Triferic Pediatric Pharmacokinetic Protocol

• ClinicalTrials.gov Identifier: NCT02595437
• Recruitment Status: Completed
• First Posted: November 3, 2015
• Results First Posted: October 25, 2018
• Last Update Posted: October 25, 2018
• Sponsor: Rockwell Medical Technologies, Inc.
• Information provided by (Responsible Party): Rockwell Medical Technologies, Inc.

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: End Stage Renal Disease
• Intervention: Drug: Triferic
• Enrollment: 22

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Triferic Via IV and Hemodialysate
Arm/Group Description	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.
Period Title: Triferic Via IV
Started	22
Completed	21
Not Completed	1
Reason Not Completed
Withdrawal by Subject	1
Period Title: Triferic Via Hemodialysate
Started	21
Completed	21
Not Completed	0

Baseline Characteristics

Arm/Group Title		Safety Population
Arm/Group Description		All patients enrolled in the study who received any amount of Triferic, regardless of whether the dose was administered intravenously or via dialysate.
Overall Number of Baseline Participants		22
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	22 participants
		11.8 (4.98)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants
	Female	11 50.0%
	Male	11 50.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants
	Hispanic or Latino	9 40.9%
	Not Hispanic or Latino	12 54.5%
	Unknown or Not Reported	1 4.5%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants
	American Indian or Alaska Native	0 0.0%
	Asian	1 4.5%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	8 36.4%
	White	8 36.4%
	More than one race	0 0.0%
	Unknown or Not Reported	5 22.7%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK) of Triferic Iron Administered IV in Pediatric CKD-5HD Patients: Cmax.
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Triferic 0.07 mg/kg Iron Intravenous: Absolute Value	Triferic 0.07 mg/kg Iron Intravenous: Baseline Corrected
Arm/Group Description:	Patients were administered Triferic intravenously 0.07 mg/kg at the same time that they received their standard of care hemodialysis. The results for this group are the absolute values.	Patients were administered Triferic intravenously 0.07 mg/kg at the same time that they received their standard of care hemodialysis. The results for this group are baseline-corrected.
Overall Number of Participants Analyzed	21	21
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: microgram/deciliter
	217; (28.0%)	114; (53.7%)

2. Primary Outcome

Title	Pharmacokinetics (PK) of Triferic Iron Administered IV in Pediatric CKD-5HD Patients: AUC(Last).
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Triferic 0.07 mg/kg Iron Intravenous: Absolute Value	Triferic 0.07 mg/kg Iron Intravenous: Baseline Corrected
Arm/Group Description:	Patients were administered Triferic intravenously 0.07 mg/kg at the same time that they received their standard of care hemodialysis. The results for this group are the absolute values.	Patients were administered Triferic intravenously 0.07 mg/kg at the same time that they received their standard of care hemodialysis. The results for this group are baseline-corrected.
Overall Number of Participants Analyzed	21	21
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours* micrograms/ deciliters
	1324; (36.5%)	419; (101.6%)

3. Primary Outcome

Title	Pharmacokinetics (PK) of Triferic Iron Administered IV in Pediatric CKD-5HD Patients: AUC(0-end).
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Triferic 0.07 mg/kg Iron Intravenous: Absolute Value	Triferic 0.07 mg/kg Iron Intravenous: Baseline Corrected
Arm/Group Description:	Patients were administered Triferic intravenously 0.07 mg/kg at the same time that they received their standard of care hemodialysis. The results for this group are the absolute values.	Patients were administered Triferic intravenously 0.07 mg/kg at the same time that they received their standard of care hemodialysis. The results for this group are baseline-corrected.
Overall Number of Participants Analyzed	21	21
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours* micrograms/ deciliters
	648; (29.3%)	237; (76.8%)

4. Secondary Outcome

Title	Pharmacokinetics (PK) of Triferic Iron Administered Via the Hemodialysate in Pediatric CKD-5HD Patients: Cmax.
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Triferic 2 Micromolar in the Hemodialysate: Absolute Value	Triferic 2 Micromolar in the Hemodialysate: Baseline Corrected
Arm/Group Description:	Patients were administered Triferic at a concentration of 2 micromolar in the hemodialysate. The results for this group are the absolute values.	Patients were administered Triferic at a concentration of 2 micromolar in the hemodialysate. The results for this group are baseline-corrected.
Overall Number of Participants Analyzed	21	21
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: micrograms/ deciliters
	261; (26.4%)	166; (54.3%)

