Iron Deficiency Anaemia, Iron Deficiency Anemia
Conditions
Keywords
Iron Deficiency Anaemia, Iron Deficiency Anemia, IDA, Intravenous iron replacement therapy, Iron deficiency, Iron isomaltoside, Ferric derisomaltose, Monofer, Monoferric, Monover, Monofar, Monoferro, Hypophosphatemia, Ferric carboxymaltose
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. Ferric carboxymaltose was administered as 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 diagnosed with IDA, caused by different aetiologies * Haemoglobin (Hb) ≤ 11 g/dL * Body weight \> 50 kg * Serum ferritin (S-ferritin) \< 100 ng/mL * Estimated glomerular filtration rate (eGFR) ≥ 65 mL/min/1.73 m2 * Serum phosphate (S-phosphate) \> 2.5 mg/dL * Intolerance or unresponsiveness to oral iron * Willingness to participate and signing the Informed Consent Form (ICF)
Exclusion criteria
include: * Acute bleeding \> 500 mL within 72 hours * Anaemia predominantly caused by factors other than IDA * Hemochromatosis or other iron storage disorders * Previous serious hypersensitivity reactions to any IV iron compounds * Treatment with IV iron within the last 30 days prior to screening * Treatment with erythropoietin or erythropoietin-stimulation agents * Red blood cell transfusion, radiotherapy, and/or chemotherapy * Received an investigational drug within the last 30 days prior to screening * Planned surgical procedure within the trial period * Hepatic enzymes \> 3 times upper limit of normal * Surgery under anaesthetic within the last 30 days prior to screening * Any non-viral infection within the last 30 days prior to screening * Alcohol or drug abuse within the past 6 months * Vitamin D deficiency * Untreated hyperparathyroidism * Kidney transplantation * Active malignant disease, disease-free for less than 5 years * History of a psychological illness or seizures * Pregnant or nursing women.
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 310 subjects were screened and 123 subjects were randomised into the trial.
Participants by arm
| Arm | Count |
|---|---|
| Iron Isomaltoside/Ferric Derisomaltose Iron isomaltoside/ferric derisomaltose, administered IV | 63 |
| Ferric Carboxymaltose Ferric carboxymaltose, administered IV | 60 |
| Total | 123 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Ferric Carboxymaltose | Total | Iron Isomaltoside/Ferric Derisomaltose |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 9 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 54 Participants | 114 Participants | 60 Participants |
| Age, Continuous | 46.3 years STANDARD_DEVIATION 11.6 | 45.1 years STANDARD_DEVIATION 11 | 43.9 years STANDARD_DEVIATION 10.4 |
| Current smoker No | 52 Participants | 109 Participants | 57 Participants |
| Current smoker Yes | 8 Participants | 14 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 36 Participants | 73 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 50 Participants | 26 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 | 40 Participants | 22 Participants |
| Iron Deficiency Anaemia (IDA) due to gynaecological blood loss Yes | 42 Participants | 83 Participants | 41 Participants |
| Race/Ethnicity, Customized Black/American Indian | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White/American Indian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 19 Participants | 41 Participants | 22 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 38 Participants | 76 Participants | 38 Participants |
| Region of Enrollment United States | 60 participants | 123 participants | 63 participants |
| Sex: Female, Male Female | 57 Participants | 118 Participants | 61 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 2 Participants |
| S-phosphate level at screening <3.5 mg/dL | 33 Participants | 65 Participants | 32 Participants |
| S-phosphate level at screening ≥3.5 mg/dL | 27 Participants | 58 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 63 | 0 / 60 |
| other Total, other adverse events | 0 / 63 | 25 / 60 |
| serious Total, serious adverse events | 1 / 63 | 0 / 60 |
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) | 45 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: [-77.4, -51.5]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 | 0.25 mg/dL | Standard Deviation 0.55 |
| Iron Isomaltoside/Ferric Derisomaltose | Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 7 | -0.06 mg/dL | Standard Deviation 0.75 |
| Iron Isomaltoside/Ferric Derisomaltose | Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 8 | -0.10 mg/dL | Standard Deviation 0.77 |
| Iron Isomaltoside/Ferric Derisomaltose | Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 14 | -0.04 mg/dL | Standard Deviation 0.75 |
| Iron Isomaltoside/Ferric Derisomaltose | Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 21 | 0.04 mg/dL | Standard Deviation 0.69 |
| Iron Isomaltoside/Ferric Derisomaltose | Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 35 | 0.24 mg/dL | Standard Deviation 0.76 |
