End Stage Renal Disease
Conditions
Keywords
Pharmacokinetics, Equivalence
Brief summary
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
An open-label, four period, randomized, crossover study of Triferic iron administered via hemodialysis compared to Triferic administered intravenously pre- and post- hemodialyzer.
Interventions
DRUGTriferic
ferric pyrophosphate citrate
Sponsors
Rockwell Medical Technologies, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Pre-assignment details
All 27 participants in the study were randomly assigned to cross-over between the three treatments on Day 3, Day 8 and Day 10.
Participants by arm
| Arm | Count |
|---|---|
| Safety Population All patients in study | 27 |
| Total | 27 |
Baseline characteristics
| Characteristic | Safety Population |
|---|---|
| Age, Continuous | 53.9 years STANDARD_DEVIATION 8.11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 23 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 27 | 0 / 27 |
| other Total, other adverse events | 1 / 27 | 0 / 27 | 1 / 27 |
| serious Total, serious adverse events | 1 / 27 | 2 / 27 | 0 / 27 |
Outcome results
Primary
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.
Time frame: 1, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 12 hours
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Triferic Via Hemodialysate | Pharmacokinetics (PK) of Triferic Iron Administered IV in Adult CKD-5HD Patients: AUC(0-end). | 1540 h*ug/dL | Geometric Coefficient of Variation 28.5 |
| Triferic Via IV Infusion (Post-dialyzer) | Pharmacokinetics (PK) of Triferic Iron Administered IV in Adult CKD-5HD Patients: AUC(0-end). | 1450 h*ug/dL | Geometric Coefficient of Variation 31.4 |
| Triferic Via Hemodialysate | Pharmacokinetics (PK) of Triferic Iron Administered IV in Adult CKD-5HD Patients: AUC(0-end). | 1500 h*ug/dL | Geometric Coefficient of Variation 31.7 |
Primary
Pharmacokinetics (PK) of Triferic Iron Administered IV in Adult CKD-5HD Patients:Cmax
Time frame: 1, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 12 hours
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Triferic Via Hemodialysate | Pharmacokinetics (PK) of Triferic Iron Administered IV in Adult CKD-5HD Patients:Cmax | 215 h*ug/dL | Geometric Coefficient of Variation 21.6 |
| Triferic Via IV Infusion (Post-dialyzer) | Pharmacokinetics (PK) of Triferic Iron Administered IV in Adult CKD-5HD Patients:Cmax | 195 h*ug/dL | Geometric Coefficient of Variation 25.6 |
| Triferic Via Hemodialysate | Pharmacokinetics (PK) of Triferic Iron Administered IV in Adult CKD-5HD Patients:Cmax | 207 h*ug/dL | Geometric Coefficient of Variation 30.4 |
Primary
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.
Time frame: 1, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 12 hours
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Triferic Via Hemodialysate | Pharmacokinetics (PK) of Triferic Iron Administered Via Hemodialysate in Adult CKD-5HD Patients: Cmax. | 207 h*ug/dL | Geometric Coefficient of Variation 30.4 |
Secondary
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.
Time frame: 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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Triferic Via Hemodialysate | Safety Endpoint: Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) Incidence of Treatment Emergent Serious Adverse Events | 2 Participants |
| Triferic Via IV Infusion (Post-dialyzer) | Safety Endpoint: Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) Incidence of Treatment Emergent Serious Adverse Events | 0 Participants |
| Triferic Via Hemodialysate | Safety Endpoint: Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) Incidence of Treatment Emergent Serious Adverse Events | 1 Participants |