A 58-Week Safety and Efficacy Trial of Ferric Citrate in Patients With ESRD on Dialysis

A Three-Period, 58-Week Safety and Efficacy Trial of KRX-0502 (Ferric Citrate) in Patients With End-Stage Renal Disease (ESRD) on Dialysis

This is up to a 58 week study comparing ferric citrate to active control for 52 weeks in ESRD dialysis patients, and subsequently comparing ferric citrate to placebo for 4 weeks.

Study Overview

• Status: Completed
• Conditions: Kidney Failure; Hyperphosphatemia
• Intervention / Treatment: Drug: ferric citrate, ca acetate, sevelamer carbonate, placebo

Detailed Description

This trial is a three-period, multicenter, safety and efficacy clinical trial. The first period is a two-week Washout Period, the second period is a 52-week randomized, open-label, active control Safety Assessment Period, and the third period is a four-week, randomized, open-label, placebo-controlled Efficacy Assessment Period in only the patients who were randomized to treatment with ferric citrate during the Safety Assessment Period. The primary objectives of this trial are to determine the long-term safety over 52 weeks of up to twelve (12) caplets/day of KRX-0502 (ferric citrate) in patients with ESRD undergoing either hemodialysis or peritoneal dialysis and to determine the efficacy of KRX-0502 (ferric citrate) in the four-week, randomized, open-label, placebo-controlled Efficacy Assessment Period.

• Study Type: Interventional
• Enrollment (Actual): 441
• Phase: Phase 3

Contacts and Locations

Study Locations

• Israel
  • Ashkelon, Israel
    • Department of Nephrology and Hypertension Brazilai Medical Center
  • Tel Aviv, Israel
    • Tel Aviv Sourasky Medical Center Nephrology Department
• Puerto Rico
  • Rio Piedras, Puerto Rico, 00936-5067
    • RCMI-Clinical Research Center Medical Sciences Campus University of Puerto Rico
  • Trujillo Alto, Puerto Rico, 00976
    • Puerto Rico Renal Health & Research Center, Inc/ Atlantic Healthcare Group, Inc
• United States
  • Arizona
    • Tempe, Arizona, United States, 85284
      • Southwest Clinical Research Institute, LLC
  • California
    • Los Angeles, California, United States, 90048
      • Tower Nephrology Medical Group
    • Los Angeles, California, United States, 90073
      • Veterans Administration Greater Los Angeles Healthcare System, West Los Angeles
    • Riverside, California, United States, 92505
      • Apex Research of Riverside
    • Whittier, California, United States, 90603
      • American Institute of Research
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
    • Westminster, Colorado, United States, 80031
      • Western Nephrology
  • Florida
    • Brandon, Florida, United States, 33511
      • PAB Clinical Research
    • Jacksonville, Florida, United States, 32216
      • Mayo Clinic
    • Jupiter, Florida, United States, 33458
      • ASA Clinical Research, LLC
    • Ocala, Florida, United States, 34471
      • Ocala Kidney Group
    • Pembroke Pines, Florida, United States, 33028
      • Pines Clinical Research, Inc.
  • Georgia
    • Augusta, Georgia, United States, 30901
      • Kidney Care Associates, LLC
    • Decatur, Georgia, United States, 30030
      • Atlanta Nephrology Referral Center
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Circle Medical Management
  • Indiana
    • Michigan City, Indiana, United States, 46360
      • Nephrology Specialists, PC
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • LSU Health Sciences Center Section of Nephrology and Hypertension Department of Internal Medicine
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Rockville Dialysis Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Holyoke, Massachusetts, United States, 01040
      • Pioneer Valley Nephrology
    • Springfield, Massachusetts, United States, 01107
      • Western new England Renal & Transplant Associates
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Pontiac, Michigan, United States, 48341
      • Michigan Kidney Consultants, PC
    • Southgate, Michigan, United States, 48195
      • Nephrology Hypertension Clinic
  • Missouri
    • Kansas City, Missouri, United States, 64128
      • Kansas City VA Medical Center
  • New York
    • Brooklyn, New York, United States, 11212
      • Brookdale Physician's Dialysis Associates
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mountain Kidney and Hypertension Associates, PA
    • Charlotte, North Carolina, United States, 28207
      • Metrolina Nephrology Associates, PA
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center Division of Nephrology
    • Wilmington, North Carolina, United States, 28401
      • Trial Management Associates
    • Winston Salem, North Carolina, United States, 27157
      • Wake Forest University School of Medicine
  • Ohio
    • Canton, Ohio, United States, 44718
      • Clinical Research Limited
    • Cincinnati, Ohio, United States, 45267
      • Division of Nephrology and Hypertension Department of Internal Medicine University of Cincinnati College of Medicine
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation Q7-150 Nephrology
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Division of Nephrology
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73116
      • Davita
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Health System
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Southeast Renal Research Institute Nephrology Associates
    • Nashville, Tennessee, United States, 37205
      • Nephrology Associates, PC
    • Nashville, Tennessee, United States, 37232-1371
      • Vanderbilt University Medical Center Clinical Trials Center
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center at Dallas
    • Houston, Texas, United States, 77030
      • Kidney Associates
    • Houston, Texas, United States, 77030
      • Nephrology, PA
    • The Woodlands, Texas, United States, 77384
      • Kidney Specialists of North Houston, PLLC
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Health Sciences Center
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont/ Fletcher Allen Health Care; Renal Services
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Nephrology Clinical Research Center
    • Fairfax, Virginia, United States, 22030
      • Clinical Research & Consulting Center, LLC
    • Fairfax, Virginia, United States, 22033
      • Nephrology Associates of Northern Virginia, Inc.
    • Hampton, Virginia, United States, 23666
      • Peninsula Kidney Associates
    • Richmond, Virginia, United States, 23249
      • McGuire VA Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Froedert Memorial Lutheran Hospital Division of Nephrology