| Ferric Carboxymaltose | Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 21 | -1.02 mg/dL | Standard Deviation 0.99 |
| Ferric Carboxymaltose | Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 1 | -0.24 mg/dL | Standard Deviation 0.61 |
| Ferric Carboxymaltose | Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 14 | -1.44 mg/dL | Standard Deviation 0.83 |
| Ferric Carboxymaltose | Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 7 | -1.15 mg/dL | Standard Deviation 0.63 |
| Ferric Carboxymaltose | Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 35 | -0.92 mg/dL | Standard Deviation 0.85 |
| Ferric Carboxymaltose | Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 8 | -1.15 mg/dL | Standard Deviation 0.64 |
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: [0.31, 0.65]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: [0.85, 1.27]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: [0.81, 1.25]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: <0.000195% CI: [1.1, 1.6]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: [0.75, 1.32]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: [0.86, 1.39]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 35 | -1.97 percentage excreted | Standard Deviation 7.29 |
| Iron Isomaltoside/Ferric Derisomaltose | Change From Baseline in Fractional Phosphate Urinary Excretion | Day 1 | -1.73 percentage excreted | Standard Deviation 4.85 |
| Iron Isomaltoside/Ferric Derisomaltose | Change From Baseline in Fractional Phosphate Urinary Excretion | Day 7 | 0.56 percentage excreted | Standard Deviation 8.3 |
| Iron Isomaltoside/Ferric Derisomaltose | Change From Baseline in Fractional Phosphate Urinary Excretion | Day 8 | 1.21 percentage excreted | Standard Deviation 7.71 |
| Iron Isomaltoside/Ferric Derisomaltose | Change From Baseline in Fractional Phosphate Urinary Excretion | Day 14 | 0.10 percentage excreted | Standard Deviation 7.34 |
| Iron Isomaltoside/Ferric Derisomaltose | Change From Baseline in Fractional Phosphate Urinary Excretion | Day 21 | 0.78 percentage excreted | Standard Deviation 9.46 |
| Ferric Carboxymaltose | Change From Baseline in Fractional Phosphate Urinary Excretion | Day 8 | 9.08 percentage excreted | Standard Deviation 11.3 |
| Ferric Carboxymaltose | Change From Baseline in Fractional Phosphate Urinary Excretion | Day 35 | 4.90 percentage excreted | Standard Deviation 11.07 |
| Ferric Carboxymaltose | Change From Baseline in Fractional Phosphate Urinary Excretion | Day 21 | 9.43 percentage excreted | Standard Deviation 12.33 |
| Ferric Carboxymaltose | Change From Baseline in Fractional Phosphate Urinary Excretion | Day 1 | 2.44 percentage excreted | Standard Deviation 5.09 |
| Ferric Carboxymaltose | Change From Baseline in Fractional Phosphate Urinary Excretion | Day 14 | 11.46 percentage excreted | Standard Deviation 13.53 |
| Ferric Carboxymaltose | Change From Baseline in Fractional Phosphate Urinary Excretion | Day 7 | 8.12 percentage excreted | Standard Deviation 9.16 |
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 | 5.13 pg/mL | Standard Deviation 13.05 |
| 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 | -19.92 pg/mL | Standard Deviation 24.57 |
| 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 | -16.07 pg/mL | Standard Deviation 25.1 |
| 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 | -3.31 pg/mL | Standard Deviation 15.93 |
| 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 | -3.37 pg/mL | Standard Deviation 16.45 |
| 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 | -3.86 pg/mL | Standard Deviation 20.08 |
| 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 | -28.89 pg/mL | Standard Deviation 30.06 |
| 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 | -20.57 pg/mL | Standard Deviation 17.56 |
| 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 | -39.04 pg/mL | Standard Deviation 27.46 |
| 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 | -38.84 pg/mL | Standard Deviation 20.86 |
| 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 | -17.94 pg/mL | Standard Deviation 26.15 |
| 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 | -39.63 pg/mL | Standard Deviation 27.11 |
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: [18.81, 29.73]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: [8.83, 22.67]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: [12.07, 28.22]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: [25.49, 38.96]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: [14.79, 30.95]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: 0.004395% CI: [3.39, 17.82]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 0.41 |
| 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 | 0.30 ng/mL | Standard Deviation 0.49 |
| 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 | 0.19 ng/mL | Standard Deviation 0.69 |
| 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 | 0.13 ng/mL | Standard Deviation 0.6 |
| 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 | 0.12 ng/mL | Standard Deviation 0.93 |
