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

Diabetic Nephropathy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01712061
• Other study ID #: B1261007
• Secondary ID: 2012-003332-23
• Status: Completed
• Phase: Phase 2
• First received: October 19, 2012
• Last updated: September 22, 2015
• Start date: December 2012
• Est. completion date: September 2014

Study information

• Verified date: September 2015
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 226
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Diabetic Nephropathies
• Diabetic Nephropathy
• Kidney Diseases

Intervention

Drug:
• PF-04634817
Three or four tablets (50mg) daily for 12 weeks, depending on baseline renal function
• Placebo
Three or four tablets (50mg) daily for 12 weeks, depending on baseline renal function

Locations

Country	Name	City	State
Argentina	Instituto de Cardiologia de Corrientes "Juana Francisca Cabral"	Corrientes
Argentina	Centro de Salud Renal Junin S.R.L.	Junin	Buenos Aires
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	Centro de Investigaciones Clinicas del Litoral S.R.L.	Santa Fe
Argentina	CETENE S.A. - Centro de Nefrologia y Dialisis	Tucumán
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Sunshine Coast Hospital & Health Service	Nambour	Queensland
Australia	Department of Nephrology	New Lambton	New South Wales
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Westmead Hospital, Department of Renal Medicine	Westmead	New South Wales
Canada	Co-Medica Research Network Inc.	Courtice	Ontario
Canada	Centre de Recherche Clinique de Laval	Laval	Quebec
Canada	Hopital Du Sacre-Coeur de Montreal Centre de recherche	Montreal	Quebec
Canada	Hopital Maisonneuve-Rosemont-Nephrology	Montreal	Quebec
Canada	OTT Healthcare Incorporated	Scarborough	Ontario
Canada	Pro-Recherche	St-Romuald	Quebec
Canada	Dr. Stephen S. Chow Medicine Professional Corporation	Toronto	Ontario
Canada	Toronto East General Medical Centre	Toronto	Ontario
Canada	BC Diabetes.ca	Vancouver	British Columbia
Canada	Vancouver General Hospital	Vancouver	British Columbia
Germany	Studienzentrum Haematologie/Onkologie/Diabetologie	Aschaffenburg
Germany	Universitatsmedizin Berlin - Charite Campus Mitte	Berlin
Germany	GWT-TUD GmbH	Dresden
Germany	Studienzentrum Karlstrasse GmbH	Duesseldorf
Germany	Profil Institut fuer Stoffwechselforschung GmbH (branch: Diabetes Praxis Essen)	Essen
Germany	Diabetes Schwerpunktpraxis / Zentrum fur Klinische Studien	Falkensee
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Dialysezentrum Elsterland	Herzberg	Brandenburg
Germany	Nephrologisches Zentrum Hoyerswerda	Hoyerswerda
Germany	Zentrum Klinische Studien Neuwied	Neuwied
Germany	Diabetologische Schwerpunktpraxis	Schwabenheim
Hong Kong	Queen Mary Hospital	Hong Kong
Hong Kong	Department of Medicine and Therapeutics	Shatin, New Territories	Hong Kong SAR
Hong Kong	Department of Medicine and Therapeutics, Prince of Wales Hospital,	Shatin, New Territories	Hong Kong SAR
Italy	AOU Consorziale Policlinico di Bari	Bari	BA
Italy	Azienda Ospedaliera Ospedali Riuniti di Foggia	Foggia
Italy	Ospedale Alessandro Manzoni	Lecco
Italy	Ospedale Versilia	Lido Camaiore. (Lucca)	Lucca
Italy	*Ospedale Versilia	Lido di Camaiore (LUCCA)	Lucca
Italy	Ospedale Versilia	Lido di Camaiore (LUCCA)	Lucca
Italy	Unita Cardiometabolica e Trials Clinici	Milano
Italy	A.O.U. Policlinico di Modena	Modena	MO
Italy	Fondazione Salvatore Maugeri Clinica del Lavoro e della Riabilitazione IRCCS	Pavia
Korea, Republic of	Chung-Ang University Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Yonsei University College of Medicine, Severance Hospital	Seoul
Malaysia	Selayang Hospital	Batu Caves	Selangor
Malaysia	Hospital Universiti Sains Malaysia	Kubong Kerian	Kelantan
Malaysia	Hospital Taiping	Taiping	Perak
Peru	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	Consultorio de Endocrinologia - LM Servicios Medicos y Endocrinologicos EIRL	Lima
Peru	Clinica Virgen Maria Auxiliadora	Piura
Poland	Stacja Dializ	Golub-Dobrzyn
Poland	Krakowskie Centrum Medyczne Sp. z.o.o.	Krakow	Malopolskie
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	KO-MED, Central Kliniczne Sp. z.o.o	Zamosc
Puerto Rico	Ponce School of Medicine - CAIMED Center	Ponce
Puerto Rico	Medical Sciences Campus University of Puerto Rico	Rio Piedras
Romania	Institutul National de Diabet, Nutritie si Boli Metabolice	Bucuresti
Romania	Spital Clinic Municipal "Dr. Gavril Curteanu" Oradea	Oradea	jud. Bihor
Romania	Elit Medical SRL, Diabet Zaharat Nutritie si Boli Metabolice	Ploiesti
Romania	Spitalul Clinic Judetean de Urgenta Timisoara	Timisoara
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Parc de Salut Mar. Hospital del Mar	Barcelona
Spain	Hospital Universitari de Girona Dr. Josep Trueta	Girona
Spain	Hospital Universitario de Bellvitge	Hospitalet de Llobregat	Barcelona
Spain	Hospital Puerta de Hierro	Majadahonda	Madrid
Spain	Hospital Universitario Dr Peset	Valencia
United States	Renal Medicine Associates	Albuquerque	New Mexico
