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Trial record 1 of 1 for:    NCT01712061
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A Phase 2 Multi-Center Study To Evaluate The Efficacy And Safety Of A Chemokine CCR2/5 Receptor Antagonist In Adults With Type 2 Diabetes And Overt Nephropathy

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ClinicalTrials.gov Identifier: NCT01712061
Recruitment Status : Completed
First Posted : October 23, 2012
Results First Posted : October 21, 2015
Last Update Posted : October 21, 2015
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE October 19, 2012
First Posted Date  ICMJE October 23, 2012
Results First Submitted Date  ICMJE September 22, 2015
Results First Posted Date  ICMJE October 21, 2015
Last Update Posted Date October 21, 2015
Study Start Date  ICMJE December 2012
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 22, 2015)
Percent Reduction From Baseline in Urinary Albumin to Creatinine Ratio (UACR) at Week 12 [ Time Frame: Baseline and Week 12 ]
The presence of albumin in the urine (macroalbuminuria) is a marker of kidney disease. Albumin and creatinine concentrations were obtained from spot urine samples.
Original Primary Outcome Measures  ICMJE
 (submitted: October 19, 2012)
Urinary albumin:creatinine ratio [ Time Frame: 12 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 22, 2015)
  • Change From Baseline in UACR at Weeks 4, 8 and 16 [ Time Frame: Baseline, Weeks 4, 8 and 16 ]
    The presence of albumin in the urine (macroalbuminuria) is a marker of kidney disease. Albumin and creatinine concentrations were obtained from spot urine samples.
  • Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) at Weeks 4, 8, 12 and 16 [ Time Frame: Baseline, Weeks 4, 8, 12 and 16 ]
    The presence of protein in the urine (proteinuria) often implies kidney disease. Protein and creatinine concentrations were obtained from spot urine samples.
  • Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Abbreviated Modified Diet in Renal Disease (MDRD) Formula at Weeks 1, 4, 8, 12 and 16 [ Time Frame: Baseline, Week 1, 4, 8, 12 and 16 ]
    eGFR was calculated using the MDRD equation and normalized to 1.73 m^2 body surface area. Age and corresponding creatinine at each visit (Weeks 1, 4, 8, 12 and 16) were used to calculate GFR
  • Change From Baseline in eGFR Using Cystatin Formula at Weeks 12 and 16 [ Time Frame: Baseline, Week 12, and Week 16 ]
    Serum cystatin C may be a more reliable endogenous marker of GFR than serum creatinine. eGFR was calculated using the Cystatin Formula and normalized to 1.73 m^2 body surface area.
  • Change From Baseline in Serum Creatinine at Weeks 1, 4, 8, 12 and 16 [ Time Frame: Baseline, Week 1, 4, 8, 12 and 16 ]
    Serum creatinine is an indicator of kidney function. Creatinine is a substance formed from the metabolism of creatine, commonly found in blood, urine, and muscle tissue. It is removed from the blood by the kidneys and excreted in urine. Normal adult blood levels of creatinine=45 to 90 micromoles per liter (mcmol/L) for females, 60 to 110 mcmol/L for males, however normal values are age-dependent. Change from baseline=creatinine level at Week 1, 4, 8, 12 or 16 minus baseline level where higher scores represented decreased kidney function.
  • Change From Baseline in Serum Cystatin C at Weeks 12 and 16 [ Time Frame: Baseline, Week 12, and Week 16 ]
    Cystatin C is a protein which is mainly used as a biomarker of kidney function. If kidney function and GFR decline, the blood levels of cystatin C rise.
  • Change From Baseline in Plasma Glycosylated Hemoglobin (HbA1c) at Weeks 4, 8, 12 and 16 [ Time Frame: Baseline, Weeks 4, 8, 12 and 16 ]
    HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. As the average amount of plasma glucose increases, the fraction of HbA1c increases in a predictable way.
  • Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 12 [ Time Frame: 1, 2, 4 hours post-dose on Day 1; 2 hours post-dose on Weeks 1, 4, 8 and 12 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 19, 2012)
  • Urinary albumin:creatinine ratio [ Time Frame: 4 weeks ]
  • Urinary albumin:creatinine ratio [ Time Frame: 8 weeks ]
  • Urinary albumin:creatinine ratio [ Time Frame: 16 weeks ]
  • Urinary protein:creatinine ratio [ Time Frame: 4 weeks ]
  • Urinary protein:creatinine ratio [ Time Frame: 8 weeks ]
  • Urinary protein:creatinine ratio [ Time Frame: 12 weeks ]
  • Urinary protein:creatinine ratio [ Time Frame: 16 weeks ]
  • Estimated glomerular filtration rate (eGFR) using the abbreviated (4 variable) Modification of Diet in Renal Disease (MDRD) formula [ Time Frame: 1 week ]
  • Estimated glomerular filtration rate (eGFR) using the abbreviated (4 variable) Modification of Diet in Renal Disease (MDRD) formula [ Time Frame: 4 weeks ]
  • Estimated glomerular filtration rate (eGFR) using the abbreviated (4 variable) Modification of Diet in Renal Disease (MDRD) formula [ Time Frame: 8 weeks ]
  • Estimated glomerular filtration rate (eGFR) using the abbreviated (4 variable) Modification of Diet in Renal Disease (MDRD) formula [ Time Frame: 12 weeks ]
  • Estimated glomerular filtration rate (eGFR) using the abbreviated (4 variable) Modification of Diet in Renal Disease (MDRD) formula [ Time Frame: 16 weeks ]
  • Estimated glomerular filtration rate (eGFR) using the eGFRcystatin formula [ Time Frame: 12 weeks ]
  • Estimated glomerular filtration rate (eGFR) using the eGFRcystatin formula [ Time Frame: 16 weeks ]
