Hypophosphatemia With Ferric Carboxymaltose Vs. Iron Dextran in Iron Deficiency Secondary to Heavy Uterine Bleeding

A Randomized, Controlled Study to Investigate the Safety and Explore the Mechanism of Hypophosphatemia With Intravenous Ferric Carboxymaltose (FCM) Versus Iron Dextran in Women With Iron Deficiency Secondary to Heavy Uterine Bleeding

The primary objective of this study is to assess the safety of an investigational intravenous iron (ferric carboxymaltose [FCM]) or an equal dose of iron dextran and explore the mechanism of hypophosphatemia following administration of FCM or that of an equal dose of iron dextran when treating women with iron deficiency anemia due to heavy uterine bleeding (HUB).

Study Overview

• Status: Completed
• Conditions: Iron Deficiency Anemia
• Intervention / Treatment: Drug: Ferric Carboxymaltose (FCM); Drug: Iron Dextran Injection

Detailed Description

To assess the safety of an investigational intravenous iron (ferric carboxymaltose [FCM]) or an equal dose of iron dextran and explore the mechanism of hypophosphatemia following administration of FCM or that of an equal dose of iron dextran when treating women with iron deficiency anemia due to heavy uterine bleeding (HUB).

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female subjects > or = to 18 years of age
• History of Heavy Uterine Bleeding within the past 6 months
• Screening visit central laboratory Hgb < 12 g/dL
• Screening Visit ferritin < or = to 100 ng/mL or < or = to 300 when transferrin saturation (TSAT) is < or = to 30%
• Demonstrate the ability to understand the requirements of the study, willingness to abide by study restrictions and to return for the required assessments

Exclusion Criteria:

• Known hypersensitivity reaction to any component of ferric carboxymaltose or iron dextran
• Previously randomized in a clinical study of ferric carboxymaltose
• Requires dialysis for treatment of chronic kidney disease
• Chronic kidney disease, marked by estimated glomerular filtration rate < 60 ml/min/1.73m squared
• Previous kidney transplant
• History of primary hypophosphatemic disorder
• Hypophosphatemia < 2.6 mg/dl
• No evidence of iron deficiency
• During the 10 day period prior to screening has been treated with intravenous iron
• During the 30 day period prior to screening or during the study period has or will be treated with erythropoiesis stimulating agents (ESA) in a regimen that is off label
• During the 30 day period prior to screening or during the study period has or will be treated with a red blood cell transfusion, radiotherapy and/or chemotherapy
• During the 30 day period prior to screening or during the study period has or will require a surgical procedure that necessitates general anesthesia
• Any non-viral infection
• Aspartate aminotransferase (AST) or Alanine Aminotransferase (ALT) at screening, as determined by central labs, greater than 1.5 times the upper limit of normal
• Known positive hepatitis with evidence of active disease
• Received an investigational drug within 30 days of screening
• Alcohol or drug abuse within the past 6 months
• Hemochromatosis or other iron storage disorders
• Malignancy history within the past 5 years other than basal or squamous cell skin cancer
• Any other laboratory abnormality, medical condition or psychiatric disorders which in the opinion of the investigator would put the subject's disease management at risk or may result in the subject being unable to comply with study requirements
• Pregnant or sexually-active female subjects who are of childbearing potential and who are not willing to use an acceptable form of contraception
• Untreated primary hyperparathyroidism
• Untreated gastrointestinal malabsorption (e.g., sprue)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ferric Carboxymaltose (FCM); 15 mg/kg up to a maximum of 1000 mg intravenous diluted in 250 cc normal saline solution administered over 15 minutes on Day 0	Drug: Ferric Carboxymaltose (FCM); 15 mg/kg up to a maximum of 1000 mg intravenous diluted in 250 cc normal saline solution administered over 15 minutes on Day 0; Other Names: Injectafer
Active Comparator: Iron Dextran Injection; Test dose of 25 mg administered over 5 minutes, if no reaction occurs then the remainder of the dose (15 mg/kg or 1000 mg including the test dose) will be administered as per investigator. The infusion must be given only when resuscitative techniques for the treatment of anaphylactic reactions are readily available.	Drug: Iron Dextran Injection; Test dose of 25 mg administered over 5 minutes, if no reaction occurs then the remainder of the dose (15 mg/kg or 1000 mg including the test dose) will be administered as per investigator. The infusion must be given only when resuscitative techniques for the treatment of anaphylactic reactions are readily available.; Other Names: Dexferrum and INFeD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Blood Markers	Changes in blood markers of phosphate	Day 35

Collaborators and Investigators

• Sponsor: American Regent, Inc.
• Investigators: Study Director: Mark Falone, MD, American Regent, Inc.

Publications and helpful links

General Publications

• Wolf M, Koch TA, Bregman DB. Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women. J Bone Miner Res. 2013 Aug;28(8):1793-803. doi: 10.1002/jbmr.1923.

Helpful Links

• FGF23; IRON; PHOSPHATE; PTH; VITAMIN D

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: October 4, 2010
• First Submitted That Met QC Criteria: March 1, 2011
• First Posted (Estimate): March 2, 2011

Study Record Updates

• Last Update Posted (Actual): February 19, 2018
• Last Update Submitted That Met QC Criteria: January 19, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Uterine Diseases; Hematologic Diseases; Hemorrhage; Anemia, Hypochromic; Anemia; Iron Metabolism Disorders; Phosphorus Metabolism Disorders; Anemia, Iron-Deficiency; Hypophosphatemia; Uterine Hemorrhage; Anticoagulants; Hematinics; Plasma Substitutes; Blood Substitutes; Dextrans; Iron-Dextran Complex
• Other Study ID Numbers: 1VIT08023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No