End Stage Renal Disease
Conditions
Keywords
dialysis, pediatric, chronic kidney disease
Brief summary
The main purpose is to determine the pharmacokinetics (PK) of Triferic iron administered intravenously in pediatric patients with chronic kidney disease on chronic hemodialysis (CKD-5HD). It is an open-label, two-period sequential dosing study.
Detailed description
This is a Phase 1/2, open-label, 2-period, single-dose study assessing the safety and pharmacokinetics (PK) of Triferic (ferric pyrophosphate citrate, or FPC) administered via dialysate and IV to pediatric patients (\< 18 years of age) receiving chronic hemodialysis (CKD-5HD). Total participation in the study is approximately three weeks and is comprised of a screening visit, two dosing (PK) visits, and a follow-up visit. Each patient will receive a single dose of Triferic administered IV into the venous blood return line over the duration of the dialysis. At the next scheduled dialysis session each patient will receive a single dose of Triferic administered via dialysate during a single hemodialysis session. Blood samples will be obtained at various times to analyze for serum iron parameters and for safety.
Interventions
DRUGTriferic
Sponsors
Rockwell Medical Technologies, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 17 Years
Healthy volunteers
No
Inclusion criteria
A patient will be eligible for inclusion in the study only if all of the following criteria are met: 1. Parents/legal guardians of the patient have the ability to understand the requirements of the study and have demonstrated a willingness to have their child comply with all study procedures by signing an institutional review board-approved informed consent form. Where applicable, assent of the patient has also been obtained for all study procedures prior to any study-related activities. 2. Patient is \<18 years of age at screening. 3. Patient has chronic kidney disease receiving in-center hemodialysis at least twice weekly for at least 1 month prior to screening. 4. Patient is receiving adequate hemodialysis as assessed by the investigator and based on a single pool Kt/V measurement \>1.2. 5. Patient has a vascular access (tunneled catheter, AV fistula or AV graft) suitable to support blood flows for hemodialysis treatment. 6. Patient has a body mass of 11 lbs (5 kg). 7. Patient is iron-replete as measured by a TSAT 20% and a ferritin \>100 micrograms/L at screening. 8. Patient has a whole blood Hgb concentration of 10.0 g/dL at screening. 9. If patient is receiving ESA, the dose has been stable (unchanged) for at least 3 weeks prior to Baseline admission. 10. Patient has appropriate laboratory values for their disease state at screening (per investigator judgment). 11. Patient has no significant abnormal findings on physical examination that would preclude participation in the study. 12. If the patient is female, she must be pre-pubertal, have had documented surgical sterilization prior to Baseline admission, or be practicing adequate birth control. All female patients 9 years of age and older, and also any who have reached menarche before age 9 years, must have a negative serum pregnancy test during screening. It is the investigator's responsibility to determine whether the patient has adequate birth control for study participation.
Exclusion criteria
A patient will not be eligible for inclusion in the study if any of the following criteria apply: 1. Patient is positive for human immunodeficiency virus (HIV) or hepatitis B by history. 2. Patient has an acute illness within 1 week of Baseline admission (patient may be screened again 2 weeks post resolution of the acute illness). 3. Patient is receiving intravenous or oral antibiotics or antifungals for any infectious process. Prophylactic antibiotics administered on a regular basis are allowed. 4. Patient has evidence of an ongoing active inflammatory process (e.g., systemic lupus erythematosus, acute or chronic active hepatitis, etc.). 5. Patient has participated in an investigational drug study within the 30 days prior to Baseline admission. 6. Administration of IV or oral iron supplements within 2 weeks prior to Baseline admission.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) of Triferic Iron Administered IV in Pediatric CKD-5HD Patients: AUC(Last). | 0, 1, 2, 4, 4.5, 5, 6, 8, 10 hours | The PK will be done by assessing the mean absolute and baseline-corrected AUC(last) of total iron with an IV infusion of Triferic at 0.07 mg iron/kg during a single dialysis session. The absolute AUC(last) includes iron that was present in the serum prior to dosing as well the iron administered, while the baseline-corrected AUC(last) factors out the iron present in the serum prior to dosing and includes the administered iron only. |
