IV Iron Safety: Evaluation of Iron Species in Healthy Subjects

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

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.

Study Overview

• Status: Completed
• Conditions: Anemia
• Intervention / Treatment: Drug: Brand sodium ferric gluconate; Drug: Generic sodium ferric gluconate

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brand sodium ferric gluconate then Generic sodium ferric gluconate; 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; brand product; Other Names: Ferrecit; Drug: Generic sodium ferric gluconate; generic product; Other Names: generic iron
Experimental: Generic sodium ferric gluconate then Brand sodium ferric gluconate; 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; brand product; Other Names: Ferrecit; Drug: Generic sodium ferric gluconate; generic product; Other Names: generic iron

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Investigators: Principal Investigator: James Polli, U of Maryland

Publications and helpful links

General Publications

• Baribeault D. Sodium ferric gluconate (SFG) in complex with sucrose for IV infusion: bioequivalence of a new generic product with the branded product in healthy volunteers. Curr Med Res Opin. 2011 Aug;27(8):1653-7. doi: 10.1185/03007995.2011.597738. Epub 2011 Jun 30.

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2017
• Primary Completion (Actual): March 22, 2019
• Study Completion (Actual): April 25, 2019

Study Registration Dates

• First Submitted: March 2, 2015
• First Submitted That Met QC Criteria: March 20, 2015
• First Posted (Estimate): March 26, 2015

Study Record Updates

• Last Update Posted (Actual): September 28, 2022
• Last Update Submitted That Met QC Criteria: September 5, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: pharmacokinetics; iron
• Additional Relevant MeSH Terms: Hematinics; Ferric Compounds; Ferric gluconate
• Other Study ID Numbers: HP-00060573

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No