Iron Deficiency Anaemia, Iron Deficiency Anemia
Conditions
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
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.
Interventions
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).
DRUGFerric carboxymaltose
Ferric carboxymaltose (Injectafer®; 50 mg/mL) was the comparator in this trial. The dose of ferric carboxymaltose for the individual subject was 750 mg, infused over at least 15 minutes at baseline and on day 7 (cumulative dose: 1500 mg).
Sponsors
Pharmacosmos A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Hypophosphatemia (S-phosphate Level <2 mg/dL) | Baseline to day 35 | Safety The incidence of hypophosphatemia (defined as s-phosphate \<2 mg/dL) at any time from baseline up to day 35. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects With Hypophosphatemia on Day 35 (S-phosphate Level <2.0 mg/dL) | Baseline to day 35 | 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 | Baseline, days 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 | Baseline, days 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 | Baseline, days 1, 7, 8, 14, 21, and 35 | 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 | Baseline, days 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 | Baseline, 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 | Baseline, 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. |
| Time With Hypophosphatemia ( S-phosphate Level <2.0 mg/dL) | Baseline to day 35 | 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. |
| 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 | 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 | Baseline, 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 | Baseline, 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 | Baseline to day 35 | 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 | Baseline, 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 | Baseline, 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 | Baseline, 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. |
| 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 | Safety Change in 1,25-Dihydroxyvitamin D (vitamin D 1.25) from baseline to days 1, 7, 8, 14, 21, and 35. |
Countries
United States
Participant flow
Recruitment details
A total of 244 subjects were screened and 122 subjects were randomised into the trial.
Participants by arm
| Arm | Count |
|---|---|
| Iron Isomaltoside/Ferric Derisomaltose Iron isomaltoside/ferric derisomaltose, administered IV | 62 |
| Ferric Carboxymaltose Ferric carboxymaltose, administered IV | 57 |
| Total | 119 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Unable to obtain venous access | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 0 |
Baseline characteristics
| Characteristic | Iron Isomaltoside/Ferric Derisomaltose | Ferric Carboxymaltose | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 3 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 57 Participants | 54 Participants | 111 Participants |
| Age, Continuous | 42.2 years STANDARD_DEVIATION 12.9 | 43.1 years STANDARD_DEVIATION 11.5 | 42.6 years STANDARD_DEVIATION 12.2 |
| Current smoker No | 53 Participants | 51 Participants | 104 Participants |
| Current smoker Yes | 9 Participants | 6 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants | 23 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 34 Participants | 73 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Iron Deficiency Anaemia (IDA) due to gynaecological blood loss No | 18 Participants | 18 Participants | 36 Participants |
| Iron Deficiency Anaemia (IDA) due to gynaecological blood loss Yes | 44 Participants | 39 Participants | 83 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Irish/Black | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Mayan Indian/Black | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 32 Participants | 27 Participants | 59 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 28 Participants | 29 Participants | 57 Participants |
| Region of Enrollment United States | 62 participants | 57 participants | 119 participants |
| Sex: Female, Male Female | 58 Participants | 54 Participants | 112 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 7 Participants |
| S-phosphate level at screening <3.5 mg/dL | 35 Participants | 32 Participants | 67 Participants |
| S-phosphate level at screening ≥3.5 mg/dL | 27 Participants | 25 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 62 | 0 / 57 |
| other Total, other adverse events | 13 / 62 | 25 / 57 |
| serious Total, serious adverse events | 0 / 62 | 1 / 57 |
Outcome results
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.
Time frame: Baseline to day 35
Population: Safety analysis set: included all subjects who received at least one dose of the investigational product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Incidence of Hypophosphatemia (S-phosphate Level <2 mg/dL) | 5 Participants |
| Ferric Carboxymaltose | Incidence of Hypophosphatemia (S-phosphate Level <2 mg/dL) | 42 Participants |
Comparison: Power:~The power was set to 80%. Assuming incidences of 15% for iron isomaltoside/ferric derisomaltose and 40% for ferric carboxymaltose, 49 subjects in each treatment group were required to detect a difference between the treatment groups. The significance level was set to 5%.p-value: <0.000195% CI: [-76.6, -49.8]Cochran-Mantel-Haenszel
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.
