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Safety Study of Soluble Ferric Pyrophosphate (SFP) in Dialysate in CKD Patients Receiving Chronic Hemodialysis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01503021
Recruitment Status : Completed
First Posted : January 2, 2012
Results First Posted : April 21, 2015
Last Update Posted : October 25, 2016
Sponsor:
Information provided by (Responsible Party):
Rockwell Medical Technologies, Inc.

Brief Summary:

The purpose of the parent study is to assess the short-term safety and tolerability of soluble ferric pyrophosphate (SFP) in dialysate administered to a large number of representative adult chronic kidney disease patients on hemodialysis (CKD-HD).

The purpose of the extension study is to assess the long-term safety and tolerability of SFP.


Condition or disease Intervention/treatment Phase
End Stage Renal Disease Chronic Kidney Disease Drug: SFP Other: Placebo Phase 3

Detailed Description:

Parent Study: randomized, double-blinded, crossover, up to 6 weeks, 700 patients. Patients were randomized to receive SFP 2 µmoles (110 µg) iron/L of dialysate in liquid bicarbonate concentrate or placebo (standard liquid bicarbonate concentrate) x 2 weeks, then a 1 week washout, then crossed over to the alternate treatment x 2 weeks.

Extension Study: open-label, single active arm, uncontrolled study, up to 53 weeks, 300 patients. Following completion of the RMTI-SFP-6 parent study, patients could enter the extension study, where they received SFP 2 µmoles (110 µg) iron/L of dialysate in liquid bicarbonate concentrate for up to 52 weeks.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 718 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blinded, Placebo-Controlled, Crossover, Multicenter Phase III Safety Study of Soluble Ferric Pyrophosphate (SFP) in Dialysate in Chronic Kidney Disease Patients Receiving Chronic Hemodialysis
Study Start Date : November 2011
Actual Primary Completion Date : January 2014
Actual Study Completion Date : January 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
SFP/Placebo
Soluble ferric pyrophosphate (SFP) 2 µmoles (110 µg) iron/L of dialysate in liquid bicarbonate concentrate x 2 weeks, then 1 week washout, then standard liquid bicarbonate concentrate without SFP x 2 weeks
Drug: SFP
Dialysis with SFP administered via the liquid bicarbonate concentrate at a concentration of 2 µmoles (110 µg) iron/L of dialysate
Other Name: Soluble ferric pyrophosphate

Other: Placebo
Dialysis with standard liquid bicarbonate concentrate without iron
Other Name: Standard liquid bicarbonate concentrate

Placebo/SFP
Standard liquid bicarbonate concentrate without SFP x 2 weeks, then 1 week washout, then soluble ferric pyrophosphate (SFP) 2 µmoles (110 µg) iron/L of dialysate in liquid bicarbonate concentrate x 2 weeks.
Drug: SFP
Dialysis with SFP administered via the liquid bicarbonate concentrate at a concentration of 2 µmoles (110 µg) iron/L of dialysate
Other Name: Soluble ferric pyrophosphate

Other: Placebo
Dialysis with standard liquid bicarbonate concentrate without iron
Other Name: Standard liquid bicarbonate concentrate




Primary Outcome Measures :
  1. Incidence of Treatment-emergent Adverse Events [ Time Frame: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study ]
    Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention.

  2. Incidence of Treatment-emergent Adverse Events of Intradialytic Hypotension [ Time Frame: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study ]
    Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. For each adverse event, investigators assessed whether the event met the protocol criteria for intradialytic hypotension. Intradialytic hypotension events were only to have been reported as adverse events if they exceeded the individual subject's baseline pattern of intradialytic hypotension.

  3. Incidence of Related Suspected Hypersensitivity Reactions [ Time Frame: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study ]
    Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. For each adverse event, investigators assessed whether the event met protocol criteria for suspected hypersensitivity reactions.


Secondary Outcome Measures :
  1. Incidence of Composite Cardiovascular Events [ Time Frame: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study ]
    Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Adverse event terms meeting criteria for composite cardiovascular events were pre-specified in the statistical analysis plan for the study.

  2. Incidence of Hemodialysis Vascular Access Thrombotic Events [ Time Frame: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study ]
    Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Adverse event terms meeting criteria for hemodialysis vascular access thrombotic events were pre-specified in the statistical analysis plan for the study.

  3. Incidence of Other Thrombotic Events [ Time Frame: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study ]
    Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Adverse event terms meeting criteria for other thrombotic events were pre-specified in the statistical analysis plan for the study.

  4. Incidence of Systemic/Serious Infections [ Time Frame: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study ]
    Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Adverse events of systemic/serious infections were defined in the statistical analysis plan for the study to include infections for which the subject was administered at least 3 doses of an IV antibiotic, and infections for which the subject was hospitalized.