| Pharmacokinetics (PK) of Triferic Iron Administered IV in Pediatric CKD-5HD Patients: AUC(0-end). | 0, 1, 2, 4, 4.5, 5, 6, 8, 10 hours | The PK will be done by assessing the mean absolute and baseline-corrected AUC(0-end) of total iron with an IV infusion of Triferic at 0.07 mg iron/kg during a single dialysis session. The absolute AUC (0-end) includes iron that was present in the serum prior to dosing as well the iron administered, while the baseline-corrected AUC (0-end) factors out the iron present in the serum prior to dosing and includes the administered iron only. |
| Pharmacokinetics (PK) of Triferic Iron Administered IV in Pediatric CKD-5HD Patients: Cmax. | 0, 1, 2, 4, 4.5, 5, 6, 8, 10 hrs | The PK will be done by assessing the mean absolute and baseline-corrected Cmax of total iron with an IV infusion of Triferic at 0.07 mg iron/kg during a single dialysis session. The absolute Cmax includes the concentration of iron that was present in the serum prior to dosing as well the iron administered, while the baseline-corrected Cmax factors out the iron present in the serum prior to dosing and includes the administered iron only. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) of Triferic Iron Administered Via the Hemodialysate in Pediatric CKD-5HD Patients: AUC(0-end). | 0, 1, 2, 4, 4.5, 5, 6, 8, 10 hours | The PK will be done by assessing the mean absolute and baseline-corrected AUC(0-end) of total iron. The absolute AUC (0-end) includes the of iron that was present in the serum prior to dosing as well the iron administered, while the baseline-corrected Cmax factors out the iron present in the serum prior to dosing and includes the administered iron only. |
| Pharmacokinetics (PK) of Triferic Iron Administered Via the Hemodialysate in Pediatric CKD-5HD Patients: Cmax. | 0, 1, 2, 4, 4.5, 5, 6, 8, 10 hours | The PK will be done by assessing the mean absolute and baseline-corrected Cmax of total iron. The absolute Cmax includes the concentration of iron that was present in the serum prior to dosing as well the iron administered, while the baseline-corrected Cmax factors out the iron present in the serum prior to dosing and includes the administered iron only. |
| Pharmacokinetics (PK) of Triferic Iron Administered Via the Hemodialysate in Pediatric CKD-5HD Patients: AUC(Last). | 0, 1, 2, 4, 4.5, 5, 6, 8, 10 hours | The PK will be done by assessing the mean absolute and baseline-corrected AUC(last) of total iron. The absolute AUC (last) includes the iron that was present in the serum prior to dosing as well the iron administered, while the baseline-corrected Cmax factors out the iron present in the serum prior to dosing and includes the administered iron only. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Treatment-emergent Adverse Events (TEAEs) | 1.5 weeks | The incidence of treatment-emergent AEs (TEAEs) and treatment-emergent serious AEs (TESAEs) will be grouped by body system. Adverse events were recorded from study Day 1 through the following up visit (approximately 1.5 weeks). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Safety Population All patients enrolled in the study who received any amount of Triferic, regardless of whether the dose was administered intravenously or via dialysate. | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Triferic Via IV | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Safety Population |
|---|---|
| Age, Continuous | 11.8 years STANDARD_DEVIATION 4.98 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 8 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 | 5 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 21 |
| other Total, other adverse events | 4 / 22 | 3 / 21 |
| serious Total, serious adverse events | 0 / 22 | 0 / 21 |
Outcome results
Primary
Pharmacokinetics (PK) of Triferic Iron Administered IV in Pediatric CKD-5HD Patients: AUC(0-end).
The PK will be done by assessing the mean absolute and baseline-corrected AUC(0-end) of total iron with an IV infusion of Triferic at 0.07 mg iron/kg during a single dialysis session. The absolute AUC (0-end) includes iron that was present in the serum prior to dosing as well the iron administered, while the baseline-corrected AUC (0-end) factors out the iron present in the serum prior to dosing and includes the administered iron only.
Time frame: 0, 1, 2, 4, 4.5, 5, 6, 8, 10 hours
Population: Pharmacokinetic Group: all patients who received at least one dose of study drug and have sufficient PK samples (a sample at the end of infusion and at least 3 samples during the elimination phase)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Triferic 0.07 mg/kg Iron Intravenous: Absolute Value | Pharmacokinetics (PK) of Triferic Iron Administered IV in Pediatric CKD-5HD Patients: AUC(0-end). | 648 hours* micrograms/ deciliters | Geometric Coefficient of Variation 29.3 |
| Triferic 0.07 mg/kg Iron Intravenous: Baseline Corrected | Pharmacokinetics (PK) of Triferic Iron Administered IV in Pediatric CKD-5HD Patients: AUC(0-end). | 237 hours* micrograms/ deciliters | Geometric Coefficient of Variation 76.8 |
Primary
Pharmacokinetics (PK) of Triferic Iron Administered IV in Pediatric CKD-5HD Patients: AUC(Last).
The PK will be done by assessing the mean absolute and baseline-corrected AUC(last) of total iron with an IV infusion of Triferic at 0.07 mg iron/kg during a single dialysis session. The absolute AUC(last) includes iron that was present in the serum prior to dosing as well the iron administered, while the baseline-corrected AUC(last) factors out the iron present in the serum prior to dosing and includes the administered iron only.
Time frame: 0, 1, 2, 4, 4.5, 5, 6, 8, 10 hours
Population: Pharmacokinetic Group: all patients who received at least one dose of study drug and have sufficient PK samples (a sample at the end of infusion and at least 3 samples during the elimination phase)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Triferic 0.07 mg/kg Iron Intravenous: Absolute Value | Pharmacokinetics (PK) of Triferic Iron Administered IV in Pediatric CKD-5HD Patients: AUC(Last). | 1324 hours* micrograms/ deciliters | Geometric Coefficient of Variation 36.5 |
| Triferic 0.07 mg/kg Iron Intravenous: Baseline Corrected | Pharmacokinetics (PK) of Triferic Iron Administered IV in Pediatric CKD-5HD Patients: AUC(Last). | 419 hours* micrograms/ deciliters | Geometric Coefficient of Variation 101.6 |
Primary
Pharmacokinetics (PK) of Triferic Iron Administered IV in Pediatric CKD-5HD Patients: Cmax.
The PK will be done by assessing the mean absolute and baseline-corrected Cmax of total iron with an IV infusion of Triferic at 0.07 mg iron/kg during a single dialysis session. The absolute Cmax includes the concentration of iron that was present in the serum prior to dosing as well the iron administered, while the baseline-corrected Cmax factors out the iron present in the serum prior to dosing and includes the administered iron only.
Time frame: 0, 1, 2, 4, 4.5, 5, 6, 8, 10 hrs
Population: Pharmacokinetic Group: all patients who received at least one dose of study drug and have sufficient PK samples (a sample at the end of infusion and at least 3 samples during the elimination phase)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Triferic 0.07 mg/kg Iron Intravenous: Absolute Value | Pharmacokinetics (PK) of Triferic Iron Administered IV in Pediatric CKD-5HD Patients: Cmax. | 217 microgram/deciliter | Geometric Coefficient of Variation 28 |
| Triferic 0.07 mg/kg Iron Intravenous: Baseline Corrected | Pharmacokinetics (PK) of Triferic Iron Administered IV in Pediatric CKD-5HD Patients: Cmax. | 114 microgram/deciliter | Geometric Coefficient of Variation 53.7 |
Secondary
Pharmacokinetics (PK) of Triferic Iron Administered Via the Hemodialysate in Pediatric CKD-5HD Patients: AUC(0-end).
The PK will be done by assessing the mean absolute and baseline-corrected AUC(0-end) of total iron. The absolute AUC (0-end) includes the of iron that was present in the serum prior to dosing as well the iron administered, while the baseline-corrected Cmax factors out the iron present in the serum prior to dosing and includes the administered iron only.
