Study to Investigate the Pharmacokinetic Comparability of Dosing Triferic AVNU IV by Continuous Infusion and IV Bolus.

Study Overview
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Brief Summary
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This study will investigate the administration of Triferic AVNU intravenously by three different administration schedules compared to continuous infusion over 3 hours

Detailed Description
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An open-label, randomized, four period sequential study of Triferic AVNU administered intravenously by three different administration schedules compared to continuous infusion over 3 hours

Official Title
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A Randomized 4 Period Study to Investigate the Pharmacokinetic Comparability of Dosing Triferic AVNU IV by Continuous Infusion and IV Bolus.

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Drug: Triferic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult hemodialysis patients ≥18 years of age. Signed informed consent to participate in the study. Stable on hemodialysis prescription for ≥3 months. Able to sustain hemodialysis 3x/week for 3 to 4 hours. Hemoglobin concentration >9.5 g/dL. Serum TSAT ≥20%. Receiving hemodialysis via AV fistula or graft. Able to receive hemodialysis for 4 hours at each session over the duration of the treatment periods. Able to receive intermittent heparin administration for anticoagulation of the dialysis circuit. Serum TIBC ≥ 150 µg/dL. Exclusion Criteria: Active bleeding disorder (GI, skin, nasal…) Receiving hemodialysis via catheter. Receiving IV iron within 10 days of the first on-study hemodialysis treatment. Receiving oral iron within 10 days of the first on-study hemodialysis treatment. Any other condition, that in the opinion of the investigator would not allow completion of the 4 hemodialysis treatments in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Triferic AVNU infusion pre-dialyzer<br>Patients will receive one (1) 6.75 mg Fe dose of Triferic AVNU by continuous infusion over 3 hours into the predialyzer blood line. | Drug: Triferic<br>* Triferic (ferric pyrophosphate citrate, FPC), an iron-replacement product, is an iron complex in which iron(III) is bound to pyrophosphate and citrate.<br>* Other names: FPC;|
| Experimental: Triferic AVNU for injection at T=0 and T= 3 hours<br>Patients will receive two (2) doses of Triferic AVNU 3.4 mg IV (2.25 mL) at T=0 and T=3 hours of hemodialysis into the venous drip chamber. | Drug: Triferic<br>* Triferic (ferric pyrophosphate citrate, FPC), an iron-replacement product, is an iron complex in which iron(III) is bound to pyrophosphate and citrate.<br>* Other names: FPC;|
| Experimental: Triferic AVNU for injection at T=0<br>Patients will receive one (1) dose of Triferic AVNU 0.08 mg/kg IV, up to 6.75 mg Fe, at T=0 of hemodialysis into the venous drip chamber. | Drug: Triferic<br>* Triferic (ferric pyrophosphate citrate, FPC), an iron-replacement product, is an iron complex in which iron(III) is bound to pyrophosphate and citrate.<br>* Other names: FPC;|
| Experimental: Triferic AVNU for injection at T=0, T=1.5 and T= 3 hours<br>Patients will receive three (3) doses of Triferic AVNU 2.25 mg Fe (1.5 mL) at T=0, T=1.5 and T=3.0 hours of hemodialysis into the venous drip chamber. | Drug: Triferic<br>* Triferic (ferric pyrophosphate citrate, FPC), an iron-replacement product, is an iron complex in which iron(III) is bound to pyrophosphate and citrate.<br>* Other names: FPC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under plasma concentration-time curve (AUC0-last pFetotal) for all Treatments A,B,C and D |  | 8 hours | 
| Area under plasma transferrin bound plasma iron concentration- time curve (AUC0-last FeTBI) for all Treatments A,B,C and D |  | 8 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma iron concentration (Cmax pFetotal) for all Treatments A,B,C and D |  | 8 hours | 
| Maximum observed transferrin bound plasma iron concentration (Cmax FeTBI) for all Treatments A,B,C and D |  | 8 hours | 
| Maximum observed serum iron concentration (Cmax sFetotal) for all Treatments A,B,C and D |  | 8 hours | 
| Area under serum Fe concentration-time curve (AUC0-last sFetotal) for all Treatments A,B,C and D |  | 8 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics