CsA levels were assessed at different visits to assess change in CsA trough levels due to CP-690,550 exposure. | 0 hour (pre-dose) on Day 57 | 
| Tacrolimus (TAC) Plasma Trough Concentration at Baseline | 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. | Screening, 0 hour (pre-dose) on Day 1 | 
| Tacrolimus (TAC) Plasma Trough Concentration at Day 8 | TAC levels were assessed at different visits to assess change in TAC trough levels due to CP-690,550 exposure. | 0 hour (pre-dose) on Day 8 | 
| Tacrolimus (TAC) Plasma Trough Concentration at Day 15 | TAC levels were assessed at different visits to assess change in TAC trough levels due to CP-690,550 exposure. | 0 hour (pre-dose) on Day 15 | 
| Tacrolimus (TAC) Plasma Trough Concentration at Day 29 | TAC levels were assessed at different visits to assess change in TAC trough levels due to CP-690,550 exposure. | 0 hour (pre-dose) on Day 29 | 
| Tacrolimus (TAC) Plasma Trough Concentration at Day 57 | TAC levels were assessed at different visits to assess change in TAC trough levels due to CP-690,550 exposure. | 0 hour (pre-dose) on Day 57 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CP-690,550, kidney transplant