Pharmacokinetics and Preliminary Bioequivalence of Triferic (Ferric Pyrophosphate Citrate) Administered Via Hemodialysate and Intravenously to Adult CKD-5HD Patients
Condition: End Stage Renal Disease
MeSH terms: Kidney Failure, Chronic
Intervention: Triferic
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: pharmacokinetics; bioequivalence

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. 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.

          2. 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.

          3. The patient must have a Screening ferritin level of ≥100μg/L.

          4. The patient must have a Screening transferrin saturation (TSAT) of 15-45%, inclusive.

          5. The patient must have a Screening total iron binding capacity (TIBC) ≥175 μg/dL.

          6. The patient must have a Screening hemoglobin (Hgb) concentration ≥9.5 g/dL.

          7. The patient must be undergoing hemodialysis at least 3x/week.

          8. 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.

          9. 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.

         10. The patient's vascular access for dialysis that will be used during the study must
             have stable function in the judgment of the Investigator.

         11. The patient must agree to discontinue all iron preparations (oral and IV) for 14 days
             prior to Baseline.

         12. 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:

          1. The patient has had an RBC or whole blood transfusion within 4 weeks prior to
             Screening.

          2. The patient requires a continuous infusion of heparin during standard hemodialysis.

          3. The patient has had administration of IV or oral iron supplements (including
             multivitamins with iron) within 14 days prior to Baseline.

          4. The patient has known active bleeding from any site other than AV fistula or graft
             (e.g., gastrointestinal, hemorrhoidal, nasal, pulmonary, etc.).

          5. 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.)

          6. The patient's vascular access for hemodialysis is a femoral catheter.

          7. The patient is scheduled to have a surgical procedure during the study.

          8. 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.

          9. The patient has a history of noncompliance with the dialysis regimen in the opinion of
             the Investigator

         10. 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.

         11. 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.)

         12. 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.

         13. The patient is known to be positive for HIV, hepatitis B, or hepatitis C (viral
             testing is not required as part of this protocol).

         14. 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).

         15. 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.

         16. The patient currently has any malignancy other than basal or squamous cell skin
             cancer.

         17. The patient has a history of drug or alcohol abuse within the 6 months prior to
             Screening.

         18. The patient participated in an investigational drug study within 30 days prior to
             Baseline.

         19. The patient has any condition that, in the opinion of the Investigator, would make it
             unlikely for the patient to complete the study.