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

  Hide Study Locations
Locations
United States, Arkansas
Medical Investigations, Inc.
Little Rock, Arkansas, United States, 72205
United States, California
North America Research Institute
Azusa, California, United States, 91702
California Institute of Renal Research
Chula Vista, California, United States, 91910
California Kidney Specialists
Covina, California, United States, 91723
Diabetes/Lipid Management and Research Center
Huntington Beach, California, United States, 92648
Tower Nephrology Medical Group
Los Angeles, California, United States, 90048
Richard S. Cherlin, MD
Los Gatos, California, United States, 95032
Providence Clinical Research
North Hollywood, California, United States, 91606
Desert Oasis Healthcare Medical Group
Palm Springs, California, United States, 92262
Central Coast Nephrology
Salinas, California, United States, 93901
California Kidney Specialists
San Dimas, California, United States, 91773
United States, Colorado
University of Colorado Denver/University of Colorado Hospital
Aurora, Colorado, United States, 80045
United States, Florida
Gulf Coast Endocrine and Diabetes Center
Clearwater, Florida, United States, 33756
Continental Research Corp.
Doral, Florida, United States, 33126
Premier Research Associate, Inc.
Hialeah, Florida, United States, 33012
Ocean Blue Medical Research Center, Inc
Miami Springs, Florida, United States, 33166
Prestige Clinical Research Center
Miami, Florida, United States, 33133
Elite Clinical Research
Miami, Florida, United States, 33144
Nephrology Associates of South Miami
Miami, Florida, United States, 33173
Tellus Clinical Research, Inc.
Miami, Florida, United States, 33173
Diabetes Care Center
New Port Richey, Florida, United States, 34652
Gulf Coast Kidney Center
New Port Richey, Florida, United States, 34652
Suncoast Clinical Research, Inc.
New Port Richey, Florida, United States, 34652
Pines Clinical Research, Inc.
Pembroke Pines, Florida, United States, 33028
United States, Illinois
Christie Clinic, LLC
Champaign, Illinois, United States, 61820
United States, Kentucky
Four Rivers Clinical Research, Inc.
Paducah, Kentucky, United States, 42003
United States, Louisiana
Crescent City Clinical Research Center
Metairie, Louisiana, United States, 70006
CTRC, Interim LSU Public Hospital
New Orleans, Louisiana, United States, 70112
Pharmacy Department, Interim LSU Public Hospital
New Orleans, Louisiana, United States, 70112
United States, Maryland
A. Kaldun Nossuli MD Research
Bethesda, Maryland, United States, 20814
United States, Massachusetts
Western New England Renal and Transplant Associates, PC
Springfield, Massachusetts, United States, 01107
United States, Michigan
Hurley Medical Center
Flint, Michigan, United States, 48503
Apex Medical Research, MI, Inc.
Flint, Michigan, United States, 48504
Troy Internal Medicine, PC
Troy, Michigan, United States, 48098
United States, Missouri
Clinical Research Consultants, LLC
Kansas City, Missouri, United States, 64111
VA Medical Center
Kansas City, Missouri, United States, 64128
United States, Nebraska
Creighton Diabetes Center
Omaha, Nebraska, United States, 68131
United States, New Mexico
Renal Medicine Associates
Albuquerque, New Mexico, United States, 87109
United States, New York
Winthrop University Hospital, Division of Nephrology and Hypertension
Mineola, New York, United States, 11501
Winthrop University Hospital, Pharmacy Department
Mineola, New York, United States, 11501
Northport VA Medical Sciences Center
Northport, New York, United States, 11768
United States, North Carolina
Mountain Kidney and Hypertension Associates, PA
Asheville, North Carolina, United States, 28801
East Carolina University Nephrology Research
Greenville, North Carolina, United States, 27834
Down East Medical Associates, P.A.
Morehead City, North Carolina, United States, 28557
Piedmont Healthcare/Research
Statesville, North Carolina, United States, 28625
Brookview Hills Research Associates, LLC
Winston-Salem, North Carolina, United States, 27103
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02903
BRAHN-Hypertension and Nephrology, Inc
Providence, Rhode Island, United States, 02904
United States, South Carolina
South Carolina Nephrology and Hypertension Center, Inc.
