Extension Study Of Stage 1 Subjects Of Study A3921009 For The Prevention Of Acute Rejection In Kidney Transplant Patient

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00263328
First received: December 6, 2005
Last updated: June 16, 2015
Last verified: June 2015
  Purpose

A new immunosuppressive drug, based on the inhibition of an important enzyme in the immune system called JAK3, is being developed by Pfizer to prevent transplant rejection. In study A3921009, kidney transplant patients were given a JAK inhibitor or tacrolimus for 6 months posttransplant. Patients who completed study A3921009 were offered the opportunity to participate in study A3921021 which will extend the evaluation of safety and efficacy of CP-690,550 versus tacrolimus through 8 years posttransplant. In treatment group 1 (control arm), subjects will continue to receive tacrolimus. In treatment groups 2 and 3, subjects will continue to receive CP-690,550. Per Amendment 4, the tacrolimus comparator arm will be discontinued.


Condition Intervention Phase
Kidney Transplantation
Drug: Tacrolimus
Drug: CP-690,550
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Multicenter, Phase 2, Open-label, Controlled, Extension Study For Stage 1 Subjects Of Study A3921009 To Evaluate The Long-term Safety And Efficacy Of Cp-690,550 Versus Tacrolimus, When Co-administered With Mycophenolate Mofetil In Renal Allograft Recipients

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Calculated Glomerular Filtration Rate (GFR) Using the Modification of Diet in Renal Disease (MDRD) Equation [ Time Frame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98) ] [ Designated as safety issue: Yes ]
    GFR: an index of kidney function. GFR described the flow rate of filtered fluid through the kidney. GFR was calculated using MDRD equation. GFR by MDRD equation = 170 * (serum creatinine [in milligrams per deciliter (mg/dL)])^(-0.999) * (age in years)^(-0.176) * (0.762 if female) * (1.18 if black) * (blood urea nitrogen [BUN] concentration [mg/dL])^(-0.170) * (serum albumin concentration [in grams per dL (g/dL)])^(0.318). A normal GFR is >90 milliliters per minute per 1.73 square meters (mL/min/1.73 m^2), although children and older people usually have a lower GFR. Lower values indicated poor kidney function. A GFR <15 mL/min/1.73 m^2 indicated kidney failure.

  • Serum Creatinine Levels [ Time Frame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98) ] [ Designated as safety issue: Yes ]
  • Kaplan-Meier Analysis of Percentage of Participants With Clinically Significant Infections by Visit [ Time Frame: Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96 ] [ Designated as safety issue: Yes ]
    Kaplan-Meier analysis of percentage of participants with clinically significant infections by time to first clinically significant infection within 96 months post-transplant. Time was defined from the date of first dose of study drug in Study A3921009 to the date of first occurrence of the event, censored at the day of the last visit or Day 2980 (the maximum scheduled day for follow-up 98 month), whichever comes earlier.

  • Kaplan-Meier Analysis of Percentage of Participants With New Onset Diabetes Mellitus, Definition 1 (NODM-1) by Visit [ Time Frame: Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96 ] [ Designated as safety issue: Yes ]
    Kaplan-Meier analysis of time to NODM-1 within 96 months post-transplant. Time was defined from the date of first dose of study drug in Study A3921009 to the date of first occurrence of the event, censored at the day of the last visit or Day 2980 (the maximum scheduled day for follow-up 98 month), whichever comes earlier. NODM-1 was defined as an event experienced by participants who were non-diabetic prior to transplantation and required treatment with oral hypoglycemic agents, anti-diabetic agents, and/or insulin for greater than or equal to (≥)30 days.

  • Percentage of Participants With Hypercholesterolemia [ Time Frame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96, and Follow-Up (Month 98) ] [ Designated as safety issue: Yes ]
    Hypercholesterolemia was defined as cholesterol levels >240 mg/dL or 6.2 mmol/L.

  • Percentage of Participants With Hypertriglyceridemia by Visit [ Time Frame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98) ] [ Designated as safety issue: Yes ]
    Hypertriglyceridemia was defined as triglyceride levels of >200 mg/dL or 2.3 mmol/L.

