Chronic Kidney Disease, Iron Deficiency Anaemia, Iron Deficiency Anemia
Conditions
Keywords
Iron Deficiency Anaemia, Iron Deficiency Anemia, IDA, Chronic Kidney Disease, CKD, Iron isomaltoside, Ferric derisomaltose, Monofer, Monoferric, Monover, Monofar, Monoferro
Brief summary
Evaluation of safety and efficacy of iron isomaltoside/ferric derisomaltose compared with iron sucrose, in subjects with both non-dialysis-dependent chronic kidney disease (NDD-CKD) and iron deficiency anaemia (IDA).
Detailed description
Iron deficiency anaemia (IDA) is a common problem associated with many chronic diseases such as chronic kidney disease (CKD). IDA can have a substantial medical and quality of life (QoL) burden on the subjects. Therapy of these subjects includes treating the underlying cause of IDA and restoring haemoglobin (Hb) concentration and iron stores. This study evaluated the safety and efficacy of iron isomaltoside/ferric derisomaltose compared with iron sucrose in subjects with both non-dialysis-dependent chronic kidney disease (NDD-CKD) and iron deficiency anaemia (IDA). The study subjects received either a single intravenous (IV) dose of iron isomaltoside/ferric derisomaltose (1000 mg at baseline) or iron sucrose (200 mg IV injections at baseline and repeated according to standard practice or physician choice up to a maximum of five times within the first two weeks starting at baseline; a cumulative dose of 1000 mg was recommended). The study subjects were monitored for up to 8 weeks 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 set to 1000 mg. The dose was diluted in 100 mL 0.9 % sodium chloride (100 mL bags) and administered as a single IV infusion over approximately 20 minutes.
DRUGIron sucrose
Iron sucrose (Venofer®; 20 mg elemental iron/mL) was the comparator in this trial. Iron sucrose was administered as 200 mg undiluted IV injections over approximately 2-5 minutes and repeated according to standard practice or physician choice up to a maximum of five times within the first two weeks starting at baseline. A cumulative dose of 1000 mg was recommended.
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
includes: 1. Men and women, ≥ 18 years 2. Hb ≤ 11 g/dL 3. Chronic renal impairment, as defined by either (i) eGFR \< 60 mL/min/1.73m2 at screening (as calculated by modification of diet in renal disease (MDRD)), or (ii) Estimated Glomerular Filtration Rate (eGFR) \< 90 mL/min/1.73m2 at screening and kidney damage as indicated by abnormalities in urine composition per medical history and/or intermediate/high risk of cardio-vascular disease based on the Framingham model 4. Screening s-ferritin ≤ 100 ng/mL, or ≤ 300 ng/mL if Transferrin Saturation (TSAT) ≤ 30 % 5. Either no Erythropoiesis Stimulating Agent (ESAs) or ESAs as a stable dose 4 weeks before randomisation 6. Willingness to participate and signing the informed consent form
Exclusion criteria
includes: 1. Anaemia predominantly caused by factors other than IDA 2. Hemochromatosis or other iron storage disorders 3. Previous serious hypersensitivity reactions to any IV iron compounds 4. Prior to screening or during the trial period; has or will be treated with a red blood cell transfusion, radiotherapy, and/or chemotherapy 5. Undergoing dialysis for treatment of CKD 6. Planned surgical procedure within the trial period 7. Decompensated liver cirrhosis or active hepatitis 8. Alcohol or drug abuse within the past 6 month. 9. Pregnant or nursing women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hemoglobin (Hb) From Baseline to Week 8 | Baseline to week 8 | Efficacy Evaluate the effect of iron isomaltoside/ferric derisomaltose vs iron sucrose in subjects with non-dialysis-dependent chronic kidney disease (NDD-CKD) and iron deficiency anaemia (IDA). Response was defined as change from baseline in hemoglobin (Hb) to week 8, i.e. ability to increase Hb in subjects with NDD-CKD and IDA, when oral iron preparations were ineffective or could not be used, or in whom the Hb measurement at screening in Investigators' opinion were sufficiently low to require rapid repletion of iron stores. |
| Incidence of Protocol-defined Serious or Severe Hypersensitivity Reactions | Baseline to week 8 | Safety For this endpoint, the number of participants with serious or severe hypersensitivity reactions were evaluated. The hypersensitivity reactions that were included in the analysis were those that started on or after the first dose of randomised treatment (i.e. treatment emergent). The terms used to define hypersensitivity were those specified by the Standardised MedDRA Queries (SMQ) for hypersensitivity, plus four additional terms: loss of consciousness, seizure, syncope, unresponsiveness. The potential hypersensitivity AEs were adjudicated in a blinded fashion by an independent Clinical Endpoint Adjudication Committee (CEAC). Results show only those participants that had adjudicated and confirmed serious or severe hypersensitivity reactions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| S-phosphate <2 mg/dL at Any Time From Baseline to Week 1, 2, 4, and 8 | Baseline, week 1, 2, 4, and 8 | Safety Results show the number of participants who had s-phosphate \<2 mg/dL at any time from baseline to week 1, 2, 4, or 8. |
| Hb Concentration Increase of ≥1 g/dL From Baseline to Week 1, 2, 4, and 8 | Baseline, week 1, 2, 4, and 8 | Efficacy Results show Hb responders to the treatment. A subject was considered a Hb responder to a certain week if an increase in Hb of at least 1 g/dL from baseline to the week in question was observed (from baseline to week 1, 2, 4, and 8). |
| Time to Change in Hb Concentration ≥1 g/dL | Baseline, week 1, 2, 4, and 8 | Efficacy Time to change in Hb concentration ≥1 g/dL. Subjects who showed Hb concentration increase of ≥1 g/dL (from baseline to week 1, 2, 4, and 8). For responders, time to Hb response was defined as the scheduled time from baseline until the visit where the first Hb response was measured. |
| Hb Concentration of >12 g/dL at Any Time From Week 1 to Week 8 | Week 1 to week 8 | Efficacy Hb concentration of \>12 g/dL at any time from week 1 to week 8. Results show the number of participants who achieved Hb concentration of \>12 g/dL at any time from week 1 to week 8. |
| Hb Concentration Increase of ≥2 g/dL at Any Time From Week 1 to Week 8 | Week 1 to week 8 | Efficacy Results show the number of participants who achieved Hb concentration increase of ≥2 g/dL at any time from week 1 to week 8. |
| S-Ferritin Concentration of ≥100 ng/mL and Transferrin Saturation (TSAT) of 20-50% at Any Time From Week 1 to Week 8 | Week 1 to week 8 | Efficacy Proportion of subjects reaching the composite endpoint of s-ferritin concentration ≥100 ng/mL and TSAT of 20-50% at any time from week 1 to 8. |
| Change in Hb Concentration From Baseline to Week 1, 2, and 4 | Baseline, week 1, 2, and 4 | Efficacy Change in Hb concentration from baseline to week 1, 2, and 4. |
| Change in S-ferritin From Baseline to Weeks 1, 2, 4, and 8 | Baseline, week 1, 2, 4, and 8 | Efficacy Changes in s-ferritin from baseline to weeks 1, 2, 4, and 8. |
| Composite Cardiovascular Adverse Events (AEs) | Baseline, week 1, 2, and 8 | Safety Results show the composite cardiovascular AEs, that started on or after the first dose of randomised treatment (i.e. treatment emergent) up to week 8. The reported potential cardiovascular AEs were adjudicated in a blinded fashion by an independent Clinical Endpoint Adjudication Committee (CEAC). The potential cardiovascular AEs included the following: * Death due to any cause * Non-fatal myocardial infarction * Non-fatal stroke * Unstable angina requiring hospitalisation * Congestive heart failure requiring hospitalisation or medical intervention * Arrhythmias * Hypertension * Hypotension Results show only those participants that had adjudicated and confirmed treatment-emergent composite cardiovascular AEs. |
| Change in Concentration of S-iron From Baseline to Week 1, 2, 4, and 8 | Baseline, week 1, 2, 4, and 8 | Efficacy Changes in the concentrations of serum iron (s-iron) from baseline to week 1, 2, 4, and 8. |
| Change in Fatigue Symptoms From Baseline to Week 1, 2, and 8 | Baseline, week 1, 2, and 8 | Efficacy Change in fatigue symptoms from baseline to week 1, 2, and 8 was measured by the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale. The Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale consisted of 13 items ranging from 0 (not at all) to 4 (very much), except items #7 and #8 which are reversed scored. The total score range is 0-52. A score of less than 30 indicated severe fatigue, and the higher the score, the better outcome/quality of life (QoL). If more than 50% of the items for a subject at a given visit were missing, the total score was not calculated. Total score was calculated as shown below: Total score= Sum of individual scores x 13 / Number of items answered |
| Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Cost of Public Transport/Taxi And Parking | Baseline | Pharmacoeconomics The Intervals in Screening for Diabetic Retinopathy (ISDR) questionnaire at the baseline visit assessed the resources used by subjects to receive treatment. Resources used on other trial activities were not included. ISDR responses were summarised using descriptive statistics. The data for this endpoint show the responses at baseline for both treatment groups. The frequency of drug administration between the 2 treatment groups is different, however, (i.e. up to a factor 5 in the iron sucrose treatment group). |
| Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Return Journey by Car | Baseline | Pharmacoeconomics The Intervals in Screening for Diabetic Retinopathy (ISDR) questionnaire at the baseline visit assessed the resources used by subjects to receive treatment. Resources used on other trial activities were not included. ISDR responses were summarised using descriptive statistics. The data for this endpoint show the responses at baseline for both treatment groups. The frequency of drug administration between the 2 treatment groups is different, however, (i.e. up to a factor 5 in the iron sucrose treatment group). |
| Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Time Spent on Visit/Helping on Visit | Baseline | Pharmacoeconomics The Intervals in Screening for Diabetic Retinopathy (ISDR) questionnaire at the baseline visit assessed the resources used by subjects to receive treatment. Resources used on other trial activities were not included. ISDR responses were summarised using descriptive statistics. The data for this endpoint show the responses at baseline for both treatment groups. The frequency of drug administration between the 2 treatment groups is different, however, (i.e. up to a factor 5 in the iron sucrose treatment group). |
| Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Participants/Others Who Took Time Off Work to Attend Visits | Baseline | Pharmacoeconomics The Intervals in Screening for Diabetic Retinopathy (ISDR) questionnaire at the baseline visit assessed the resources used by subjects to receive treatment. Resources used on other trial activities were not included. ISDR responses were summarised using descriptive statistics. The data for this endpoint show the responses at baseline for both treatment groups. The frequency of drug administration between the 2 treatment groups is different, however, (i.e. up to a factor 5 in the iron sucrose treatment group). |
| Health Care Resource Use Questionnaire | Baseline | Pharmacoeconomics Resources used by the health care staff (per administration), measured by the health care resource use questionnaire. The questionnaire assessed the time used by the health care staff during administration of the investigational product and the administration time (including the observational time). The health care participants included in the evaluation were: investigator, pharmacist, physician, study coordinator, study nurse. The data for this endpoint show the responses at baseline for both treatment groups. The frequency of drug administration between the 2 treatment groups is different (i.e. up to a factor 5 more frequent in the iron sucrose treatment group). |
| Change in Transferrin Saturation (TSAT) From Baseline to Week 1, 2, 4, and 8 | Baseline, week 1, 2, 4, and 8 | Efficacy Changes in transferrin saturation (TSAT) from baseline to week 1, 2, 4, and 8. |
| Time to First Composite Cardiovascular Safety AE | Baseline, week 1, 2, 4, and 8 | Safety Time to first composite cardiovascular AE was defined as the actual time in days from first dose of treatment until the date of the composite cardiovascular AE. For subjects not reporting a composite cardiovascular AE, the time was censored at the date of the last attended visit. Only the adjudicated and confirmed composite cardiovascular safety AEs, as judged by the CEAC, were considered for this endpoint. Time to first composite cardiovascular AE was defined as the actual time in days from first dose of treatment until the date of the composite cardiovascular AE. For subjects not reporting a composite cardiovascular AE, the time was censored at the date of the last attended visit. |
Countries
United States
Participant flow
Recruitment details
A total of 2560 subjects were screened and 1538 subjects were randomised into the trial.
