Dose Ranging Study of Dialysate Containing Soluble Iron to Treat Subjects With End Stage Renal Disease (ESRD) Receiving Chronic Hemodialysis

Phase 2

Completed

Conditions: End-Stage Renal Disease (ESRD)

Interventions: Device: Standard Bicarbonate Solution
Drug: Soluble Ferric Pyrophosphate

Registration Number: NCT00548249

Lead Sponsor: Rockwell Medical Technologies, Inc.

Brief Summary: The purpose of this study is to determine whether Dialysate containing soluble iron (Soluble Ferric Pyrophosphate) is safe and effective in maintaining physiological iron levels during chronic hemodialysis.

Detailed Description: The study was designed to evaluate the efficacy of SFP-containing dialysate solution in maintaining physiological iron levels during chronic hemodialysis, as measured by the primary endpoint of the percent of patients whose Hemoglobin (Hgb) decreased by at least 1.0 gram/ deciliter (g/dL) from baseline. The efficacy and safety findings are to be used to determine the optimal concentration of SFP needed to safely maintain iron levels, compensating for iron losses during chronic hemodialysis.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 131

Inclusion Criteria

Adult subject ≥ 18 years of age undergoing chronic hemodialysis for end-stage renal disease (ESRD) three times a week
Hemoglobin (Hgb) values on two successive screening/baseline measures immediately prior to the start of the study averaging 10.1 to 11.5 grams/ deciliter (g/dL), inclusive
Transferrin Saturation (TSAT) values that average 20% or more, but not exceeding 35%, prior to dialysis measured during the screening period
Ferritin values that average 200 to 800 micrograms/ liter (µg/L), inclusive, measured during the screening period. An average ferritin above 800 µg/L but no greater than 1200 µg/L is allowed if the average TSAT is 20% to no greater than 25%.
Except for vascular access surgery, subject has no hospitalization in previous three months for a significant illness that, in the opinion of the Investigator, confers a significant risk of hospitalization during the course of the study. No blood transfusions within the last 4 weeks are allowed.
Subject has an adequate dialyzer blood flow rate that is acceptable to the Principal Investigator

Exclusion Criteria

Hemoglobin (Hgb) values on two successive baseline/screening measurements that average ≥ 11.6g/dL
Subject with a current malignancy involving a site other than skin
Subject with a history of drug or alcohol abuse within the last six months
Subject believed to be unable to complete the entire study (e.g., due to a concurrent disease, life expectancy of less than a year)
Subject who the Principal Investigator considers will be placed at increased risk by the study procedures
Subject requiring hemodialysis more than 3 times per week on a regular basis.
Subject who is unable to discontinue oral iron or intravenous iron supplements for the duration of the study
Subject who is pregnant
Subject considered incompetent to give an informed consent
Subject with a positive test for Hepatitis B Surface Antigen within the past 30 days or during screening
Subject with known HIV infection (if this is not known, no HIV testing will be performed)
Subject with cirrhosis of the liver based on histological criteria or clinical criteria (presence of ascites, esophageal varices, spider nevi, or history of hepatic encephalopathy). Subject with hepatitis C, in the absence of cirrhosis, is not excluded from participation in the study if ALT and AST levels are below 2 times the upper limit of normal consistently during the 2 months preceding enrollment
Subject with active tuberculosis, fungal, viral, or parasitic infection
Subject with active bacterial infection requiring antibiotic therapy
Subject with pre-dialysis Corrected Q-wave to T-wave (QTc) interval ≥ 470 milliseconds (ms)
Subject with a history of hypokalemia, decompensated heart failure, or family history of Long QT Syndrome that in the Investigator's judgment poses a risk for Torsades de Pointe during the study
Subject using concomitant medications known to prolong QT/QTc interval (See Appendix I, TABLE A)
Subject receiving more than 60,000 units or 120 micrograms of erythropoietin (Epogen®, Procrit®, or Aranesp®) per week
Subject has participated in another clinical trial within 30 days of signing Informed Consent

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
0 µg iron/dL of dialysate	Standard Bicarbonate Solution	Placebo 0 micrograms (µg) of iron/ deciliter (dL) of dialysate
5 µg iron/dL of dialysate	Soluble Ferric Pyrophosphate	5 micrograms (µg) of iron/ deciliter (dL) of dialysate
10 µg iron/dL of dialysate	Soluble Ferric Pyrophosphate	10 micrograms (µg) of iron/ deciliter (dL) of dialysate
12 µg iron/dL of dialysate	Soluble Ferric Pyrophosphate	12 micrograms (µg) of iron/ deciliter (dL) of dialysate
15 µg iron/dL of dialysate	Soluble Ferric Pyrophosphate	15 micrograms (µg) of iron/ deciliter (dL) of dialysate

Primary Outcome Measures

Name	Time	Method
Percent of Subjects Whose Hemoglobin (Hgb) Decreases by a Total of 1.0 Grams/ Deciliter (g/dL) (or More) From Baseline on Each of Two Successive Measurements.	up to 26 weeks	Efficacy of a Soluble Ferric Pyrophosphate (SFP)-containing dialysate solution in maintaining physiological iron levels during chronic HD, as measured by the percent of subjects whose hgb decreases by a total of 1.0 g/dL (or more) from baseline on each of two successive measurements. Hemoglobin was obtained weekly at the mid-week dialysis treatments and compared to baseline value (average of two hgb measurements obtained at the two consecutive baseline visits prior to randomization).

Secondary Outcome Measures

Name	Time	Method
Number of Subjects With a Rise in Hemoglobin (Hgb) to 12.6 g/dL or More on Two Separate Occasions Measured One Week Apart.	two separate sessions measured one week apart.
Time in Days for Hgb to Decrease by a Total of > = 1.0 g/dL From Baseline on Each of Two Successive Measurements in Each Treatment Group.	Up to 26 weeks	Kaplan-Meier Estimate of Time to First Hgb Decrease by \>= 1.0 g/dL
Reticulocyte Hemoglobin (CHr) Values Every Four Weeks, and at the End of the Subject's Treatment.	Every 4 weeks	Efficacy of SFP administration in dialysate solution as measured by Chr values every four weeks, and at the end of the Subject's Treatment (up to 26 weeks).
Number of Subjects With Infection Episodes Requiring Antibiotic or Anti-fungal Therapy in Each Treatment Group.	At each dialysis session for up to 26 weeks
Change From Baseline in Hemoglobin (Hgb)	two time points: baseline and final evaluation (last post baseline assessment, up to 26 weeks)