  • Kaplan-Meier Analysis of Percentage of Participants With First Biopsy Proven Acute Rejection (BPAR) by Visit [ Time Frame: Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96 ] [ Designated as safety issue: Yes ]
    Kaplan-Meier analysis of percentage of participants with first BPAR by time to first BPAR within 96 months post-transplant. BPAR was defined as acute/active cellular rejection (Category 4 of the Banff Classification), based on the assessment of the renal allograft biopsy by a central, blinded pathologist. Time was defined from the date of first dose of study drug in Study A3921009 to the date of first occurrence of the event, censored at the day of the last visit or Day 2980 (the maximum scheduled day for follow-up 98 month), whichever comes earlier.

  • Kaplan-Meier Analysis of Percentage of Participants With Treatment Failure by Visit [ Time Frame: Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96 ] [ Designated as safety issue: Yes ]
    Kaplan-Meier analysis of percentage of participants with treatment failure by time to treatment failure within 96 months post-transplant. Time was defined from the date of first dose of study drug in Study A3921009 to the date of first occurrence of the event, censored at the day of the last visit or Day 2980 (the maximum scheduled day for follow-up 98 month), whichever comes earlier. Treatment failure was defined as the first occurrence of BPAR, death, graft loss or premature discontinuation of trial medication for any reason.


Secondary Outcome Measures:
  • Calculated GFR Using the Nankivell Equation (mL/Min) [ Time Frame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98) ] [ Designated as safety issue: Yes ]
    GFR: an index of kidney function. GFR described the flow rate of filtered fluid through the kidney. GFR was measured directly or estimated using established formulas. GFR was estimated by creatinine clearance (CLcr; in mL/min]) using Nankivell equation. CLcr by Nankivell equation= (6.7 per serum creatinine [in millimoles per liter (mmol/L)]) plus (0.25*body weight [in kilograms (kg)]) minus (0.5*serum urea [mmol/dL, where 1 mg/dL BUN=0.36 mmol/L urea]) minus (100 per height [in meters] square) plus (35 for male/25 for female). A normal GFR is >90 mL/min, although children and older people usually have a lower GFR. Lower values indicated poor kidney function. A GFR <15 mL/min indicated kidney failure.

  • Calculated GFR Using Cockcroft-Gault Equation (mL/Min) [ Time Frame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98) ] [ Designated as safety issue: Yes ]
    GFR: an index of kidney function. GFR described the flow rate of filtered fluid through the kidney. GFR was calculated using Cockcroft-Gault equation. GFR by Cockcroft-Gault equation= body weight (kg)*(140 minus age in years) divided by (72*serum creatinine [mg/dL]). For females value obtained was multiplied by 0.85. A normal GFR is >90 mL/min, although children and older people usually have a lower GFR. Lower values indicated poor kidney function. A GFR <15 mL/min indicated kidney failure.

  • Reciprocal of Serum Creatinine [ Time Frame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98) ] [ Designated as safety issue: Yes ]
  • Kaplan-Meier Analysis of Percentage of Participants With NODM, Definition 2 (NODM-2) by Visit [ Time Frame: Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96 ] [ Designated as safety issue: Yes ]
    Kaplan-Meier analysis of percentage of participants with NODM-2 by time to NODM-2 within 96 months post-transplant. Time was defined from the date of first dose of study drug in Study A3921009 to the date of first occurrence of the event, censored at the day of the last visit or Day 2980 (the maximum scheduled day for follow-up 98 month), whichever comes earlier. NODM-2 was defined as an event experienced by a transplanted subject who meets any of the following criteria: (a) NODM-1; or (b) Symptoms of diabetes plus 2 casual serum glucose levels ≥200 mg/dL separated by at least approximately 24 hours. Casual was defined as any time of day without regard to time since last meal; or (c) Fasting serum glucose ≥126 mg/dL on 2 different occasions separated by at least approximately 24 hours. Fasting was defined as no caloric intake for at least 8 hours; or (d) 2-hour serum glucose ≥200 mg/dL during an OGTT (Oral Glucose Tolerance Test).