United States	Mountain Kidney and Hypertension Associates, PA	Asheville	North Carolina
United States	University of Colorado Denver/University of Colorado Hospital	Aurora	Colorado
United States	North America Research Institute	Azusa	California
United States	A. Kaldun Nossuli MD Research	Bethesda	Maryland
United States	Burke Internal Medicine & Research	Burke	Virginia
United States	Clinical Research Institute of Northern Virginia, Inc.	Burke	Virginia
United States	Christie Clinic, LLC	Champaign	Illinois
United States	California Institute of Renal Research	Chula Vista	California
United States	Gulf Coast Endocrine and Diabetes Center	Clearwater	Florida
United States	California Kidney Specialists	Covina	California
United States	Continental Research Corp.	Doral	Florida
United States	Apex Medical Research, MI, Inc.	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	East Carolina University Nephrology Research	Greenville	North Carolina
United States	Independent Clinical Research	Greenville	Texas
United States	Premier Research Associate, Inc.	Hialeah	Florida
United States	Clinical Trial Network	Houston	Texas
United States	Southwest Houston Research LTD	Houston	Texas
United States	Southwest Nephrology Associates, LLP	Houston	Texas
United States	Diabetes/Lipid Management and Research Center	Huntington Beach	California
United States	Clinical Research Consultants, LLC	Kansas City	Missouri
United States	VA Medical Center	Kansas City	Missouri
United States	Medical Investigations, Inc.	Little Rock	Arkansas
United States	Tower Nephrology Medical Group	Los Angeles	California
United States	Richard S. Cherlin, MD	Los Gatos	California
United States	Manassas Clinical Research Center	Manassas	Virginia
United States	The Endocrine Clinic, PC	Memphis	Tennessee
United States	Crescent City Clinical Research Center	Metairie	Louisiana
United States	Elite Clinical Research	Miami	Florida
United States	Nephrology Associates of South Miami	Miami	Florida
United States	Prestige Clinical Research Center	Miami	Florida
United States	Tellus Clinical Research, Inc.	Miami	Florida
United States	Ocean Blue Medical Research Center, Inc	Miami Springs	Florida
United States	Zablocki Veterans Affairs Medical Center	Milwaukee	Wisconsin
United States	Winthrop University Hospital, Division of Nephrology and Hypertension	Mineola	New York
United States	Winthrop University Hospital, Pharmacy Department	Mineola	New York
United States	Down East Medical Associates, P.A.	Morehead City	North Carolina
United States	Nephrology Associates, P.C.	Nashville	Tennessee
United States	CTRC, Interim LSU Public Hospital	New Orleans	Louisiana
United States	Pharmacy Department, Interim LSU Public Hospital	New Orleans	Louisiana
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	Providence Clinical Research	North Hollywood	California
United States	Northport VA Medical Sciences Center	Northport	New York
United States	Creighton Diabetes Center	Omaha	Nebraska
United States	South Carolina Nephrology and Hypertension Center, Inc.	Orangeburg	South Carolina
United States	Four Rivers Clinical Research, Inc.	Paducah	Kentucky
United States	Desert Oasis Healthcare Medical Group	Palm Springs	California
United States	Pines Clinical Research, Inc.	Pembroke Pines	Florida
United States	BRAHN-Hypertension and Nephrology, Inc	Providence	Rhode Island
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Southwest Nephrology Associates, LLP	Richmond	Texas
United States	Southern Utah Kidney and Hypertension	Saint George	Utah
United States	Central Coast Nephrology	Salinas	California
United States	Briggs Clinical Research, LLC	San Antonio	Texas
United States	Clinical Advancement Center, PLLC	San Antonio	Texas
United States	San Antonio Kidney Disease Center Physicians Group, P.L.L.C.	San Antonio	Texas
United States	California Kidney Specialists	San Dimas	California
United States	Western New England Renal and Transplant Associates, PC	Springfield	Massachusetts
United States	Piedmont Healthcare/Research	Statesville	North Carolina
United States	Southwest Nephrology Associates, LLP	Sugar Land	Texas
United States	Troy Internal Medicine, PC	Troy	Michigan
United States	Brookview Hills Research Associates, LLC	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  Germany,  Hong Kong,  Italy,  Korea, Republic of,  Malaysia,  Peru,  Poland,  Puerto Rico,  Romania,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	Yes
Other	Change From Baseline in Pulse Rate at Weeks 1, 4, 8, 12 and 16		Baseline, Weeks 1, 4, 8, 12 and 16	Yes
Other	Change From Baseline in Body Weight at Weeks 1, 4, 8, 12 and 16		Baseline, Weeks 1, 4, 8, 12 and 16	Yes
Other	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)	Yes
Other	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	Yes
Other	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	Yes
Other	Number of Participants With Increased Fasting Blood Glucose		Baseline up to Week 16 (follow-up visit)	Yes
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No

External Links

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