  5. Incidence of Serious Adverse Events [ Time Frame: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study ]
    Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. For each adverse event, investigators assessed whether the event met seriousness criteria.


Other Outcome Measures:
  1. Serum Iron Change From Pre-dialysis to Post-dialysis at Week 2 [ Time Frame: Pre-dialysis and post-dialysis during study week 2 of the Parent (Crossover) Study ]
    Serum iron was assessed from samples obtained pre-dialysis and post-dialysis at a single hemodialysis during study week 2. Because of the crossover nature of the study, the week 2 values reflect effects of SFP in the SFP/Placebo arm and effects of Placebo in the Placebo/SFP arm.

  2. Serum Iron Change From Pre-dialysis to Post-dialysis at Week 5 [ Time Frame: Pre-dialysis and post-dialysis during study week 5 of the Parent (Crossover) Study ]
    Serum iron was assessed from samples obtained pre-dialysis and post-dialysis at a single hemodialysis during study week 5. Because of the crossover nature of the study, the week 5 values reflect effects of Placebo in the SFP/Placebo arm and effects of SFP in the Placebo/SFP arm.

  3. Unsaturated Iron-binding Capacity Change From Pre-dialysis to Post-dialysis at Week 2 [ Time Frame: Pre-dialysis and post-dialysis during study week 2 of the Parent (Crossover) Study ]
    Unsaturated iron-binding capacity was assessed from samples obtained pre-dialysis and post-dialysis at a single hemodialysis during study week 2. Because of the crossover nature of the study, the week 2 values reflect effects of SFP in the SFP/Placebo arm and effects of Placebo in the Placebo/SFP arm.

  4. Unsaturated Iron-binding Capacity Change From Pre-dialysis to Post-dialysis at Week 5 [ Time Frame: Pre-dialysis and post-dialysis during study week 5 of the Parent (Crossover) Study ]
    Unsaturated iron-binding capacity was assessed from samples obtained pre-dialysis and post-dialysis at a single hemodialysis during study week 5. Because of the crossover nature of the study, the week 5 values reflect effects of Placebo in the SFP/Placebo arm and effects of SFP in the Placebo/SFP arm.

  5. Transferrin Saturation Change From Pre-dialysis to Post-dialysis at Week 2 [ Time Frame: Pre-dialysis and post-dialysis during study week 2 of the Parent (Crossover) Study ]
    Transferrin saturation (based on TIBC derived from transferrin levels) was assessed from samples obtained pre-dialysis and post-dialysis at a single hemodialysis during study week 2. Because of the crossover nature of the study, the week 2 values reflect effects of SFP in the SFP/Placebo arm and effects of Placebo in the Placebo/SFP arm.

  6. Transferrin Saturation Change From Pre-dialysis to Post-dialysis at Week 5 [ Time Frame: Pre-dialysis and post-dialysis during study week 5 of the Parent (Crossover) Study ]
    Transferrin saturation (based on TIBC derived from transferrin levels) was assessed from samples obtained pre-dialysis and post-dialysis at a single hemodialysis during study week 5. Because of the crossover nature of the study, the week 5 values reflect effects of Placebo in the SFP/Placebo arm and effects of SFP in the Placebo/SFP arm.

  7. Ferritin [ Time Frame: Baseline, up to 53 weeks for Extension Study ]
    The baseline and end of treatment predialysis ferritin levels were evaluated for the 52-week extension study to determine whether soluble ferric pyrophosphate increases iron stores.

  8. Serum Iron [ Time Frame: Baseline, up to 53 weeks for Extension Study ]
    The baseline and end of treatment predialysis serum iron levels were evaluated for the 52-week extension study to determine the effect of soluble ferric pyrophosphate on serum iron.

  9. Transferrin Saturation [ Time Frame: Baseline, up to 53 weeks for Extension Study ]
    The baseline and end of treatment predialysis transferrin saturation were evaluated for the 52-week extension study to confirm clearance of iron derived from soluble ferric pyrophosphate.

  10. Incidence of Patients Meeting Hy's Law Criteria [ Time Frame: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study ]
    The peak alanine aminotransferase and the peak total bilirubin levels were evaluated per patient. Laboratory values for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Patients with alanine aminotransferase more than three times the upper limit of normal and also total bilirubin more than two times the upper limit of normal are counted.



Information from the National Library of Medicine

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Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Parent Study, Double Blinded, Crossover:

Key Inclusion Criteria:

  1. Adult ≥ 18 years of age.
  2. Has chronic kidney disease (CKD) receiving maintenance hemodialysis (HD) (CKD-HD subjects) and regularly undergoing 2 or more dialysis sessions per week.
  3. Stable pre-dialysis Hgb ≥ 9.0 to ≤ 12.5 g/dL.
  4. Stable pre-dialysis TSAT ≥ 15% to ≤ 45%.
  5. Stable pre-dialysis ferritin ≥ 100 to ≤ 1200 µg/L (1200 ng/mL).

