A 4-Week Dose-Ranging and Efficacy Trial of KRX-0502 (Ferric Citrate) in Patients With End-Stage Renal Disease

• ClinicalTrials.gov Identifier: NCT01074125
• Recruitment Status: Completed
• First Posted: February 24, 2010
• Results First Posted: December 4, 2014
• Last Update Posted: December 4, 2014
• Sponsor: Keryx Biopharmaceuticals
• Collaborator: Collaborative Study Group (CSG)
• Information provided by (Responsible Party): Keryx Biopharmaceuticals

Study Description

Brief Summary:

This is a research study for people with high blood phosphorus levels who are on dialysis. This medical condition can cause weakening of the bones and damage other organs. This can lead to many health problems, and sometimes death. Phosphorus is in much of the food we eat, and is helpful to us in small amounts. Patients with kidney failure have trouble getting rid of the phosphorus eaten in food. Dialysis can help remove some of the phosphorus, but often patients must take a phosphate binder like PhosLo®, Renagel®, or Renvela® to bring the blood phosphorus levels back to normal. The purpose of this study is to see if KRX-0502 (ferric citrate) is safe and effective as a phosphate binder.

Condition or disease	Intervention/treatment	Phase
Hyperphosphatemia; End-Stage Renal Disease	Drug: ferric citrate	Phase 3

Detailed Description:

There will be a screening visit about 4 weeks receiving study drug. Upon qualifying for the study after the screening visit, patients will then be asked to stop taking their current phosphate binder for about 2 weeks. Then, if patients continue to qualify for the study, they will be entered in the study that lasts about 28 days. Study visits will happen every week during the patient's usual dialysis appointments. There will be a total of up to 9 visits for this study, and total participation time could last up to 8 weeks.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 154 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 4-Week Dose-Ranging and Efficacy Trial of KRX-0502 (Ferric Citrate) in Patients With End-Stage Renal Disease (ESRD) Following a Two-Week Washout Period
• Study Start Date: May 2010
• Actual Primary Completion Date: November 2010
• Actual Study Completion Date: November 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1 g/day; 1 g/day KRX-0502 (ferric citrate)	Drug: ferric citrate; 1, 6, or 8 g/day taken within 1 hour of meals or snacks daily for 28 days; Other Name: KRX-0502
Experimental: 6 g/day; 6 g/day KRX-0502 (ferric citrate)	Drug: ferric citrate; 1, 6, or 8 g/day taken within 1 hour of meals or snacks daily for 28 days; Other Name: KRX-0502
Experimental: 8 g/day; 8 g/day KRX-0502 (ferric citrate)	Drug: ferric citrate; 1, 6, or 8 g/day taken within 1 hour of meals or snacks daily for 28 days; Other Name: KRX-0502

Outcome Measures

Primary Outcome Measures :

1. Change in Serum Phosphorus From Baseline to End of Treatment [ Time Frame: Baseline and day 28 ]
   Mean change from baseline was calculated separately for each treatment arm (LOCF)

Secondary Outcome Measures :

1. Pairwise Comparison of the Mean Change in Serum Phosphorus From Baseline to the End of Treatment [ Time Frame: Baseline and day 28 ]
   Mean change from baseline was calculated separately for each treatment arm. Only subjects that have both baseline and end of treatment serum phosphorus scores were analyzed for this outcome.
2. Proportion of Patient With a Serum Phosphorus ≤5.5 mg/dL at the End of Treatment [ Time Frame: Baseline and day 28 ]
   proportion was calculated separately for each treatment arm

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Males or non-pregnant, non-lactating females
• Age > 18 years
• On thrice weekly hemodialysis or peritoneal dialysis for at least the previous three months prior to Screening Visit (Visit 0)
• Serum phosphorus levels ≥ 3.5 mg/dL and < 8.0 mg/dL at Screening Visit (Visit 0)
• Serum phosphorus levels > 6.0 mg/dL during the washout period (Visits 2 or 3)
• Taking 3 to 15 tablets/capsules per day of 667mg calcium acetate or 800 mg sevelamer (hydrochloride or carbonate), or any combination of these agents as reported by the patient at Screening Visit (Visit 0)
• Serum ferritin <1000micrograms/L and Transferrin Saturation (TSAT) <50% at the Screening Visit (Visit 0)
• Willingness to be discontinued from current phosphate binder(s) and initiated on KRX-0502 (ferric citrate)
• Willing and able to give informed consent
• Willing and able to stay on a constant dose of Vitamin D (or its analogs) and Sensipar (cinacalcet) for the treatment period, if applicable.

