Safety and Efficacy of High Dose Intravenous Ferric Carboxymaltose vs. Standard Medical Care in the Treatment of Iron Deficiency Anemia

Abstract

Purpose: This trial evaluates the safety and efficacy of intravenous (IV) Ferric Carboxymaltose (FCM) compared to standard medical care (SMC) in the management of iron deficiency anemia (IDA). Methods: FCM is a stable non-dextran iron compound developed for high dose rapid IV administration. Two open label, randomized controlled trials were conducted at 95 sites. In one, multiple doses of FCM were administered (md). In the other a single dose (sd) was given. Subjects with IDA were eligible if age 18-85 and not on dialysis, with hemoglobin (Hb) ≤ 12 g/dL, ferritin ≤100 ng/mL, and transferrin ≤30%. Subjects were randomized in a 1:1 ratio to receive FCM or SMC (oral or IV iron or no iron). In the md study, subjects in the FCM group got 750 mg (15 mg/kg) undiluted @ 100 mg/min weekly in order to replenish their iron deficit (calculated by the Ganzoni formula) up to 2250 mg total. Subjects in the sd trial got one injection of FCM, 750 mg @ 100 mg/min. Results: Enrollment in the md study was: 343-FCM, 360-SMC; in the sd study it was: 366-FCM, 369-SMC. There was a significantly greater increase in Hb, hematocrit, and ferritin from baseline to Day 30 observed with FCM compared to SMC (p ≤ 0.001). The overall adverse event (AE) rate was similar in both studies. The most frequent AEs were constipation, diarrhea, nausea, vomiting, abdominal pain, dizziness, and headache. More vomiting and constipation were noted in the SMC group. Low serum phosphate values were frequently observed after FCM treatment (48% in md), but were not associated with other clinical sequelae. There was 1 drug-related serious AE in the FCM group (constipation) and 2 in the SMC group (renal infarct, hypotension). Other serious adverse events occurred equally in the two groups. There was 1 death in the SMC group (pneumonia). There were no serious hypersensitivity reactions or deaths in the FCM group. Conclusion: IV iron is often preferred for treating IDA associated with renal disease, bleeding, poor absorption (gastric bypass or Celiac disease) or oral intolerance. There is an unmet need for safe IV iron available in large single doses. Iron dextrans are associated with a substantial risk of fatal anaphylaxis (and high doses are not FDA approved). The available non-dextran irons must also be administered in low doses (usually ≤ 200 mg) necessitating multiple visits. This study demonstrated that FCM and SMC both replenish iron. FCM was well tolerated with similar AE rates in the FCM and SMC groups. The majority of AEs were not severe; there were no deaths in the FCM group. FCM may be safely administered at high dose in an outpatient setting taking < 10 min per dose, requiring fewer clinic visits and fewer venipunctures. Disclosure: Luitpold Pharmaceuticals Dr. Barish - Investigator research support, Dr. Bregman - Medical Director, Luitpold Ms. Butcher - Project Manager, Luitpold, Mr. Koch - Project Manager, Luitpold., Dr. Morris - Statistician, Luitpold. This research was supported by an industry grant from Luitpold Pharmaceuticals.