Clinical trial NCT03237065: Incidence of Hypophosphatemia After Treatment With Iron Isomaltoside/Ferric Derisomaltose or 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-05)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Iron Deficiency Anaemia
Iron Deficiency Anemia
Keywords: Iron Deficiency Anaemia
Iron Deficiency Anemia
IDA
Iron deficiency
Intravenous iron replacement therapy
Iron isomaltoside
Ferric derisomaltose
Hypophosphatemia
Ferric carboxymaltose
Monofer
Monoferric
Monover
Monofar
Monoferro
Lead sponsor: Pharmacosmos A/S
Sponsor class: INDUSTRY
First posted: 2017-08-02
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion criteria include:

* Subjects having 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.

Primary outcomes:
measure: Incidence of Hypophosphatemia (S-phosphate Level <2 mg/dL)
timeFrame: Baseline to day 35
Secondary outcomes:
measure: Time With Hypophosphatemia ( S-phosphate Level <2.0 mg/dL)
timeFrame: Baseline to day 35
measure: Proportion of Subjects With Hypophosphatemia on Day 35 (S-phosphate Level <2.0 mg/dL)
timeFrame: Baseline to day 35
measure: Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35
timeFrame: Baseline, days 1, 7, 8, 14, 21, and 35
measure: Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35
timeFrame: Baseline, days 1, 7, 8, 14, 21, and 35
measure: Change From Baseline in Fractional Phosphate Urinary Excretion
timeFrame: Baseline, days 1, 7, 8, 14, 21, and 35
measure: Change in Concentration of (Intact) Fibroblast Growth Factor 23 (iFGF23) From Baseline to Day 1, 7, 8, 14, 21, and 35
timeFrame: Baseline, days 1, 7, 8, 14, 21, and 35
measure: Change in C-terminal Fibroblast Growth Factor 23 (cFGF23) From Baseline to Days 1, 7, 8, 14, 21, and 35
timeFrame: Baseline, days 1, 7, 8, 14, 21, and 35
measure: Change in Vitamin 25-Hydroxyvitamin D (Vitamin D 25) From Baseline to Days 1, 7, 8, 14, 21, and 35
timeFrame: Baseline, days 1, 7, 8, 14, 21, and 35
measure: Change in 1,25-Dihydroxyvitamin D (Vitamin D 1.25) From Baseline to Days 1, 7, 8, 14, 21, and 35
timeFrame: Baseline, days 1, 7, 8, 14, 21, and 35
measure: Change in 24,25-Dihydroxyvitamin D (Vitamin D 24.25) From Baseline to Days 1, 7, 8, 14, 21, and 35
timeFrame: Baseline, days 1, 7, 8, 14, 21, and 35
measure: Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35
timeFrame: Baseline, days 1, 7, 8, 14, 21, and 35
measure: Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35
timeFrame: Baseline, days 1, 7, 8, 14, 21, and 35
measure: Incidence of Protocol-defined Serious or Severe Hypersensitivity Reactions
timeFrame: Baseline to day 35
measure: Change in Hemoglobin (Hb) Per Gram Iron From Baseline to Days 1, 7, 8, 14, 21, and 35
timeFrame: Baseline, days 1, 7, 8, 14, 21, and 35
measure: Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35
timeFrame: Baseline, days 1, 7, 8, 14, 21, and 35
measure: Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35
timeFrame: Baseline, days 1, 7, 8, 14, 21, and 35
Other outcomes:
Locations:
city: Muscle Shoals
country: United States
facility: Pharmacosmos Investigational Site
state: Alabama
city: Doral
country: United States
facility: Pharmacosmos Investigational Site
state: Florida
city: Miami Lakes
country: United States
facility: Pharmacosmos Investigational Site
state: Florida
city: Miami
country: United States
facility: Pharmacosmos Investigational Site
state: Florida
city: Miami
country: United States
facility: Pharmacosmos Investigational Site
state: Florida
city: Orlando
country: United States
facility: Pharmacosmos Investigational Site
state: Florida
city: Idaho Falls
country: United States
facility: Pharmacosmos Investigational Site
state: Idaho
city: Oak Brook
country: United States
facility: Pharmacosmos Investigational Site
state: Illinois
city: Flint
country: United States
facility: Pharmacosmos investigational Site
state: Michigan
city: Saint Louis
country: United States
facility: Pharmacosmos Investigational Site
state: Missouri
city: Las Vegas
country: United States
facility: Pharmacosmos Investigational Site
state: Nevada
city: Albuquerque
country: United States
facility: Pharmacosmos Investigational Site
state: New Mexico
city: Morehead City
country: United States
facility: Pharmacosmos Investigational Site
state: North Carolina
city: Raleigh
country: United States
facility: Pharmacosmos Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Pharmacosmos Investigational Site
state: North Carolina
Study officials:
affiliation: Pharmacosmos A/S
name: Pharmacosmos A/S Clinical and Non-clinical Research
role: STUDY_DIRECTOR
References:
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
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.