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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

Phase 2
Completed
Conditions
Diabetic Nephropathy
Interventions
Drug: Placebo
Registration Number
NCT01712061
Lead Sponsor
Pfizer
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 available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
226
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 2 PlaceboPlacebo-
Arm 1 PF-04634817PF-04634817-
Primary Outcome Measures
NameTimeMethod
Percent Reduction From Baseline in Urinary Albumin to Creatinine Ratio (UACR) at Week 12Baseline 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.

Secondary Outcome Measures
NameTimeMethod
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 16Baseline, 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 Plasma Glycosylated Hemoglobin (HbA1c) at Weeks 4, 8, 12 and 16Baseline, 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.

Change From Baseline in eGFR Using Cystatin Formula at Weeks 12 and 16Baseline, 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.

Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 121, 2, 4 hours post-dose on Day 1; 2 hours post-dose on Weeks 1, 4, 8 and 12
Change From Baseline in UACR at Weeks 4, 8 and 16Baseline, 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 Serum Creatinine at Weeks 1, 4, 8, 12 and 16Baseline, 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 Urinary Protein to Creatinine Ratio (UPCR) at Weeks 4, 8, 12 and 16Baseline, 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 Serum Cystatin C at Weeks 12 and 16Baseline, 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.

Trial Locations

Locations (138)

Co-Medica Research Network Inc.

🇨🇦

Courtice, Ontario, Canada

Hospital Universitario Vall d'Hebron

🇪🇸

Barcelona, Spain

Clinical Trial Network

🇺🇸

Houston, Texas, United States

Southwest Houston Research LTD

🇺🇸

Houston, Texas, United States

Liverpool Hospital

🇦🇺

Liverpool, New South Wales, Australia

Toronto East General Medical Centre

🇨🇦

Toronto, Ontario, Canada

Dr. Stephen S. Chow Medicine Professional Corporation

🇨🇦

Toronto, Ontario, Canada

Centro de Salud Renal Junin S.R.L.

🇦🇷

Junin, Buenos Aires, Argentina

Royal Melbourne Hospital

🇦🇺

Parkville, Victoria, Australia

Nephrologisches Zentrum Hoyerswerda

🇩🇪

Hoyerswerda, Germany

A.O.U. Policlinico di Modena

🇮🇹

Modena, MO, Italy

Unita Cardiometabolica e Trials Clinici

🇮🇹

Milano, Italy

KO-MED, Central Kliniczne Sp. z.o.o

🇵🇱

Zamosc, Poland

Ponce School of Medicine - CAIMED Center

🇵🇷

Ponce, Puerto Rico

North America Research Institute

🇺🇸

Azusa, California, United States

California Kidney Specialists

🇺🇸

San Dimas, California, United States

Tower Nephrology Medical Group

🇺🇸

Los Angeles, California, United States

Gulf Coast Endocrine and Diabetes Center

🇺🇸

Clearwater, Florida, United States

Continental Research Corp.

🇺🇸

Doral, Florida, United States

Prestige Clinical Research Center

🇺🇸

Miami, Florida, United States

Elite Clinical Research

🇺🇸

Miami, Florida, United States

Nephrology Associates of South Miami

🇺🇸

Miami, Florida, United States

Pines Clinical Research, Inc.

🇺🇸

Pembroke Pines, Florida, United States

Four Rivers Clinical Research, Inc.

🇺🇸

Paducah, Kentucky, United States

Hurley Medical Center

🇺🇸

Flint, Michigan, United States

Apex Medical Research, MI, Inc.

🇺🇸

Flint, Michigan, United States

Mountain Kidney and Hypertension Associates, PA

🇺🇸

Asheville, North Carolina, United States

East Carolina University Nephrology Research

🇺🇸

Greenville, North Carolina, United States

Piedmont Healthcare/Research

🇺🇸

Statesville, North Carolina, United States

Department of Nephrology

🇦🇺

New Lambton, New South Wales, Australia

Nephrology Associates, P.C.

🇺🇸

Nashville, Tennessee, United States

Clinical Advancement Center, PLLC

🇺🇸

San Antonio, Texas, United States

Briggs Clinical Research, LLC

🇺🇸

San Antonio, Texas, United States

San Antonio Kidney Disease Center Physicians Group, P.L.L.C.

🇺🇸

San Antonio, Texas, United States

*Ospedale Versilia

🇮🇹

Lido di Camaiore (LUCCA), Lucca, Italy

Hospital Puerta de Hierro

🇪🇸

Majadahonda, Madrid, Spain

Ospedale Versilia

🇮🇹

Lido di Camaiore (LUCCA), Lucca, Italy

Creighton Diabetes Center

🇺🇸

Omaha, Nebraska, United States

Zablocki Veterans Affairs Medical Center

🇺🇸

Milwaukee, Wisconsin, United States

A. Kaldun Nossuli MD Research

🇺🇸

Bethesda, Maryland, United States

California Institute of Renal Research

🇺🇸

Chula Vista, California, United States

Medical Investigations, Inc.

