Triferic Pediatric Pharmacokinetic Protocol | NCT02595437

NCT02595437

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Triferic via IV and Hemodialysate	Experimental	On study Day 1, patients will receive IV Triferic iron 0.07 mg/kg diluted in an appropriate amount of D5W administered as a 100 mL infusion into the venous return port of the blood lines during the time the patient is receiving dialysis.The rate of administration will be calculated as such that the entire amount will be administered over the course of the dialysis treatment. On study Day 3, Triferic will be mixed with the liquid bicarbonate concentrate used in the preparation of the hemodialysate solution. This will result in a final Triferic iron concentration in the dialysate of 2 µM (110 µg/L). The patients will receive Triferic via the hemodialysate over the course of the dialysis treatment.	Drug: Triferic

Name	Type	Description	Arm Group Labels	Other Names
Triferic	Drug		Triferic via IV and Hemodialysate	ferric pyrophosphate citrate FPC

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	0, 1, 2, 4, 4.5, 5, 6, 8, 10 hrs
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.	0, 1, 2, 4, 4.5, 5, 6, 8, 10 hours
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.	0, 1, 2, 4, 4.5, 5, 6, 8, 10 hours

Secondary Outcomes

Measure	Description	Time Frame
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.

Other Outcomes

Measure	Description	Time Frame
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).	1.5 weeks

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

A patient will be eligible for inclusion in the study only if all of the following criteria are met:

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.
Patient is <18 years of age at screening.
Patient has chronic kidney disease receiving in-center hemodialysis at least twice weekly for at least 1 month prior to screening.
Patient is receiving adequate hemodialysis as assessed by the investigator and based on a single pool Kt/V measurement >1.2.
Patient has a vascular access (tunneled catheter, AV fistula or AV graft) suitable to support blood flows for hemodialysis treatment.
Patient has a body mass of 11 lbs (5 kg).
Patient is iron-replete as measured by a TSAT 20% and a ferritin >100 micrograms/L at screening.
Patient has a whole blood Hgb concentration of 10.0 g/dL at screening.
If patient is receiving ESA, the dose has been stable (unchanged) for at least 3 weeks prior to Baseline admission.
Patient has appropriate laboratory values for their disease state at screening (per investigator judgment).
Patient has no significant abnormal findings on physical examination that would preclude participation in the study.
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:

Patient is positive for human immunodeficiency virus (HIV) or hepatitis B by history.
Patient has an acute illness within 1 week of Baseline admission (patient may be screened again 2 weeks post resolution of the acute illness).
Patient is receiving intravenous or oral antibiotics or antifungals for any infectious process. Prophylactic antibiotics administered on a regular basis are allowed.
Patient has evidence of an ongoing active inflammatory process (e.g., systemic lupus erythematosus, acute or chronic active hepatitis, etc.).
Patient has participated in an investigational drug study within the 30 days prior to Baseline admission.
Administration of IV or oral iron supplements within 2 weeks prior to Baseline admission.

Name	Affiliation	Role
Raymond D Pratt, MD FACP	Rockwell Medical, Inc	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Children's Hospital of Alabama		Birmingham	Alabama	35233	United States
Loma Linda University Hospital

ID	Title	Description
FG000	Triferic Via IV and Hemodialysate	Triferic was administered via IV infusion on study Day 1, and then mixed with the liquid bicarbonate and administered via hemodialysate on study Day 3.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	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.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

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)

Posted

Geometric Mean

Geometric Coefficient of Variation

microgram/deciliter

0, 1, 2, 4, 4.5, 5, 6, 8, 10 hrs

ID	Title	Description
OG000	Triferic 0.07 mg/kg Iron Intravenous: Absolute Value

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	IV Exposure	Patients in this population had received Triferic via IV infusion only at the time of onset of the adverse event.

ID	Term
D007676	Kidney Failure, Chronic
D051436	Renal Insufficiency, Chronic

ID	Term
D051437	Renal Insufficiency
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases

ID	Term
C049051	ferric pyrophosphate
C032360	spleen fibrinolytic proteinase (human)