| 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 | 0.06 ng/mL | Standard Deviation 0.89 |
| 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 | 0.75 ng/mL | Standard Deviation 0.93 |
| 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 | 0.13 ng/mL | Standard Deviation 0.51 |
| 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 | 0.95 ng/mL | Standard Deviation 0.98 |
| 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 | 0.72 ng/mL | Standard Deviation 0.78 |
| 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 | 0.60 ng/mL | Standard Deviation 0.99 |
| 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 | 0.71 ng/mL | Standard Deviation 0.84 |
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: 0.055295% CI: [-0.34, 0]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: 0.002395% CI: [-0.6, -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: 0.000895% CI: [-0.8, -0.21]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: [-1.11, -0.49]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: 0.000695% CI: [-1.01, -0.28]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: 0.001495% CI: [-0.94, -0.23]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 | -2.7 pg/mL | Standard Deviation 28.6 |
| 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 | 6.8 pg/mL | Standard Deviation 26.9 |
| 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 | 4.9 pg/mL | Standard Deviation 25.2 |
| 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 14 | -8.6 pg/mL | Standard Deviation 25.7 |
| 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 | -0.9 pg/mL | Standard Deviation 39.7 |
| 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 | -10.5 pg/mL | Standard Deviation 25.6 |
| 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 | 66.7 pg/mL | Standard Deviation 96.6 |
| 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 | 103.6 pg/mL | Standard Deviation 89.5 |
| 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 | 106.1 pg/mL | Standard Deviation 114.9 |
| 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 | 70.3 pg/mL | Standard Deviation 78.4 |
| 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 | 34.7 pg/mL | Standard Deviation 64.2 |
| 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 | 305.9 pg/mL | Standard Deviation 262.3 |
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: [-131.04, -80.45]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: [-82.95, -38.58]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: [-368.15, -218.3]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: [-151.6, -83.33]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: [-101.8, -40.61]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: [-54.92, -19.39]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 | -742.3 RU/mL | Standard Deviation 800.7 |
| 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 | -723.6 RU/mL | Standard Deviation 801.6 |
| 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 | -648.9 RU/mL | Standard Deviation 757.5 |
| 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 | -717.9 RU/mL | Standard Deviation 798.2 |
| 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 | -678.1 RU/mL | Standard Deviation 783.5 |
| 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 | -660.1 RU/mL | Standard Deviation 806.7 |
| Ferric Carboxymaltose | Change in C-terminal Fibroblast Growth Factor 23 (cFGF23) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | -458.9 RU/mL | Standard Deviation 658.9 |
| Ferric Carboxymaltose | Change in C-terminal Fibroblast Growth Factor 23 (cFGF23) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 1 | -390.2 RU/mL | Standard Deviation 665.7 |
| Ferric Carboxymaltose | Change in C-terminal Fibroblast Growth Factor 23 (cFGF23) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | -401.5 RU/mL | Standard Deviation 661.5 |
| Ferric Carboxymaltose | Change in C-terminal Fibroblast Growth Factor 23 (cFGF23) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | -477.5 RU/mL | Standard Deviation 652 |
| Ferric Carboxymaltose | Change in C-terminal Fibroblast Growth Factor 23 (cFGF23) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | -481.3 RU/mL | Standard Deviation 653.7 |
| Ferric Carboxymaltose | Change in C-terminal Fibroblast Growth Factor 23 (cFGF23) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | -284.2 RU/mL | Standard Deviation 638.6 |
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: [-136.42, -61.76]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: [-72.8, -25.9]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: [-242.47, -140.09]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: [-137.19, -64.2]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: [-71.78, -24.96]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: 0.141195% CI: [-35.04, 5.06]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 | -0.16 g/dL per g of iron | Standard Deviation 1.29 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Hemoglobin (Hb) Per Gram Iron From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | 0.65 g/dL per g of iron | Standard Deviation 0.86 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Hemoglobin (Hb) Per Gram Iron From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | 0.50 g/dL per g of iron | Standard Deviation 1.14 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Hemoglobin (Hb) Per Gram Iron From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | 1.55 g/dL per g of iron | Standard Deviation 1.53 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Hemoglobin (Hb) Per Gram Iron From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | 1.68 g/dL per g of iron | Standard Deviation 1.4 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Hemoglobin (Hb) Per Gram Iron From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | 2.16 g/dL per g of iron | Standard Deviation 1.62 |
| Ferric Carboxymaltose | Change in Hemoglobin (Hb) Per Gram Iron From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | 1.44 g/dL per g of iron | Standard Deviation 0.97 |
| Ferric Carboxymaltose | Change in Hemoglobin (Hb) Per Gram Iron From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 1 | 0.28 g/dL per g of iron | Standard Deviation 1.82 |
| Ferric Carboxymaltose | Change in Hemoglobin (Hb) Per Gram Iron From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | 1.16 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 7 | 0.94 g/dL per g of iron | Standard Deviation 1.49 |
| Ferric Carboxymaltose | Change in Hemoglobin (Hb) Per Gram Iron From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | 1.94 g/dL per g of iron | Standard Deviation 1.02 |
| Ferric Carboxymaltose | Change in Hemoglobin (Hb) Per Gram Iron From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | 0.64 g/dL per g of iron | Standard Deviation 0.81 |
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: 0.461895% CI: [-0.82, 0.37]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: 0.36695% CI: [-0.54, 0.2]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: 0.85895% CI: [-0.25, 0.3]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: 0.025795% CI: [0.05, 0.74]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: 0.001695% CI: [0.19, 0.77]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: 0.018595% CI: [0.07, 0.76]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 | -1.3 pg/mL | Standard Deviation 20.2 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | -4.6 pg/mL | Standard Deviation 26.6 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | 1.8 pg/mL | Standard Deviation 27.9 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | 3.2 pg/mL | Standard Deviation 30.6 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | -3.1 pg/mL | Standard Deviation 22.8 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | 0.2 pg/mL | Standard Deviation 27.9 |
| Ferric Carboxymaltose | Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | 17.2 pg/mL | Standard Deviation 34.9 |
| Ferric Carboxymaltose | Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 1 | 0.7 pg/mL | Standard Deviation 21.3 |
| Ferric Carboxymaltose | Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | 16.7 pg/mL | Standard Deviation 33.7 |
| Ferric Carboxymaltose | Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | 7.8 pg/mL | Standard Deviation 26.6 |
| Ferric Carboxymaltose | Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | 22.1 pg/mL | Standard Deviation 41.2 |
| Ferric Carboxymaltose | Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | 2.6 pg/mL | Standard Deviation 29.2 |
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: 0.744795% CI: [-7.96, 5.71]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: 0.036395% CI: [-18.78, -0.63]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: 0.924295% CI: [-10.56, 9.59]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: 0.060295% CI: [-22.84, 0.49]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: [-28.68, -7.73]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: 0.003195% CI: [-32.75, -6.83]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 | 0.04 mg/dL | Standard Deviation 0.18 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | 0.02 mg/dL | Standard Deviation 0.16 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | 0.03 mg/dL | Standard Deviation 0.19 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | 0.02 mg/dL | Standard Deviation 0.22 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | 0.08 mg/dL | Standard Deviation 0.19 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | 0.02 mg/dL | Standard Deviation 0.21 |
| Ferric Carboxymaltose | Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | -0.03 mg/dL | Standard Deviation 0.21 |
| Ferric Carboxymaltose | Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 1 | 0.00 mg/dL | Standard Deviation 0.2 |
| Ferric Carboxymaltose | Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | -0.08 mg/dL | Standard Deviation 0.22 |
| Ferric Carboxymaltose | Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | -0.07 mg/dL | Standard Deviation 0.22 |
| Ferric Carboxymaltose | Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | -0.03 mg/dL | Standard Deviation 0.2 |
| Ferric Carboxymaltose | Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | -0.03 mg/dL | Standard Deviation 0.2 |
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: 0.26795% CI: [-0.029, 0.104]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: 0.00495% CI: [0.028, 0.142]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: 0.047295% CI: [0.001, 0.127]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: 0.00595% CI: [0.031, 0.171]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: 0.006195% CI: [0.029, 0.172]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: 0.128295% CI: [-0.016, 0.126]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 | 82.0 ng/mL | Standard Deviation 58.3 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | 261.7 ng/mL | Standard Deviation 184.2 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | 248.1 ng/mL | Standard Deviation 182.4 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | 133.9 ng/mL | Standard Deviation 109.9 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | 97.2 ng/mL | Standard Deviation 127.6 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | 46.8 ng/mL | Standard Deviation 63 |
| Ferric Carboxymaltose | Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | 179.2 ng/mL | Standard Deviation 135 |
| Ferric Carboxymaltose | Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 1 | 94.7 ng/mL | Standard Deviation 62.4 |
| Ferric Carboxymaltose | Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | 352.9 ng/mL | Standard Deviation 223.4 |
| Ferric Carboxymaltose | Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | 289.5 ng/mL | Standard Deviation 173 |
| Ferric Carboxymaltose | Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | 108.9 ng/mL | Standard Deviation 107.3 |
| Ferric Carboxymaltose | Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | 325.8 ng/mL | Standard Deviation 220.1 |
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: 0.192295% CI: [-37.26, 7.57]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: 0.560195% CI: [-80.24, 43.68]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: 0.045995% CI: [-140.74, -1.3]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: [-268.82, -145.84]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: 0.00195% CI: [-124.81, -32.39]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: 0.000295% CI: [-88.75, -28.82]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 8 | 6.3 percentage of saturation | Standard Deviation 34.7 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | 3.1 percentage of saturation | Standard Deviation 32.3 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | 4.8 percentage of saturation | Standard Deviation 32.6 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | 10.2 percentage of saturation | Standard Deviation 34.8 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | 6.8 percentage of saturation | Standard Deviation 31.1 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 1 | 118.9 percentage of saturation | Standard Deviation 52 |
| Ferric Carboxymaltose | Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | 14.7 percentage of saturation | Standard Deviation 10.8 |
| Ferric Carboxymaltose | Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 1 | 85.7 percentage of saturation | Standard Deviation 40.4 |
| Ferric Carboxymaltose | Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | 12.9 percentage of saturation | Standard Deviation 11.2 |
| Ferric Carboxymaltose | Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | 61.2 percentage of saturation | Standard Deviation 43 |
| Ferric Carboxymaltose | Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | 16.4 percentage of saturation | Standard Deviation 11.3 |
| Ferric Carboxymaltose | Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | 16.6 percentage of saturation | Standard Deviation 11.7 |
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: [26.3, 55.33]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: 0.008995% CI: [1.69, 11.53]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: [-54.92, -32.03]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: 0.37395% CI: [-5.41, 2.04]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: 0.477895% CI: [-6.15, 2.9]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: 0.357595% CI: [-5.44, 1.98]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 | 0.04 ng/mL | Standard Deviation 2.26 |
| 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 | 0.81 ng/mL | Standard Deviation 3.34 |
| 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 | 0.32 ng/mL | Standard Deviation 3.35 |
| 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 | 0.71 ng/mL | Standard Deviation 5.17 |
| 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 21 | 0.78 ng/mL | Standard Deviation 6.03 |
| 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 | -0.24 ng/mL | Standard Deviation 6.44 |
| Ferric Carboxymaltose | Change in Vitamin 25-Hydroxyvitamin D (Vitamin D 25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 21 | -0.90 ng/mL | Standard Deviation 4.7 |
| Ferric Carboxymaltose | Change in Vitamin 25-Hydroxyvitamin D (Vitamin D 25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 1 | 0.32 ng/mL | Standard Deviation 2.26 |
| Ferric Carboxymaltose | Change in Vitamin 25-Hydroxyvitamin D (Vitamin D 25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 14 | -1.29 ng/mL | Standard Deviation 5.14 |
| Ferric Carboxymaltose | Change in Vitamin 25-Hydroxyvitamin D (Vitamin D 25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 7 | -0.94 ng/mL | Standard Deviation 3.93 |
| Ferric Carboxymaltose | Change in Vitamin 25-Hydroxyvitamin D (Vitamin D 25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 35 | -0.72 ng/mL | Standard Deviation 4.34 |
| Ferric Carboxymaltose | Change in Vitamin 25-Hydroxyvitamin D (Vitamin D 25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Day 8 | -0.07 ng/mL | Standard Deviation 5.07 |
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: 0.56295% CI: [-1.08, 0.59]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: 0.012695% CI: [0.38, 3.12]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: 0.60895% CI: [-1.19, 2.02]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: 0.037995% CI: [0.12, 4.05]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: 0.236895% CI: [-0.78, 3.12]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: 0.828795% CI: [-2.18, 1.75]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 | 1 Participants |
| Ferric Carboxymaltose | Incidence of Protocol-defined Serious or Severe Hypersensitivity Reactions | 0 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) | 1 Participants |
| Ferric Carboxymaltose | Proportion of Subjects With Hypophosphatemia on Day 35 ( S-phosphate Level <2.0 mg/dL) | 24 Participants |
Comparison: Iron isomaltoside/ferric derisomaltose will be 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: [-52.2, -23.3]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 | 9.31 Percentage change from baseline | Standard Deviation 18.98 |
| Iron Isomaltoside/Ferric Derisomaltose | Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 7 | 0.55 Percentage change from baseline | Standard Deviation 23.15 |
| Iron Isomaltoside/Ferric Derisomaltose | Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 8 | -0.95 Percentage change from baseline | Standard Deviation 24.02 |
| Iron Isomaltoside/Ferric Derisomaltose | Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 14 | 1.13 Percentage change from baseline | Standard Deviation 25.21 |
| Iron Isomaltoside/Ferric Derisomaltose | Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 21 | 2.85 Percentage change from baseline | Standard Deviation 22.66 |
| Iron Isomaltoside/Ferric Derisomaltose | Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 35 | 9.69 Percentage change from baseline | Standard Deviation 24.55 |
| Ferric Carboxymaltose | Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 21 | -30.11 Percentage change from baseline | Standard Deviation 30.79 |
| Ferric Carboxymaltose | Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 1 | -5.94 Percentage change from baseline | Standard Deviation 16.59 |
| Ferric Carboxymaltose | Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 14 | -42.59 Percentage change from baseline | Standard Deviation 24.81 |
| Ferric Carboxymaltose | Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 7 | -33.68 Percentage change from baseline | Standard Deviation 17.53 |
| Ferric Carboxymaltose | Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 35 | -27.58 Percentage change from baseline | Standard Deviation 27.47 |
| Ferric Carboxymaltose | Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Day 8 | -34.03 Percentage change from baseline | Standard Deviation 17.61 |
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: [10.32, 20.79]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: [26.62, 39.84]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: [25.71, 39.84]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: [33.89, 50.32]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: <0.000195% CI: [23.09, 41.48]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: [27.33, 44.78]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) | 15 days |
| Ferric Carboxymaltose | Time With Hypophosphatemia ( S-phosphate Level <2.0 mg/dL) | 29 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: 0.8979Log Rank
Post Hoc
Incidence of S-phosphate Level ≤1.0 mg/dL at Any Time From Baseline to Day 35
Safety Incidence of hypophosphatemia (defined as s-phosphate level ≤1 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 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 | 7 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: 0.00595% CI: [-20.1, -3.6]Cochran-Mantel-Haenszel