Exclusion Criteria:

• Parathyroidectomy within six months prior to Screening Visit (Visit 0)
• Actively symptomatic gastrointestinal bleeding or inflammatory bowel disease
• Serum phosphorus levels >10.0 mg/dL documented in all of the three monthly laboratories (done routinely in the dialysis unit) in the three months prior to the Screening Visit (Visit 0)
• History of multiple drug allergies or intolerances
• History of malignancy in the last five years (treated cervical or non-melanomatous skin cancer may be permitted if approved by CCC)
• Previous intolerance to oral ferric citrate
• Absolute requirement for oral iron therapy
• Absolute requirement for Vitamin C (multivitamins [Nephrocaps, Renaphro, etc.] allowed)
• Absolute requirement for calcium-, magnesium-, or aluminum-containing drugs with meals
• Psychiatric disorder that interferes with the patient's ability to comply with the study protocol
• Inability to tolerate oral drug intake
• Planned surgery or hospitalization during the trial (scheduled outpatient access surgery allowed)
• 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
• Receipt of any investigational drug within 30 days of Screening Visit (Visit 0)
• Inability to cooperate with study personnel or history of noncompliance
• Unsuitable for this trial per Principal Investigator's clinical judgment

Contacts and Locations

Locations

United States, Colorado

Western Nephrology

Westminster, Colorado, United States, 80031

United States, Florida

Pines Clinical Research, Inc.

Pembroke Pines, Florida, United States, 33028

United States, Georgia

Kidney Care Associates, LLC

Augusta, Georgia, United States, 30901

United States, Illinois

Circle Medical Management

Chicago, Illinois, United States, 60607

United States, Massachusetts

Western New England Renal & Transplant Associates

Springfield, Massachusetts, United States, 01107

United States, New York

Brookdale Physician's Dialysis Associates

Brooklyn, New York, United States, 11212

United States, Ohio

DCI

Cincinnati, Ohio, United States, 45206

Cleveland Clinical Foundation Fresenius East (Fairhill)

Cleveland, Ohio, United States, 44104

The Ohio State University Cramblett Medical Clinic

Columbus, Ohio, United States, 43210

United States, Tennessee

Southeast Renal Research Institute

Chattanooga, Tennessee, United States, 37404

Nephrology Associates, PC

Nashville, Tennessee, United States, 37205

Meharry Medical College Clinical Research Center

Nashville, Tennessee, United States, 37208

Vanderbilt University Medical Center Clinical Trials Center

Nashville, Tennessee, United States, 37232-1371

United States, Texas

Kidney Associates

Houston, Texas, United States, 77030

United States, Wisconsin

Centre Point Dialysis

West Allis, Wisconsin, United States, 53214

Puerto Rico

RCMI- Clinical Research Center Medical Sciences Campus University of Puerto Rico

Rio Piedras, Puerto Rico, 00936-5067

Sponsors and Collaborators

Keryx Biopharmaceuticals

Collaborative Study Group (CSG)

Investigators

• Study Chair: Julia B Lewis, MD; Collaborative Study Group (CSG)

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Dwyer JP, Sika M, Schulman G, Chang IJ, Anger M, Smith M, Kaplan M, Zeig S, Koury MJ, Blumenthal SS, Lewis JB; Collaborative Study Group. Dose-response and efficacy of ferric citrate to treat hyperphosphatemia in hemodialysis patients: a short-term randomized trial. Am J Kidney Dis. 2013 May;61(5):759-66. doi: 10.1053/j.ajkd.2012.11.041. Epub 2013 Jan 29.

• Responsible Party: Keryx Biopharmaceuticals
• ClinicalTrials.gov Identifier: NCT01074125
• Other Study ID Numbers: KRX-0502-305
• First Posted: February 24, 2010
• Results First Posted: December 4, 2014
• Last Update Posted: December 4, 2014
• Last Verified: December 2014

Keywords provided by Keryx Biopharmaceuticals:

Hyperphosphatemia; ESRD; Dialysis; End Stage Renal Disease; Phosphorus; Renal; Kidney

Additional relevant MeSH terms:

Kidney Diseases; Kidney Failure, Chronic; Hyperphosphatemia; Urologic Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Phosphorus Metabolism Disorders; Metabolic Diseases