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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

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

Conditions
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Hyperphosphatemia, End-stage Renal Disease, Renal Failure Chronic Requiring Hemodialysis

Intervention / Treatment
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* Drug: ferric citrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and non-pregnant, non-lactating females Age > 18 years On thrice weekly hemodialysis for at least the previous three months prior to screening Serum phosphorus levels ≥ 2.5 mg/dL and < 8.5 mg/dL at Screening Visit (Visit 0) Serum phosphorus levels > 5.5 mg/dL at Study Drug Initiation Visit (Visit 3) 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 Serum ferritin <1000micrograms/L and Transferrin Saturation (TSAT) <50% Willing to be discontinued from current phosphate binder(s) and initiated on KRX-0502 (ferric citrate) Willing and able to give informed consent Exclusion Criteria: Parathyroidectomy within six months prior to Screening Visit (Visit 0) Actively symptomatic gastrointestinal bleeding and inflammatory bowel disease 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) History of multiple drug allergies History of malignancy in the last five years (treated cervical or skin cancer may be permitted if approved by Keryx) Previous intolerance to oral ferric citrate Absolute requirement for oral iron therapy Absolute requirement for Vitamin C (multivitamins [Centrum, 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 study (scheduled outpatient access surgery allowed) 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 Receipt of any investigational drug within 30 days of randomization Inability to cooperate with study personnel or history of noncompliance Prior exposure to ferric citrate Patients with hemochromatosis or Thalassemia

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| KRX-0502 (ferric citrate)<br>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<br>* KRX-0502 will be supplied as one caplet of ferric citrate containing 210 mg of ferric iron as ferric citrate<br>* Other names: KRX-0502;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hyperphosphatemia, end-stage renal disease, ESRD, hemodialysis, diabetes, dialysis