Orangeburg, South Carolina, United States, 29118
United States, Tennessee
The Endocrine Clinic, PC
Memphis, Tennessee, United States, 38119
Nephrology Associates, P.C.
Nashville, Tennessee, United States, 37205
United States, Texas
Independent Clinical Research
Greenville, Texas, United States, 75402
Clinical Trial Network
Houston, Texas, United States, 77074
Southwest Nephrology Associates, LLP
Houston, Texas, United States, 77074
Southwest Houston Research LTD
Houston, Texas, United States, 77099
Southwest Nephrology Associates, LLP
Richmond, Texas, United States, 77469
Clinical Advancement Center, PLLC
San Antonio, Texas, United States, 78215
Briggs Clinical Research, LLC
San Antonio, Texas, United States, 78224
San Antonio Kidney Disease Center Physicians Group, P.L.L.C.
San Antonio, Texas, United States, 78229
Southwest Nephrology Associates, LLP
Sugar Land, Texas, United States, 77478
United States, Utah
Southern Utah Kidney and Hypertension
Saint George, Utah, United States, 84770
United States, Virginia
Burke Internal Medicine & Research
Burke, Virginia, United States, 22015
Clinical Research Institute of Northern Virginia, Inc.
Burke, Virginia, United States, 22015
Manassas Clinical Research Center
Manassas, Virginia, United States, 20110
United States, Wisconsin
Zablocki Veterans Affairs Medical Center
Milwaukee, Wisconsin, United States, 53295
Argentina
Centro de Salud Renal Junin S.R.L.
Junin, Buenos Aires, Argentina, 6000
Centro de Investigaciones Medicas - Clinica de Fracturas y Ortopedia
Mar del Plata, Buenos Aires, Argentina, B7600DHK
Instituto de Investigaciones Clinicas Quilmes S.R.L
Quilmes, Buenos Aires, Argentina, B1878GEG
Instituto de Cardiologia de Corrientes "Juana Francisca Cabral"
Corrientes, Argentina, W3400AMZ
Centro de Investigaciones Clinicas del Litoral S.R.L.
Santa Fe, Argentina, 3000
CETENE S.A. - Centro de Nefrologia y Dialisis
Tucumán, Argentina, T4000IIO
Australia, New South Wales
Liverpool Hospital
Liverpool, New South Wales, Australia, 2170
Department of Nephrology
New Lambton, New South Wales, Australia, 2305
Westmead Hospital, Department of Renal Medicine
Westmead, New South Wales, Australia, 2145
Australia, Queensland
Sunshine Coast Hospital & Health Service
Nambour, Queensland, Australia, 4560
Australia, Victoria
Box Hill Hospital
Box Hill, Victoria, Australia, 3128
Monash Medical Centre
Clayton, Victoria, Australia, 3168
Royal Melbourne Hospital
Parkville, Victoria, Australia, 3050
Canada, British Columbia
Vancouver General Hospital
Vancouver, British Columbia, Canada, V5Z 1L8
BC Diabetes.ca
Vancouver, British Columbia, Canada, V5Z 1M9
Canada, Ontario
Co-Medica Research Network Inc.