5. Secondary Outcome

Title	Pharmacokinetics (PK) of Triferic Iron Administered Via the Hemodialysate in Pediatric CKD-5HD Patients: AUC(Last).
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Triferic 2 Micromolar Via Hemodialysate: Absolute Value	Triferic 2 Micromolar Via Hemodialysate: Baseline Corrected
Arm/Group Description:	Patients were administered Triferic at a concentration of 2 micromolar in the hemodialysate. The results for this group are the absolute values.	Patients were administered Triferic at a concentration of 2 micromolar in the hemodialysate. The results for this group are baseline-corrected.
Overall Number of Participants Analyzed	21	21
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours* micrograms/ deciliters
	1453; (59.6%)	682; (82.9%)

6. Secondary Outcome

Title	Pharmacokinetics (PK) of Triferic Iron Administered Via the Hemodialysate in Pediatric CKD-5HD Patients: AUC(0-end).
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Triferic 2 Micromolar Via Hemodialysate: Absolute Value	Triferic 2 Micromolar Via Hemodialysate: Baseline Corrected
Arm/Group Description:	Patients were administered Triferic at a concentration of 2 micromolar in the hemodialysate. The results for this group are the absolute values.	Patients were administered Triferic at a concentration of 2 micromolar in the hemodialysate. The results for this group are baseline-corrected.
Overall Number of Participants Analyzed	21	21
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours* micrograms/ deciliters
	763; (38.5%)	387; (79.6%)

7. Other Pre-specified Outcome

Title	Treatment-emergent Adverse Events (TEAEs)
Description	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

Outcome Measure Data

Analysis Population Description

Safety Population: all patients who received any amount of study medication are included in the safety population.

Arm/Group Title	IV Exposure	IV and Hemodialysate Exposure
Arm/Group Description:	Patients in this population had been exposed to Triferic via IV infusion only at the time of onset of the adverse event.	Patients in this population had been exposed to Triferic via the IV infusion and via hemodialysate at the time of the onset of the adverse event.
Overall Number of Participants Analyzed	22	21
Measure Type: Count of Participants; Unit of Measure: Participants
	4 18.2%	3 14.3%

Adverse Events

Time Frame	1.5 weeks
Adverse Event Reporting Description	Adverse events were collected from date of enrollment through the date of final study visit. The total time period of collection was approximately one and a half weeks.
Arm/Group Title	IV Exposure		IV and Hemodialysate Exposure
Arm/Group Description	Patients in this population had received Triferic via IV infusion only at the time of onset of the adverse event.		Patients in this population had received Triferic via IV infusion and via hemodialysate at the time of onset of the adverse event.
All-Cause Mortality
	IV Exposure		IV and Hemodialysate Exposure
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/22 (0.00%)		0/21 (0.00%)
Serious Adverse Events
	IV Exposure		IV and Hemodialysate Exposure
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0.00%)		0/21 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	IV Exposure		IV and Hemodialysate Exposure
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/22 (18.18%)		3/21 (14.29%)
Cardiac disorders
Tachycardia † 1	0/22 (0.00%)	0	1/21 (4.76%)	1
Gastrointestinal disorders
Nausea † 1	2/22 (9.09%)	2	0/21 (0.00%)	0
Abdominal Pain † 1	1/22 (4.55%)	1	0/21 (0.00%)	0
Abdominal pain upper † 1	1/22 (4.55%)	1	0/21 (0.00%)	0
Constipation † 1	0/22 (0.00%)	0	1/21 (4.76%)	1
General disorders
Axillary Pain † 1	0/22 (0.00%)	0	1/21 (4.76%)	1
Musculoskeletal and connective tissue disorders
Back Pain † 1	1/22 (4.55%)	1	0/21 (0.00%)	0
Nervous system disorders
Dizziness † 1	1/22 (4.55%)	1	0/21 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	1/22 (4.55%)	1	0/21 (0.00%)	0
Vascular disorders
Hypotension † 1	0/22 (0.00%)	0	1/21 (4.76%)	1
1 Term from vocabulary, MedDRA (18.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Clinical Project Manager
• Organization: Rockwell Medical, Inc
• Phone: 248-960-9009
• EMail: sgrimberg@rockwellmed.com

• Responsible Party: Rockwell Medical Technologies, Inc.
• ClinicalTrials.gov Identifier: NCT02595437
• Other Study ID Numbers: RMFPC-11
• First Submitted: October 30, 2015
• First Posted: November 3, 2015
• Results First Submitted: August 27, 2018
• Results First Posted: October 25, 2018
• Last Update Posted: October 25, 2018