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

Phase 1

Completed

Conditions: Kidney Transplant

Interventions: Drug: CP-690,550 15 mg BID
Drug: CP-690,550 5 mg BID
Drug: Placebo
Drug: CP-690,550 30 mg BID

Registration Number: NCT01710033

Lead Sponsor: Pfizer

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 28

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CP-690,550 15 mg BID	CP-690,550 15 mg BID	-
CP-690,550 5 mg BID	CP-690,550 5 mg BID	-
Placebo	Placebo	-
CP-690,550 30 mg BID	CP-690,550 30 mg BID	-

Primary Outcome Measures

Name	Time	Method
Tacrolimus (TAC) Plasma Trough Concentration at Day 15	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.
Mycophenolic Acid (MPA) Plasma Trough Concentration at Baseline	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	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	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).
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
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
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) 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	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	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.
Plasma Decay Half-Life (t1/2) For CP-690,550	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	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	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	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	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	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.
Tacrolimus (TAC) Plasma Trough Concentration at Baseline	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.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) For CP-690,550	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	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	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	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	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	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 Day 29	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	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	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.