Time frame: Baseline, days 1, 7, 8, 14, 21, and 35
Population: Safety analysis set: included all subjects who received at least one dose of the investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 1 | 0.19 mg/dL | Standard Deviation 0.57 |
| Iron Isomaltoside/Ferric Derisomaltose | Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 7 | -0.44 mg/dL | Standard Deviation 0.57 |
| Iron Isomaltoside/Ferric Derisomaltose | Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 8 | -0.46 mg/dL | Standard Deviation 0.64 |
| Iron Isomaltoside/Ferric Derisomaltose | Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 14 | -0.32 mg/dL | Standard Deviation 0.6 |
| Iron Isomaltoside/Ferric Derisomaltose | Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 21 | -0.09 mg/dL | Standard Deviation 0.66 |
| Iron Isomaltoside/Ferric Derisomaltose | Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 35 | 0.11 mg/dL | Standard Deviation 0.49 |
| Ferric Carboxymaltose | Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 21 | -1.27 mg/dL | Standard Deviation 0.88 |
| Ferric Carboxymaltose | Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 1 | -0.18 mg/dL | Standard Deviation 0.5 |
| Ferric Carboxymaltose | Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 14 | -1.47 mg/dL | Standard Deviation 0.8 |
| Ferric Carboxymaltose | Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 7 | -0.89 mg/dL | Standard Deviation 0.74 |
| Ferric Carboxymaltose | Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 35 | -0.99 mg/dL | Standard Deviation 0.96 |
| Ferric Carboxymaltose | Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 8 | -1.14 mg/dL | Standard Deviation 0.74 |
Comparison: Day 1~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: <0.000195% CI: [0.3, 0.62]Mixed model for repeated measures
Comparison: Day 7~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: <0.000195% CI: [0.32, 0.76]Mixed model for repeated measures
Comparison: Day 8~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: <0.000195% CI: [0.49, 0.96]Mixed model for repeated measures
Comparison: Day 14~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: <0.000195% CI: [0.99, 1.46]Mixed model for repeated measures
Comparison: Day 21~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: <0.000195% CI: [0.98, 1.51]Mixed model for repeated measures
Comparison: Day 35~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: <0.000195% CI: [0.91, 1.43]Mixed model for repeated measures
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 %.
Time frame: Baseline, days 1, 7, 8, 14, 21, and 35
Population: Safety analysis set: included all subjects who received at least one dose of the investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Change From Baseline in Fractional Phosphate Urinary Excretion | Day 1 | 0.54 percentage excreted | Standard Deviation 4.26 |
| Iron Isomaltoside/Ferric Derisomaltose | Change From Baseline in Fractional Phosphate Urinary Excretion | Day 7 | 1.33 percentage excreted | Standard Deviation 5.04 |
| Iron Isomaltoside/Ferric Derisomaltose | Change From Baseline in Fractional Phosphate Urinary Excretion | Day 8 | 2.29 percentage excreted | Standard Deviation 5.18 |
| Iron Isomaltoside/Ferric Derisomaltose | Change From Baseline in Fractional Phosphate Urinary Excretion | Day 14 | -0.11 percentage excreted | Standard Deviation 4.59 |
| Iron Isomaltoside/Ferric Derisomaltose | Change From Baseline in Fractional Phosphate Urinary Excretion | Day 21 | -0.04 percentage excreted | Standard Deviation 4.18 |
| Iron Isomaltoside/Ferric Derisomaltose | Change From Baseline in Fractional Phosphate Urinary Excretion | Day 35 | 1.07 percentage excreted | Standard Deviation 4.96 |
| Ferric Carboxymaltose | Change From Baseline in Fractional Phosphate Urinary Excretion | Day 21 | 6.42 percentage excreted | Standard Deviation 6.7 |
| Ferric Carboxymaltose | Change From Baseline in Fractional Phosphate Urinary Excretion | Day 1 | 1.77 percentage excreted | Standard Deviation 5.15 |
| Ferric Carboxymaltose | Change From Baseline in Fractional Phosphate Urinary Excretion | Day 14 | 8.50 percentage excreted | Standard Deviation 8.95 |
| Ferric Carboxymaltose | Change From Baseline in Fractional Phosphate Urinary Excretion | Day 7 | 4.90 percentage excreted | Standard Deviation 6.48 |
| Ferric Carboxymaltose | Change From Baseline in Fractional Phosphate Urinary Excretion | Day 35 | 5.21 percentage excreted | Standard Deviation 7.74 |
| Ferric Carboxymaltose | Change From Baseline in Fractional Phosphate Urinary Excretion | Day 8 | 6.05 percentage excreted | Standard Deviation 5.71 |
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.
Time frame: Baseline, days 1, 7, 8, 14, 21, and 35
Population: Safety analysis set: included all subjects who received at least one dose of the investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Change in 1,25-Dihydroxyvitamin D (Vitamin D 1.25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 1 | 5.89 pg/mL | Standard Deviation 10.6 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in 1,25-Dihydroxyvitamin D (Vitamin D 1.25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | -16.78 pg/mL | Standard Deviation 17.81 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in 1,25-Dihydroxyvitamin D (Vitamin D 1.25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | -12.93 pg/mL | Standard Deviation 17.81 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in 1,25-Dihydroxyvitamin D (Vitamin D 1.25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | -0.40 pg/mL | Standard Deviation 16.54 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in 1,25-Dihydroxyvitamin D (Vitamin D 1.25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | 0.33 pg/mL | Standard Deviation 16.11 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in 1,25-Dihydroxyvitamin D (Vitamin D 1.25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | 0.05 pg/mL | Standard Deviation 15.33 |
| Ferric Carboxymaltose | Change in 1,25-Dihydroxyvitamin D (Vitamin D 1.25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | -24.02 pg/mL | Standard Deviation 29 |
| Ferric Carboxymaltose | Change in 1,25-Dihydroxyvitamin D (Vitamin D 1.25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 1 | -16.97 pg/mL | Standard Deviation 13.29 |
| Ferric Carboxymaltose | Change in 1,25-Dihydroxyvitamin D (Vitamin D 1.25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | -36.14 pg/mL | Standard Deviation 26.4 |
| Ferric Carboxymaltose | Change in 1,25-Dihydroxyvitamin D (Vitamin D 1.25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | -23.92 pg/mL | Standard Deviation 30.68 |
| Ferric Carboxymaltose | Change in 1,25-Dihydroxyvitamin D (Vitamin D 1.25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | -12.67 pg/mL | Standard Deviation 25.01 |
| Ferric Carboxymaltose | Change in 1,25-Dihydroxyvitamin D (Vitamin D 1.25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | -35.59 pg/mL | Standard Deviation 26.05 |
Comparison: Day 1~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: <0.000195% CI: [17.66, 25.95]Mixed model for repeated measures
Comparison: Day 7~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.292395% CI: [-4.05, 13.33]Mixed model for repeated measures
Comparison: Day 8~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: <0.000195% CI: [12.37, 26.74]Mixed model for repeated measures
Comparison: Day 14~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: <0.000195% CI: [25.96, 40.14]Mixed model for repeated measures
Comparison: Day 21~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: <0.000195% CI: [14.2, 29.43]Mixed model for repeated measures
Comparison: Day 35~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.02595% CI: [1.16, 16.9]Mixed model for repeated measures
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.
Time frame: Baseline, days 1, 7, 8, 14, 21, and 35
Population: Safety analysis set: included all subjects who received at least one dose of the investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Change in 24,25-Dihydroxyvitamin D (Vitamin D 24.25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 1 | 0.02 ng/mL | Standard Deviation 0.45 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in 24,25-Dihydroxyvitamin D (Vitamin D 24.25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | 0.31 ng/mL | Standard Deviation 0.84 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in 24,25-Dihydroxyvitamin D (Vitamin D 24.25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | 0.22 ng/mL | Standard Deviation 0.84 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in 24,25-Dihydroxyvitamin D (Vitamin D 24.25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | 0.10 ng/mL | Standard Deviation 0.75 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in 24,25-Dihydroxyvitamin D (Vitamin D 24.25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | 0.01 ng/mL | Standard Deviation 0.55 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in 24,25-Dihydroxyvitamin D (Vitamin D 24.25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | 0.00 ng/mL | Standard Deviation 0.77 |
| Ferric Carboxymaltose | Change in 24,25-Dihydroxyvitamin D (Vitamin D 24.25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | 0.50 ng/mL | Standard Deviation 0.76 |
| Ferric Carboxymaltose | Change in 24,25-Dihydroxyvitamin D (Vitamin D 24.25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 1 | 0.07 ng/mL | Standard Deviation 0.32 |
| Ferric Carboxymaltose | Change in 24,25-Dihydroxyvitamin D (Vitamin D 24.25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | 0.55 ng/mL | Standard Deviation 0.68 |
| Ferric Carboxymaltose | Change in 24,25-Dihydroxyvitamin D (Vitamin D 24.25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | 0.26 ng/mL | Standard Deviation 0.49 |
| Ferric Carboxymaltose | Change in 24,25-Dihydroxyvitamin D (Vitamin D 24.25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | 0.23 ng/mL | Standard Deviation 0.65 |
| Ferric Carboxymaltose | Change in 24,25-Dihydroxyvitamin D (Vitamin D 24.25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | 0.38 ng/mL | Standard Deviation 0.46 |
Comparison: Day 1~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.513495% CI: [-0.22, 0.11]Mixed model for repeated measures
Comparison: Day 7~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.757995% CI: [-0.24, 0.32]Mixed model for repeated measures
Comparison: Day 8~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.316995% CI: [-0.41, 0.14]Mixed model for repeated measures
Comparison: Day 14~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.001895% CI: [-0.76, -0.18]Mixed model for repeated measures
Comparison: Day 21~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.000395% CI: [-0.77, -0.24]Mixed model for repeated measures
Comparison: Day 35~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.106395% CI: [-0.5, 0.05]Mixed model for repeated measures
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.
Time frame: Baseline, days 1, 7, 8, 14, 21, and 35
Population: Safety analysis set: included all subjects who received at least one dose of the investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Change in Concentration of (Intact) Fibroblast Growth Factor 23 (iFGF23) From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 1 | -4.18 pg/mL | Standard Deviation 18.2 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Concentration of (Intact) Fibroblast Growth Factor 23 (iFGF23) From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 7 | 16.97 pg/mL | Standard Deviation 45.44 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Concentration of (Intact) Fibroblast Growth Factor 23 (iFGF23) From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 8 | 8.09 pg/mL | Standard Deviation 36.06 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Concentration of (Intact) Fibroblast Growth Factor 23 (iFGF23) From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 14 | -5.35 pg/mL | Standard Deviation 24.09 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Concentration of (Intact) Fibroblast Growth Factor 23 (iFGF23) From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 21 | -9.13 pg/mL | Standard Deviation 28.95 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Concentration of (Intact) Fibroblast Growth Factor 23 (iFGF23) From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 35 | -9.17 pg/mL | Standard Deviation 23.87 |
| Ferric Carboxymaltose | Change in Concentration of (Intact) Fibroblast Growth Factor 23 (iFGF23) From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 21 | 54.49 pg/mL | Standard Deviation 74.78 |
| Ferric Carboxymaltose | Change in Concentration of (Intact) Fibroblast Growth Factor 23 (iFGF23) From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 1 | 93.38 pg/mL | Standard Deviation 88.21 |
| Ferric Carboxymaltose | Change in Concentration of (Intact) Fibroblast Growth Factor 23 (iFGF23) From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 14 | 74.07 pg/mL | Standard Deviation 90.35 |
| Ferric Carboxymaltose | Change in Concentration of (Intact) Fibroblast Growth Factor 23 (iFGF23) From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 7 | 33.60 pg/mL | Standard Deviation 57.37 |
| Ferric Carboxymaltose | Change in Concentration of (Intact) Fibroblast Growth Factor 23 (iFGF23) From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 35 | 10.52 pg/mL | Standard Deviation 39.94 |
| Ferric Carboxymaltose | Change in Concentration of (Intact) Fibroblast Growth Factor 23 (iFGF23) From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 8 | 259.16 pg/mL | Standard Deviation 210.82 |
Comparison: Day 1~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: <0.000195% CI: [-119.8, -73.8]Mixed model for repeated measures
Comparison: Day 7~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.106495% CI: [-34.9, 3.4]Mixed model for repeated measures
Comparison: Day 8~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: <0.000195% CI: [-307.2, -196.2]Mixed model for repeated measures
Comparison: Day 14~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: <0.000195% CI: [-103.7, -54.5]Mixed model for repeated measures
Comparison: Day 21~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: <0.000195% CI: [-83, -40.5]Mixed model for repeated measures
Comparison: Day 35~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.003995% CI: [-30.1, -5.9]Mixed model for repeated measures
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.
Time frame: Baseline, days 1, 7, 8, 14, 21, and 35
Population: Safety analysis set: included all subjects who received at least one dose of the investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Change in C-terminal Fibroblast Growth Factor 23 (cFGF23) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 1 | -677.38 RU/mL | Standard Deviation 758.35 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in C-terminal Fibroblast Growth Factor 23 (cFGF23) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | -692.44 RU/mL | Standard Deviation 800.04 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in C-terminal Fibroblast Growth Factor 23 (cFGF23) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | -753.40 RU/mL | Standard Deviation 803.63 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in C-terminal Fibroblast Growth Factor 23 (cFGF23) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | -740.37 RU/mL | Standard Deviation 822.35 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in C-terminal Fibroblast Growth Factor 23 (cFGF23) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | -743.99 RU/mL | Standard Deviation 805.24 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in C-terminal Fibroblast Growth Factor 23 (cFGF23) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | -737.46 RU/mL | Standard Deviation 791.86 |
| Ferric Carboxymaltose | Change in C-terminal Fibroblast Growth Factor 23 (cFGF23) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | -986.30 RU/mL | Standard Deviation 1815.76 |
| Ferric Carboxymaltose | Change in C-terminal Fibroblast Growth Factor 23 (cFGF23) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 1 | -843.21 RU/mL | Standard Deviation 1756.37 |
| Ferric Carboxymaltose | Change in C-terminal Fibroblast Growth Factor 23 (cFGF23) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | -925.02 RU/mL | Standard Deviation 1783.26 |
| Ferric Carboxymaltose | Change in C-terminal Fibroblast Growth Factor 23 (cFGF23) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | -924.44 RU/mL | Standard Deviation 1748.37 |
| Ferric Carboxymaltose | Change in C-terminal Fibroblast Growth Factor 23 (cFGF23) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | -943.91 RU/mL | Standard Deviation 1741.96 |
| Ferric Carboxymaltose | Change in C-terminal Fibroblast Growth Factor 23 (cFGF23) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | -853.50 RU/mL | Standard Deviation 1877.89 |
Comparison: Day 1~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.124395% CI: [-131.1, 16.1]Mixed model for repeated measures
Comparison: Day 7~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.554795% CI: [-49.7, 91]Mixed model for repeated measures
Comparison: Day 8~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.000595% CI: [-234.7, -76.6]Mixed model for repeated measures
Comparison: Day 14~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.351695% CI: [-86, 31.5]Mixed model for repeated measures
Comparison: Day 21~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.198895% CI: [-62.3, 13.7]Mixed model for repeated measures
Comparison: Day 35~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.437995% CI: [-18.6, 41.2]Mixed model for repeated measures
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.
Time frame: Baseline, days 1, 7, 8, 14, 21, and 35
Population: Intention-To-Treat (ITT) analysis set: included all randomised subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Change in Hemoglobin (Hb) Per Gram Iron From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 1 | 0.21 g/dL per g of iron | Standard Deviation 0.8 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Hemoglobin (Hb) Per Gram Iron From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | 0.99 g/dL per g of iron | Standard Deviation 1.13 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Hemoglobin (Hb) Per Gram Iron From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | 1.08 g/dL per g of iron | Standard Deviation 1.21 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Hemoglobin (Hb) Per Gram Iron From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | 1.68 g/dL per g of iron | Standard Deviation 1.13 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Hemoglobin (Hb) Per Gram Iron From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | 1.82 g/dL per g of iron | Standard Deviation 0.97 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Hemoglobin (Hb) Per Gram Iron From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | 2.21 g/dL per g of iron | Standard Deviation 1.21 |
| Ferric Carboxymaltose | Change in Hemoglobin (Hb) Per Gram Iron From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | 1.63 g/dL per g of iron | Standard Deviation 0.87 |
| Ferric Carboxymaltose | Change in Hemoglobin (Hb) Per Gram Iron From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 1 | 0.46 g/dL per g of iron | Standard Deviation 1.1 |
| Ferric Carboxymaltose | Change in Hemoglobin (Hb) Per Gram Iron From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | 1.30 g/dL per g of iron | Standard Deviation 0.85 |
| Ferric Carboxymaltose | Change in Hemoglobin (Hb) Per Gram Iron From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | 1.41 g/dL per g of iron | Standard Deviation 1.16 |
| Ferric Carboxymaltose | Change in Hemoglobin (Hb) Per Gram Iron From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | 2.00 g/dL per g of iron | Standard Deviation 0.9 |
| Ferric Carboxymaltose | Change in Hemoglobin (Hb) Per Gram Iron From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | 0.84 g/dL per g of iron | Standard Deviation 0.68 |
Comparison: Day 1~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.088295% CI: [-0.67, 0.05]Mixed model for repeated measures
Comparison: Day 7~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.094195% CI: [-0.74, 0.06]Mixed model for repeated measures
Comparison: Day 8~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.062895% CI: [-0.02, 0.66]Mixed model for repeated measures
Comparison: Day 14~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.005695% CI: [0.14, 0.79]Mixed model for repeated measures
Comparison: Day 21~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.049295% CI: [0, 0.55]Mixed model for repeated measures
Comparison: Day 35~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.088295% CI: [-0.05, 0.64]Mixed model for repeated measures
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.
Time frame: Baseline, days 1, 7, 8, 14, 21, and 35
Population: Safety analysis set: included all subjects who received at least one dose of the investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 1 | -0.07 pg/mL | Standard Deviation 18.93 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | -1.72 pg/mL | Standard Deviation 24.41 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | -0.17 pg/mL | Standard Deviation 21.03 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | 7.39 pg/mL | Standard Deviation 24.17 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | 0.67 pg/mL | Standard Deviation 19.36 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | -1.58 pg/mL | Standard Deviation 22.86 |
| Ferric Carboxymaltose | Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | 22.80 pg/mL | Standard Deviation 38.82 |
| Ferric Carboxymaltose | Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 1 | -7.02 pg/mL | Standard Deviation 25.83 |
| Ferric Carboxymaltose | Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | 22.22 pg/mL | Standard Deviation 31.14 |
| Ferric Carboxymaltose | Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | 0.73 pg/mL | Standard Deviation 29.37 |
| Ferric Carboxymaltose | Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | 22.19 pg/mL | Standard Deviation 33.21 |
| Ferric Carboxymaltose | Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | -3.26 pg/mL | Standard Deviation 27.12 |
Comparison: Day 1~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.216695% CI: [-2.72, 11.85]Mixed model for repeated measures
Comparison: Day 7~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.299795% CI: [-13.47, 4.19]Mixed model for repeated measures
Comparison: Day 8~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.922195% CI: [-7.75, 8.56]Mixed model for repeated measures
Comparison: Day 14~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.003495% CI: [-26.07, -5.32]Mixed model for repeated measures
Comparison: Day 21~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.000295% CI: [-33.93, -11.16]Mixed model for repeated measures
Comparison: Day 35~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: <0.000195% CI: [-35.42, -14.21]Mixed model for repeated measures
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.