  • Total Cholesterol Levels by Visit [ Time Frame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98) ] [ Designated as safety issue: Yes ]
  • Low-Density Lipoprotein (LDL) Levels by Visit [ Time Frame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98) ] [ Designated as safety issue: Yes ]
  • High-Density Lipoprotein (HDL) Levels by Visit [ Time Frame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98) ] [ Designated as safety issue: Yes ]
  • Ratio of Total Serum Cholesterol Level to HDL Level by Visit [ Time Frame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98) ] [ Designated as safety issue: Yes ]
  • Percentage of Participants With Ratio of Total Serum Cholesterol to Serum HDL Cholesterol <5 by Visit [ Time Frame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98) ] [ Designated as safety issue: Yes ]
  • Ratio of Serum LDL Level to HDL Level by Visit [ Time Frame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98) ] [ Designated as safety issue: Yes ]
  • Percentage of Participants With Ratio of Serum LDL Cholesterol to Serum HDL Cholesterol <3.5 by Visit [ Time Frame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98) ] [ Designated as safety issue: Yes ]
  • Serum Triglyceride Levels by Visit [ Time Frame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98) ] [ Designated as safety issue: Yes ]
  • Percentage of Participants Requiring Lipid-Lowering Agents by Visit [ Time Frame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96 ] [ Designated as safety issue: Yes ]
  • Percentage of Participants Requiring Anti-Hypertensive Medication by Visit [ Time Frame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96 ] [ Designated as safety issue: Yes ]
  • Percentage of Participants Requiring Diabetes Agents (Oral Hypoglycemic Agents, Anti-Diabetic Agents, or Insulin) by Visit [ Time Frame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96 ] [ Designated as safety issue: Yes ]
  • Epstein Barr Virus (EBV) Deooxyribonucleic Acid (DNA) Levels Determined Using Polymerase Chain Reaction (PCR) by Visit [ Time Frame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96 ] [ Designated as safety issue: Yes ]
    Calculated as number of copies per 500 mg DNA.

  • Percentage of Participants With EBV DNA Determined Using PCR by Specific Cutoff Categories (in Number of Copies/PCR) and Visit [ Time Frame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96 and Follow-Up (Month 98) ] [ Designated as safety issue: Yes ]
    EBV DNA PCR categories included 0, 1-50, 51-100, 101-1000, and >1000 copies/PCR.

  • BK Virus (BKV) DNA Levels Determined Using PCR by Visit [ Time Frame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98) ] [ Designated as safety issue: Yes ]
    Calculated as number of copies per PCR. Per protocol, BKV DNA PCR was performed on tofacitinib-treated participants only.

  • Percentage of Participants With BKV DNA Determined Using PCR by Specific Cutoff Categories (in Number of Copies/PCR) and Visit [ Time Frame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98) ] [ Designated as safety issue: Yes ]
    Cutoff categories for BKV DNA were 0-199 and ≥200 copies/PCR. Per protocol, BKV DNA PCR was performed on tofacitinib-treated participants only.

  • Kaplan-Meier Analysis of Percentage of Participants With Cytomegalovirus (CMV) Disease by Visit [ Time Frame: Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96 ] [ Designated as safety issue: Yes ]
    Kaplan-Meier analysis of percentage of participants with CMV disease within 96 months post-transplant. Time was defined from the date of first dose of study drug in Study A3921009 to the date of first occurrence of the event, censored at the day of the last visit or Day 2980 (the maximum scheduled day for follow-up 98 month), whichever comes earlier. CMV disease was an adverse event associated with the preferred term 'CMV infection'.

  • Kaplan-Meier Analysis of Percentage of Participants With First Biopsy-Proven Chronic Allograft Nephropathy (BPCAN) by Visit [ Time Frame: Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96 ] [ Designated as safety issue: Yes ]
    Kaplan-Meier analysis of percentage of participants with first BPCAN by time to first BPCAN within 96 months post-transplant. BPCAN was defined as chronic allograft nephropathy (Category 5 of the Banff Classification), based on the assessment of the renal allograft biopsy by a central, blinded pathologist. Time was defined from the date of first dose of study drug in Study A3921009 to the date of first occurrence of the event, censored at the day of the last visit or Day 2980 (the maximum scheduled day for follow-up 98 month), whichever comes earlier. Includes BPCAN diagnosed on biopsies done for cause and ready by the central pathologist.

  • Cumulative Percentage of Participants With a First Antibody-Mediated Rejection or First BPAR [ Time Frame: Months 12, 18, 24, 36, 48, 60, 72, 84, 96, and Follow-Up (Month 98) ] [ Designated as safety issue: Yes ]
    Antibody-mediated rejection is defined as Category 2 and BPAR is defined as Category 4 of the Banff Classification, based on the assessment of the renal allograft biopsy by a central, blinded pathologist. Acute humoral rejection was categorized as Grades I, II, III and acute/active cellular rejection was categorized as Grades IA, IB, IIA, IIB, and III. Only participants with first BPAR were included.