Key Exclusion Criteria:

  1. Any previous exposure to SFP.
  2. Therapy with intravenous, intramuscular or oral iron at any time between the first/screening visit and the randomization visit, or anticipated requirement for iron supplementation during the study period.
  3. Non-tunneled vascular catheter for dialysis.
  4. Scheduled for kidney transplant within the next 8 weeks.
  5. Active infection requiring systemic antimicrobial or antifungal therapy within 2 weeks prior to screening, or during screening period prior to randomization.
  6. Hospitalization within 1 month prior to screening (except for vascular access surgery).

Extension Study, Open Label, Single Active Arm:

Key Inclusion Criteria:

  1. Participated in Parent Study RMTI-SFP-6 and completed the follow-up/early term visit.
  2. Hemoglobin ≤12.0 g/dL at screening.
  3. TSAT ≤45% at screening. (Excursion of TSAT by ≤10% outside this range permitted only if all other inclusion/exclusion criteria are met).
  4. Serum ferritin ≤1000 µg/L at screening. (Excursion of ferritin by ≤10% outside this range permitted only if all other inclusion/exclusion criteria are met).

Key Exclusion Criteria:

  1. Had a serious adverse event attributable (i.e., probably, possibly, or definitely related) to study drug or had an adverse event attributable to study drug that necessitated premature withdrawal from the double-blind, placebo-controlled crossover phase of the parent study RMTI-SFP-6.
  2. Non-tunneled vascular catheter for dialysis.
  3. Scheduled for kidney transplant within 12 weeks after entry into extension phase.
  4. Active infection requiring systemic antimicrobial or antifungal therapy within 2 weeks prior to dosing.
  5. Pregnancy or intention to become pregnant during the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01503021


Locations
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United States, Alabama
Mobile, Alabama, United States, 36688
United States, California
Northridge, California, United States, 91324
United States, Colorado
Arvada, Colorado, United States, 80002
Westminster, Colorado, United States, 80031
United States, Florida
Lauderhill, Florida, United States, 33319
United States, Georgia
Marietta, Georgia, United States, 30060
United States, Illinois
Chicago, Illinois, United States, 60616
Peoria, Illinois, United States, 61603
United States, Indiana
Columbus, Indiana, United States, 47201
United States, Kansas
Wichita, Kansas, United States, 67214
United States, Louisiana
Baton Rouge, Louisiana, United States, 70808
Shreveport, Louisiana, United States, 71101
United States, Maryland
Camp Springs, Maryland, United States, 20748
United States, Mississippi
Gulfport, Mississippi, United States, 39501
McComb, Mississippi, United States, 39648
Tupelo, Mississippi, United States, 38801
United States, Missouri
St. Peters, Missouri, United States, 63376
United States, Nebraska
Lincoln, Nebraska, United States, 68510
United States, Nevada
Reno, Nevada, United States, 89511
United States, North Carolina
Rocky Mount, North Carolina, United States, 27804
United States, Ohio
Dayton, Ohio, United States, 45428
United States, South Carolina
Columbia, South Carolina, United States, 29209
United States, Texas
Research Across America
Houston, Texas, United States, 75234
Houston, Texas, United States, 77051
Irving, Texas, United States, 75061
Mission, Texas, United States, 78572
Temple, Texas, United States, 76508
Tyler, Texas, United States, 75701
Canada, Ontario
Courtice, Ontario, Canada, L1E 3C3
Canada, Quebec
Montreal, Quebec, Canada, H3A 1A1
Canada, Saskatchewan
Regina, Saskatchewan, Canada, 54P 0W5
Sponsors and Collaborators
Rockwell Medical Technologies, Inc.
Investigators
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Study Director: Ray Pratt, MD Rockwell Medical, Inc

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Responsible Party: Rockwell Medical Technologies, Inc.
ClinicalTrials.gov Identifier: NCT01503021    
Other Study ID Numbers: RMTI-SFP-6
First Posted: January 2, 2012    Key Record Dates
Results First Posted: April 21, 2015
Last Update Posted: October 25, 2016
Last Verified: September 2016
Keywords provided by Rockwell Medical Technologies, Inc.:
Soluble ferric pyrophosphate
Chronic kidney disease
Chronic hemodialysis
Ferric pyrophosphate citrate
Additional relevant MeSH terms:
Layout table for MeSH terms
Kidney Diseases
Renal Insufficiency, Chronic
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency
Iron
Dialysis Solutions
Pharmaceutical Solutions
Trace Elements
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs