Iron Deficiency Anemia
Conditions
Brief summary
The purpose of this study is to compare safety and the oxidative stress potential of two doses of an investigational IV iron, ferric carboxymaltose (FCM), compared to an equal single dose of IV iron sucrose or IV iron dextran in the treatment of Iron Deficiency Anemia (IDA) in female subjects.
Detailed description
This was a Phase 2a, open-label, multicenter, randomized study that compared the safety and oxidative stress potential of FCM vs. IV iron sucrose or IV iron dextran in female subjects with IDA. Subjects with a diagnosis of IDA who required iron supplementation met all inclusion and no exclusion criteria, and had given informed consent were randomized. The duration of the study for each subject was a maximum of 6 weeks. Eligible subjects were randomized in a 1:1 ratio to FCM (Group A) or IV iron sucrose or IV iron dextran (Group B). Group A subjects received a single undiluted dose of iron as FCM by a slow IV injection on Day 0. Cohort I received 500 mg and Cohort II received 750 mg. Group B subjects received a single dose of iron as IV iron sucrose or as IC iron dextran on Day 0. Cohort I receive 500 mg iron sucrose and Cohort II received 750 mg iron dextran. Iron dextran administration was preceded by a 25 mg test dose 1 hour prior to infusion. All subjects had laboratory assessments at Baseline, 2 hours post-infusion, 24 hours post-infusion, Day 7 (drawn at the same time of day \[within 4 hours\] as the 24-hour visit), and Day 30 (drawn at the same time of day \[within 4 hours\] as the the 24-hour visit). On Days 7 and 30, the safety evalutation for all subjects included treatment-emergent adverse event reporting, concomitant medication review, physical examination including vital signs, and laboratory assessments. Any subject who withdrew from the study received a follow-up phone call 30 days after they received study drug.
Interventions
One 500 mg dose at 100 mg/minute (Cohort I) or 750 mg dose at 100 mg/minute (Cohort II)
DRUGIron Sucrose / Iron Dextran
One 500 mg dose of IV iron sucrose administered over 4 hours (Cohort I), or a 750 mg dose of IV iron dextran administered as a 25 mg test dose over 5 minutes followed by a 725 mg dose over 3 hours if no adverse reaction to test dose is observed after 60 minutes (Cohort II)
Sponsors
American Regent, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Female subjects 18-50 years of age and able to give informed consent. * If post-partum, at least 10 days post delivery at Day 0. * Screening Visit local laboratory Hgb \< or = to 10 g/dL or \< or = to 12 g/dL with symptoms (dizziness and/or fatigue). * Screening Visit ferritin \< or = to 100 ng/mL or \< or = to 300 when TSAT is \< or = to 30%. * Documented unsatisfactory response or intolerance to oral iron.
Exclusion criteria
* Previous participation in a ferric carboxymaltose (FCM) clinical trial. * Known hypersensitivity reaction to any component of ferric carboxymaltose, Venofer, or Dexferrum. * History of drug allergy or any history of rheumatoid arthritis or other autoimmune diseases. * Current anemia not attributed to iron deficiency. * During the 10 day period prior to screening has been treated with antibiotics. * During the 30 day period prior to screening or during the study period has or will be treated with erythropoiesis stimulating agents. * Active malignancy within 5 years. Basal or squamous cell skin cancer is not exclusionary. * During the 30 day period prior to screening or during the study period has or will require a surgical procedure that necessitates general anesthesia. * Current (acute or chronic) infection other than viral upper respiratory tract infection. * AST or ALT at screening greater than 1.5 times the upper limit of normal. * Known positive hepatitis B with evidence of active hepatitis. * Known positive HIV-1/HIV-2 antibodies (anti-HIV). * Patient has an active diagnosis of asthma and is currently using an anti- asthmatic therapy. * Received an investigational drug within 30 days of screening. * Alcohol or drug abuse within the past 6 months. * Hemochromatosis or other iron storage disorders. * Systolic blood pressure \> or = to 180 or \< 80 mmHg or diastolic blood pressure \> or = to 100 or \< 40 mmHg at screening or Day 0. * Chronic kidney disease. * Chronic inflammatory condition including but not limited to Lupus and Rheumatoid Arthritis. * Pre-term delivery \< 32 weeks. * Emergent C-section delivery. * Significant cardiovascular disease, including but not limited to myocardial infarction or unstable angina within 6 months prior to study inclusion or current history of NYHA Class III or IV congestive heart failure. * Any other laboratory abnormality, medical condition or psychiatric disorder which in the opinion of the investigator puts the subject's disease management at risk or may result in the subject being unable to comply with study requirements. * Night shift workers. * Breastfeeding planned on or after Day 0. * Pregnant or sexually-active female subjects who are of childbearing potential and who don't use an acceptable form of contraception.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | Change from Baseline to Day 30 |
Countries
United States
Participant flow
Recruitment details
Hospitals and Medical Clinics. December 6, 2010 through October 13, 2012.
