Incidence of Hypophosphatemia After Treatment With Iron Isomaltoside/Ferric Derisomaltose vs Ferric Carboxymaltose in Subjects With Iron Deficiency Anaemia

Iron Deficiency Anemia Clinical Trial

Official title:

A Randomized, Open-label, Comparative Trial Comparing the Incidence of Hypophosphatemia in Relation to Treatment With Iron Isomaltoside/Ferric Derisomaltose and Ferric Carboxymaltose in Subjects With Iron Deficiency Anaemia (Phosphare-IDA-04)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03238911
• Other study ID #: P-Monofer-IDA-04
• Status: Completed
• Phase: Phase 3
• Start date: October 24, 2017
• Est. completion date: June 19, 2018

Study information

• Verified date: February 2020
• Source: Pharmacosmos A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The trial was designed to evaluate the incidence of unintended hypophosphatemia (low level of phosphate in the blood) in subjects with iron deficiency anaemia (IDA).

Description:

This trial was designed to evaluate the effect of IV iron isomaltoside/ferric derisomaltose compared with IV ferric carboxymaltose on s-phosphate in subjects with IDA caused by different etiologies.

The subjects received either a single intravenous (IV) dose of iron isomaltoside/ferric derisomaltose (1000 mg at baseline) or two IV doses of ferric carboxymaltose (one dose 750 mg at baseline and a second dose 750 mg on day 7; cumulative dose: 1500 mg). The study subjects were monitored for up to 35 days from baseline.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 123
• Est. completion date: June 19, 2018
• Est. primary completion date: June 19, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria include:

• Subjects diagnosed with IDA, caused by different aetiologies

• Haemoglobin (Hb) = 11 g/dL

• Body weight > 50 kg

• Serum ferritin (S-ferritin) < 100 ng/mL

• Estimated glomerular filtration rate (eGFR) = 65 mL/min/1.73 m2

• Serum phosphate (S-phosphate) > 2.5 mg/dL

• Intolerance or unresponsiveness to oral iron

• Willingness to participate and signing the Informed Consent Form (ICF)

Exclusion Criteria include:

• Acute bleeding > 500 mL within 72 hours

• Anaemia predominantly caused by factors other than IDA

• Hemochromatosis or other iron storage disorders

• Previous serious hypersensitivity reactions to any IV iron compounds

• Treatment with IV iron within the last 30 days prior to screening

• Treatment with erythropoietin or erythropoietin-stimulation agents

• Red blood cell transfusion, radiotherapy, and/or chemotherapy

• Received an investigational drug within the last 30 days prior to screening

• Planned surgical procedure within the trial period

• Hepatic enzymes > 3 times upper limit of normal

• Surgery under anaesthetic within the last 30 days prior to screening

• Any non-viral infection within the last 30 days prior to screening

• Alcohol or drug abuse within the past 6 months

• Vitamin D deficiency

• Untreated hyperparathyroidism

• Kidney transplantation

• Active malignant disease, disease-free for less than 5 years

• History of a psychological illness or seizures

• Pregnant or nursing women.

Related Conditions & MeSH terms

• Anemia
• Anemia, Iron-Deficiency
• Deficiency Diseases
• Hypophosphatemia
• Iron Deficiency Anaemia
• Iron Deficiency Anemia

Intervention

Drug:
• Iron isomaltoside/ferric derisomaltose
Iron isomaltoside/ferric derisomaltose (Monofer®/Monoferric®; 100 mg/mL) was the test product in this trial. The dose of iron isomaltoside/ferric derisomaltose for the individual subject was a single IV infusion of 1000 mg (10 mL containing 1000 mg iron isomaltoside/ferric derisomaltose diluted in 100 mL 0.9 % sodium chloride), given over approximately 20 minutes (50 mg iron/min) at baseline (cumulative dose: 1000 mg).
• Ferric carboxymaltose
Ferric carboxymaltose (Injectafer®; 50 mg/mL) was the comparator in this trial. Ferric carboxymaltose was administered as 750 mg, infused over at least 15 minutes at baseline and on day 7 (cumulative dose: 1500 mg).

Locations

Country	Name	City	State
United States	Pharmacosmos Investigational Site	Clearwater	Florida
United States	Pharmacosmos Investigational Site	Houston	Texas
United States	Pharmacosmos Investigational Site	Indianapolis	Indiana
United States	Pharmacosmos Investigational Site	Lancaster	Pennsylvania
United States	Pharmacosmos Investigational Site	Leesburg	Virginia
United States	Pharmacosmos Investigational Site	Los Angeles	California
United States	Pharmacosmos Investigational Site	Metairie	Louisiana
United States	Pharmacosmos Investigational Site	Miami	Florida
United States	Pharmacosmos Investigational Site	Miami	Florida
United States	Pharmacosmos Investigational Site	Miami	Florida
United States	Pharmacosmos Investigational Site 1	Miami	Florida
United States	Pharmacosmos Investigational Site 2	Miami	Florida
United States	Pharmacosmos Investigational Site	Orem	Utah
United States	Pharmacosmos Investigational Site	Sacramento	California
United States	Pharmacosmos Investigational Site	Santa Ana	California
United States	Pharmacosmos Investigational Site	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Pharmacosmos A/S

Country where clinical trial is conducted

United States, 

References & Publications (1)