Time frame: Baseline, days 1, 7, 8, 14, 21, and 35
Population: Safety analysis set: included all subjects who received at least one dose of the investigational product
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 1 | -0.002 mg/dL | Standard Deviation 0.198 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | 0.020 mg/dL | Standard Deviation 0.206 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | 0.016 mg/dL | Standard Deviation 0.206 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | -0.090 mg/dL | Standard Deviation 0.5 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | 0.030 mg/dL | Standard Deviation 0.204 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | 0.012 mg/dL | Standard Deviation 0.212 |
| Ferric Carboxymaltose | Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | -0.016 mg/dL | Standard Deviation 0.194 |
| Ferric Carboxymaltose | Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 1 | 0.047 mg/dL | Standard Deviation 0.168 |
| Ferric Carboxymaltose | Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | -0.054 mg/dL | Standard Deviation 0.251 |
| Ferric Carboxymaltose | Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | -0.003 mg/dL | Standard Deviation 0.219 |
| Ferric Carboxymaltose | Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | -0.015 mg/dL | Standard Deviation 0.211 |
| Ferric Carboxymaltose | Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | -0.016 mg/dL | Standard Deviation 0.186 |
Comparison: Day 1~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.304895% CI: [-0.1, 0.03]Mixed model for repeated measures
Comparison: Day 7~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.164195% CI: [-0.02, 0.13]Mixed model for repeated measures
Comparison: Day 8~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.133395% CI: [-0.02, 0.12]Mixed model for repeated measures
Comparison: Day 14~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.938595% CI: [-0.17, 0.16]Mixed model for repeated measures
Comparison: Day 21~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.040895% CI: [0, 0.14]Mixed model for repeated measures
Comparison: Day 35~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.237695% CI: [-0.03, 0.12]Mixed model for repeated measures
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.
Time frame: Baseline, days 1, 7, 8, 14, 21, and 35
Population: Intention-To-Treat (ITT) analysis set: included all randomised subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 1 | 72.47 ng/mL | Standard Deviation 81.88 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | 252.39 ng/mL | Standard Deviation 163.85 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | 219.36 ng/mL | Standard Deviation 148.84 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | 144.39 ng/mL | Standard Deviation 100.06 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | 98.81 ng/mL | Standard Deviation 92.42 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | 56.27 ng/mL | Standard Deviation 70.64 |
| Ferric Carboxymaltose | Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | 232.59 ng/mL | Standard Deviation 212.77 |
| Ferric Carboxymaltose | Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 1 | 76.96 ng/mL | Standard Deviation 79.11 |
| Ferric Carboxymaltose | Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | 379.42 ng/mL | Standard Deviation 282.26 |
| Ferric Carboxymaltose | Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | 279.15 ng/mL | Standard Deviation 215.17 |
| Ferric Carboxymaltose | Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | 126.20 ng/mL | Standard Deviation 157.49 |
| Ferric Carboxymaltose | Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | 313.44 ng/mL | Standard Deviation 229.39 |
Comparison: Day 1~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.656895% CI: [-35.3, 22.3]Mixed model for repeated measures
Comparison: Day 7~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.492995% CI: [-94, 45.5]Mixed model for repeated measures
Comparison: Day 8~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.011395% CI: [-162.3, -21.1]Mixed model for repeated measures
Comparison: Day 14~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: <0.000195% CI: [-318.4, -162.3]Mixed model for repeated measures
Comparison: Day 21~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: <0.000195% CI: [-196.1, -74]Mixed model for repeated measures
Comparison: Day 35~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.003995% CI: [-113.2, -22.2]Mixed model for repeated measures
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.
Time frame: Baseline, days 1, 7, 8, 14, 21, and 35
Population: Intention-To-Treat (ITT) analysis set: included all randomised subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 1 | 121.77 percentage of saturation | Standard Deviation 53.11 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | 15.05 percentage of saturation | Standard Deviation 10 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | 12.27 percentage of saturation | Standard Deviation 9.59 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | 10.34 percentage of saturation | Standard Deviation 7.68 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | 10.61 percentage of saturation | Standard Deviation 9.81 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | 9.87 percentage of saturation | Standard Deviation 8.49 |
| Ferric Carboxymaltose | Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | 16.19 percentage of saturation | Standard Deviation 10.59 |
| Ferric Carboxymaltose | Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 1 | 83.78 percentage of saturation | Standard Deviation 42.38 |
| Ferric Carboxymaltose | Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | 16.74 percentage of saturation | Standard Deviation 12.61 |
| Ferric Carboxymaltose | Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | 12.92 percentage of saturation | Standard Deviation 28.49 |
| Ferric Carboxymaltose | Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | 14.43 percentage of saturation | Standard Deviation 9.62 |
| Ferric Carboxymaltose | Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | 73.44 percentage of saturation | Standard Deviation 34.31 |
Comparison: Day 1~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.050395% CI: [0, 48.5]Mixed model for repeated measures
Comparison: Day 7~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.579495% CI: [-5.5, 9.8]Mixed model for repeated measures
Comparison: Day 8~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: <0.000195% CI: [-70.1, -54.3]Mixed model for repeated measures
Comparison: Day 14~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.000195% CI: [-10.4, -3.5]Mixed model for repeated measures
Comparison: Day 21~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.000895% CI: [-9.1, -2.4]Mixed model for repeated measures
Comparison: Day 35~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.00495% CI: [-8.1, -1.6]Mixed model for repeated measures
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.
Time frame: Baseline, days 1, 7, 8, 14, 21, and 35
Population: Safety analysis set: included all subjects who received at least one dose of the investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Change in Vitamin 25-Hydroxyvitamin D (Vitamin D 25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 1 | -0.39 ng/mL | Standard Deviation 1.86 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Vitamin 25-Hydroxyvitamin D (Vitamin D 25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | -0.39 ng/mL | Standard Deviation 3.17 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Vitamin 25-Hydroxyvitamin D (Vitamin D 25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | -0.92 ng/mL | Standard Deviation 3.51 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Vitamin 25-Hydroxyvitamin D (Vitamin D 25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | -1.46 ng/mL | Standard Deviation 4.11 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Vitamin 25-Hydroxyvitamin D (Vitamin D 25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | -1.23 ng/mL | Standard Deviation 4.65 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Vitamin 25-Hydroxyvitamin D (Vitamin D 25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | -0.43 ng/mL | Standard Deviation 6.1 |
| Ferric Carboxymaltose | Change in Vitamin 25-Hydroxyvitamin D (Vitamin D 25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | 0.13 ng/mL | Standard Deviation 4.11 |
| Ferric Carboxymaltose | Change in Vitamin 25-Hydroxyvitamin D (Vitamin D 25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 1 | -0.25 ng/mL | Standard Deviation 2.5 |
| Ferric Carboxymaltose | Change in Vitamin 25-Hydroxyvitamin D (Vitamin D 25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | 0.67 ng/mL | Standard Deviation 3.83 |
| Ferric Carboxymaltose | Change in Vitamin 25-Hydroxyvitamin D (Vitamin D 25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | 0.61 ng/mL | Standard Deviation 3.3 |
| Ferric Carboxymaltose | Change in Vitamin 25-Hydroxyvitamin D (Vitamin D 25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | -0.66 ng/mL | Standard Deviation 4.6 |
| Ferric Carboxymaltose | Change in Vitamin 25-Hydroxyvitamin D (Vitamin D 25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | 0.83 ng/mL | Standard Deviation 3.56 |
Comparison: Day 1~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.686995% CI: [-1.06, 0.7]Mixed model for repeated measures
Comparison: Day 7~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.103795% CI: [-2.29, 0.22]Mixed model for repeated measures
Comparison: Day 8~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.021395% CI: [-2.99, -0.25]Mixed model for repeated measures
Comparison: Day 14~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.017695% CI: [-3.47, -0.34]Mixed model for repeated measures
Comparison: Day 21~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.099995% CI: [-3.01, 0.27]Mixed model for repeated measures
Comparison: Day 35~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: 0.887895% CI: [-1.77, 2.04]Mixed model for repeated measures
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.
Time frame: Baseline to day 35
Population: Safety analysis set: included all subjects who received at least one dose of the investigational product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Incidence of Protocol-defined Serious or Severe Hypersensitivity Reactions | 0 Participants |
| Ferric Carboxymaltose | Incidence of Protocol-defined Serious or Severe Hypersensitivity Reactions | 2 Participants |
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.
Time frame: Baseline to day 35
Population: Safety analysis set: included all subjects who received at least one dose of the investigational product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Proportion of Subjects With Hypophosphatemia on Day 35 (S-phosphate Level <2.0 mg/dL) | 0 Participants |
| Ferric Carboxymaltose | Proportion of Subjects With Hypophosphatemia on Day 35 (S-phosphate Level <2.0 mg/dL) | 25 Participants |
Comparison: Iron isomaltoside/ferric derisomaltose was compared to ferric carboxymaltose by estimation of the risk difference and the associated 95 % CI, adjusting for strata (type of underlying disease (women with IDA due to gynaecological blood losses; yes/no) and screening s-phosphate level (\< or ≥ 3.5 mg/dL)) using the Cochran-Mantel-Haenszel method.p-value: <0.000195% CI: [-57.7, -31.6]Cochran-Mantel-Haenszel
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.
Time frame: Baseline, days 1, 7, 8, 14, 21, and 35
Population: Safety analysis set: included all subjects who received at least one dose of the investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 1 | 6.89 Percentage change from baseline | Standard Deviation 16.02 |
| Iron Isomaltoside/Ferric Derisomaltose | Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 8 | -12.32 Percentage change from baseline | Standard Deviation 18.5 |
| Iron Isomaltoside/Ferric Derisomaltose | Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 14 | -8.66 Percentage change from baseline | Standard Deviation 16.27 |
| Iron Isomaltoside/Ferric Derisomaltose | Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 21 | -1.23 Percentage change from baseline | Standard Deviation 19.15 |
| Iron Isomaltoside/Ferric Derisomaltose | Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 35 | 3.88 Percentage change from baseline | Standard Deviation 14.19 |
| Iron Isomaltoside/Ferric Derisomaltose | Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 7 | -11.99 Percentage change from baseline | Standard Deviation 15.38 |
| Ferric Carboxymaltose | Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 14 | -43.54 Percentage change from baseline | Standard Deviation 22 |
| Ferric Carboxymaltose | Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 1 | -4.34 Percentage change from baseline | Standard Deviation 15.28 |
| Ferric Carboxymaltose | Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 7 | -25.83 Percentage change from baseline | Standard Deviation 20.54 |
| Ferric Carboxymaltose | Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 35 | -28.63 Percentage change from baseline | Standard Deviation 28.14 |
| Ferric Carboxymaltose | Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 8 | -33.36 Percentage change from baseline | Standard Deviation 19.95 |
| Ferric Carboxymaltose | Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 21 | -37.71 Percentage change from baseline | Standard Deviation 24.87 |
Comparison: Day 1~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: <0.000195% CI: [9.38, 18.59]Mixed model for repeated measures
Comparison: Day 7~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: <0.000195% CI: [9.45, 22.23]Mixed model for repeated measures
Comparison: Day 8~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: <0.000195% CI: [14.72, 28.59]Mixed model for repeated measures
Comparison: Day 14~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: <0.000195% CI: [29.28, 43.06]Mixed model for repeated measures
Comparison: Day 21~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: <0.000195% CI: [29.99, 45.72]Mixed model for repeated measures
Comparison: Day 35~Change from baseline was analysed using a Restricted Maximum Likelihood (REML)- based Mixed Model for Repeated Measures (MMRM) approach. All subjects with post baseline data were included with their observed data.~The model included the fixed, categorical effects of treatment, strata, day, treatment-by-day interaction, as well as the continuous, fixed covariates of the parameters baseline value, and baseline value-by-day interaction.p-value: <0.000195% CI: [26.8, 42.26]Mixed model for repeated measures
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.
Time frame: Baseline to day 35
Population: Safety analysis set: included all subjects who received at least one dose of the investigational product.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Time With Hypophosphatemia ( S-phosphate Level <2.0 mg/dL) | 11 days |
| Ferric Carboxymaltose | Time With Hypophosphatemia ( S-phosphate Level <2.0 mg/dL) | 28 days |
Comparison: The time with hypophosphatemia from baseline to day 35 was estimated by a Kaplan- Meier plot. The treatment groups were compared by a log-rank test. Only subjects who had one or more s-phosphate value(s) \<2 mg/dL were included.p-value: 0.0511Log Rank
Post Hoc
Incidence of S-phosphate Level ≤1.0 mg/dL at Any Time From Baseline to Day 35
Safety Incidence of s-phosphate level ≤1.0 mg/dL at any time from baseline to day 35.
Time frame: Baseline to day 35
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Incidence of S-phosphate Level ≤1.0 mg/dL at Any Time From Baseline to Day 35 | 0 Participants |
| Ferric Carboxymaltose | Incidence of S-phosphate Level ≤1.0 mg/dL at Any Time From Baseline to Day 35 | 6 Participants |
Comparison: The rate difference with 95% Newcombe confidence interval, adjusted for stratum using the Cochran-Mantel-Haenszel method, could not be estimated due to lack of events. Thus, the unadjusted treatment difference is presented together with 95% Wald-based confidence interval. The p-value is based on the Cochran-Mantel-Haenszel statistics.p-value: 0.00995% CI: [-18.8, -2.6]Cochran-Mantel-Haenszel