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
Drug: PF-04634817

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

Group	Intervention	Description
Arm 2 Placebo	Placebo	-
Arm 1 PF-04634817	PF-04634817	-

Primary Outcome Measures

Name	Time	Method
Percent Reduction From Baseline in Urinary Albumin to Creatinine Ratio (UACR) at Week 12	Baseline 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

Name	Time	Method
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	Baseline, 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 16	Baseline, 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 16	Baseline, 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 12	1, 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 16	Baseline, 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 16	Baseline, 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 16	Baseline, 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 16	Baseline, 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): Medical Investigations, Inc.
🇺🇸
Little Rock, Arkansas, United States
North America Research Institute
🇺🇸
Azusa, California, United States
California Institute of Renal Research
🇺🇸
Chula Vista, California, United States
California Kidney Specialists
🇺🇸
San Dimas, California, United States
Diabetes/Lipid Management and Research Center
🇺🇸
Huntington Beach, California, United States
Tower Nephrology Medical Group
🇺🇸
Los Angeles, California, United States
Richard S. Cherlin, MD
🇺🇸
Los Gatos, California, United States
Providence Clinical Research
🇺🇸
North Hollywood, California, United States
Desert Oasis Healthcare Medical Group
🇺🇸
Palm Springs, California, United States
Central Coast Nephrology
🇺🇸
Salinas, California, United States
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Medical Investigations, Inc.
🇺🇸Little Rock, Arkansas, United States