Wolf M, Rubin J, Achebe M, Econs M, Peacock M, Imel E, Thomsen L, Carpenter T, Weber T, Zoller H. Effects of iron isomaltoside versus ferric carboxymaltose on hormonal control of phosphate homeostasis: The PHOSPHARE-IDA04/05 randomized controlled trials.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Hypophosphatemia (S-phosphate Level <2 mg/dL)	Safety; The incidence of hypophosphatemia (defined as s-phosphate <2 mg/dL) at any time from baseline up to day 35.	Baseline to day 35
Secondary	Time With Hypophosphatemia ( S-phosphate Level <2.0 mg/dL)	Safety; Time with hypophosphatemia (i.e. time with s-phosphate level < 2.0 mg/dL) from baseline up to day 35.; The time with hypophosphatemia was calculated as the actual number of days from the first day where s-phosphate was <2 mg/dL until the first day when s-phosphate was =2 mg/dL. If the subject did not reach s-phosphate =2 mg/dL, the subject was regarded as censored on day 35.	Baseline to day 35
Secondary	Proportion of Subjects With Hypophosphatemia on Day 35 ( S-phosphate Level <2.0 mg/dL)	Safety; Evaluate the proportion of subjects with hypophosphatemia (s-phosphate level <2.0 mg/dL) on day 35.	Baseline to day 35
Secondary	Absolute [?] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35	Safety; Absolute [?] changes in s-phosphate from baseline to day 1, 7, 8, 14, 21, and 35.	Baseline, days 1, 7, 8, 14, 21, and 35
Secondary	Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35	Safety; Relative [%] changes in s-phosphate from baseline to day 1, 7, 8, 14, 21, and 35.	Baseline, days 1, 7, 8, 14, 21, and 35
Secondary	Change From Baseline in Fractional Phosphate Urinary Excretion	Safety; Change in absolute fractional phosphate urinary excretion from baseline to days 1, 7, 8, 14, 21, and 35.; Fractional excretion of phosphate (FEPi) is calculated as ([phosphate in urine X creatinine in serum]/[phosphate in serum X creatinine in urine]) X 100, and the unit is %.	Baseline, days 1, 7, 8, 14, 21, and 35
Secondary	Change in Concentration of (Intact) Fibroblast Growth Factor 23 (iFGF23) From Baseline to Day 1, 7, 8, 14, 21, and 35	Safety; Change in concentration of (Intact) Fibroblast Growth Factor 23 (iFGF23) from baseline to day 1, 7, 8, 14, 21, and 35.	Baseline, days 1, 7, 8, 14, 21, and 35
Secondary	Change in C-terminal Fibroblast Growth Factor 23 (cFGF23) From Baseline to Days 1, 7, 8, 14, 21, and 35	Safety; Change in C-terminal Fibroblast Growth Factor 23 (cFGF23) from baseline to days 1, 7, 8, 14, 21, and 35.	Baseline, days 1, 7, 8, 14, 21, and 35
Secondary	Change in Vitamin 25-Hydroxyvitamin D (Vitamin D 25) From Baseline to Days 1, 7, 8, 14, 21, and 35	Safety; Change in vitamin 25-Hydroxyvitamin D (vitamin D 25) from baseline to days 1, 7, 8, 14, 21, and 35.	Baseline, days 1, 7, 8, 14, 21, and 35
Secondary	Change in 1,25-Dihydroxyvitamin D (Vitamin D 1.25) From Baseline to Days 1, 7, 8, 14, 21, and 35	Safety; Change in 1,25-Dihydroxyvitamin D (vitamin D 1.25) from baseline to days 1, 7, 8, 14, 21, and 35.	Baseline, days 1, 7, 8, 14, 21, and 35
Secondary	Change in 24,25-Dihydroxyvitamin D (Vitamin D 24.25) From Baseline to Days 1, 7, 8, 14, 21, and 35	Safety; Change in 24,25-Dihydroxyvitamin D (vitamin D 24.25) from baseline to days 1, 7, 8, 14, 21, and 35	Baseline, days 1, 7, 8, 14, 21, and 35
Secondary	Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35	Safety; Change in intact Parathyroid hormone (PTH) from baseline to days 1, 7, 8, 14, 21, and 35.	Baseline, days 1, 7, 8, 14, 21, and 35
Secondary	Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35	Safety; Change in ionized calcium from baseline to days 1, 7, 8, 14, 21, and 35.	Baseline, days 1, 7, 8, 14, 21, and 35
Secondary	Incidence of Protocol-defined Serious or Severe Hypersensitivity Reactions	Safety; For this endpoint, the number of participants with serious or severe hypersensitivity reactions were evaluated.	Baseline to day 35
Secondary	Change in Hemoglobin (Hb) Per Gram Iron From Baseline to Days 1, 7, 8, 14, 21, and 35	Efficacy; Change in hemoglobin (Hb) per gram iron from baseline to days 1, 7, 8, 14, 21, and 35.	Baseline, days 1, 7, 8, 14, 21, and 35
Secondary	Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35	Efficacy; Change in s-ferritin from baseline to days 1, 7, 8, 14, 21, and 35.	Baseline, days 1, 7, 8, 14, 21, and 35
Secondary	Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35	Efficacy; Change in Transferrin Saturation (TSAT) from baseline to days 1, 7, 8, 14, 21, and 35.; TSAT is the value of serum iron divided by the total iron-binding capacity and the unit is %, which referrers to % of iron-binding sites of transferrin being occupied by iron.	Baseline, days 1, 7, 8, 14, 21, and 35

External Links

•   Effects of iron isomaltoside/ferric derisomaltose versus ferric carboxymaltose on hormonal control of phosphate homeostasis