End Stage Renal Disease
Conditions
Keywords
pharmacokinetics, bioequivalence
Brief 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.
Interventions
DRUGTriferic
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 65 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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) of Triferic Iron Administered Via Hemodialysate in Adult CKD-5HD Patients: Cmax. | 1, 2, 3, 4, 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: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantified Concentration (AUC(Last)). | 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 13 days | Safety will be documented by recording the incidence of treatment-emergent adverse events (TEAEs) |
| Number of Participants With Treatment-emergent Serious Adverse Events (TEAEs) | 13 days | Safety will be documented by recording the incidence of treatment-emergent serious adverse events (TESAEs) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Safety Population All 13 participants completed every arm of the study. Therefore, the baseline demographic characteristics of the Safety Population as a whole also reflect the characteristics of each arm of the study. | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Safety Population |
|---|---|
| Age, Continuous | 49.2 years STANDARD_DEVIATION 8.84 |
| C-reactive protein | .8 milligram/deciliter STANDARD_DEVIATION 0.81 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 174.3 centimeters STANDARD_DEVIATION 9.22 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 12 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 | 1 Participants |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 11 Participants |
| Weight | 98.7 kg STANDARD_DEVIATION 19.34 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 13 | 0 / 13 |
| other Total, other adverse events | 1 / 13 | 2 / 13 | 0 / 13 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 | 0 / 13 |
Outcome results
Primary
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.
Time frame: 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours
Population: While all subjects were included in PK analysis, some PK samples were below the lower limit of quantitation (BLQ) of the bioanalytical lab assay. Therefore, the number of subjects analyzed differs from the overall total number of study participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Triferic Via Hemodialysate | 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)). | 621 hours*microgram/deciliter | Standard Deviation 355 |
| Triferic Via IV Infusion Pre-dialyzer | 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)). | 630 hours*microgram/deciliter | Standard Deviation 275 |
| Triferic IV Infusion Post-dialyzer | 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)). | 524 hours*microgram/deciliter | Standard Deviation 272 |
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, 4, 5, 6, 8, 10, and 12 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Triferic Via Hemodialysate | Pharmacokinetics (PK) of Triferic Iron Administered Via Hemodialysate in Adult CKD-5HD Patients: Cmax. | 124 microgram per deciliter | Standard Deviation 49.9 |
| Triferic Via IV Infusion Pre-dialyzer | Pharmacokinetics (PK) of Triferic Iron Administered Via Hemodialysate in Adult CKD-5HD Patients: Cmax. | 131 microgram per deciliter | Standard Deviation 30.5 |
| Triferic IV Infusion Post-dialyzer | Pharmacokinetics (PK) of Triferic Iron Administered Via Hemodialysate in Adult CKD-5HD Patients: Cmax. | 124 microgram per deciliter | Standard Deviation 42.4 |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Safety will be documented by recording the incidence of treatment-emergent adverse events (TEAEs)
Time frame: 13 days
Population: Safety Population (all enrolled subjects)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Triferic Via Hemodialysate | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 1 Participants |
| Triferic Via IV Infusion Pre-dialyzer | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 2 Participants |
| Triferic IV Infusion Post-dialyzer | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 0 Participants |
Secondary
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)
Time frame: 13 days
Population: Safety Population (all enrolled subjects)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Triferic Via Hemodialysate | Number of Participants With Treatment-emergent Serious Adverse Events (TEAEs) | 0 Participants |
| Triferic Via IV Infusion Pre-dialyzer | Number of Participants With Treatment-emergent Serious Adverse Events (TEAEs) | 0 Participants |
| Triferic IV Infusion Post-dialyzer | Number of Participants With Treatment-emergent Serious Adverse Events (TEAEs) | 0 Participants |