🇺🇸

Little Rock, Arkansas, United States

Richard S. Cherlin, MD

🇺🇸

Los Gatos, California, United States

Diabetes/Lipid Management and Research Center

🇺🇸

Huntington Beach, California, United States

Providence Clinical Research

🇺🇸

North Hollywood, California, United States

Central Coast Nephrology

🇺🇸

Salinas, California, United States

Desert Oasis Healthcare Medical Group

🇺🇸

Palm Springs, California, United States

Premier Research Associate, Inc.

🇺🇸

Hialeah, Florida, United States

Ocean Blue Medical Research Center, Inc

🇺🇸

Miami Springs, Florida, United States

Tellus Clinical Research, Inc.

🇺🇸

Miami, Florida, United States

Diabetes Care Center

🇺🇸

New Port Richey, Florida, United States

Gulf Coast Kidney Center

🇺🇸

New Port Richey, Florida, United States

Suncoast Clinical Research, Inc.

🇺🇸

New Port Richey, Florida, United States

Christie Clinic, LLC

🇺🇸

Champaign, Illinois, United States

Crescent City Clinical Research Center

🇺🇸

Metairie, Louisiana, United States

Western New England Renal and Transplant Associates, PC

🇺🇸

Springfield, Massachusetts, United States

Renal Medicine Associates

🇺🇸

Albuquerque, New Mexico, United States

Winthrop University Hospital, Division of Nephrology and Hypertension

🇺🇸

Mineola, New York, United States

Troy Internal Medicine, PC

🇺🇸

Troy, Michigan, United States

Winthrop University Hospital, Pharmacy Department

🇺🇸

Mineola, New York, United States

Northport VA Medical Sciences Center

🇺🇸

Northport, New York, United States

Down East Medical Associates, P.A.

🇺🇸

Morehead City, North Carolina, United States

BRAHN-Hypertension and Nephrology, Inc

🇺🇸

Providence, Rhode Island, United States

The Endocrine Clinic, PC

🇺🇸

Memphis, Tennessee, United States

South Carolina Nephrology and Hypertension Center, Inc.

🇺🇸

Orangeburg, South Carolina, United States

Independent Clinical Research

🇺🇸

Greenville, Texas, United States

Southwest Nephrology Associates, LLP

🇺🇸

Sugar Land, Texas, United States

Clinical Research Institute of Northern Virginia, Inc.

🇺🇸

Burke, Virginia, United States

Southern Utah Kidney and Hypertension

🇺🇸

Saint George, Utah, United States

Burke Internal Medicine & Research

🇺🇸

Burke, Virginia, United States

Manassas Clinical Research Center

🇺🇸

Manassas, Virginia, United States

Centro de Investigaciones Clinicas del Litoral S.R.L.

🇦🇷

Santa Fe, Argentina

Centro de Investigaciones Medicas - Clinica de Fracturas y Ortopedia

🇦🇷

Mar del Plata, Buenos Aires, Argentina

Instituto de Investigaciones Clinicas Quilmes S.R.L

🇦🇷

Quilmes, Buenos Aires, Argentina

Instituto de Cardiologia de Corrientes "Juana Francisca Cabral"

🇦🇷

Corrientes, Argentina

CETENE S.A. - Centro de Nefrologia y Dialisis

🇦🇷

Tucumán, Argentina

Box Hill Hospital

🇦🇺

Box Hill, Victoria, Australia

Westmead Hospital, Department of Renal Medicine

🇦🇺

Westmead, New South Wales, Australia

Sunshine Coast Hospital & Health Service

🇦🇺

Nambour, Queensland, Australia

BC Diabetes.ca

🇨🇦

Vancouver, British Columbia, Canada

Monash Medical Centre

🇦🇺

Clayton, Victoria, Australia

Vancouver General Hospital

🇨🇦

Vancouver, British Columbia, Canada

Centre de Recherche Clinique de Laval

🇨🇦

Laval, Quebec, Canada

OTT Healthcare Incorporated

🇨🇦

Scarborough, Ontario, Canada

Hopital Maisonneuve-Rosemont-Nephrology

🇨🇦

Montreal, Quebec, Canada

Pro-Recherche

🇨🇦

St-Romuald, Quebec, Canada

Hopital Du Sacre-Coeur de Montreal Centre de recherche

🇨🇦

Montreal, Quebec, Canada

Dialysezentrum Elsterland

🇩🇪

Herzberg, Brandenburg, Germany

Studienzentrum Haematologie/Onkologie/Diabetologie

🇩🇪

Aschaffenburg, Germany

Universitatsmedizin Berlin - Charite Campus Mitte

🇩🇪

Berlin, Germany

Studienzentrum Karlstrasse GmbH

🇩🇪

Duesseldorf, Germany

Profil Institut fuer Stoffwechselforschung GmbH (branch: Diabetes Praxis Essen)

🇩🇪

Essen, Germany

GWT-TUD GmbH

🇩🇪

Dresden, Germany

Diabetes Schwerpunktpraxis / Zentrum fur Klinische Studien

🇩🇪

Falkensee, Germany

Medizinische Hochschule Hannover

🇩🇪

Hannover, Germany

Department of Medicine and Therapeutics, Prince of Wales Hospital,

🇭🇰

Shatin, New Territories, Hong Kong SAR, Hong Kong

Department of Medicine and Therapeutics

🇭🇰

Shatin, New Territories, Hong Kong SAR, Hong Kong

Zentrum Klinische Studien Neuwied

🇩🇪

Neuwied, Germany

Queen Mary Hospital

🇭🇰

Hong Kong, Hong Kong

Diabetologische Schwerpunktpraxis

🇩🇪

Schwabenheim, Germany

AOU Consorziale Policlinico di Bari

🇮🇹

Bari, BA, Italy

Ospedale Alessandro Manzoni

🇮🇹

Lecco, Italy

Azienda Ospedaliera Ospedali Riuniti di Foggia

🇮🇹

Foggia, Italy

Fondazione Salvatore Maugeri Clinica del Lavoro e della Riabilitazione IRCCS

🇮🇹

Pavia, Italy

Hospital Universiti Sains Malaysia

🇲🇾

Kubong Kerian, Kelantan, Malaysia

Yonsei University College of Medicine, Severance Hospital

🇰🇷

Seoul, Korea, Republic of

Chung-Ang University Hospital

🇰🇷

Seoul, Korea, Republic of

Hospital Taiping

🇲🇾

Taiping, Perak, Malaysia

Consultorio de Endocrinologia - LM Servicios Medicos y Endocrinologicos EIRL

🇵🇪

Lima, Peru

Selayang Hospital

🇲🇾

Batu Caves, Selangor, Malaysia

Casa de Diabetes y Nutricion

🇵🇪

Lima, Peru

Centro de Investigacion y Atencion Cardiovascular S.A.C. - Clinica Novocardio

🇵🇪

Lima, Peru

Clinica Maison de Sante ¿ Sede este

🇵🇪

Lima, Peru

Clinica Virgen Maria Auxiliadora

🇵🇪

Piura, Peru

Krakowskie Centrum Medyczne Sp. z.o.o.

🇵🇱

Krakow, Malopolskie, Poland

Stacja Dializ

🇵🇱

Golub-Dobrzyn, Poland

LANDA Specjalistyczne Gabinety Lekarskie

🇵🇱

Krakow, Poland

SCM Sp. z.o.o

🇵🇱

Krakow, Poland

Klinika Nefrologii, Hipertensjologii i Transplantologii Nerek

🇵🇱

Lodz, Poland

NZOZ TRI-medica

🇵🇱

Lodz, Poland

CSK MSW w Warszawie Klinika Chorob Wewnetrznych Endokrynologii i Diabetologii

🇵🇱

Warszawa, Poland

Spital Clinic Municipal "Dr. Gavril Curteanu" Oradea

🇷🇴

Oradea, jud. Bihor, Romania

Medical Sciences Campus University of Puerto Rico

🇵🇷

Rio Piedras, Puerto Rico

Elit Medical SRL, Diabet Zaharat Nutritie si Boli Metabolice

🇷🇴

Ploiesti, Romania

Spitalul Clinic Judetean de Urgenta Timisoara

🇷🇴

Timisoara, Romania

Institutul National de Diabet, Nutritie si Boli Metabolice

🇷🇴

Bucuresti, Romania

Hospital Universitario de Bellvitge

🇪🇸

Hospitalet de Llobregat, Barcelona, Spain

Parc de Salut Mar. Hospital del Mar

🇪🇸

Barcelona, Spain

Hospital Universitari de Girona Dr. Josep Trueta

🇪🇸

Girona, Spain

Hospital Universitario Dr Peset

🇪🇸

Valencia, Spain

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

University of Colorado Denver/University of Colorado Hospital

🇺🇸

Aurora, Colorado, United States

Clinical Research Consultants, LLC

🇺🇸

Kansas City, Missouri, United States

VA Medical Center

🇺🇸

Kansas City, Missouri, United States

Brookview Hills Research Associates, LLC

🇺🇸

Winston-Salem, North Carolina, United States

CTRC, Interim LSU Public Hospital

🇺🇸

New Orleans, Louisiana, United States

Pharmacy Department, Interim LSU Public Hospital

🇺🇸

New Orleans, Louisiana, United States

Rhode Island Hospital

🇺🇸

Providence, Rhode Island, United States

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