  • Cumulative Percentage of Participants With Ordered Categorical Severity of First BPCAN [ Time Frame: Months 12, 18, 24, 36, 48, 60, 72, 84, and 96 ] [ Designated as safety issue: Yes ]
    Ordered categorical severity of first BPCAN was classified according to the Banff Classification. Grade I: mild, grade II: moderate and grade III: severe interstitial fibrosis and tubular atrophy/loss. (Racusen et al: The Banff classification, 1999).

  • Kaplan-Meier Analysis of Percentage of Participants With Efficacy Failure by Visit [ Time Frame: Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96 ] [ Designated as safety issue: Yes ]
    Kaplan-Meier analysis of percentage of participants with efficacy failure by time to first efficacy failure within 96 months post-transplant. Time was defined from the date of first dose of study drug in Study A3921009 to the date of first occurrence of the event, censored at the day of the last visit or Day 2980 (the maximum scheduled day for follow-up 98 month), whichever comes earlier. Efficacy failure was defined as first occurrence of BPAR, death, or graft loss.

  • Kaplan-Meier Analysis of Percentage of Participants With Graft Survival by Visit [ Time Frame: Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96 ] [ Designated as safety issue: Yes ]
    Kaplan-Meier analysis of percentage of participants with graft survival by time to graft loss within 96 months post-transplant. Time was defined from the date of first dose of study drug in Study A3921009 to the date of first occurrence of the event, censored at the day of the last visit or Day 2980 (the maximum scheduled day for follow-up 98 month), whichever comes earlier. Graft loss was defined as graft nephrectomy, retransplantation, return to dialysis for ≥6 consecutive weeks, or death.

  • Kaplan-Meier Analysis of Percentage of Participants Surviving by Visit [ Time Frame: Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96 ] [ Designated as safety issue: Yes ]
    Kaplan-Meier analysis of percentage of participants surviving by time to event (death) within 96 months post-transplant. Time was defined from the date of first dose of study drug in Study A3921009 to the date of first occurrence of the event, censored at the day of the last visit or Day 2980 (the maximum scheduled day for follow-up 98 month), whichever comes earlier.

  • Kaplan-Meier Analysis of Percentage of Participants With Rejection by Visit [ Time Frame: Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96 ] [ Designated as safety issue: Yes ]
    Kaplan-Meier analysis of percentage of participants with rejection by time to rejection within 96 months post-transplant. Time was defined from the date of first dose of study drug in Study A3921009 to the date of first occurrence of the event, censored at the day of the last visit or Day 2980 (the maximum scheduled day for follow-up 98 month), whichever comes earlier. Rejection was defined as first occurrence of BPAR, antibody-mediated rejection or suspicious for acute rejection. This included biopsies read by the central pathologist.

  • Absolute Cluster of Differentiation (CD) 8+, CD19+, CD4+, and CD56+ Flouresence Activated Cell Sorting (FACS) Counts (Cells/uL) by Visit [ Time Frame: Months 12 and 24 ] [ Designated as safety issue: No ]
  • Hemoglobin A1c (HbA1c) Levels by Visit [ Time Frame: Months 12, 24, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96 and Follow-up (Month 98) ] [ Designated as safety issue: No ]
  • Homeostatic Model Assessment (HOMA)-%B by Visit [ Time Frame: Months 12 and 24 ] [ Designated as safety issue: No ]
    HOMA-%B = (20 times [*] fasting serum insulin) divided by (/) (fasting serum glucose minus [-] 3.5). HOMA-%B was only performed in participants who were non-diabetic prior to kidney transplantation and who did not require treatment with oral hypoglycemic agents, anti-diabetic agents, and/or insulin prior to the time of measurements.

  • Ratio of Fasting Serum Proinsulin (Pmol/L) to Insulin (Pmol/L) by Visit [ Time Frame: Months 12 and 24 ] [ Designated as safety issue: No ]
    Measured only in participants who were non-diabetic prior to kidney transplantation and who did not require treatment with oral hypoglycemic agents, anti-diabetic agents, and/or insulin prior to the time of measurement.

  • Area Under the Curve (AUC) of Serum Glucose (mg*h/dL) Measured During Oral Glucose Tolerance Test (OGTT) by Visit [ Time Frame: Months 12 and 24 ] [ Designated as safety issue: No ]
    Only performed in participants who were non-diabetic prior to kidney transplantation and who did not require treatment with oral hypoglycemic agents, anti-diabetic agents, and/or insulin.