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:

1. Males or non-pregnant, non-breast-feeding females
2. Age ≥18 years
3. On thrice-weekly hemodialysis or on peritoneal dialysis for at least the previous three months prior to Screening
4. Serum phosphorus ≥6.0 mg/dL for study entry
5. Taking less than 3-18 pills/day of current phosphate binder
6. Willing to be discontinued from current phosphate binder(s) and initiated on ferric citrate
7. Willing and able to give informed consent
8. Life expectancy >1 year

Exclusion Criteria:

1. Parathyroidectomy within six months prior to Screening
2. Actively symptomatic gastrointestinal bleeding or inflammatory bowel disease
3. History of multiple drug allergies or intolerances
4. History of malignancy in the last five years (treated cervical or non-melanomatous skin cancer may be permitted if approved by CCC)
5. Previous intolerance to oral ferric citrate
6. Intolerance to oral iron-containing products
7. Psychiatric disorder that interferes with the patient's ability to comply with the study protocol
8. Inability to tolerate oral drug intake
9. Intolerance to calcium acetate and sevelamer carbonate
10. Any other medical condition that renders the patient unable to or unlikely to complete the trial or that would interfere with optimal participation in the trial or produce significant risk to the patient
11. Receipt of any investigational drug within 30 days of Screening Visit (Visit 0)
12. Inability to cooperate with study personnel or history of noncompliance
13. Unsuitable for this trial per Investigator's clinical judgment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: ferric citrate, ca acetate, sevelamer carbonate, placebo; All intervention doses will be based on serum phosphorus levels and/or drug label requirements; Other Names: PhosLo; KRX-0502; Renvela; Zerenex
ACTIVE_COMPARATOR: Active Control; PhosLo (calcium acetate) Renvela (sevelamer carbonate)	Drug: ferric citrate, ca acetate, sevelamer carbonate, placebo; All intervention doses will be based on serum phosphorus levels and/or drug label requirements; Other Names: PhosLo; KRX-0502; Renvela; Zerenex
EXPERIMENTAL: KRX-0502 (Ferric Citrate); ferric citrate	Drug: ferric citrate, ca acetate, sevelamer carbonate, placebo; All intervention doses will be based on serum phosphorus levels and/or drug label requirements; Other Names: PhosLo; KRX-0502; Renvela; Zerenex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean Serum Phosphorus From Baseline (Week 52) to the End of the Efficacy Assessment Period (EAP; Week 56)	Patients who completed the 52-week Safety Assessment Period (SAP) on KRX-0502 (ferric citrate) were randomized in a 1:1 ratio to receive either KRX-0502 (ferric citrate) or Placebo for 4 weeks.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean Serum Ferritin From Baseline to Week 52		52 weeks
Change in Mean Serum Transferrin Saturation (TSAT) From Baseline to the End of the Safety Assessment Period (Week 52)		52 weeks
IV Iron Analysis	Full Analysis Population, cumulative IV Iron administration from Baseline to the end of the Safety Assessment Period (Week 52)	52 weeks
ESA Analysis	Full analysis population, cumulative Erythropoiesis-stimulating agent (ESA) administration from baseline to the end of the Safety Assessment Period (Week 52)	52 weeks

Collaborators and Investigators

• Sponsor: Keryx Biopharmaceuticals
• Investigators: Study Chair: Samuel Blumenthal, MD, Collaborative Study Group

Publications and helpful links

General Publications

• Rodby RA, Umanath K, Niecestro R, Bond TC, Sika M, Lewis J, Dwyer JP; Collaborative Study Group. Ferric Citrate, an Iron-Based Phosphate Binder, Reduces Health Care Costs in Patients on Dialysis Based on Randomized Clinical Trial Data. Drugs R D. 2015 Sep;15(3):271-9. doi: 10.1007/s40268-015-0103-y.

Helpful Links

• Sponsor Website

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (ACTUAL): January 1, 2013
• Study Completion (ACTUAL): February 1, 2013

Study Registration Dates

• First Submitted: August 26, 2010
• First Submitted That Met QC Criteria: August 27, 2010
• First Posted (ESTIMATE): August 30, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): December 10, 2014
• Last Update Submitted That Met QC Criteria: December 8, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: dialysis; ESRD; peritoneal dialysis; end-stage renal disease; renal failure; hemodialysis; chronic renal insufficiency; kidney failure; hemodialysis (HD); phosphate binder; peritoneal dialysis (PD)
• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Phosphorus Metabolism Disorders; Renal Insufficiency; Hyperphosphatemia; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Sevelamer
• Other Study ID Numbers: KRX-0502-304