Trial Outcomes & Findings for Pharmacokinetics and Preliminary Bioequivalence of Triferic (Ferric Pyrophosphate Citrate) Administered Via Hemodialysate and Intravenously to Adult CKD-5HD Patients (NCT NCT02739100)

Last Updated: 2019-02-01

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

13 participants

Primary outcome timeframe

1, 2, 3, 4, 5, 6, 8, 10, and 12 hours

Results posted on

2019-02-01

Participant Flow

Participant milestones

Participant milestones
Measure	All Participants In this cross-over study, all enrolled participants underwent blood sampling over 12 hours for pharmacokinetic (PK) purposes on Day 1. On Days 3, 8, and 10 participants received the following three treatments in a randomized sequence (one treatment per study day): Triferic 2 micromolar via hemodialysate, Triferic 6.6. mg intravenously pre-dialyzer over 3 hours, and Triferic 6.6 mg intravenously post-dialyzer over 3 hours. Blood sampling was conducted over a 12 hour period on each treatment day for PK purposes.
Overall Study STARTED	13
Overall Study Triferic 2 Micromolar Via Hemodialysate	13
Overall Study Triferic 6.6 mg IV Predialyzer	13
Overall Study Triferic 6.6. mg IV Post-dialyzer	13
Overall Study COMPLETED	13
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetics and Preliminary Bioequivalence of Triferic (Ferric Pyrophosphate Citrate) Administered Via Hemodialysate and Intravenously to Adult CKD-5HD Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Safety Population n=13 Participants 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.
Age, Continuous	49.2 years STANDARD_DEVIATION 8.84 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	13 participants n=5 Participants
Height	174.3 centimeters STANDARD_DEVIATION 9.22 • n=5 Participants
Weight	98.7 kg STANDARD_DEVIATION 19.34 • n=5 Participants
C-reactive protein	.8 milligram/deciliter STANDARD_DEVIATION .81 • n=5 Participants

PRIMARY outcome

Timeframe: 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours

Outcome measures

Outcome measures
Measure	Triferic Via Hemodialysate n=13 Participants 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. Triferic	Triferic Via IV Infusion Pre-dialyzer n=13 Participants Patients will receive a single 6.6-mg dose of Triferic iron administered IV over 4 hrs during hemodialysis via the unused heparin infusion line (pre-dialyzer).	Triferic IV Infusion Post-dialyzer n=13 Participants Patients will receive a single 6.6-mg dose of Triferic iron administered IV over 4 hrs during hemodialysis via an infusion port (post-dialyzer).
Pharmacokinetics (PK) of Triferic Iron Administered Via Hemodialysate in Adult CKD-5HD Patients: Cmax.	124 microgram per deciliter Standard Deviation 49.9	131 microgram per deciliter Standard Deviation 30.5	124 microgram per deciliter Standard Deviation 42.4

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Triferic Via Hemodialysate n=12 Participants 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. Triferic	Triferic Via IV Infusion Pre-dialyzer n=10 Participants Patients will receive a single 6.6-mg dose of Triferic iron administered IV over 4 hrs during hemodialysis via the unused heparin infusion line (pre-dialyzer).	Triferic IV Infusion Post-dialyzer n=13 Participants Patients will receive a single 6.6-mg dose of Triferic iron administered IV over 4 hrs during hemodialysis via an infusion port (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)).	621 hours*microgram/deciliter Standard Deviation 355	630 hours*microgram/deciliter Standard Deviation 275	524 hours*microgram/deciliter Standard Deviation 272

SECONDARY outcome

Timeframe: 13 days

Population: Safety Population (all enrolled subjects)

Safety will be documented by recording the incidence of treatment-emergent adverse events (TEAEs)

Outcome measures

Outcome measures
Measure	Triferic Via Hemodialysate n=13 Participants 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. Triferic	Triferic Via IV Infusion Pre-dialyzer n=13 Participants Patients will receive a single 6.6-mg dose of Triferic iron administered IV over 4 hrs during hemodialysis via the unused heparin infusion line (pre-dialyzer).	Triferic IV Infusion Post-dialyzer n=13 Participants Patients will receive a single 6.6-mg dose of Triferic iron administered IV over 4 hrs during hemodialysis via an infusion port (post-dialyzer).
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	1 Participants	2 Participants	0 Participants

SECONDARY outcome

Timeframe: 13 days

Population: Safety Population (all enrolled subjects)

Safety will be documented by recording the incidence of treatment-emergent serious adverse events (TESAEs)

Outcome measures

Outcome measures
Measure	Triferic Via Hemodialysate n=13 Participants 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. Triferic	Triferic Via IV Infusion Pre-dialyzer n=13 Participants Patients will receive a single 6.6-mg dose of Triferic iron administered IV over 4 hrs during hemodialysis via the unused heparin infusion line (pre-dialyzer).	Triferic IV Infusion Post-dialyzer n=13 Participants Patients will receive a single 6.6-mg dose of Triferic iron administered IV over 4 hrs during hemodialysis via an infusion port (post-dialyzer).
Number of Participants With Treatment-emergent Serious Adverse Events (TEAEs)	0 Participants	0 Participants	0 Participants

Adverse Events

Triferic Via Hemodialysate

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Triferic Via IV Infusion Pre-dialyzer

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Triferic IV Infusion Post-dialyzer

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Triferic Via Hemodialysate n=13 participants at risk 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. Triferic	Triferic Via IV Infusion Pre-dialyzer n=13 participants at risk Patients will receive a single 6.6-mg dose of Triferic iron administered IV over 4 hrs during hemodialysis via the unused heparin infusion line (pre-dialyzer).	Triferic IV Infusion Post-dialyzer n=13 participants at risk Patients will receive a single 6.6-mg dose of Triferic iron administered IV over 4 hrs during hemodialysis via an infusion port (post-dialyzer).
Musculoskeletal and connective tissue disorders pain in extremity	7.7% 1/13 • Number of events 1	0.00% 0/13	0.00% 0/13
Gastrointestinal disorders vomiting	0.00% 0/13	7.7% 1/13 • Number of events 1	0.00% 0/13
Gastrointestinal disorders nausea	0.00% 0/13	7.7% 1/13 • Number of events 1	0.00% 0/13
Infections and infestations upper respiratory tract infection	0.00% 0/13	7.7% 1/13 • Number of events 1	0.00% 0/13

Additional Information

Clinical Project Manager

Rockwell Medical, Inc

Phone: 248-960-9009

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60