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

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

• Triferic (Drug), also known as ferric pyrophosphate citrate, FPC: ferric pyrophosphate citrate

Primary outcomes

• Pharmacokinetics (PK) of Triferic Iron Administered Via Hemodialysate in Adult CKD-5HD Patients: Cmax. [1, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 12 hours]: 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.
• 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). [1, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 12 hours]: 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.

Secondary outcomes

• Safety Endpoint: Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) Incidence of Treatment Emergent Serious Adverse Events [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]: 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.

Sex: All, ages: 18 Years to 80 Years

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 be 18-80 years of age inclusive at the time of consent.
3. 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.
4. The patient must have a Screening ferritin level of ≥100µg/L.
5. The patient must have a Screening transferrin saturation (TSAT) of 15-45%, inclusive.
6. The patient must have a Screening hemoglobin (Hgb) concentration ≥9.0 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 90 days prior to HD #1.
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 the start of HD#1 and throughout the study.
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 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.).
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 is scheduled to have a surgical procedure during the study.
7. 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.
8. The patient has a history of noncompliance with the dialysis regimen in the opinion of the Investigator.
9. 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.

Participant flow

Outcome results

• Pharmacokinetics (PK) of Triferic Iron Administered Via Hemodialysate in Adult CKD-5HD Patients: Cmax. (Primary), Geometric mean, h*ug/dL: Triferic Via Hemodialysate 207 +/- 30.4
• Pharmacokinetics (PK) of Triferic Iron Administered IV in Adult CKD-5HD Patients:Cmax (Primary), Geometric mean, h*ug/dL: Triferic Via IV Infusion( Pre-dialyzer) 215 +/- 21.6; Triferic Via IV Infusion (Post-dialyzer) 195 +/- 25.6; Triferic Via Hemodialysate 207 +/- 30.4
• Pharmacokinetics (PK) of Triferic Iron Administered IV in Adult CKD-5HD Patients: AUC(0-end). (Primary), Geometric mean, h*ug/dL: Triferic Via IV Infusion( Pre-dialyzer) 1540 +/- 28.5; Triferic Via IV Infusion (Post-dialyzer) 1450 +/- 31.4; Triferic Via Hemodialysate 1500 +/- 31.7
• Safety Endpoint: Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) Incidence of Treatment Emergent Serious Adverse Events (Secondary), Count of participants, Participants: Triferic Via IV Infusion( Pre-dialyzer) 2; Triferic Via IV Infusion (Post-dialyzer) 0; Triferic Via Hemodialysate 1

Adverse events

Time frame: Adverse events will be recorded on the AE CRF from the start of HD #1 (Day 1) through the end of study participation or 7 days after the last dose of Triferic (Day 10).

Serious adverse events by term

Other adverse events by term

• Study Protocol and Statistical Analysis Plan (PDF, 2017-09-18)

• Thomas Marbury, Principal investigator, Orlando Clinical Research Center