Pre-assignment details
Discontinuation prior to dosing included lost to follow-up, subject request, and selection criteria/study compliance. A total of 19 subjects were excluded from the population of subjects evaluated for efficacy and safety-5 randomized to FCM 500mg, 2 randomized to FCM 750mg, 6 randomized to iron sucrose 500mg, and 6 randomized to iron dextran 750mg.
Participants by arm
| Arm | Count |
|---|---|
| Ferric Carboxymaltose (FCM) Cohort I Intravenous iron
Ferric Carboxymaltose (FCM): One 500 mg dose at 100 mg/minute (Cohort I) | 14 |
| Iron Sucrose Cohort I Intravenous iron
Iron Sucrose: One 500 mg dose of IV iron sucrose administered over 4 hours (Cohort I) | 12 |
| Ferric Carboxymaltose (FCM) Cohort II Intravenous iron
Ferric Carboxymaltose (FCM): One 750 mg dose at 100 mg/minute (Cohort II) | 10 |
| Iron Dextran Cohort II Intravenous iron
Iron Dextran: One 750 mg dose of IV iron dextran administered as a 25 mg test dose over 5 minutes followed by a 725 mg dose over 3 hours if no adverse reaction to test dose is observed after 60 minutes (Cohort II) | 13 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 3 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Overall Study | Selection criteria/compliance | 2 | 1 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Iron Sucrose Cohort I | Ferric Carboxymaltose (FCM) Cohort II | Ferric Carboxymaltose (FCM) Cohort I | Iron Dextran Cohort II | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 10 Participants | 14 Participants | 13 Participants | 49 Participants |
| Age, Continuous | 29.6 years STANDARD_DEVIATION 9.93 | 39.2 years STANDARD_DEVIATION 7.97 | 32.1 years STANDARD_DEVIATION 7.66 | 39.2 years STANDARD_DEVIATION 9.21 | 34.8 years STANDARD_DEVIATION 9.48 |
| Region of Enrollment United States | 12 participants | 10 participants | 14 participants | 13 participants | 49 participants |
| Sex: Female, Male Female | 12 Participants | 10 Participants | 14 Participants | 13 Participants | 49 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 24 | 10 / 25 |
| serious Total, serious adverse events | 0 / 24 | 2 / 25 |
Outcome results
Primary
Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane)
Time frame: Change from Baseline to Day 30
Population: Only subjects with both a Baseline and at least one post-Baseline value are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ferric Carboxymaltose (FCM) Cohort I | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | Carbonyl | -11.90 mg | Standard Deviation 52.55 |
| Ferric Carboxymaltose (FCM) Cohort I | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | 8-isoprostane | 141.46 mg | Standard Deviation 892.16 |
| Iron Sucrose Cohort I | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | 8-isoprostane | -369.50 mg | Standard Deviation 957.06 |
| Iron Sucrose Cohort I | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | Carbonyl | -1.06 mg | Standard Deviation 38.722 |
| Ferric Carboxymaltose (FCM) Cohort II | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | Carbonyl | -12.37 mg | Standard Deviation 32.91 |
| Ferric Carboxymaltose (FCM) Cohort II | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | 8-isoprostane | 8.83 mg | Standard Deviation 81.2 |
| Iron Dextran Cohort II | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | Carbonyl | -11.14 mg | Standard Deviation 48.57 |
| Iron Dextran Cohort II | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | 8-isoprostane | 32.28 mg | Standard Deviation 233.41 |
Primary
Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane)
Time frame: Change from baseline to 2 hours post end IV infusion
Population: Only subjects with both a baseline and at least one post baseline value are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ferric Carboxymaltose (FCM) Cohort I | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | Carbonyl | 2.07 mg | Standard Deviation 38.21 |
| Ferric Carboxymaltose (FCM) Cohort I | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | 8-isoprostane | 151.59 mg | Standard Deviation 833.75 |
| Iron Sucrose Cohort I | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | 8-isoprostane | -420.02 mg | Standard Deviation 803.52 |
| Iron Sucrose Cohort I | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | Carbonyl | 6.05 mg | Standard Deviation 24.69 |
| Ferric Carboxymaltose (FCM) Cohort II | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | Carbonyl | -8.66 mg | Standard Deviation 43.15 |
| Ferric Carboxymaltose (FCM) Cohort II | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | 8-isoprostane | -2.64 mg | Standard Deviation 30.44 |
| Iron Dextran Cohort II | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | Carbonyl | -5.98 mg | Standard Deviation 23.71 |
| Iron Dextran Cohort II | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | 8-isoprostane | -5.92 mg | Standard Deviation 216.66 |
Primary
Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane)
Time frame: Change from baseline to 24 hours post end IV infusion
Population: Only subjects with both a baseline and at least one post baseline value are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ferric Carboxymaltose (FCM) Cohort I | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | 8-isoprostane | 198.67 mg | Standard Deviation 864.29 |
| Ferric Carboxymaltose (FCM) Cohort I | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | Carbonyl | 8.63 mg | Standard Deviation 23.24 |
| Iron Sucrose Cohort I | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | 8-isoprostane | 119.26 mg | Standard Deviation 575.29 |
| Iron Sucrose Cohort I | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | Carbonyl | -6.92 mg | Standard Deviation 21.49 |
| Ferric Carboxymaltose (FCM) Cohort II | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | Carbonyl | 8.94 mg | Standard Deviation 87.05 |
| Ferric Carboxymaltose (FCM) Cohort II | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | 8-isoprostane | -23.96 mg | Standard Deviation 60.01 |
| Iron Dextran Cohort II | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | Carbonyl | -11.57 mg | Standard Deviation 40.3 |
| Iron Dextran Cohort II | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | 8-isoprostane | 38.02 mg | Standard Deviation 190.07 |
Primary
Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane)
Time frame: Change from baseline to Day 7 post end IV infusion
Population: Only subjects with both a baseline and at least one post baseline value are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ferric Carboxymaltose (FCM) Cohort I | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | Carbonyl | 11.69 mg | Standard Deviation 36.43 |
| Ferric Carboxymaltose (FCM) Cohort I | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | 8-isoprostane | 263.52 mg | Standard Deviation 896.57 |
| Iron Sucrose Cohort I | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | 8-isoprostane | -417.89 mg | Standard Deviation 1030.83 |
| Iron Sucrose Cohort I | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | Carbonyl | -24.03 mg | Standard Deviation 65.55 |
| Ferric Carboxymaltose (FCM) Cohort II | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | Carbonyl | -18.20 mg | Standard Deviation 45.92 |
| Ferric Carboxymaltose (FCM) Cohort II | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | 8-isoprostane | -29.35 mg | Standard Deviation 56.88 |
| Iron Dextran Cohort II | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | Carbonyl | -12.10 mg | Standard Deviation 54.85 |
| Iron Dextran Cohort II | Changes From Baseline in Markers of Oxidative Stress (Carbonyl and 8-isoprostane) | 8-isoprostane | -58.04 mg | Standard Deviation 159.58 |