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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetic Nephropathy
• Intervention / Treatment: Drug: PF-04634817; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 226
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Corrientes, Argentina, W3400AMZ
    • Instituto de Cardiología de Corrientes "Juana Francisca Cabral"
  • Santa Fe, Argentina, 3000
    • Centro de Investigaciones Clinicas del Litoral S.R.L.
  • Tucumán, Argentina, T4000IIO
    • CETENE S.A. - Centro de Nefrologia y Dialisis
  • Buenos Aires
    • Junin, Buenos Aires, Argentina, 6000
      • Centro de Salud Renal Junin S.R.L.
    • Mar del Plata, Buenos Aires, Argentina, B7600DHK
      • Centro de Investigaciones Medicas - Clinica de Fracturas y Ortopedia
    • Quilmes, Buenos Aires, Argentina, B1878GEG
      • Instituto de Investigaciones Clinicas Quilmes S.R.L
• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital
    • New Lambton, New South Wales, Australia, 2305
      • Department of Nephrology
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital, Department of Renal Medicine
  • Queensland
    • Nambour, Queensland, Australia, 4560
      • Sunshine Coast Hospital & Health Service
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1L8
      • Vancouver General Hospital
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • BC Diabetes.ca
  • Ontario
    • Courtice, Ontario, Canada, L1E 3C3
      • Co-Medica Research Network Inc.
    • Scarborough, Ontario, Canada, M1H 3G4
      • OTT Healthcare Incorporated
    • Toronto, Ontario, Canada, M4C 5T2
      • Toronto East General Medical Centre
    • Toronto, Ontario, Canada, M4C 5T2
      • Dr. Stephen S. Chow Medicine Professional Corporation
  • Quebec
    • Laval, Quebec, Canada, H7T 2P5
      • Centre de Recherche Clinique de Laval
    • Montreal, Quebec, Canada, H1T 2M4
      • Hopital Maisonneuve-Rosemont-Nephrology
    • Montreal, Quebec, Canada, H4J 1C5
      • Hopital Du Sacre-Coeur de Montreal Centre de recherche
    • St-Romuald, Quebec, Canada, G6W 5M6
      • Pro-Recherche
• Germany
  • Aschaffenburg, Germany, 63739
    • Studienzentrum Haematologie/Onkologie/Diabetologie
  • Berlin, Germany, 10117
    • Universitätsmedizin Berlin - Charité Campus Mitte
  • Dresden, Germany, 01307
    • GWT-TUD GmbH
  • Duesseldorf, Germany, 40210
    • Studienzentrum Karlstrasse GmbH
  • Essen, Germany, 45136
    • Profil Institut fuer Stoffwechselforschung GmbH (branch: Diabetes Praxis Essen)
  • Falkensee, Germany, 14612
    • Diabetes Schwerpunktpraxis / Zentrum fur Klinische Studien
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Hoyerswerda, Germany, 02977
    • Nephrologisches Zentrum Hoyerswerda
  • Neuwied, Germany, D-56564
    • Zentrum Klinische Studien Neuwied
  • Schwabenheim, Germany, 55270
    • Diabetologische Schwerpunktpraxis
  • Brandenburg
    • Herzberg, Brandenburg, Germany, 04916
      • Dialysezentrum Elsterland
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Hong Kong SAR
    • Shatin, New Territories, Hong Kong SAR, Hong Kong
      • Department of Medicine and Therapeutics, Prince of Wales Hospital,
    • Shatin, New Territories, Hong Kong SAR, Hong Kong
      • Department of Medicine and Therapeutics
• Italy
  • Foggia, Italy, 71100
    • Azienda Ospedaliera Ospedali Riuniti di Foggia
  • Lecco, Italy, 23900
    • Ospedale Alessandro Manzoni
  • Milano, Italy, 20132
    • Unita Cardiometabolica e Trials Clinici
  • Pavia, Italy, 27100
    • Fondazione Salvatore Maugeri Clinica del Lavoro e della Riabilitazione IRCCS
  • BA
    • Bari, BA, Italy, 70124
      • AOU Consorziale Policlinico di Bari
  • Lucca
    • Lido Camaiore. (Lucca), Lucca, Italy, 55041
      • Ospedale Versilia
    • Lido di Camaiore (LUCCA), Lucca, Italy, 55043
      • *Ospedale Versilia
    • Lido di Camaiore (LUCCA), Lucca, Italy, 55043
      • Ospedale Versilia
  • MO
    • Modena, MO, Italy, 41124
      • A.O.U. Policlinico di Modena
• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 156-755
    • Chung-Ang University Hospital
  • Seoul, Korea, Republic of, 120-752
    • Yonsei University College of Medicine, Severance Hospital
• Malaysia
  • Kelantan
    • Kubong Kerian, Kelantan, Malaysia, 16150
      • Hospital Universiti Sains Malaysia
  • Perak
    • Taiping, Perak, Malaysia, 34000
      • Hospital Taiping
  • Selangor
    • Batu Caves, Selangor, Malaysia, 68100
      • Selayang Hospital
• Peru
  • Lima, Peru, 17
    • Casa de Diabetes y Nutricion
  • Lima, Peru, 27
    • Centro de Investigacion y Atencion Cardiovascular S.A.C. - Clinica Novocardio
  • Lima, Peru, 27
    • Consultorio de Endocrinologia - LM Servicios Medicos y Endocrinologicos EIRL
  • Lima, Peru, LIMA 33
    • Clinica Maison de Sante ¿ Sede este
  • Piura, Peru, 073
    • Clinica Virgen Maria Auxiliadora
• Poland
  • Golub-Dobrzyn, Poland, 87-400
    • Stacja Dializ
  • Krakow, Poland, 30-015
    • Landa Specjalistyczne Gabinety Lekarskie
  • Krakow, Poland, 31-559
    • SCM Sp. z.o.o
  • Lodz, Poland, 93-338
    • NZOZ TRI-medica
  • Lodz, Poland, 92-013
    • Klinika Nefrologii, Hipertensjologii i Transplantologii Nerek
  • Warszawa, Poland, 02-507
    • CSK MSW w Warszawie Klinika Chorob Wewnetrznych Endokrynologii i Diabetologii
  • Zamosc, Poland, 22-400
    • KO-MED, Central Kliniczne Sp. z.o.o
  • Malopolskie
    • Krakow, Malopolskie, Poland, 31-501
      • Krakowskie Centrum Medyczne Sp. z.o.o.
• Puerto Rico
  • Ponce, Puerto Rico, 00716
    • Ponce School of Medicine - CAIMED Center
  • Rio Piedras, Puerto Rico, 00935
    • Medical Sciences Campus University of Puerto Rico
• Romania
  • Bucuresti, Romania, 020475
    • Institutul National De Diabet, Nutritie si Boli Metabolice
  • Ploiesti, Romania, 100018
    • Elit Medical SRL, Diabet Zaharat Nutritie si Boli Metabolice
  • Timisoara, Romania, 300736
    • Spitalul Clinic Judetean de Urgenta Timisoara
  • jud. Bihor
    • Oradea, jud. Bihor, Romania, 410469
      • Spital Clinic Municipal "Dr. Gavril Curteanu" Oradea
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain, 08003
    • Parc de Salut Mar. Hospital del Mar
  • Girona, Spain, 17007
    • Hospital Universitari de Girona Dr. Josep Trueta
  • Valencia, Spain, 46017
    • Hospital Universitario Dr Peset
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitario de Bellvitge
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Puerta de Hierro
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Medical Investigations, Inc.
  • California
    • Azusa, California, United States, 91702
      • North America Research Institute
    • Chula Vista, California, United States, 91910
      • California Institute of Renal Research
    • Covina, California, United States, 91723
      • California Kidney Specialists
    • Huntington Beach, California, United States, 92648
      • Diabetes/Lipid Management and Research Center
    • Los Angeles, California, United States, 90048
      • Tower Nephrology Medical Group
    • Los Gatos, California, United States, 95032
      • Richard S. Cherlin, MD
    • North Hollywood, California, United States, 91606
      • Providence Clinical Research
    • Palm Springs, California, United States, 92262
      • Desert Oasis Healthcare Medical Group
    • Salinas, California, United States, 93901
      • Central Coast Nephrology
    • San Dimas, California, United States, 91773
      • California Kidney Specialists
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver/University of Colorado Hospital
  • Florida
    • Clearwater, Florida, United States, 33756
      • Gulf Coast Endocrine and Diabetes Center
    • Doral, Florida, United States, 33126
      • Continental Research Corp.
    • Hialeah, Florida, United States, 33012
      • Premier Research Associate, Inc.
    • Miami, Florida, United States, 33144
      • Elite Clinical Research
    • Miami, Florida, United States, 33173
      • Nephrology Associates of South Miami
    • Miami, Florida, United States, 33133
      • Prestige Clinical Research Center
    • Miami, Florida, United States, 33173
      • Tellus Clinical Research, Inc.
    • Miami Springs, Florida, United States, 33166
      • Ocean Blue Medical Research Center, Inc
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research, Inc.
    • New Port Richey, Florida, United States, 34652
      • Diabetes Care Center
    • New Port Richey, Florida, United States, 34652
      • Gulf Coast Kidney Center
    • Pembroke Pines, Florida, United States, 33028
      • Pines Clinical Research, Inc.
  • Illinois
    • Champaign, Illinois, United States, 61820
      • Christie Clinic, LLC
  • Kentucky
    • Paducah, Kentucky, United States, 42003
      • Four Rivers Clinical Research, Inc.
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Crescent City Clinical Research Center
    • New Orleans, Louisiana, United States, 70112
      • CTRC, Interim LSU Public Hospital
    • New Orleans, Louisiana, United States, 70112
      • Pharmacy Department, Interim LSU Public Hospital
  • Maryland
    • Bethesda, Maryland, United States, 20814
      • A. Kaldun Nossuli MD Research
  • Massachusetts
    • Springfield, Massachusetts, United States, 01107
      • Western New England Renal and Transplant Associates, PC
  • Michigan
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Flint, Michigan, United States, 48504
      • Apex Medical Research, MI, Inc.
