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Triferic Pediatric Pharmacokinetic Protocol

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ClinicalTrials.gov Identifier: NCT02595437
Recruitment Status : Completed
First Posted : November 3, 2015
Results First Posted : October 25, 2018
Last Update Posted : October 25, 2018
Sponsor:
Information provided by (Responsible Party):
Rockwell Medical Technologies, Inc.

Tracking Information
First Submitted Date  ICMJE October 30, 2015
First Posted Date  ICMJE November 3, 2015
Results First Submitted Date  ICMJE August 27, 2018
Results First Posted Date  ICMJE October 25, 2018
Last Update Posted Date October 25, 2018
Study Start Date  ICMJE November 1, 2015
Actual Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 26, 2018)
  • Pharmacokinetics (PK) of Triferic Iron Administered IV in Pediatric CKD-5HD Patients: Cmax. [ Time Frame: 0, 1, 2, 4, 4.5, 5, 6, 8, 10 hrs ]
    The PK will be done by assessing the mean absolute and baseline-corrected Cmax of total iron with an IV infusion of Triferic at 0.07 mg iron/kg during a single dialysis session. The absolute Cmax includes the concentration of iron that was present in the serum prior to dosing as well the iron administered, while the baseline-corrected Cmax factors out the iron present in the serum prior to dosing and includes the administered iron only.
  • Pharmacokinetics (PK) of Triferic Iron Administered IV in Pediatric CKD-5HD Patients: AUC(Last). [ Time Frame: 0, 1, 2, 4, 4.5, 5, 6, 8, 10 hours ]
    The PK will be done by assessing the mean absolute and baseline-corrected AUC(last) of total iron with an IV infusion of Triferic at 0.07 mg iron/kg during a single dialysis session. The absolute AUC(last) includes iron that was present in the serum prior to dosing as well the iron administered, while the baseline-corrected AUC(last) factors out the iron present in the serum prior to dosing and includes the administered iron only.
  • Pharmacokinetics (PK) of Triferic Iron Administered IV in Pediatric CKD-5HD Patients: AUC(0-end). [ Time Frame: 0, 1, 2, 4, 4.5, 5, 6, 8, 10 hours ]
    The PK will be done by assessing the mean absolute and baseline-corrected AUC(0-end) of total iron with an IV infusion of Triferic at 0.07 mg iron/kg during a single dialysis session. The absolute AUC (0-end) includes iron that was present in the serum prior to dosing as well the iron administered, while the baseline-corrected AUC (0-end) factors out the iron present in the serum prior to dosing and includes the administered iron only.
Original Primary Outcome Measures  ICMJE
 (submitted: November 2, 2015)
  • Pharmacokinetics (PK) of Triferic iron administered IV in pediatric CKD-5HD patients: Cmax. [ Time Frame: 9 hours ]
    The PK will be done by assessing the mean absolute and baseline-corrected Cmax of total iron and transferrin-bound iron with an IV infusion of Triferic at 0.07 mg iron/kg during a single dialysis session.
  • Pharmacokinetics (PK) of Triferic iron administered IV in pediatric CKD-5HD patients: AUC(0-t). [ Time Frame: 9 hours ]
    The PK will be done by assessing the mean absolute and baseline-corrected AUC(0-t) of total iron and transferrin-bound iron with an IV infusion of Triferic at 0.07 mg iron/kg during a single dialysis session.
  • Pharmacokinetics (PK) of Triferic iron administered IV in pediatric CKD-5HD patients: AUC(0-end). [ Time Frame: 9 hours ]
    The PK will be done by assessing the mean absolute and baseline-corrected AUC(0-end) of total iron and transferrin-bound iron with an IV infusion of Triferic at 0.07 mg iron/kg during a single dialysis session.
  • Pharmacokinetics (PK) of Triferic iron administered IV in pediatric CKD-5HD patients: AUC(inf). [ Time Frame: 9 hours ]
    The PK will be done by assessing the mean absolute and baseline-corrected AUC(inf) of total iron and transferrin-bound iron with an IV infusion of Triferic at 0.07 mg iron/kg during a single dialysis session.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 26, 2018)
  • Pharmacokinetics (PK) of Triferic Iron Administered Via the Hemodialysate in Pediatric CKD-5HD Patients: Cmax. [ Time Frame: 0, 1, 2, 4, 4.5, 5, 6, 8, 10 hours ]
    The PK will be done by assessing the mean absolute and baseline-corrected Cmax of total iron. The absolute Cmax includes the concentration of iron that was present in the serum prior to dosing as well the iron administered, while the baseline-corrected Cmax factors out the iron present in the serum prior to dosing and includes the administered iron only.
  • Pharmacokinetics (PK) of Triferic Iron Administered Via the Hemodialysate in Pediatric CKD-5HD Patients: AUC(Last). [ Time Frame: 0, 1, 2, 4, 4.5, 5, 6, 8, 10 hours ]
    The PK will be done by assessing the mean absolute and baseline-corrected AUC(last) of total iron. The absolute AUC (last) includes the iron that was present in the serum prior to dosing as well the iron administered, while the baseline-corrected Cmax factors out the iron present in the serum prior to dosing and includes the administered iron only.
  • Pharmacokinetics (PK) of Triferic Iron Administered Via the Hemodialysate in Pediatric CKD-5HD Patients: AUC(0-end). [ Time Frame: 0, 1, 2, 4, 4.5, 5, 6, 8, 10 hours ]
    The PK will be done by assessing the mean absolute and baseline-corrected AUC(0-end) of total iron. The absolute AUC (0-end) includes the of iron that was present in the serum prior to dosing as well the iron administered, while the baseline-corrected Cmax factors out the iron present in the serum prior to dosing and includes the administered iron only.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 2, 2015)
  • Pharmacokinetics (PK) of Triferic iron administered via the hemodialysate in pediatric CKD-5HD patients: Cmax. [ Time Frame: 9 hours ]
    The PK will be done by assessing the mean absolute and baseline-corrected Cmax of total iron and transferrin-bound iron. Additional parameters may be calculated for subjects with sufficient PK sampling, including CL, λz, and half life in addition to mean absolute and baseline-corrected AUC(inf).
  • Pharmacokinetics (PK) of Triferic iron administered via the hemodialysate in pediatric CKD-5HD patients: Tmax. [ Time Frame: 9 hours ]
    The PK will be done by assessing the mean absolute and baseline-corrected Tmax of total iron and transferrin-bound iron.
  • Pharmacokinetics (PK) of Triferic iron administered via the hemodialysate in pediatric CKD-5HD patients: AUC(0-t). [ Time Frame: 9 hours ]
    The PK will be done by assessing the mean absolute and baseline-corrected AUC(0-t) of total iron and transferrin-bound iron.
  • Pharmacokinetics (PK) of Triferic iron administered via the hemodialysate in pediatric CKD-5HD patients: AUC(0-end). [ Time Frame: 9 hours ]
    The PK will be done by assessing the mean absolute and baseline-corrected AUC(0-end) of total iron and transferrin-bound iron.
  • Pharmacokinetics (PK) of Triferic iron administered IV in different age sub-groups: total iron. [ Time Frame: 9 hours ]
    The analysis will be done by determining the mean baseline-corrected PK parameters of total iron with Triferic administered IV for the following age groups: < 6 years, 6 - 12 years, >12 years.
  • Pharmacokinetics (PK) of Triferic iron administered IV in different age sub-groups: transferrin-bound iron. [ Time Frame: 9 hours ]
    The analysis will be done by determining the mean baseline-corrected PK parameters of transferrin-bound iron with Triferic administered IV for the following age groups: < 6 years, 6 - 12 years, >12 years.
  • Ratio of pharmacokinetic (PK) parameters of Triferic via IV to Triferic via dialysate [ Time Frame: 9 hours ]
    The ratio of the mean baseline-corrected PK parameters obtained for total iron with Triferic-iron administered IV to those obtained for total iron with Triferic-iron administered via dialysate will be calculated, for each age group and across all groups. The IV infusion of Triferic can provide an estimate of relative zero order rate of input and can be useful to estimate the total amount of iron delivered via dialysate.
  • Transferrin concentration [ Time Frame: 2.5 - 4.5 hours (depending on duration of hemodialysis) ]
    Transferrin concentration will be measured at time = 0 and time = end of hemodialysis to assess the effect of hemoconcentration on the serum iron parameters.
  • Dialysance of Triferic iron [ Time Frame: 2.5 - 4.5 hours (depending on duration of hemodialysis) ]
    The dialysance of Triferic iron will be explored by measuring the dialysate inlet and outlet iron concentrations at various times during administration of Triferic via hemodialysate. The cumulative difference in iron concentrations can be used to estimate net iron delivery via dialysate.
  • Clearance [ Time Frame: 9 hours ]
    The serum concentration data for total iron following IV administration of Triferic can also be used to estimate the total systemic clearance (CL) as a PK parameter to assist in estimating the fraction of CL related to hemodialysis.
Current Other Pre-specified Outcome Measures
 (submitted: September 26, 2018)
Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 1.5 weeks ]
The incidence of treatment-emergent AEs (TEAEs) and treatment-emergent serious AEs (TESAEs) will be grouped by body system. Adverse events were recorded from study Day 1 through the following up visit (approximately 1.5 weeks).
Original Other Pre-specified Outcome Measures
 (submitted: November 2, 2015)
  • Treatment-emergent adverse events (TEAEs) [ Time Frame: approximately 3 weeks (from first dose of Triferic until 7 days after the last dose of Triferic) ]
    The incidence of treatment-emergent AEs (TEAEs) and treatment-emergent serious AEs (TESAEs) will be grouped by body system.
  • Post-dialysis serum iron and transferrin saturation (TSAT) [ Time Frame: 3 weeks ]
    Post-dialysis serum iron and TSAT results will be summarized. Baseline and Follow-up values will be summarized separately. Changes from baseline will be summarized.
 
Descriptive Information
Brief Title  ICMJE Triferic Pediatric Pharmacokinetic Protocol
Official Title  ICMJE Pharmacokinetics of Triferic (Ferric Pyrophosphate Citrate) Administered Via Dialysate and IV to Pediatric Patients on Chronic Hemodialysis
Brief Summary The main purpose is to determine the pharmacokinetics (PK) of Triferic iron administered intravenously in pediatric patients with chronic kidney disease on chronic hemodialysis (CKD-5HD). It is an open-label, two-period sequential dosing study.
Detailed Description

This is a Phase 1/2, open-label, 2-period, single-dose study assessing the safety and pharmacokinetics (PK) of Triferic (ferric pyrophosphate citrate, or FPC) administered via dialysate and IV to pediatric patients (< 18 years of age) receiving chronic hemodialysis (CKD-5HD).

Total participation in the study is approximately three weeks and is comprised of a screening visit, two dosing (PK) visits, and a follow-up visit.

Each patient will receive a single dose of Triferic administered IV into the venous blood return line over the duration of the dialysis. At the next scheduled dialysis session each patient will receive a single dose of Triferic administered via dialysate during a single hemodialysis session.

Blood samples will be obtained at various times to analyze for serum iron parameters and for safety.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE End Stage Renal Disease
Intervention  ICMJE Drug: Triferic
Other Names:
  • ferric pyrophosphate citrate
  • FPC
Study Arms  ICMJE Experimental: Triferic via IV and Hemodialysate
On study Day 1, patients will receive IV Triferic iron 0.07 mg/kg diluted in an appropriate amount of D5W administered as a 100 mL infusion into the venous return port of the blood lines during the time the patient is receiving dialysis.The rate of administration will be calculated as such that the entire amount will be administered over the course of the dialysis treatment. On study Day 3, Triferic will be mixed with the liquid bicarbonate concentrate used in the preparation of the hemodialysate solution. This will result in a final Triferic iron concentration in the dialysate of 2 µM (110 µg/L). The patients will receive Triferic via the hemodialysate over the course of the dialysis treatment.
Intervention: Drug: Triferic
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 18, 2017)
22
Original Estimated Enrollment  ICMJE
 (submitted: November 2, 2015)
24
Actual Study Completion Date  ICMJE January 2017
Actual Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

A patient will be eligible for inclusion in the study only if all of the following criteria are met:

  1. Parents/legal guardians of the patient have the ability to understand the requirements of the study and have demonstrated a willingness to have their child comply with all study procedures by signing an institutional review board-approved informed consent form. Where applicable, assent of the patient has also been obtained for all study procedures prior to any study-related activities.
  2. Patient is <18 years of age at screening.
  3. Patient has chronic kidney disease receiving in-center hemodialysis at least twice weekly for at least 1 month prior to screening.
  4. Patient is receiving adequate hemodialysis as assessed by the investigator and based on a single pool Kt/V measurement >1.2.
  5. Patient has a vascular access (tunneled catheter, AV fistula or AV graft) suitable to support blood flows for hemodialysis treatment.
  6. Patient has a body mass of 11 lbs (5 kg).
  7. Patient is iron-replete as measured by a TSAT 20% and a ferritin >100 micrograms/L at screening.
  8. Patient has a whole blood Hgb concentration of 10.0 g/dL at screening.
  9. If patient is receiving ESA, the dose has been stable (unchanged) for at least 3 weeks prior to Baseline admission.
  10. Patient has appropriate laboratory values for their disease state at screening (per investigator judgment).
  11. Patient has no significant abnormal findings on physical examination that would preclude participation in the study.
  12. If the patient is female, she must be pre-pubertal, have had documented surgical sterilization prior to Baseline admission, or be practicing adequate birth control. All female patients 9 years of age and older, and also any who have reached menarche before age 9 years, must have a negative serum pregnancy test during screening. It is the investigator's responsibility to determine whether the patient has adequate birth control for study participation.

Exclusion Criteria:

A patient will not be eligible for inclusion in the study if any of the following criteria apply:

  1. Patient is positive for human immunodeficiency virus (HIV) or hepatitis B by history.
  2. Patient has an acute illness within 1 week of Baseline admission (patient may be screened again 2 weeks post resolution of the acute illness).
  3. Patient is receiving intravenous or oral antibiotics or antifungals for any infectious process. Prophylactic antibiotics administered on a regular basis are allowed.
  4. Patient has evidence of an ongoing active inflammatory process (e.g., systemic lupus erythematosus, acute or chronic active hepatitis, etc.).
  5. Patient has participated in an investigational drug study within the 30 days prior to Baseline admission.
  6. Administration of IV or oral iron supplements within 2 weeks prior to Baseline admission.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02595437
Other Study ID Numbers  ICMJE RMFPC-11
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Rockwell Medical Technologies, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Rockwell Medical Technologies, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Raymond D Pratt, MD FACP Rockwell Medical, Inc
PRS Account Rockwell Medical Technologies, Inc.
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP