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

Primary Purpose

Iron Deficiency Anaemia, Iron Deficiency Anemia

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Iron isomaltoside/ferric derisomaltose
Ferric carboxymaltose
Sponsored by
Pharmacosmos A/S
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Iron Deficiency Anaemia focused on measuring Iron Deficiency Anaemia, Iron Deficiency Anemia, IDA, Intravenous iron replacement therapy, Iron deficiency, Iron isomaltoside, Ferric derisomaltose, Monofer, Monoferric, Monover, Monofar, Monoferro, Hypophosphatemia, Ferric carboxymaltose

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Pharmacosmos Investigational Site
  • Pharmacosmos Investigational Site
  • Pharmacosmos Investigational Site
  • Pharmacosmos Investigational Site
  • Pharmacosmos Investigational Site
  • Pharmacosmos Investigational Site 1
  • Pharmacosmos Investigational Site 2
  • Pharmacosmos Investigational Site
  • Pharmacosmos Investigational Site
  • Pharmacosmos Investigational Site
  • Pharmacosmos Investigational Site
  • Pharmacosmos Investigational Site
  • Pharmacosmos Investigational Site
  • Pharmacosmos Investigational Site
  • Pharmacosmos Investigational Site
  • Pharmacosmos Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Iron isomaltoside/ferric derisomaltose

Ferric carboxymaltose

Arm Description

Administered IV

Administered IV

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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 %.
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.
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.
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.
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.
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
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.
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.
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.
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.
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.
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.

Full Information

First Posted
July 6, 2017
Last Updated
February 24, 2020
Sponsor
Pharmacosmos A/S
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1. Study Identification

Unique Protocol Identification Number
NCT03238911
Brief Title
Incidence of Hypophosphatemia After Treatment With Iron Isomaltoside/Ferric Derisomaltose vs Ferric Carboxymaltose in Subjects With Iron Deficiency Anaemia
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)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
October 24, 2017 (Actual)
Primary Completion Date
June 19, 2018 (Actual)
Study Completion Date
June 19, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pharmacosmos A/S

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief 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).
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Iron Deficiency Anaemia, Iron Deficiency Anemia
Keywords
Iron Deficiency Anaemia, Iron Deficiency Anemia, IDA, Intravenous iron replacement therapy, Iron deficiency, Iron isomaltoside, Ferric derisomaltose, Monofer, Monoferric, Monover, Monofar, Monoferro, Hypophosphatemia, Ferric carboxymaltose

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
123 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Iron isomaltoside/ferric derisomaltose
Arm Type
Experimental
Arm Description
Administered IV
Arm Title
Ferric carboxymaltose
Arm Type
Active Comparator
Arm Description
Administered IV
Intervention Type
Drug
Intervention Name(s)
Iron isomaltoside/ferric derisomaltose
Other Intervention Name(s)
Monofer®, Monoferric®, Monover®, Monofar®, Monoferro®
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Ferric carboxymaltose
Other Intervention Name(s)
Injectafer®, Ferinject®
Intervention Description
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).
Primary Outcome Measure Information:
Title
Incidence of Hypophosphatemia (S-phosphate Level <2 mg/dL)
Description
Safety The incidence of hypophosphatemia (defined as s-phosphate <2 mg/dL) at any time from baseline up to day 35.
Time Frame
Baseline to day 35
Secondary Outcome Measure Information:
Title
Time With Hypophosphatemia ( S-phosphate Level <2.0 mg/dL)
Description
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.
Time Frame
Baseline to day 35
Title
Proportion of Subjects With Hypophosphatemia on Day 35 ( S-phosphate Level <2.0 mg/dL)
Description
Safety Evaluate the proportion of subjects with hypophosphatemia (s-phosphate level <2.0 mg/dL) on day 35.
Time Frame
Baseline to day 35
Title
Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35
Description
Safety Absolute [∆] changes in s-phosphate from baseline to day 1, 7, 8, 14, 21, and 35.
Time Frame
Baseline, days 1, 7, 8, 14, 21, and 35
Title
Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35
Description
Safety Relative [%] changes in s-phosphate from baseline to day 1, 7, 8, 14, 21, and 35.
Time Frame
Baseline, days 1, 7, 8, 14, 21, and 35
Title
Change From Baseline in Fractional Phosphate Urinary Excretion
Description
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 %.
Time Frame
Baseline, days 1, 7, 8, 14, 21, and 35
Title
Change in Concentration of (Intact) Fibroblast Growth Factor 23 (iFGF23) From Baseline to Day 1, 7, 8, 14, 21, and 35
Description
Safety Change in concentration of (Intact) Fibroblast Growth Factor 23 (iFGF23) from baseline to day 1, 7, 8, 14, 21, and 35.
Time Frame
Baseline, days 1, 7, 8, 14, 21, and 35
Title
Change in C-terminal Fibroblast Growth Factor 23 (cFGF23) From Baseline to Days 1, 7, 8, 14, 21, and 35
Description
Safety Change in C-terminal Fibroblast Growth Factor 23 (cFGF23) from baseline to days 1, 7, 8, 14, 21, and 35.
Time Frame
Baseline, days 1, 7, 8, 14, 21, and 35
Title
Change in Vitamin 25-Hydroxyvitamin D (Vitamin D 25) From Baseline to Days 1, 7, 8, 14, 21, and 35
Description
Safety Change in vitamin 25-Hydroxyvitamin D (vitamin D 25) from baseline to days 1, 7, 8, 14, 21, and 35.
Time Frame
Baseline, days 1, 7, 8, 14, 21, and 35
Title
Change in 1,25-Dihydroxyvitamin D (Vitamin D 1.25) From Baseline to Days 1, 7, 8, 14, 21, and 35
Description
Safety Change in 1,25-Dihydroxyvitamin D (vitamin D 1.25) from baseline to days 1, 7, 8, 14, 21, and 35.
Time Frame
Baseline, days 1, 7, 8, 14, 21, and 35
Title
Change in 24,25-Dihydroxyvitamin D (Vitamin D 24.25) From Baseline to Days 1, 7, 8, 14, 21, and 35
Description
Safety Change in 24,25-Dihydroxyvitamin D (vitamin D 24.25) from baseline to days 1, 7, 8, 14, 21, and 35
Time Frame
Baseline, days 1, 7, 8, 14, 21, and 35
Title
Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35
Description
Safety Change in intact Parathyroid hormone (PTH) from baseline to days 1, 7, 8, 14, 21, and 35.
Time Frame
Baseline, days 1, 7, 8, 14, 21, and 35
Title
Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35
Description
Safety Change in ionized calcium from baseline to days 1, 7, 8, 14, 21, and 35.
Time Frame
Baseline, days 1, 7, 8, 14, 21, and 35
Title
Incidence of Protocol-defined Serious or Severe Hypersensitivity Reactions
Description
Safety For this endpoint, the number of participants with serious or severe hypersensitivity reactions were evaluated.
Time Frame
Baseline to day 35
Title
Change in Hemoglobin (Hb) Per Gram Iron From Baseline to Days 1, 7, 8, 14, 21, and 35
Description
Efficacy Change in hemoglobin (Hb) per gram iron from baseline to days 1, 7, 8, 14, 21, and 35.
Time Frame
Baseline, days 1, 7, 8, 14, 21, and 35
Title
Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35
Description
Efficacy Change in s-ferritin from baseline to days 1, 7, 8, 14, 21, and 35.
Time Frame
Baseline, days 1, 7, 8, 14, 21, and 35
Title
Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35
Description
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.
Time Frame
Baseline, days 1, 7, 8, 14, 21, and 35

10. Eligibility

Sex
All
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pharmacosmos A/S Clinical and Non-clinical Research
Organizational Affiliation
Pharmacosmos A/S
Official's Role
Study Director
Facility Information:
Facility Name
Pharmacosmos Investigational Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90036
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Sacramento
State/Province
California
ZIP/Postal Code
95831
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Santa Ana
State/Province
California
ZIP/Postal Code
92704
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33759
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33125
Country
United States
Facility Name
Pharmacosmos Investigational Site 1
City
Miami
State/Province
Florida
ZIP/Postal Code
33126
Country
United States
Facility Name
Pharmacosmos Investigational Site 2
City
Miami
State/Province
Florida
ZIP/Postal Code
33126
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33144
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67206
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Metairie
State/Province
Louisiana
ZIP/Postal Code
70001
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Lancaster
State/Province
Pennsylvania
ZIP/Postal Code
17605
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77024
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Orem
State/Province
Utah
ZIP/Postal Code
84058
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Leesburg
State/Province
Virginia
ZIP/Postal Code
20176
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
Citation
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. Journal of the Endocrine Society, Volume 3, Issue Supplement_1, April-May 2019, OR13-3, https://doi.org/10.1210/js.2019-OR13-3
Results Reference
result
PubMed Identifier
32016310
Citation
Wolf M, Rubin J, Achebe M, Econs MJ, Peacock M, Imel EA, Thomsen LL, Carpenter TO, Weber T, Brandenburg V, Zoller H. Effects of Iron Isomaltoside vs Ferric Carboxymaltose on Hypophosphatemia in Iron-Deficiency Anemia: Two Randomized Clinical Trials. JAMA. 2020 Feb 4;323(5):432-443. doi: 10.1001/jama.2019.22450.
Results Reference
derived
Links:
URL
https://doi.org/10.1210/js.2019-OR13-3
Description
Effects of iron isomaltoside/ferric derisomaltose versus ferric carboxymaltose on hormonal control of phosphate homeostasis

Learn more about this trial

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

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