IV Iron Safety: Evaluation of Iron Species in Healthy Subjects

Phase 4

Completed

• Conditions: Anemia
• Interventions: Drug: Brand sodium ferric gluconate; Drug: Generic sodium ferric gluconate

• Registration Number: NCT02399449
• Lead Sponsor: University of Maryland, Baltimore

Brief Summary

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

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 Timeline

• Study First Submitted: 2015-03-02
• Study First Submitted QC: 2015-03-20
• Study First Posted: 2015-03-26
• Study Start: 2017-09-15
• Primary Completion: 2019-03-22
• Study Completion: 2019-04-25
• Results First Submitted: 2020-11-05
• Status Verified: 2022-09
• Results First Submitted QC: 2022-09-05
• Last Update Submitted: 2022-09-05
• Results First Posted: 2022-09-28
• Last Update Posted: 2022-09-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 110

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Brand sodium ferric gluconate then Generic sodium ferric gluconate	Brand 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)
Brand sodium ferric gluconate then Generic sodium ferric gluconate	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)
Generic sodium ferric gluconate then Brand sodium ferric gluconate	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)
Generic sodium ferric gluconate then Brand sodium ferric gluconate	Generic 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)

Primary Outcome Measures

Name	Time	Method
Non-transferrin Bound Iron	0-36 hr	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).

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University of Maryland; 🇺🇸 Baltimore, Maryland, United States