  • AUC of Serum Insulin (microU*h/mL) Measured During OGTT by Visit [ Time Frame: Months 12 and 24 ] [ Designated as safety issue: No ]
    The OGTT was performed only in participants who were non-diabetic prior to kidney transplantation and who did not require treatment with oral hypoglycemic agents, anti-diabetic agents, and/or insulin.

  • HOMA Insulin Resistance (IR) by Visit [ Time Frame: Months 12 and 24 ] [ Designated as safety issue: No ]
    HOMA-IR=fasting serum insulin*fasting serum glucose/22.5. Measurement only performed in participants who were non-diabetic prior to kidney transplantation and who do not require treatment with oral hypoglycemic agents, anti diabetic agents, and/or insulin prior to the time of measurement.

  • Fasting Serum Glucose Levels (mg/dL) by Visit [ Time Frame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98) ] [ Designated as safety issue: Yes ]
  • Tofacitinib Concentrations in Plasma (ng/mL) by Visit [ Time Frame: Months 9, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-up (Month 98) ] [ Designated as safety issue: No ]
  • Trough Levels of Tacrolimus (ng/mL) by Visit [ Time Frame: Months 9, 12, 18, 24, 30, 36, 42, 48, 54, 60, and 72 and Follow-up (Month 98) ] [ Designated as safety issue: No ]
  • Short-Form 36 Version 2 (SF-36 v2) Mental Component Summary (MCS) and Physical Component Summary (PCS) Scores by Visit and Scale [ Time Frame: Months 12, 18, and 24 ] [ Designated as safety issue: No ]
    The SF-36 is a general health status questionnaire that assesses 8 domains of functional health and well being: Physical Functioning, 36-Item Short-Form Health Survey (SF-36) is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as physical and mental component scores (PCS and MCS). Total of 11 variables were analyzed (8 subscales, 2 composite subscales and Question 2 "how would you rate your health in general now?" (range 1= better, 5= worst). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).

  • Change From Baseline in SF-36 v2 MCS and PCS Scores by Visit and Scale [ Time Frame: Baseline, Months 12, 18, and 24 ] [ Designated as safety issue: No ]
    SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as PCS and MCS. Total of 11 variables were analyzed (8 subscales, 2 composite subscales and Question 2 "how would you rate your health in general now?" (range 1= better, 5= worst). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Negative change from baseline represented improvement.

  • SF-36 v2 Subscale Scores by Visit [ Time Frame: Months 12, 18, and 24 ] [ Designated as safety issue: No ]
    SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as PCS and MCS. Total of 11 variables were analyzed (8 subscales, 2 composite subscales and Question 2 "how would you rate your health in general now?" (range 1= better, 5= worst). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).

  • Change From Baseline in SF-36 v2 Subscale Scores by Visit [ Time Frame: Baseline, Months 12, 18, and 24 ] [ Designated as safety issue: No ]
    SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as PCS and MCS. Total of 11 variables were analyzed (8 subscales, 2 composite subscales and Question 2 "how would you rate your health in general now?" (range 1= better, 5= worst). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Negative change from baseline represented improvement.

  • End Stage Renal Disease Symptom Checklist (ESRD-SCL) Transplanation Module Scores by Visit and Scale [ Time Frame: Months 12, 18, and 24 ] [ Designated as safety issue: No ]
    ESRD-SCL: 43-item, disease-specific, self-administered questionnaire. Participants' rated question "At the moment, how much do you suffer?" for each item on 5-point scale, ranged from 0 (not at all) to 4 (extremely). Consisted of 6 subscales: cardiac and renal dysfunction (Range, 0-28), increased growth of gum and hair (Range, 0-20), limited cognitive capacity (Range, 0-32), limited physical capacity (Range, 0-40), side effects (SEs) of corticosteroids (Range, 0-20), transplantation associated psychological distress (TAPD; Range, 0-32); higher scores=greater dysfunction for each subscale. Total score: 0-172, higher scores=greater dysfunction.

