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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Rockwell Medical Technologies, Inc.
ClinicalTrials.gov Identifier:
NCT01503021
First received: December 29, 2011
Last updated: April 21, 2015
Last verified: April 2015
  Purpose

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 Intervention Phase
End Stage Renal Disease
Chronic Kidney Disease
Drug: SFP
Other: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Rockwell Medical Technologies, Inc.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • 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 ] [ Designated as safety issue: Yes ]
    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:
  • Incidence of Composite Cardiovascular Events [ Time Frame: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study ] [ Designated as safety issue: Yes ]
    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.

  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • Incidence of Other Thrombotic Events [ Time Frame: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study ] [ Designated as safety issue: Yes ]
    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.

  • Incidence of Systemic/Serious Infections [ Time Frame: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study ] [ Designated as safety issue: Yes ]
    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.

  • Incidence of Serious Adverse Events [ Time Frame: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study ] [ Designated as safety issue: Yes ]
    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:
  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • Ferritin [ Time Frame: Baseline, up to 53 weeks for Extension Study ] [ Designated as safety issue: Yes ]
    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.

  • Serum Iron [ Time Frame: Baseline, up to 53 weeks for Extension Study ] [ Designated as safety issue: Yes ]
    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.

  • Transferrin Saturation [ Time Frame: Baseline, up to 53 weeks for Extension Study ] [ Designated as safety issue: Yes ]
    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.

  • 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 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 718
Study Start Date: November 2011
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01503021

  Show 31 Study Locations
Sponsors and Collaborators
Rockwell Medical Technologies, Inc.
Investigators
Study Director: Ajay Gupta, MD Rockwell Medical Technologies, Inc.
  More Information

No publications provided

Responsible Party: Rockwell Medical Technologies, Inc.
ClinicalTrials.gov Identifier: NCT01503021     History of Changes
Other Study ID Numbers: RMTI-SFP-6
Study First Received: December 29, 2011
Results First Received: April 3, 2015
Last Updated: April 21, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Rockwell Medical Technologies, Inc.:
Soluble ferric pyrophosphate
Chronic kidney disease
Chronic hemodialysis
Ferric pyrophosphate citrate

Additional relevant MeSH terms:
Kidney Failure, Chronic
Kidney Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Urologic Diseases
Dialysis Solutions
Iron
Growth Substances
Micronutrients
Pharmaceutical Solutions
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Trace Elements

ClinicalTrials.gov processed this record on July 29, 2015