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

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

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.

Study Overview

• Status: Completed
• Conditions: Kidney Transplant
• Intervention / Treatment: Drug: Placebo; Drug: CP-690,550 5 mg BID; Drug: CP-690,550 15 mg BID; Drug: CP-690,550 30 mg BID

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• • • Pfizer Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • Pfizer Investigational Site
    • Birmingham, Alabama, United States, 35249-6860
      • Pfizer Investigational Site
    • Birmingham, Alabama, United States, 35294-6862
      • Pfizer Investigational Site
  • California
    • Los Angeles, California, United States, 90057
      • Pfizer Investigational Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Pfizer Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Pfizer Investigational Site
  • Missouri
    • St Louis, Missouri, United States, 63110-1093
      • Pfizer Investigational Site
    • St. Louis, Missouri, United States, 63110-1092
      • Pfizer Investigational Site
  • New Jersey
    • Livingston, New Jersey, United States, 07039
      • Pfizer Investigational Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: September 1, 2003
• Primary Completion (Actual): April 1, 2005
• Study Completion (Actual): April 1, 2005

Study Registration Dates

• First Submitted: October 16, 2012
• First Submitted That Met QC Criteria: October 16, 2012
• First Posted (Estimate): October 18, 2012

Study Record Updates

• Last Update Posted (Estimate): December 26, 2012
• Last Update Submitted That Met QC Criteria: November 26, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: kidney transplant; CP-690,550
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tofacitinib
• Other Study ID Numbers: A3921007