Pharmacokinetics and Preliminary Bioequivalence 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 determine the pharmacokinetics (PK) of Triferic iron administered via hemodialysate and via two different intravenous routes in adult patients with chronic kidney disease on chronic hemodialysis (CKD-5HD). It is an open-label, randomized single dose study.

Official Title
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Pharmacokinetics and Preliminary Bioequivalence 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 have been undergoing chronic hemodialysis for chronic kidney disease for at least 3 months, and is 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 total iron binding capacity (TIBC) ≥175 μg/dL. The patient must have a Screening hemoglobin (Hgb) concentration ≥9.5 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 28 days prior to Baseline. 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 Baseline. 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) within 14 days prior to Baseline. 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's vascular access for hemodialysis is a femoral catheter. 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 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. The patient has any current febrile illness (e.g., oral temperature ≥100.4°F, 38.0°C). (The patient may subsequently become eligible at least 1 week after resolution of the illness.) The patient has known bacterial, tuberculosis, fungal, viral, or parasitic infection requiring anti-microbial therapy or anticipated to require anti-microbial therapy during the patient's participation in this study. The patient is known to be positive for HIV, hepatitis B, or hepatitis C (viral testing is not required as part of this protocol). The patient has cirrhosis of the liver based on histological criteria or clinical criteria (e.g., presence of ascites, esophageal varices, multiple spider nevi, or history of hepatic encephalopathy). The patient has ALT and/or AST levels consistently greater than twice the upper limit of normal at any time during the two months prior to Baseline. The patient currently has any malignancy other than basal or squamous cell skin cancer. The patient has a history of drug or alcohol abuse within the 6 months prior to Screening. The patient participated in an investigational drug study within 30 days prior to Baseline. The patient has any condition that, in the opinion of the Investigator, would make it unlikely for the patient to complete the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 via the hemodialysate over the course of the dialysis treatment. Intervention Drug: Triferic | Drug: Triferic<br> <br> * Other names: FPC;|
| Experimental: Triferic via IV infusion<br>Patients will receive a single 6.6-mg dose of Triferic iron administered IV over 4 hrs during hemodialysis via the unused heparin infusion line (pre-dialyzer). Intervention: Drug: Triferic | Drug: Triferic<br> <br> * Other names: FPC;|
| Experimental: Triferic IV infusion<br>Patients will receive a single 6.6-mg dose of Triferic iron administered IV over 4 hrs during hemodialysis via an infusion port (post-dialyzer). Intervention: Drug: Triferic | Drug: Triferic<br> <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, 4, 5, 6, 8, 10, and 12 hours | 
| Pharmacokinetics (PK) of Triferic Iron Administered IV in Adult CKD-5HD Patients: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantified Concentration (AUC(Last)). | The PK will be done by assessing the mean area under the serum concentration-time curve from time zero to the time of the last quantified concentration (AUC(last)) and comparing between Triferic administered via hemodialysate and Triferic administered at a fixed IV dose of 6.6 mg iron/kg (pre-dialyzer and post-dialyzer) during a single dialysis session. | 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Safety will be documented by recording the incidence of treatment-emergent adverse events (TEAEs) | 13 days | 
| Number of Participants With Treatment-emergent Serious Adverse Events (TEAEs) | Safety will be documented by recording the incidence of treatment-emergent serious adverse events (TESAEs) | 13 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetics, bioequivalence