Trial of a New Formulation of KRX-0502 (Ferric Citrate) in Patients With End-Stage Renal Disease

A 6-Week Feasibility Trial of a New Formulation of KRX-0502 (Ferric Citrate) in Patients With End-Stage Renal Disease (ESRD)

The objective of this study is to see if KRX-0502 (ferric citrate) is safe and effective as a dietary phosphate binder in controlling and managing serum phosphorus levels in patients with end-stage renal disease (ESRD).

Study Overview

• Status: Completed
• Conditions: Hyperphosphatemia; End-stage Renal Disease; Renal Failure Chronic Requiring Hemodialysis
• Intervention / Treatment: Drug: ferric citrate

Detailed Description

This is a multi-center, non-blinded, efficacy and tolerability trial in patients with ESRD on dialysis three times per week. Approximately 24 patients (approximately twelve diabetic patients and approximately twelve non-diabetic patients) in Israel will be initiated on KRX-0502 (ferric citrate). The study will consist of a two-week washout period immediately followed by a six-week treatment period in. Patients will be initiated on study drug over two to three weeks.

• Study Type: Observational
• Enrollment (Actual): 22

Contacts and Locations

Study Locations

• Israel
  • Ashkelon, Israel, 78306
    • Barzilai Medical Center Ben-Gurion University
  • Jerusalem, Israel, 91120
    • Hadassah University Hospital-Ein Kerem
  • Zerifin, Israel, 70300
    • Assaf Haraofeh Medical Center

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Patients selected from pool of dialysis patients at each clinic.

Description

Inclusion Criteria:

1. Males and non-pregnant, non-lactating females
2. Age > 18 years
3. On thrice weekly hemodialysis for at least the previous three months prior to screening
4. Serum phosphorus levels ≥ 2.5 mg/dL and < 8.5 mg/dL at Screening Visit (Visit 0)
5. Serum phosphorus levels > 5.5 mg/dL at Study Drug Initiation Visit (Visit 3)
6. Taking 3 to 18 tablets/capsules/day of calcium acetate calcium carbonate, lanthanum carbonate, sevelamer (hydrochloride or carbonate), or any combination of these agents as reported by the patient at screening
7. Serum ferritin <1000micrograms/L and Transferrin Saturation (TSAT) <50%
8. Willing to be discontinued from current phosphate binder(s) and initiated on KRX-0502 (ferric citrate)
9. Willing and able to give informed consent

Exclusion Criteria:

1. Parathyroidectomy within six months prior to Screening Visit (Visit 0)
2. Actively symptomatic gastrointestinal bleeding and inflammatory bowel disease
3. Serum phosphorus levels >10.0 mg/dL documented in the three monthly laboratories (done routinely in the dialysis unit) in the three months prior to the Screening Visit (Visit 0)
4. History of multiple drug allergies
5. History of malignancy in the last five years (treated cervical or skin cancer may be permitted if approved by Keryx)
6. Previous intolerance to oral ferric citrate
7. Absolute requirement for oral iron therapy
8. Absolute requirement for Vitamin C (multivitamins [Centrum, Nephrocaps, Renaphro, etc.] allowed)
9. Absolute requirement for calcium, magnesium, or aluminum containing drugs with meals
10. Psychiatric disorder that interferes with the patient's ability to comply with the study protocol
11. Inability to tolerate oral drug intake
12. Planned surgery or hospitalization during the study (scheduled outpatient access surgery allowed)
13. Any other medical condition that renders the patient unable to or unlikely to complete the study or that would interfere with optimal participation in the study or produce significant risk to the patient
14. Receipt of any investigational drug within 30 days of randomization
15. Inability to cooperate with study personnel or history of noncompliance
16. Prior exposure to ferric citrate
17. Patients with hemochromatosis or Thalassemia

Study Plan

How is the study designed?

Design Details

• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

KRX-0502 (ferric citrate); KRX-0502 will be supplied as one caplet of ferric citrate containing 210 mg of ferric iron as ferric citrate. All patients initiated on study drug will start with a fixed dose of KRX-0502 (ferric citrate) of 6 caplets per day. Patients will be titrated at Visits 4, 5, and 6 based on serum phosphorus lab results. If serum phosphorus levels go below normal, there will be a decrease in pills; if serum phosphorus levels go above normal, there wil be an increase in pills. The maximum number of KRX-0502 (ferric citrate) caplets per day will be 12, or 12 g/day of ferric citrate. Patients will take study drug orally with meals or snacks or within one hour after their meals or snacks.

Drug: ferric citrate; KRX-0502 will be supplied as one caplet of ferric citrate containing 210 mg of ferric iron as ferric citrate; Other Names: KRX-0502

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The Primary Outcome of This Trial Will be the Change in Serum Phosphorus From Baseline to End of Treatment After a Four Week Treatment Period.	4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
The Incidence of Treatment-emergent Adverse Events (New or Worsened From Study Drug Initiation) Will be Summarized by Body System, Severity, Type of Adverse Event, and Presumed Relationship to the Study Drug.	6 weeks

Collaborators and Investigators

• Sponsor: Keryx Biopharmaceuticals
• Investigators: Principal Investigator: Itamar Raz, MD, Hadassah University Hospital-Ein Kerem

Publications and helpful links

General Publications

• Hsu CH, Patel SR, Young EW. New phosphate binding agents: ferric compounds. J Am Soc Nephrol. 1999 Jun;10(6):1274-80. doi: 10.1681/ASN.V1061274.
• Yang WC, Yang CS, Hou CC, Wu TH, Young EW, Hsu CH. An open-label, crossover study of a new phosphate-binding agent in haemodialysis patients: ferric citrate. Nephrol Dial Transplant. 2002 Feb;17(2):265-70. doi: 10.1093/ndt/17.2.265.

Helpful Links

• Sponsor Website

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: August 27, 2009
• First Submitted That Met QC Criteria: August 27, 2009
• First Posted (Estimate): August 28, 2009

Study Record Updates

• Last Update Posted (Estimate): December 5, 2014
• Last Update Submitted That Met QC Criteria: November 19, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: diabetes; dialysis; ESRD; end-stage renal disease; hemodialysis; hyperphosphatemia
• Additional Relevant MeSH Terms: Metabolic Diseases; Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Phosphorus Metabolism Disorders; Kidney Diseases; Kidney Failure, Chronic; Hyperphosphatemia
• Other Study ID Numbers: KRX-0502-202