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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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01712061
First received: October 19, 2012
Last updated: September 22, 2015
Last verified: September 2015
  Purpose
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.

Condition Intervention Phase
Diabetic Nephropathy
Drug: PF-04634817
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Percent Reduction From Baseline in Urinary Albumin to Creatinine Ratio (UACR) at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    The presence of albumin in the urine (macroalbuminuria) is a marker of kidney disease. Albumin and creatinine concentrations were obtained from spot urine samples.


Secondary Outcome Measures:
  • Change From Baseline in UACR at Weeks 4, 8 and 16 [ Time Frame: Baseline, Weeks 4, 8 and 16 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Pulse Rate at Weeks 1, 4, 8, 12 and 16 [ Time Frame: Baseline, Weeks 1, 4, 8, 12 and 16 ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Body Weight at Weeks 1, 4, 8, 12 and 16 [ Time Frame: Baseline, Weeks 1, 4, 8, 12 and 16 ] [ Designated as safety issue: Yes ]
  • Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern [ Time Frame: Baseline up to Week 16 (follow-up visit) ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]

Enrollment: 226
Study Start Date: December 2012
Study Completion Date: September 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1 PF-04634817 Drug: PF-04634817
Three or four tablets (50mg) daily for 12 weeks, depending on baseline renal function
Placebo Comparator: Arm 2 Placebo Drug: Placebo
Three or four tablets (50mg) daily for 12 weeks, depending on baseline renal function

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT01712061

  Show 142 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01712061     History of Changes
Other Study ID Numbers: B1261007  2012-003332-23 
Study First Received: October 19, 2012
Results First Received: September 22, 2015
Last Updated: September 22, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Diabetic nephropathy
type 2 diabetes
albuminuria
chemokine antagonist

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Kidney Diseases
Diabetic Nephropathies
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Urologic Diseases
Diabetes Complications

ClinicalTrials.gov processed this record on September 23, 2016