Courtice, Ontario, Canada, L1E 3C3
OTT Healthcare Incorporated
Scarborough, Ontario, Canada, M1H 3G4
Dr. Stephen S. Chow Medicine Professional Corporation
Toronto, Ontario, Canada, M4C 5T2
Toronto East General Medical Centre
Toronto, Ontario, Canada, M4C 5T2
Canada, Quebec
Centre de Recherche Clinique de Laval
Laval, Quebec, Canada, H7T 2P5
Hopital Maisonneuve-Rosemont-Nephrology
Montreal, Quebec, Canada, H1T 2M4
Hopital Du Sacre-Coeur de Montreal Centre de recherche
Montreal, Quebec, Canada, H4J 1C5
Pro-Recherche
St-Romuald, Quebec, Canada, G6W 5M6
Germany
Dialysezentrum Elsterland
Herzberg, Brandenburg, Germany, 04916
Studienzentrum Haematologie/Onkologie/Diabetologie
Aschaffenburg, Germany, 63739
Universitatsmedizin Berlin - Charite Campus Mitte
Berlin, Germany, 10117
GWT-TUD GmbH
Dresden, Germany, 01307
Studienzentrum Karlstrasse GmbH
Duesseldorf, Germany, 40210
Profil Institut fuer Stoffwechselforschung GmbH (branch: Diabetes Praxis Essen)
Essen, Germany, 45136
Diabetes Schwerpunktpraxis / Zentrum fur Klinische Studien
Falkensee, Germany, 14612
Medizinische Hochschule Hannover
Hannover, Germany, 30625
Nephrologisches Zentrum Hoyerswerda
Hoyerswerda, Germany, 02977
Zentrum Klinische Studien Neuwied
Neuwied, Germany, D-56564
Diabetologische Schwerpunktpraxis
Schwabenheim, Germany, 55270
Hong Kong
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
Queen Mary Hospital
Hong Kong, Hong Kong
Italy
AOU Consorziale Policlinico di Bari
Bari, BA, Italy, 70124
Ospedale Versilia
Lido Camaiore. (Lucca), Lucca, Italy, 55041
*Ospedale Versilia
Lido di Camaiore (LUCCA), Lucca, Italy, 55043
Ospedale Versilia
Lido di Camaiore (LUCCA), Lucca, Italy, 55043
A.O.U. Policlinico di Modena
Modena, MO, Italy, 41124
Azienda Ospedaliera Ospedali Riuniti di Foggia
Foggia, Italy, 71100
Ospedale Alessandro Manzoni
Lecco, Italy, 23900
Unita Cardiometabolica e Trials Clinici
Milano, Italy, 20132
Fondazione Salvatore Maugeri Clinica del Lavoro e della Riabilitazione IRCCS
Pavia, Italy, 27100
Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of, 110-744
Yonsei University College of Medicine, Severance Hospital
Seoul, Korea, Republic of, 120-752
Chung-Ang University Hospital
Seoul, Korea, Republic of, 156-755
Malaysia
Hospital Universiti Sains Malaysia
Kubong Kerian, Kelantan, Malaysia, 16150
Hospital Taiping
Taiping, Perak, Malaysia, 34000
Selayang Hospital
Batu Caves, Selangor, Malaysia, 68100
Peru
Casa de Diabetes y Nutricion
Lima, Peru, 17
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, 27
Clinica Maison de Sante ¿ Sede este
Lima, Peru, LIMA 33
Clinica Virgen Maria Auxiliadora
Piura, Peru, 073
Poland
Krakowskie Centrum Medyczne Sp. z.o.o.
Krakow, Malopolskie, Poland, 31-501
Stacja Dializ
Golub-Dobrzyn, Poland, 87-400
LANDA Specjalistyczne Gabinety Lekarskie
Krakow, Poland, 30-015
SCM Sp. z.o.o
Krakow, Poland, 31-559
Klinika Nefrologii, Hipertensjologii i Transplantologii Nerek
Lodz, Poland, 92-013
NZOZ TRI-medica
Lodz, Poland, 93-338
CSK MSW w Warszawie Klinika Chorob Wewnetrznych Endokrynologii i Diabetologii
Warszawa, Poland, 02-507
KO-MED, Central Kliniczne Sp. z.o.o
Zamosc, Poland, 22-400
Puerto Rico
Ponce School of Medicine - CAIMED Center
Ponce, Puerto Rico, 00716
Medical Sciences Campus University of Puerto Rico
Rio Piedras, Puerto Rico, 00935
Romania
Spital Clinic Municipal "Dr. Gavril Curteanu" Oradea
Oradea, jud. Bihor, Romania, 410469
Institutul National de Diabet, Nutritie si Boli Metabolice
Bucuresti, Romania, 020475
Elit Medical SRL, Diabet Zaharat Nutritie si Boli Metabolice
Ploiesti, Romania, 100018
Spitalul Clinic Judetean de Urgenta Timisoara
Timisoara, Romania, 300736
Spain
Hospital Universitario de Bellvitge
Hospitalet de Llobregat, Barcelona, Spain, 08907
Hospital Puerta de Hierro
Majadahonda, Madrid, Spain, 28222
Parc de Salut Mar. Hospital del Mar
Barcelona, Spain, 08003
Hospital Universitario Vall d'Hebron
Barcelona, Spain, 08035
Hospital Universitari de Girona Dr. Josep Trueta
Girona, Spain, 17007
Hospital Universitario Dr Peset
Valencia, Spain, 46017
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 August 23, 2016