  • Change From Baseline in ESRD-SCL Transplantation Module Scores by Visit and Scale [ Time Frame: Baseline, Months 12, 18, and 24 ] [ Designated as safety issue: No ]
    ESRD-SCL: 43-item, disease-specific, self-administered questionnaire. Participants' rated question "At the moment, how much do you suffer?" for each item on 5-point scale, ranged from 0 (not at all) to 4 (extremely). Consisted of 6 subscales: cardiac and renal dysfunction (Range, 0-28), increased growth of gum and hair (Range, 0-20), limited cognitive capacity (Range, 0-32), limited physical capacity (Range, 0-40), SEs of corticosteroids (Range, 0-20),TAPD (Range, 0-32); higher scores=greater dysfunction for each subscale. Total score: 0-172, higher scores=greater dysfunction.

  • Number of Events Including Visits, Surgeries, Tests or Devices as Assessed Using Health Care Resource Utilization (HCRU) Questionnaire [ Time Frame: Months 12, 18, and 24 ] [ Designated as safety issue: No ]
    HCRU assessed healthcare usage during previous 3 months for direct or indirect medical cost domains. Any number of events including visits to doctor or other healthcare professionals (HCP), non-medical practitioner, hospital ER treatment, hospitalizations, number of surgeries, diagnostic tests, and devices/aids used were reported.


Enrollment: 46
Study Start Date: December 2005
Study Completion Date: June 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Treatment group 1
Standard of care
Drug: Tacrolimus
Standard of care
Experimental: Treatment group 2
Treatment group 2 also receives mycophenolate mofetil
Drug: CP-690,550
CP-690,550 5 mg BID
Experimental: Treatment group 3
Treatment group 3 does not receive mycophenolate mofetil
Drug: CP-690,550
CP-690,550 10 mg BID

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Enrollment in Stage 1 of Study A3921009 and have completed 6-months of treatment with trial medications (CP-690,550 or tacrolimus)
  • Recipient of a first-time kidney transplant

Exclusion Criteria:

  • Subject with any untreated condition that may affect drug absorption (eg, gastrectomy or clinically significant diabetic gastroenteropathy).
  • Subjects who are on the waiting list for a second kidney transplant or any non-renal organ transplants.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00263328

Locations
United States, California
St. Vincent Medical Center
Los Angeles, California, United States, 90057
Transplant Research Institute
Los Angeles, California, United States, 90057
Multi Organ Transplant Center
Los Angeles, California, United States, 90057
Stanford School of Medicine
Palo Alto, California, United States, 94304
Sharp Memorial Hospital
San Diego, California, United States, 92123
California Institute of Renal Research
San Diego, California, United States, 92123
Balboa Institute of Transplantation
San Diego, California, United States, 92123
California Pacific Medical Center
San Francisco, California, United States, 94115
University of California, San Francisco, Kidney Transplant Unit
San Francisco, California, United States, 94143
Stanford University Medical Center
Stanford, California, United States, 94305
United States, Colorado
University of Colorado Health Sciences Center
Aurora, Colorado, United States, 80045
University of Colorado Health Sciences Center Renal Clinical Trials Office
Aurora, Colorado, United States, 80045
United States, Illinois
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
Northwestern University-Feinberg School of Medicine, Division of Organ Transplantation
Chicago, Illinois, United States, 60611
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New York
Recanati/Miller Transplantation Institute
New York, New York, United States, 10029
New York Presbyterian Hospital / Weill Cornell Medical Center
New York, New York, United States, 10065
Jack J Dreyfus Clinic
New York, New York, United States, 10021
United States, Oregon
Northwest Renal Clinic
Portland, Oregon, United States, 97210
Legacy Good Samaritan Hospital
Portland, Oregon, United States, 97210
Legacy Transplant Services
Portland, Oregon, United States, 97210
United States, Texas
Annette C & Harold C Simmons Transplant Institute
Dallas, Texas, United States, 75246
Baylor University Medical Center
Dallas, Texas, United States, 75246
Dallas Transplant Institute
Dallas, Texas, United States, 75204
Baylor All Saints Medical Center
Fort Worth, Texas, United States, 76104
United States, Wisconsin
Froedtert Memorial Lutheran Hospital
Milwaukee, Wisconsin, United States, 53226
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00263328     History of Changes
Other Study ID Numbers: A3921021
Study First Received: December 6, 2005
Results First Received: April 2, 2015
Last Updated: June 16, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
immunosuppression
JAK3 inhibitor
kidney transplant
tofacitinib
Xeljanz
CP-690
550
tacromilus
mycophenolate mofetil

Additional relevant MeSH terms:
Mycophenolate mofetil
Mycophenolic Acid
Tacrolimus
Tofacitinib
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on July 30, 2015