    • Troy, Michigan, United States, 48098
      • Troy Internal Medicine, PC
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Clinical Research Consultants, LLC
    • Kansas City, Missouri, United States, 64128
      • VA Medical Center
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • Creighton Diabetes Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Renal Medicine Associates
  • New York
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital, Division of Nephrology and Hypertension
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital, Pharmacy Department
    • Northport, New York, United States, 11768
      • Northport VA Medical Sciences Center
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mountain Kidney and Hypertension Associates, PA
    • Greenville, North Carolina, United States, 27834
      • East Carolina University Nephrology Research
    • Morehead City, North Carolina, United States, 28557
      • Down East Medical Associates, P.A.
    • Statesville, North Carolina, United States, 28625
      • Piedmont Healthcare/Research
    • Winston-Salem, North Carolina, United States, 27103
      • Brookview Hills Research Associates, LLC
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
    • Providence, Rhode Island, United States, 02904
      • BRAHN-Hypertension and Nephrology, Inc
  • South Carolina
    • Orangeburg, South Carolina, United States, 29118
      • South Carolina Nephrology and Hypertension Center, Inc.
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • The Endocrine Clinic, PC
    • Nashville, Tennessee, United States, 37205
      • Nephrology Associates, P.C.
  • Texas
    • Greenville, Texas, United States, 75402
      • Independent Clinical Research
    • Houston, Texas, United States, 77074
      • Clinical Trial Network
    • Houston, Texas, United States, 77099
      • Southwest Houston Research Ltd
    • Houston, Texas, United States, 77074
      • Southwest Nephrology Associates, LLP
    • Richmond, Texas, United States, 77469
      • Southwest Nephrology Associates, LLP
    • San Antonio, Texas, United States, 78215
      • Clinical Advancement Center, PLLC
    • San Antonio, Texas, United States, 78229
      • San Antonio Kidney Disease Center Physicians Group, P.L.L.C.
    • San Antonio, Texas, United States, 78224
      • Briggs Clinical Research, LLC
    • Sugar Land, Texas, United States, 77478
      • Southwest Nephrology Associates, LLP
  • Utah
    • Saint George, Utah, United States, 84770
      • Southern Utah Kidney and Hypertension
  • Virginia
    • Burke, Virginia, United States, 22015
      • Burke Internal Medicine & Research
    • Burke, Virginia, United States, 22015
      • Clinical Research Institute of Northern Virginia, Inc.
    • Manassas, Virginia, United States, 20110
      • Manassas Clinical Research Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53295
      • Zablocki Veterans Affairs Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Reduction From Baseline in Urinary Albumin to Creatinine Ratio (UACR) at 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.	Baseline and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in UACR at 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.	Baseline, Weeks 4, 8 and 16
Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) at 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.	Baseline, Weeks 4, 8, 12 and 16
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	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	Baseline, Week 1, 4, 8, 12 and 16
Change From Baseline in eGFR Using Cystatin Formula at Weeks 12 and 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.	Baseline, Week 12, and Week 16
Change From Baseline in Serum Creatinine at Weeks 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.	Baseline, Week 1, 4, 8, 12 and 16
Change From Baseline in Serum Cystatin C at Weeks 12 and 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.	Baseline, Week 12, and Week 16
Change From Baseline in Plasma Glycosylated Hemoglobin (HbA1c) at 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.	Baseline, Weeks 4, 8, 12 and 16
Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 12		1, 2, 4 hours post-dose on Day 1; 2 hours post-dose on Weeks 1, 4, 8 and 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16		Baseline, Weeks 1, 4, 8, 12 and 16
Change From Baseline in Pulse Rate at Weeks 1, 4, 8, 12 and 16		Baseline, Weeks 1, 4, 8, 12 and 16
Change From Baseline in Body Weight at Weeks 1, 4, 8, 12 and 16		Baseline, Weeks 1, 4, 8, 12 and 16
Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern	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).	Baseline up to Week 16 (follow-up visit)
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings	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.	Baseline, Weeks 1, 4 and 12
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	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.	Baseline up to 28 days after last study drug administration
Number of Participants With Increased Fasting Blood Glucose		Baseline up to Week 16 (follow-up visit)

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: December 1, 2012
• Primary Completion (ACTUAL): September 1, 2014
• Study Completion (ACTUAL): September 1, 2014

Study Registration Dates

• First Submitted: October 19, 2012
• First Submitted That Met QC Criteria: October 19, 2012
• First Posted (ESTIMATE): October 23, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): October 21, 2015
• Last Update Submitted That Met QC Criteria: September 22, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: type 2 diabetes; albuminuria; Diabetic nephropathy; chemokine antagonist
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 2; Kidney Diseases; Diabetic Nephropathies
• Other Study ID Numbers: B1261007; 2012-003332-23 (EUDRACT_NUMBER)