Time frame: 0, 1, 2, 4, 4.5, 5, 6, 8, 10 hours
Population: Pharmacokinetic Group: all patients who received at least one dose of study drug and have sufficient PK samples (a sample at the end of infusion and at least 3 samples during the elimination phase)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Triferic 0.07 mg/kg Iron Intravenous: Absolute Value | Pharmacokinetics (PK) of Triferic Iron Administered Via the Hemodialysate in Pediatric CKD-5HD Patients: AUC(0-end). | 763 hours* micrograms/ deciliters | Geometric Coefficient of Variation 38.5 |
| Triferic 0.07 mg/kg Iron Intravenous: Baseline Corrected | Pharmacokinetics (PK) of Triferic Iron Administered Via the Hemodialysate in Pediatric CKD-5HD Patients: AUC(0-end). | 387 hours* micrograms/ deciliters | Geometric Coefficient of Variation 79.6 |
Secondary
Pharmacokinetics (PK) of Triferic Iron Administered Via the Hemodialysate in Pediatric CKD-5HD Patients: AUC(Last).
The PK will be done by assessing the mean absolute and baseline-corrected AUC(last) of total iron. The absolute AUC (last) includes the iron that was present in the serum prior to dosing as well the iron administered, while the baseline-corrected Cmax factors out the iron present in the serum prior to dosing and includes the administered iron only.
Time frame: 0, 1, 2, 4, 4.5, 5, 6, 8, 10 hours
Population: Pharmacokinetic Group: all patients who received at least one dose of study drug and have sufficient PK samples (a sample at the end of infusion and at least 3 samples during the elimination phase)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Triferic 0.07 mg/kg Iron Intravenous: Absolute Value | Pharmacokinetics (PK) of Triferic Iron Administered Via the Hemodialysate in Pediatric CKD-5HD Patients: AUC(Last). | 1453 hours* micrograms/ deciliters | Geometric Coefficient of Variation 59.6 |
| Triferic 0.07 mg/kg Iron Intravenous: Baseline Corrected | Pharmacokinetics (PK) of Triferic Iron Administered Via the Hemodialysate in Pediatric CKD-5HD Patients: AUC(Last). | 682 hours* micrograms/ deciliters | Geometric Coefficient of Variation 82.9 |
Secondary
Pharmacokinetics (PK) of Triferic Iron Administered Via the Hemodialysate in Pediatric CKD-5HD Patients: Cmax.
The PK will be done by assessing the mean absolute and baseline-corrected Cmax of total iron. The absolute Cmax includes the concentration of iron that was present in the serum prior to dosing as well the iron administered, while the baseline-corrected Cmax factors out the iron present in the serum prior to dosing and includes the administered iron only.
Time frame: 0, 1, 2, 4, 4.5, 5, 6, 8, 10 hours
Population: Pharmacokinetic Group: all patients who received at least one dose of study drug and have sufficient PK samples (a sample at the end of infusion and at least 3 samples during the elimination phase)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Triferic 0.07 mg/kg Iron Intravenous: Absolute Value | Pharmacokinetics (PK) of Triferic Iron Administered Via the Hemodialysate in Pediatric CKD-5HD Patients: Cmax. | 261 micrograms/ deciliters | Geometric Coefficient of Variation 26.4 |
| Triferic 0.07 mg/kg Iron Intravenous: Baseline Corrected | Pharmacokinetics (PK) of Triferic Iron Administered Via the Hemodialysate in Pediatric CKD-5HD Patients: Cmax. | 166 micrograms/ deciliters | Geometric Coefficient of Variation 54.3 |
Other Pre-specified
Treatment-emergent Adverse Events (TEAEs)
The incidence of treatment-emergent AEs (TEAEs) and treatment-emergent serious AEs (TESAEs) will be grouped by body system. Adverse events were recorded from study Day 1 through the following up visit (approximately 1.5 weeks).
Time frame: 1.5 weeks
Population: Safety Population: all patients who received any amount of study medication are included in the safety population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Triferic 0.07 mg/kg Iron Intravenous: Absolute Value | Treatment-emergent Adverse Events (TEAEs) | 4 Participants |
| Triferic 0.07 mg/kg Iron Intravenous: Baseline Corrected | Treatment-emergent Adverse Events (TEAEs) | 3 Participants |