Anemia
Conditions
Keywords
iron, pharmacokinetics
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.
Interventions
DRUGBrand sodium ferric gluconate
brand product
DRUGGeneric sodium ferric gluconate
generic product
Sponsors
University of Maryland, Baltimore
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Countries
United States
Participant flow
Pre-assignment details
Enrollment number is the number of participants who signed a consent form, per local IRB requirements.
Participants by arm
| Arm | Count |
|---|---|
| Brand Sodium Ferric Gluconate Then Generic Sodium Ferric Gluconate Crossover trial. Each arm will receive Brand sodium ferric gluconate then Generic sodium ferric gluconate
Brand sodium ferric gluconate: brand product
Generic sodium ferric gluconate: generic product | 25 |
| Generic Sodium Ferric Gluconate Then Brand Sodium Ferric Gluconate Crossover trial. Each arm will receive Generic sodium ferric gluconate then Brand sodium ferric gluconate
Brand sodium ferric gluconate: brand product
Generic sodium ferric gluconate: generic product | 24 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 9 |
Baseline characteristics
| Characteristic | Generic Sodium Ferric Gluconate Then Brand Sodium Ferric Gluconate | Total | Brand Sodium Ferric Gluconate Then Generic Sodium Ferric Gluconate |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 49 Participants | 25 Participants |
| Age, Continuous | 36 years | 35 years | 34 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 15 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 9 Participants | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 19 Participants | 7 Participants |
| Region of Enrollment United States | 24 participants | 49 participants | 25 participants |
| Sex: Female, Male Female | 12 Participants | 23 Participants | 11 Participants |
| Sex: Female, Male Male | 12 Participants | 26 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 46 |
| other Total, other adverse events | 13 / 47 | 3 / 46 |
| serious Total, serious adverse events | 1 / 47 | 0 / 46 |
Outcome results
Primary
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).
Time frame: 0-36 hr
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Brand Sodium Ferric Gluconate | Non-transferrin Bound Iron | 56230 ppb x hours | Standard Error 2910 |
| Generic Sodium Ferric Gluconate | Non-transferrin Bound Iron | 61250 ppb x hours | Standard Error 3410 |
Secondary
Plasma Total Iron
area under curve of plasma total iron. Units are concentration x time (i.e. ppb x hr).
Time frame: 0-36 hr
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Brand Sodium Ferric Gluconate | Plasma Total Iron | 132800 ppb x hours | Standard Error 4700 |
| Generic Sodium Ferric Gluconate | Plasma Total Iron | 134700 ppb x hours | Standard Error 5100 |
Secondary
Transferrin Bound Iron
area under curve of transferrin bound iron. Units are concentration x time (i.e. ppb x hr).
Time frame: 0-36 hr
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Brand Sodium Ferric Gluconate | Transferrin Bound Iron | 96760 ppb x hours | Standard Error 3680 |
| Generic Sodium Ferric Gluconate | Transferrin Bound Iron | 91740 ppb x hours | Standard Error 3980 |