IV Iron Safety: Evaluation of Iron Species in Healthy Subjects

Study Overview
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Brief Summary
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An approved treatment for anemia or low blood count due to chronic kidney disease is IV (intravenous, given into the vein) injection of an iron treatment. IV iron increases iron in the blood. Many IV iron therapies are now available in both brand name and generic forms. One common IV iron product is sodium ferric gluconate (SFG) sold as brand name Ferrlecit. Recently, a generic version of Ferrlecit was approved but was felt to be possibly more toxic than the brand product. The purpose of this research project is to see if the brand and generic IV iron products produce the same amount of iron in the blood in healthy volunteers, including an iron form that more toxic than other iron forms.

Detailed Description
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A generic version of Ferrlecit was approved in 2011 and is available. Shortly after the approval of the generic, a 'Reflections Paper on Non-Clinical Studies for Generic Nanoparticle Iron Medicinal Product Applications' was published by the European Medicines Agency. The authors of this paper proposed that generic iron preparations deliver increased levels of 'labile iron' to the plasma resulting in oxidative damage and toxicity. As such, studies measuring the in vivo levels of free or labile iron from generic versus brand iron-preparations were recommended. The primary outcome will be the assessment of non-inferiority of the generic colloid product against the reference colloid product with respect to non-transferrin bound iron (NTBI), after single-dose i.v. administration of brand and generic sodium ferric gluconate injections in n=48 healthy subjects.

Official Title
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Evaluation of Iron Species in Healthy Subjects Treated With Generic and Reference Sodium Ferric Gluconate

Conditions
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Anemia

Intervention / Treatment
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* Drug: Brand sodium ferric gluconate
* Drug: Generic sodium ferric gluconate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: View 1 Males or female, with age 18-65 years old, systolic blood pressure within 90-150, and diastolic blood pressure within 60-90 View 2 Healthy volunteers: Subjects in good health including being iron replete and not anemic, as determined by screening evaluation that is not greater than 30 days before the first drug study visit View 3 Willing to avoid caffeine containing products 24 hours prior to and day of study visits View 4 Willing to stop all OTC medications for 24 hours prior to and during study visits View 5 Able to provide informed consent Exclusion Criteria: View 1 Presence of significant medical disease (including cardiovascular, pulmonary, hematologic, endocrine, immunologic, neurologic, gastrointestinal or psychiatric) View 2 Subjects who are iron deficient or with iron overload View 3 Presence of hepatic or renal disease View 4 Pregnant women, breast feeding or trying to become pregnant View 5 Excessive alcohol use (i.e. current physical, behavioral, or personal manifestations related to the abuse or dependency on alcohol) View 6 Routine use (i.e. daily or weekly) prescription medication except birth control pills View 7 Currently taking iron in any form (e.g. oral or IV) View 8 Allergic to IV iron, including sodium ferric gluconate, or any of its inactive components, including benzyl alcohol View 9 Undergoing therapy for solid tumor or blood malignancy View 10 Any condition in which in the opinion of the PI or medical physician would increase risk to the subject or interfere with the integrity of the study View 11 Donated blood within last 56 days of screening. Received IV iron or RBC transfusion(s) 10 days prior to screening. Plan to donate blood, or receive IV iron or RBC transfusion(s), during the study period.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brand sodium ferric gluconate then Generic sodium ferric gluconate<br>Crossover trial. Each arm will receive Brand sodium ferric gluconate (single dose of 125mg) then Generic sodium ferric gluconate (single dose of 125mg) | Drug: Brand sodium ferric gluconate<br>* brand product<br>* Other names: Ferrecit;Drug: Generic sodium ferric gluconate<br>* generic product<br>* Other names: generic iron;|
| Experimental: Generic sodium ferric gluconate then Brand sodium ferric gluconate<br>Crossover trial. Each arm will receive Generic sodium ferric gluconate (single dose of 125mg) then Brand sodium ferric gluconate (single dose of 125mg) | Drug: Brand sodium ferric gluconate<br>* brand product<br>* Other names: Ferrecit;Drug: Generic sodium ferric gluconate<br>* generic product<br>* Other names: generic iron;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-transferrin Bound Iron | area under curve of non-transferrin bound iron. Non-transferrin bound iron is the difference between plasma total iron and transferrin bound iron, both of which were directly quantified. Units are concentration x time (i.e. ppb x hr). | 0-36 hr | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Total Iron | area under curve of plasma total iron. Units are concentration x time (i.e. ppb x hr). | 0-36 hr | 
| Transferrin Bound Iron | area under curve of transferrin bound iron. Units are concentration x time (i.e. ppb x hr). | 0-36 hr | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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iron, pharmacokinetics