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A 6-Month Study Of CP-690,550 Versus Tacrolimus In Kidney Transplant Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00106639
First received: March 28, 2005
Last updated: February 6, 2013
Last verified: February 2013
  Purpose

This Phase 2 study was designed to evaluate the safety and efficacy of 2 dose levels of CP-690,550 (15 mg twice daily and 30 mg twice) against tacrolimus, in combination with basiliximab induction, mycophenolate mofetil and corticosteroids, in kidney transplant patients. Stage 1 was to randomize approximately 54 subjects. After all Stage 1 subjects had completed 6 months of treatment, Stage 2 was to randomize an additional 195 subjects to the same treatment groups.


Condition Intervention Phase
Kidney Transplantation
Drug: CP-690,550
Drug: tacrolimus
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 6-Month, Phase 2, Multicenter, Randomized, Open-Label, Comparative Study Of 2 Dose Levels Of CP-690,550 Administered Concomitantly With IL-2 Receptor Antagonist Induction Therapy, Mycophenolate Mofetil And Corticosteroids Versus A Tacrolimus-Based Immunosuppressive Regimen For The Prevention Of Allograft Rejection In De Novo Renal Allograft Recipients

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of Participants With First Biopsy Proven Acute Rejection (BPAR) at Month 6 [ Time Frame: Baseline up to Month 6 ] [ Designated as safety issue: No ]
    BPAR categorized as acute rejection as interpreted by the central blinded pathologist according to the Banff 97 working classification.

  • Glomerular Filtration Rate (GFR) by Nankivell Equation at Month 6 [ Time Frame: Month 6 ] [ Designated as safety issue: Yes ]
    GFR: index of kidney function described the flow rate of filtered fluid through the kidney. GFR was measured directly or estimated using established formulas. GFR was calculated by creatinine clearance (CLcr) using Nankivell equation. CLcr by Nankivell equation= (6.7 per serum creatinine) plus (0.25*body weight) minus (0.5*serum urea) minus (100 per square height) plus (35 for male/25 for female). A normal GFR is >90 milliliter/minute (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.


Secondary Outcome Measures:
  • Number of Participants With Treatment Failure [ Time Frame: Month 3, 6 ] [ Designated as safety issue: Yes ]
    Treatment failure was defined as the first occurrence of BPAR, graft loss, participant's death or premature discontinuation of study medication for any reason.

  • Number of Participants With First Biopsy Proven Acute Rejection (BPAR) at Month 3 [ Time Frame: Baseline up to Month 3 ] [ Designated as safety issue: No ]
    BPAR categorized as acute rejection as interpreted by the central blinded pathologist according to the Banff 97 working classification.

  • Number of Participants With First Biopsy Proven Chronic Allograft Nephropathy (BPCAN) [ Time Frame: Month 3, 6 ] [ Designated as safety issue: No ]
    BPCAN categorized as chronic allograft nephropathy as interpreted by the central blinded pathologist according to the Banff 97 working classification.

  • Number of Participants With Ordered Categorical Severity of First Biopsy Proven Acute Rejection (BPAR) [ Time Frame: Month 3, 6 ] [ Designated as safety issue: No ]
    Ordered categorical severity of first BPAR was classified according to the Banff Classification. Grade IA: moderate tubulitis, grade IB: severe tubulitis, grade IIA: mild to moderate intimal arteritis, grade IIB: severe intimal arteritis, grade III: transmural arteritis. (Racusen et al: The Banff classification, 1999).

  • Number of Participants With Ordered Categorical Severity of First Biopsy Proven Chronic Allograft Nephropathy (BPCAN) [ Time Frame: Month 3, 6 ] [ Designated as safety issue: No ]
    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).

  • Number of Participants With Efficacy Failure [ Time Frame: Month 3, 6 ] [ Designated as safety issue: No ]
    Efficacy failure was the first occurrence of BPAR, graft loss or participant's death.

  • Number of Participants With Graft Loss [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
    Graft loss was defined as graft nephrectomy, participant's death due to graft loss, re-transplantation, or return to dialysis for greater than or equal to (>=) 6 consecutive weeks.

  • Number of Participants Who Died [ Time Frame: Month 6 ] [ Designated as safety issue: Yes ]
  • Number of Participants With Rejection [ Time Frame: Month 3, 6 ] [ Designated as safety issue: Yes ]
    Rejection was defined as first occurrence of BPAR, antibody mediated rejection, or suspicious for acute rejection.

  • Population Pharmacokinetics (PK) [ Time Frame: Pre-dose on Day 1, 3, 7, 14, Month 1, 3, 6, between 1 to 2 hours post-dose at Month 3 and between 3 to 4 hours post-dose at Month 6 ] [ Designated as safety issue: No ]
    Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.

  • Fluorescence-Activated Cell Sorting (FACS) of Lymphocyte Subsets [ Time Frame: Baseline, Day 14, Month 1, 3, 6 ] [ Designated as safety issue: No ]
    The absolute cell counts of cluster of differentiation 8 (CD8): Cytotoxic T-lymphocytes reactive with major histocompatibility complex-1 (MHC-I), CD19: B- Lymphocytes, CD56: natural killer cells were determined using FACS, a specialized type of flow cytometry which sorts a heterogeneous mixture based upon the specific light scattering and fluorescent characteristics of each cell.

  • Reticulocyte Count [ Time Frame: Baseline, Day 14, Month 1, 3, 6 ] [ Designated as safety issue: Yes ]
    Reticulocytes are slightly immature red blood cells in the blood. Reticulocyte counts are reported as cells*10^3 per cubic millimeter (cells*10^3/mm^3).

  • Trough Levels of Tacrolimus (TAC) [ Time Frame: Pre-dose on Day 14, Month 1, 3, 6 ] [ Designated as safety issue: Yes ]
  • 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) [ Time Frame: Baseline, Month 6 ] [ 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 physical and mental component scores (CS). 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).

  • End-Stage Renal Disease Symptom Checklist-Transplantation Module (ESRD-SCL) [ Time Frame: Baseline, Month 6 ] [ 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 (Ra) 0(not at all)to 4(extremely).Consisted of 6 subscales:cardiac and renal dysfunction;Ra 0-28,increased(In) growth of gum and hair;Ra 0-20,limited cognitive capacity;Ra 0-32,limited physical capacity;Ra 0-40,side effects (SEs) of corticosteroids;Ra 0-20,transplantation associated psychological distress(TAPD);Ra 0-32(higher scores=greater dysfunction for each subscale).Total score:0-172,higher scores=greater dysfunction.

  • Healthcare Resource Utilization Questionnaire (HCRUQ) [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: No ]
    Healthcare Resource Utilization Questionnaire (HCRUQ) was used to assess healthcare resources which included number of events such as physician and other health professional visits, number of treatments or diagnostic tests, number of hospitalizations, and number of emergency room visits.

  • Healthcare Resource Utilization Questionnaire (HCRUQ) - 5th Question [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
    Fifth question in the HCRUQ was "Upon discharge from the hospital, did you return to your previous place of residence?" and number of participants who responded "yes or no" to the question was reported.

  • Glomerular Filtration Rate (GFR) by Cockcroft-Gault [ Time Frame: Day 14, Month 1, 3, 6 ] [ Designated as safety issue: Yes ]
    GFR: index of kidney function described the flow rate of filtered fluid through the kidney. GFR was measured directly or estimated using established formulas. GFR was calculated using Cockcroft-Gault equation. GFR by Cockcroft-Gault equation= body weight*(140 minus age in years) divided by (72*serum creatinine). 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.

  • Glomerular Filtration Rate (GFR) by Modification of Diet in Renal Disease (MDRD) Equation [ Time Frame: Day 14, Month 1, 3, 6 ] [ Designated as safety issue: Yes ]
    GFR: index of kidney function described the flow rate of filtered fluid through the kidney. GFR was measured directly or estimated using established formulas. GFR was calculated using MDRD equation. GFR by MDRD equation= 170 * (serum creatinine) ^ (-0.999)*(age in years)^(-0.176)*(0.762 if female) * (1.18 if black)*(blood urea nitrogen concentration)^(-0.170)*(serum albumin concentration)^(0.318). Normal GFR is >90 mL/min/1.73 square meter (m^2), although children and older people usually have a lower GFR. Lower values indicated poor kidney function. A GFR <15 mL/min indicated kidney failure.

  • Glomerular Filtration Rate (GFR) by Reciprocal of Serum Creatinine (1/sCr) [ Time Frame: Day 14, Month 1, 3, 6 ] [ Designated as safety issue: Yes ]
    GFR is a measure of renal function. The reciprocal of serum creatinine is an estimate of GFR.

  • Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Month 8 (2 months follow-up) ] [ Designated as safety issue: Yes ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 2 months after last dose that were absent before treatment or that worsened relative to pretreatment state.

  • Number of Participants With First Clinically Significant Infection [ Time Frame: Month 3, 6 ] [ Designated as safety issue: Yes ]
    Clinically significant (Viral, Bacterial and Fungal) infection was defined as the presence of presumed or documented infection confirmed by culture, biopsy, genomic or serologic findings post-randomization and required hospitalization or anti-infective treatment, or otherwise deemed significant by the Investigator.

  • Number of Participants With New Onset Diabetes Mellitus (NODM) [ Time Frame: Month 3, 6 ] [ Designated as safety issue: Yes ]
  • Fasting Serum Glucose Levels [ Time Frame: Baseline, Day 14, Month 1, 3, 6 ] [ Designated as safety issue: Yes ]
  • Number of Participants With Hypercholesterolemia [ Time Frame: Baseline, Day 14, Month 1, 3, 6 ] [ Designated as safety issue: Yes ]
    Hypercholesterolemia is a condition characterized by very high levels of cholesterol in the blood. Hypercholesterolemia was defined as a value of total serum cholesterol greater than 240 mg/dL.

  • Total Serum Cholesterol, Low Density Lipoprotein (LDL) and High Density Lipoprotein (HDL) Levels [ Time Frame: Baseline, Day 14, Month 1, 3, 6 ] [ Designated as safety issue: Yes ]
  • Number of Participants With Hypertriglyceridemia [ Time Frame: Baseline, Day 14, Month 1, 3, 6 ] [ Designated as safety issue: Yes ]
    Hypertriglyceridemia was defined as a value of triglycerides greater than 200 mg/dL.

  • Supine Systolic and Diastolic Blood Pressure (BP) [ Time Frame: Baseline, Day 2, 3, 14, Month 1, 3, 6 ] [ Designated as safety issue: Yes ]
  • Number of Participants With Drug Usage [ Time Frame: Baseline, Day 14, Month 1, 3, 6 ] [ Designated as safety issue: No ]
    Lipid lowering agents, antihypertensive agents, oral hypoglycemic agents (OHA) , anti-diabetic agents (ADA) and insulin drug usage was collected.

  • Epstein Barr Virus (EBV) and Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) Load [ Time Frame: Baseline, Month 1, 3, 6 for CMV; Baseline, Day 14, Month 1, 3, 6 for EBV ] [ Designated as safety issue: Yes ]
  • BK Virus (BKV) Deoxyribonucleic Acid (DNA) Load [ Time Frame: Baseline, Month 1, 3, 6 ] [ Designated as safety issue: Yes ]
  • Number of Participants With Cytomegalovirus (CMV) Disease [ Time Frame: Month 3, 6 ] [ Designated as safety issue: Yes ]
  • Total White Blood Cells (WBC), Absolute Basophil, Absolute Eosinophil, Absolute Lymphocyte, Absolute Monocyte, Absolute Neutrophil [ Time Frame: Baseline, Day 14, Month 1, 3, 6 ] [ Designated as safety issue: Yes ]
  • Absolute Platelet Levels [ Time Frame: Baseline, Day 14, Month 1, 3, 6 ] [ Designated as safety issue: Yes ]
  • Hemoglobin Level [ Time Frame: Baseline, Day 14, Month 1, 3, 6 ] [ Designated as safety issue: Yes ]
    Hemoglobin is the protein molecule in red blood cells that carries oxygen from the lungs to the body's tissues and returns carbon dioxide from the tissues back to the lungs.

  • Hematocrit Level [ Time Frame: Baseline, Day 14, Month 1, 3, 6 ] [ Designated as safety issue: Yes ]
    The hematocrit is recorded as the percentage of volume of red blood cells (RBCs) in a blood sample.

  • Alanine Aminotransferase (ALT) Level [ Time Frame: Baseline, Day 14, Month 1, 3, 6 ] [ Designated as safety issue: Yes ]
    ALT is the enzyme found in the liver and it is measured to see if the liver is damaged or diseased.

  • Electrocardiogram (ECG) Parameters [ Time Frame: Baseline, Month 3, 6 ] [ Designated as safety issue: Yes ]
    ECG parameters included PR interval, QT interval, corrected QT using Bazett's formula (QTcB) and QTc using Fridericia's formula (QTcF) interval, and QRS width.

  • Number of Participants With Discontinuation [ Time Frame: Month 1, 2, 3, 4, 5, 6 ] [ Designated as safety issue: No ]

Enrollment: 61
Study Start Date: May 2005
Study Completion Date: July 2006
Primary Completion Date: July 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CP-690,550 15 mg BID Drug: CP-690,550
15 mg twice daily
Experimental: CP-690,550 30 mg BID Drug: CP-690,550
30 mg twice daily
Active Comparator: tacrolimus Drug: tacrolimus
dose adjusted according to level

  Eligibility

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

Inclusion Criteria:

  • Recipient of a first-time kidney transplant
  • Between the ages of 18 and 70 years, inclusive

Exclusion Criteria:

  • Recipient of any non-kidney transplant
  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: NCT00106639

Locations
United States, California
Pfizer Investigational Site
Los Angeles, California, United States, 90057
Pfizer Investigational Site
Los Angeles, California, United States, 92356
Pfizer Investigational Site
Palo Alto, California, United States, 94304
Pfizer Investigational Site
San Diego, California, United States, 92123
Pfizer Investigational Site
San Francisco, California, United States, 94143-0780
Pfizer Investigational Site
San Francisco, California, United States, 94115
Pfizer Investigational Site
Stanford, California, United States, 94305
United States, Colorado
Pfizer Investigational Site
Denver, Colorado, United States, 80262
United States, Illinois
Pfizer Investigational Site
Chicago, Illinois, United States, 60611
United States, Louisiana
Pfizer Investigational Site
New Orleans, Louisiana, United States, 70112
United States, Missouri
Pfizer Investigational Site
St. Louis, Missouri, United States, 63110
Pfizer Investigational Site
St. Louis, Missouri, United States, 63110-1092
United States, New Jersey
Pfizer Investigational Site
Livingston, New Jersey, United States, 07039
United States, New York
Pfizer Investigational Site
New York, New York, United States, 10029
Pfizer Investigational Site
New York, New York, United States, 10021
United States, Oregon
Pfizer Investigational Site
Portland, Oregon, United States, 97210
United States, Texas
Pfizer Investigational Site
Dallas, Texas, United States, 75246
Pfizer Investigational Site
Dallas, Texas, United States, 75204
United States, Virginia
Pfizer Investigational Site
Richmond, Virginia, United States, 23298
United States, Wisconsin
Pfizer Investigational Site
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: NCT00106639     History of Changes
Other Study ID Numbers: A3921009
Study First Received: March 28, 2005
Results First Received: December 6, 2012
Last Updated: February 6, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
tofacitinib
CP-690550
kidney transplant

Additional relevant MeSH terms:
Tacrolimus
Tofacitinib
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on November 24, 2014