  • Serum creatinine [ Time Frame: 1 week ]
  • Serum creatinine [ Time Frame: 4 weeks ]
  • Serum creatinine [ Time Frame: 8 weeks ]
  • Serum creatinine [ Time Frame: 12 weeks ]
  • Serum creatinine [ Time Frame: 16 weeks ]
  • Serum cystatin C [ Time Frame: 12 weeks ]
  • Serum cystatin C [ Time Frame: 16 weeks ]
  • Plasma glycosylated hemoglobin [ Time Frame: 4 weeks ]
  • Plasma glycosylated hemoglobin [ Time Frame: 8 weeks ]
  • Plasma glycosylated hemoglobin [ Time Frame: 12 weeks ]
  • Plasma glycosylated hemoglobin [ Time Frame: 16 weeks ]
Current Other Pre-specified Outcome Measures
 (submitted: September 22, 2015)
  • Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 [ Time Frame: Baseline, Weeks 1, 4, 8, 12 and 16 ]
  • Change From Baseline in Pulse Rate at Weeks 1, 4, 8, 12 and 16 [ Time Frame: Baseline, Weeks 1, 4, 8, 12 and 16 ]
  • Change From Baseline in Body Weight at Weeks 1, 4, 8, 12 and 16 [ Time Frame: Baseline, Weeks 1, 4, 8, 12 and 16 ]
  • Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern [ Time Frame: Baseline up to Week 16 (follow-up visit) ]
    The following laboratory parameters were analyzed for abnormalities at any time point mentioned in the timeframe: clinical chemistry (sodium, potassium, chloride, bicarbonate, phosphate, glucose, blood urea nitrogen [BUN], creatinine, albumin, calcium, bilirubin [total, direct, and indirect], gamma-glutamyl transferase [GGT], alanine aminotransferase [ALT], aspartate aminotransferase [AST], lactic dehydrogenase [LDH], alkaline phosphatase, creatine phosphokinase [CPK], uric acid, amylase and lipase); hematology (hemoglobin, hematocrit, red blood cell [RBC] count, white blood cell [WBC] count with differential, and platelet count); FSH (for postmenopausal women who had been amenorrheic for less than 2 years prior to screening).
  • Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings [ Time Frame: Baseline, Weeks 1, 4 and 12 ]
    Criteria for potentially clinically important ECG values were defined as: PR interval >=300 milliseconds (msec) or >=25%/50% increase when baseline is >200 msec and ≥50% increase when baseline is less than or equal to (<=)200 msec; QRS interval >=140 msec or >=50% increase from baseline (IFB); QTc >=450 msec or >=30 msec increase; corrected QT interval using Fridericia's formula (QTcF) >=450 msec or >=30 msec increase.
  • Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 28 days after last study drug administration ]
    An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. A 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 treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-serious AEs.
  • Number of Participants With Increased Fasting Blood Glucose [ Time Frame: Baseline up to Week 16 (follow-up visit) ]
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 2 Multi-Center Study To Evaluate The Efficacy And Safety Of A Chemokine CCR2/5 Receptor Antagonist In Adults With Type 2 Diabetes And Overt Nephropathy
Official Title  ICMJE A Phase 2, Randomized, Double-blind, Placebo-controlled, Parallel Group, Multi-center Study To Evaluate The Efficacy And Safety Of Once-daily Administration Of A Chemokine Ccr2/5 Receptor Antagonist (Pf-04634817) In Adults With Type 2 Diabetes And Overt Nephropathy
Brief Summary The study hypothesis under test is that administration of a CCR2/5 antagonist to subjects with type 2 diabetes and overt nephropathy will result in a reduction in urinary albumin, a surrogate for improved glomerular filtration.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Diabetic Nephropathy
Intervention  ICMJE
  • Drug: PF-04634817
    Three or four tablets (50mg) daily for 12 weeks, depending on baseline renal function
  • Drug: Placebo
    Three or four tablets (50mg) daily for 12 weeks, depending on baseline renal function
Study Arms  ICMJE
  • Active Comparator: Arm 1 PF-04634817
    Intervention: Drug: PF-04634817
  • Placebo Comparator: Arm 2 Placebo
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 20, 2014)
226
Original Estimated Enrollment  ICMJE
 (submitted: October 19, 2012)
176
Actual Study Completion Date  ICMJE September 2014
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Clinical diagnosis of type 2 diabetes together with stages 2, 3a, 3b or 4 CKD, based on an eGFR of 20-75 mL/min/1.73m2.
  • Evidence of persistent, overt albuminuria; defined as a UACR >=300 mg/g (>=33.9 mg/mmol) or UPCR >=390 mg/g (44.1 mg/mmol), or equivalent, for 3 months or longer.
  • Stable background therapy of RAAS inhibition (ie, an ACE inhibitor and/or an ARB, which may also include an aldosterone antagonist in double RAAS but not triple RAAS inhibitor therapy) for at least 3 months before screening and to be maintained for the duration of the study.

Exclusion Criteria:

  • Subjects with CKD resulting from type 1 diabetes or non-diabetic CKD.
  • Subjects who are diagnosed with autosomal dominant polycystic kidney disease (ADPCKD), severe peripheral vascular disease (PVD) or obstructive uropathy.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Canada,   Germany,   Hong Kong,   Italy,   Korea, Republic of,   Malaysia,   Peru,   Poland,   Puerto Rico,   Romania,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01712061
Other Study ID Numbers  ICMJE B1261007
2012-003332-23 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date September 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP