Equivalence of Triferic® (Ferric Pyrophosphate Citrate) Administered Via Hemodialysate and Intravenously to Adult CKD-5HD Patients

Study Overview
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Brief Summary
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The main purpose is to establish the equivalence of Triferic iron administered via dialysate into the arterial blood line and into the venous blood line

Detailed Description
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An open-label, four period, randomized, crossover study of Triferic iron administered via hemodialysis compared to Triferic administered intravenously pre- and post- hemodialyzer.

Official Title
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Equivalence of Triferic® (Ferric Pyrophosphate Citrate) Administered Via Hemodialysate and Intravenously to Adult CKD-5HD Patients

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Drug: Triferic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient must be able to provide informed consent and have personally signed and dated the written informed consent document before completing any study-related procedures. The patient must be 18-80 years of age inclusive at the time of consent. The patient must have been undergoing chronic hemodialysis for chronic kidney disease for at least 3 months, and be expected to remain on hemodialysis and be able to complete the study. The patient must have a Screening ferritin level of ≥100µg/L. The patient must have a Screening transferrin saturation (TSAT) of 15-45%, inclusive. The patient must have a Screening hemoglobin (Hgb) concentration ≥9.0 g/dL. The patient must be undergoing hemodialysis at least 3x/week. The patient must have at least a minimally adequate measured dialysis dose defined as single-pool Kt/V (dialyzer clearance of urea multiplied by dialysis time, divided by patient's total body water) ≥1.2, or KIDt/V (online dialyzer clearance measured using ionic dialysance multiplied by dialysis time, divided by patient's total body water) ≥1.2 measured within the 90 days prior to HD #1. Patient is receiving, or can receive anticoagulation for dialysis by a single dose of unfractionated heparin or low molecular weight heparin pre-dialysis; or by intermittent IV heparin bolus. The patient's vascular access for dialysis that will be used during the study must have stable function in the judgment of the Investigator. The patient must agree to discontinue all iron preparations (oral and IV) for 14 days prior to the start of HD#1 and throughout the study. Female patients must not be pregnant or breastfeeding. They must have been amenorrheic for the past year or be surgically sterile or agree to not become pregnant by continuous use of an effective birth control method acceptable to the Investigator for the duration of their participation in the study. Exclusion Criteria: The patient has had an RBC or whole blood transfusion within 4 weeks prior to Screening. The patient requires a continuous infusion of heparin during standard hemodialysis. The patient has had administration of IV or oral iron supplements (including multivitamins with iron or iron based phosphate binders) within 14 days prior to the start of HD #1. (The patient may subsequently become eligible if additional time elapses and all other eligibility criteria are met.). The patient has known active bleeding from any site other than AV fistula or graft (e.g., gastrointestinal, hemorrhoidal, nasal, pulmonary, etc.). The patient has a living kidney donor identified or living-donor kidney transplant scheduled to occur during study participation. (Note: Patients awaiting deceased-donor transplant need not be excluded.) The patient is scheduled to have a surgical procedure during the study. The patient has had a hospitalization within the 4 weeks prior to Screening (except for vascular access surgery) that, in the opinion of the Investigator, confers a significant risk of hospitalization during the course of the study. The patient has a history of noncompliance with the dialysis regimen in the opinion of the Investigator. The patient has a known ongoing active inflammatory disorder (other than CKD), such as systemic lupus erythematosus, rheumatoid arthritis, or other collagen-vascular disease, that currently requires systemic anti-inflammatory or immunomodulatory therapy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Triferic via Hemodialysate<br>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 over 4 hrs at one hemodialysis session. | Drug: Triferic<br>* ferric pyrophosphate citrate<br>* Other names: FPC;|
| Experimental: Triferic via IV infusion( pre-dialyzer)<br>Patients will receive a single 6.5-mg dose of Triferic iron administered IV over 3 hrs during hemodialysis via arterial blood line (pre-dialyzer) | Drug: Triferic<br>* ferric pyrophosphate citrate<br>* Other names: FPC;|
| Experimental: Triferic via IV infusion (post-dialyzer)<br>Patients will receive a single 6.5-mg dose of Triferic iron administered IV over 3 hrs during hemodialysis via venous blood line (post-dialyzer) | Drug: Triferic<br>* ferric pyrophosphate citrate<br>* Other names: FPC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of Triferic Iron Administered Via Hemodialysate in Adult CKD-5HD Patients: Cmax. | The PK will be done by assessing the mean Cmax of total serum iron from Triferic administered via hemodialysate, compared to Triferic administered at a fixed IV dose of 6.6 mg iron/kg during a single dialysis session. | 1, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 12 hours | 
| Pharmacokinetics (PK) of Triferic Iron Administered IV in Adult CKD-5HD Patients:Cmax |  | 1, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 12 hours | 
| Pharmacokinetics (PK) of Triferic Iron Administered IV in Adult CKD-5HD Patients: AUC(0-end). | The PK will be done by assessing the mean AUC(0-end) of total serum iron from Triferic administered via hemodialysate, compared to Triferic administered at a fixed IV dose of 6.5 mg iron/kg during a single dialysis session. | 1, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Endpoint: Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) Incidence of Treatment Emergent Serious Adverse Events | Safety will be documented by recording the incidence of treatment-emergent serious adverse events (TESAEs).The number of patients that experienced treatment emergent serious adverse events will be quantified. Please see the adverse event table for specifics. | From the start of the HD #1 through the end of study participation or 7 days after the last dose of Triferic, whichever is later, assessed up to 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics, Equivalence