Participants by arm
| Arm | Count |
|---|---|
| Iron Isomaltoside/Ferric Derisomaltose Iron isomaltoside/ferric derisomaltose, administered IV | 1,027 |
| Iron Sucrose Iron sucrose, administered IV | 511 |
| Total | 1,538 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 2 |
| Overall Study | Lost to Follow-up | 13 | 7 |
| Overall Study | Moved, poor venous access, transport | 6 | 4 |
| Overall Study | Non-serious AE | 1 | 2 |
| Overall Study | Not treated | 2 | 2 |
| Overall Study | Physician Decision | 5 | 3 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | Serious AE | 7 | 3 |
| Overall Study | Sponsor Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 19 | 9 |
Baseline characteristics
| Characteristic | Iron Sucrose | Iron Isomaltoside/Ferric Derisomaltose | Total |
|---|---|---|---|
| Age, Continuous | 69.3 years STANDARD_DEVIATION 12.3 | 68.3 years STANDARD_DEVIATION 12.3 | 68.6 years STANDARD_DEVIATION 12.3 |
| Age, Customized 65-84 years | 316 participants | 608 participants | 924 participants |
| Age, Customized > 84 years | 44 participants | 82 participants | 126 participants |
| Age, Customized Between 18 and 65 years | 151 participants | 337 participants | 488 participants |
| Current smoker NO | 458 participants | 909 participants | 1367 participants |
| Current smoker YES | 53 participants | 118 participants | 171 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 248 Participants | 476 Participants | 724 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 263 Participants | 551 Participants | 814 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Central Indian | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Guyanese | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Hispanic | 3 participants | 4 participants | 7 participants |
| Race/Ethnicity, Customized Indigenous Mexican | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Mexican | 3 participants | 4 participants | 7 participants |
| Race/Ethnicity, Customized Mixed (Caucasian and Native american) | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Other (Mixed: not declared) | 0 participants | 1 participants | 1 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 16 Participants | 27 Participants |
| Race (NIH/OMB) Black or African American | 117 Participants | 264 Participants | 381 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 11 Participants | 17 Participants |
| Race (NIH/OMB) White | 375 Participants | 731 Participants | 1106 Participants |
| Region of Enrollment United States | 511 participants | 1027 participants | 1538 participants |
| Sex: Female, Male Female | 329 Participants | 633 Participants | 962 Participants |
| Sex: Female, Male Male | 182 Participants | 394 Participants | 576 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 1,019 | 3 / 506 |
| other Total, other adverse events | 56 / 1,019 | 34 / 506 |
| serious Total, serious adverse events | 83 / 1,019 | 50 / 506 |
Outcome results
Primary
Change in Hemoglobin (Hb) From Baseline to Week 8
Efficacy Evaluate the effect of iron isomaltoside/ferric derisomaltose vs iron sucrose in subjects with non-dialysis-dependent chronic kidney disease (NDD-CKD) and iron deficiency anaemia (IDA). Response was defined as change from baseline in hemoglobin (Hb) to week 8, i.e. ability to increase Hb in subjects with NDD-CKD and IDA, when oral iron preparations were ineffective or could not be used, or in whom the Hb measurement at screening in Investigators' opinion were sufficiently low to require rapid repletion of iron stores.
Time frame: Baseline to week 8
Population: Intention to treat (ITT). All randomised subjects.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Change in Hemoglobin (Hb) From Baseline to Week 8 | 1.22 g/dL |
| Iron Sucrose | Change in Hemoglobin (Hb) From Baseline to Week 8 | 1.14 g/dL |
Comparison: Power:~With N=1000 subjects in the iron isomaltoside/ferric derisomaltose treatment group and with N=500 subjects in the iron sucrose treatment group, assuming no difference between the treatment groups and assuming a common standard deviation (SD) of 1.5 g/dL, the power was 100% for demonstrating non-inferiority of the change in Hb from baseline to week 8, using a non-inferiority margin of -0.5 g/dL.~The significance level was set to 5%.95% CI: [-0.06, 0.23]
Primary
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. The hypersensitivity reactions that were included in the analysis were those that started on or after the first dose of randomised treatment (i.e. treatment emergent). The terms used to define hypersensitivity were those specified by the Standardised MedDRA Queries (SMQ) for hypersensitivity, plus four additional terms: loss of consciousness, seizure, syncope, unresponsiveness. The potential hypersensitivity AEs were adjudicated in a blinded fashion by an independent Clinical Endpoint Adjudication Committee (CEAC). Results show only those participants that had adjudicated and confirmed serious or severe hypersensitivity reactions.
Time frame: Baseline to week 8
Population: Safety analysis set. All randomised 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 | 3 Participants |
| Iron Sucrose | Incidence of Protocol-defined Serious or Severe Hypersensitivity Reactions | 0 Participants |
Comparison: Power:~With N=1000 subjects in the iron isomaltoside/ferric derisomaltose, the power was 88% to demonstrate that the upper bound of the 95% CI of the incidence of treatment-emergent serious and/or severe non-serious hypersensitivity AEs was less than 3%.~The significance level was set to 5%.95% CI: [0.06, 0.86]
Comparison: Risk difference between iron isomaltoside/ferric derisomaltose and iron sucrose was assessed for the individual trial with 95% Newcombe CI adjusted for stratum using the Cochran-Mantel-Haenszel method.95% CI: [-0.19, 0.77]
Comparison: Risk difference between iron isomaltoside/ferric derisomaltose and iron sucrose was assessed for the pooled FERWON-IDA and FERWON-NEPHRO trials (2008 subjects treated with iron isomaltoside/ferric derisomaltose and 1000 subjects treated with iron sucrose) with 95% Newcombe CI adjusted for stratum using the Cochran-Mantel-Haenszel method.95% CI: [-0.57, 0.48]
Secondary
Change in Concentration of S-iron From Baseline to Week 1, 2, 4, and 8
Efficacy Changes in the concentrations of serum iron (s-iron) from baseline to week 1, 2, 4, and 8.
Time frame: Baseline, week 1, 2, 4, and 8
Population: ITT. All randomised subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Change in Concentration of S-iron From Baseline to Week 1, 2, 4, and 8 | Week 8 | 7.1 μg/dL | Standard Deviation 91.3 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Concentration of S-iron From Baseline to Week 1, 2, 4, and 8 | Week 1 | 34.8 μg/dL | Standard Deviation 99.7 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Concentration of S-iron From Baseline to Week 1, 2, 4, and 8 | Week 2 | 11.1 μg/dL | Standard Deviation 90.6 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Concentration of S-iron From Baseline to Week 1, 2, 4, and 8 | Week 4 | 6.5 μg/dL | Standard Deviation 91.2 |
| Iron Sucrose | Change in Concentration of S-iron From Baseline to Week 1, 2, 4, and 8 | Week 4 | 10.2 μg/dL | Standard Deviation 38.3 |
| Iron Sucrose | Change in Concentration of S-iron From Baseline to Week 1, 2, 4, and 8 | Week 8 | 12.4 μg/dL | Standard Deviation 41.9 |
| Iron Sucrose | Change in Concentration of S-iron From Baseline to Week 1, 2, 4, and 8 | Week 2 | 12.4 μg/dL | Standard Deviation 44.1 |
| Iron Sucrose | Change in Concentration of S-iron From Baseline to Week 1, 2, 4, and 8 | Week 1 | 11.1 μg/dL | Standard Deviation 71.1 |
Comparison: Week 1~Change in s-iron from baseline to week 1 was analysed using a Mixed Model for Repeated Measurement (MMRM) including treatment, week, treatment-by-week interaction, and strata as factors and baseline value and baseline value-by-week interaction as covariates.~The estimated treatment differences based on the least square means of the treatment-by week interaction effects are presented by week, including 95% CIs and corresponding p-value.p-value: <0.000195% CI: [20.4, 32.7]Mixed model for repeated measures
Comparison: Week 2~Change in s-iron from baseline to week 2 was analysed using a Mixed Model for Repeated Measurement (MMRM) including treatment, week, treatment-by-week interaction, and strata as factors and baseline value and baseline value-by-week interaction as covariates.~The estimated treatment differences based on the least square means of the treatment-by week interaction effects are presented by week, including 95% CIs and corresponding p-value.p-value: 0.222995% CI: [-1.2, 5.1]Mixed model for repeated measures
Comparison: Week 4~Change in s-iron from baseline to week 4 was analysed using a Mixed Model for Repeated Measurement (MMRM) including treatment, week, treatment-by-week interaction, and strata as factors and baseline value and baseline value-by-week interaction as covariates.~The estimated treatment differences based on the least square means of the treatment-by week interaction effects are presented by week, including 95% CIs and corresponding p-value.p-value: 0.904695% CI: [-2.9, 2.6]Mixed model for repeated measures
Comparison: Week 8~Change in s-iron from baseline to week 8 was analysed using a Mixed Model for Repeated Measurement (MMRM) including treatment, week, treatment-by-week interaction, and strata as factors and baseline value and baseline value-by-week interaction as covariates.~The estimated treatment differences based on the least square means of the treatment-by week interaction effects are presented by week, including 95% CIs and corresponding p-value.p-value: 0.130795% CI: [-5.8, 0.8]Mixed model for repeated measures
Secondary
Change in Fatigue Symptoms From Baseline to Week 1, 2, and 8
Efficacy Change in fatigue symptoms from baseline to week 1, 2, and 8 was measured by the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale. The Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale consisted of 13 items ranging from 0 (not at all) to 4 (very much), except items #7 and #8 which are reversed scored. The total score range is 0-52. A score of less than 30 indicated severe fatigue, and the higher the score, the better outcome/quality of life (QoL). If more than 50% of the items for a subject at a given visit were missing, the total score was not calculated. Total score was calculated as shown below: Total score= Sum of individual scores x 13 / Number of items answered
Time frame: Baseline, week 1, 2, and 8
Population: ITT. All randomised subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Change in Fatigue Symptoms From Baseline to Week 1, 2, and 8 | Week 1 | 5.04 score on a scale | Standard Deviation 8.85 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Fatigue Symptoms From Baseline to Week 1, 2, and 8 | Week 2 | 7.29 score on a scale | Standard Deviation 9.84 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Fatigue Symptoms From Baseline to Week 1, 2, and 8 | Week 8 | 9.13 score on a scale | Standard Deviation 11.09 |
| Iron Sucrose | Change in Fatigue Symptoms From Baseline to Week 1, 2, and 8 | Week 1 | 5.01 score on a scale | Standard Deviation 7.93 |
| Iron Sucrose | Change in Fatigue Symptoms From Baseline to Week 1, 2, and 8 | Week 2 | 7.63 score on a scale | Standard Deviation 9.74 |
| Iron Sucrose | Change in Fatigue Symptoms From Baseline to Week 1, 2, and 8 | Week 8 | 9.07 score on a scale | Standard Deviation 11.4 |
Comparison: Week 1~Change in fatigue symptoms score from baseline to week 1 was analysed using MMRM including treatment, week, treatment-by-week interaction, and strata as factors and baseline score and baseline score-by-week interaction as covariates.p-value: 0.819695% CI: [-0.73, 0.92]Mixed model for repeated measures
Comparison: Week 2~Change in fatigue symptoms score from baseline to week 2 was analysed using MMRM including treatment, week, treatment-by-week interaction, and strata as factors and baseline score and baseline score-by-week interaction as covariates.p-value: 0.713295% CI: [-1.06, 0.73]Mixed model for repeated measures
Comparison: Week 8~Change in fatigue symptoms score from baseline to week 8 was analysed using MMRM including treatment, week, treatment-by-week interaction, and strata as factors and baseline score and baseline score-by-week interaction as covariates.p-value: 0.58695% CI: [-0.71, 1.25]Mixed model for repeated measures
Secondary
Change in Hb Concentration From Baseline to Week 1, 2, and 4
Efficacy Change in Hb concentration from baseline to week 1, 2, and 4.
Time frame: Baseline, week 1, 2, and 4
Population: ITT. All randomised subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Change in Hb Concentration From Baseline to Week 1, 2, and 4 | Week 1 | 0.44 g/dL | Standard Deviation 0.94 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Hb Concentration From Baseline to Week 1, 2, and 4 | Week 2 | 0.77 g/dL | Standard Deviation 1.16 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Hb Concentration From Baseline to Week 1, 2, and 4 | Week 4 | 1.08 g/dL | Standard Deviation 1.32 |
| Iron Sucrose | Change in Hb Concentration From Baseline to Week 1, 2, and 4 | Week 1 | 0.21 g/dL | Standard Deviation 1.02 |
| Iron Sucrose | Change in Hb Concentration From Baseline to Week 1, 2, and 4 | Week 2 | 0.50 g/dL | Standard Deviation 1.15 |
| Iron Sucrose | Change in Hb Concentration From Baseline to Week 1, 2, and 4 | Week 4 | 0.90 g/dL | Standard Deviation 1.33 |
Comparison: Week 1~Change in Hb concentration from baseline to week 1 was analysed using a MMRM including treatment, week, treatment-by-week interaction, and strata as factors and baseline value and baseline value-by-week interaction as covariates.p-value: <0.000195% CI: [0.12, 0.31]Mixed model for repeated measures
Comparison: Week 2~Change in Hb concentration from baseline to week 2 was analysed using a MMRM including treatment, week, treatment-by-week interaction, and strata as factors and baseline value and baseline value-by-week interaction as covariates.p-value: <0.000195% CI: [0.14, 0.36]Mixed model for repeated measures
Comparison: Week 4~Change in Hb concentration from baseline to week 4 was analysed using a MMRM including treatment, week, treatment-by-week interaction, and strata as factors and baseline value and baseline value-by-week interaction as covariates.p-value: 0.020895% CI: [0.02, 0.28]Mixed model for repeated measures
Secondary
Change in S-ferritin From Baseline to Weeks 1, 2, 4, and 8
Efficacy Changes in s-ferritin from baseline to weeks 1, 2, 4, and 8.
Time frame: Baseline, week 1, 2, 4, and 8
Population: ITT. All randomised subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Change in S-ferritin From Baseline to Weeks 1, 2, 4, and 8 | Week 1 | 492.4 ng/mL | Standard Deviation 309.7 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in S-ferritin From Baseline to Weeks 1, 2, 4, and 8 | Week 2 | 381.2 ng/mL | Standard Deviation 283.8 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in S-ferritin From Baseline to Weeks 1, 2, 4, and 8 | Week 4 | 258.4 ng/mL | Standard Deviation 214.5 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in S-ferritin From Baseline to Weeks 1, 2, 4, and 8 | Week 8 | 191.3 ng/mL | Standard Deviation 196.1 |
| Iron Sucrose | Change in S-ferritin From Baseline to Weeks 1, 2, 4, and 8 | Week 8 | 187.9 ng/mL | Standard Deviation 210.6 |
| Iron Sucrose | Change in S-ferritin From Baseline to Weeks 1, 2, 4, and 8 | Week 1 | 183.9 ng/mL | Standard Deviation 129.4 |
| Iron Sucrose | Change in S-ferritin From Baseline to Weeks 1, 2, 4, and 8 | Week 4 | 255.4 ng/mL | Standard Deviation 265.6 |
| Iron Sucrose | Change in S-ferritin From Baseline to Weeks 1, 2, 4, and 8 | Week 2 | 292.4 ng/mL | Standard Deviation 210.4 |
Comparison: Week 1~Change in concentrations of s-ferritin from baseline to week 1 was analysed using a MMRM including treatment, week, treatment-by-week interaction, and strata as factors and baseline value and baseline value-by-week interaction as covariates.~The estimated treatment differences based on the least square means of the treatment by-week interaction effects are presented by week, include 95% CIs and corresponding p-value.p-value: <0.000195% CI: [280.7, 337.8]Mixed model for repeated measures
Comparison: Week 2~Change in concentrations of s-ferritin from baseline to week 2 was analysed using MMRM including treatment, week, treatment-by-week interaction, and strata as factors and baseline value and baseline value-by-week interaction as covariates.~The estimated treatment differences based on the least square means of the treatment by-week interaction effects are presented by week, include 95% CIs and corresponding p-value.p-value: <0.000195% CI: [67.9, 123.7]Mixed model for repeated measures
Comparison: Week 4~Change in concentrations of s-ferritin from baseline to week 4 was analysed using MMRM including treatment, week, treatment-by-week interaction, and strata as factors and baseline value and baseline value-by-week interaction as covariates.~The estimated treatment differences based on the least square means of the treatment by-week interaction effects are presented by week, include 95% CIs and corresponding p-value.p-value: 0.783495% CI: [-21.2, 28.1]Mixed model for repeated measures
Comparison: Week 8~Change in concentrations of s-ferritin from baseline to week 8 was analysed using MMRM including treatment, week, treatment-by-week interaction, and strata as factors and baseline value and baseline value-by-week interaction as covariates.~The estimated treatment differences based on the least square means of the treatment by-week interaction effects are presented by week, include 95% CIs and corresponding p-value.p-value: 0.762195% CI: [-18.1, 24.7]Mixed model for repeated measures
Secondary
Change in Transferrin Saturation (TSAT) From Baseline to Week 1, 2, 4, and 8
Efficacy Changes in transferrin saturation (TSAT) from baseline to week 1, 2, 4, and 8.
Time frame: Baseline, week 1, 2, 4, and 8
Population: ITT. All randomised subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Change in Transferrin Saturation (TSAT) From Baseline to Week 1, 2, 4, and 8 | Week 1 | 12.10 percent | Standard Deviation 31.99 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Transferrin Saturation (TSAT) From Baseline to Week 1, 2, 4, and 8 | Week 2 | 5.84 percent | Standard Deviation 29.79 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Transferrin Saturation (TSAT) From Baseline to Week 1, 2, 4, and 8 | Week 4 | 4.99 percent | Standard Deviation 30 |
| Iron Isomaltoside/Ferric Derisomaltose | Change in Transferrin Saturation (TSAT) From Baseline to Week 1, 2, 4, and 8 | Week 8 | 5.10 percent | Standard Deviation 30.17 |
| Iron Sucrose | Change in Transferrin Saturation (TSAT) From Baseline to Week 1, 2, 4, and 8 | Week 8 | 5.93 percent | Standard Deviation 12.86 |
| Iron Sucrose | Change in Transferrin Saturation (TSAT) From Baseline to Week 1, 2, 4, and 8 | Week 1 | 4.31 percent | Standard Deviation 23.1 |
| Iron Sucrose | Change in Transferrin Saturation (TSAT) From Baseline to Week 1, 2, 4, and 8 | Week 4 | 5.59 percent | Standard Deviation 12.31 |
| Iron Sucrose | Change in Transferrin Saturation (TSAT) From Baseline to Week 1, 2, 4, and 8 | Week 2 | 5.64 percent | Standard Deviation 14.35 |
Comparison: Week 1~Change in TSAT from baseline to week 1 was analysed using MMRM including treatment, week, treatment-by-week interaction, and strata as factors and baseline value and baseline value-by-week interaction as covariates.~The estimated treatment differences based on the least square means of the treatment by-week interaction effects are presented by week, include 95% CIs and corresponding p-value.p-value: <0.000195% CI: [6.9, 10.7]Mixed model for repeated measures
Comparison: Week 2~Change in TSAT from baseline to week 2 was analysed using MMRM including treatment, week, treatment-by-week interaction, and strata as factors and baseline value and baseline value-by-week interaction as covariates.~The estimated treatment differences based on the least square means of the treatment by-week interaction effects are presented by week, include 95% CIs and corresponding p-value.p-value: 0.012995% CI: [0.3, 2.4]Mixed model for repeated measures
Comparison: Week 4~Change in TSAT from baseline to week 4 was analysed using MMRM including treatment, week, treatment-by-week interaction, and strata as factors and baseline value and baseline value-by-week interaction as covariates.~The estimated treatment differences based on the least square means of the treatment by-week interaction effects are presented by week, include 95% CIs and corresponding p-value.p-value: 0.240395% CI: [-0.4, 1.5]Mixed model for repeated measures
Comparison: Week 8~Change in TSAT from baseline to week 8 was analysed using MMRM including treatment, week, treatment-by-week interaction, and strata as factors and baseline value and baseline value-by-week interaction as covariates.~The estimated treatment differences based on the least square means of the treatment by-week interaction effects are presented by week, include 95% CIs and corresponding p-value.p-value: 0.809495% CI: [-0.9, 1.2]Mixed model for repeated measures
Secondary
Composite Cardiovascular Adverse Events (AEs)
Safety Results show the composite cardiovascular AEs, that started on or after the first dose of randomised treatment (i.e. treatment emergent) up to week 8. The reported potential cardiovascular AEs were adjudicated in a blinded fashion by an independent Clinical Endpoint Adjudication Committee (CEAC). The potential cardiovascular AEs included the following: * Death due to any cause * Non-fatal myocardial infarction * Non-fatal stroke * Unstable angina requiring hospitalisation * Congestive heart failure requiring hospitalisation or medical intervention * Arrhythmias * Hypertension * Hypotension Results show only those participants that had adjudicated and confirmed treatment-emergent composite cardiovascular AEs.
Time frame: Baseline, week 1, 2, and 8
Population: Safety analysis set. All randomised subjects who received at least one dose of the investigational product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Composite Cardiovascular Adverse Events (AEs) | 42 Participants |
| Iron Sucrose | Composite Cardiovascular Adverse Events (AEs) | 35 Participants |
Comparison: Adjudicated and confirmed treatment-emergent composite cardiovascular AEs. Any treatment emergent composite cardiovascular AEs were included in the statistical evaluation. The overall incidence of adjudicated and confirmed composite cardiovascular AEs was tabulated and compared between the treatment groups by a Fisher's exact test.p-value: 0.0248Fisher Exact
Secondary
Hb Concentration Increase of ≥1 g/dL From Baseline to Week 1, 2, 4, and 8
Efficacy Results show Hb responders to the treatment. A subject was considered a Hb responder to a certain week if an increase in Hb of at least 1 g/dL from baseline to the week in question was observed (from baseline to week 1, 2, 4, and 8).
Time frame: Baseline, week 1, 2, 4, and 8
Population: ITT. All randomised subjects.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Hb Concentration Increase of ≥1 g/dL From Baseline to Week 1, 2, 4, and 8 | Responder YES week 8 | 474 Participants |
| Iron Isomaltoside/Ferric Derisomaltose | Hb Concentration Increase of ≥1 g/dL From Baseline to Week 1, 2, 4, and 8 | Responder YES week 2 | 339 Participants |
| Iron Isomaltoside/Ferric Derisomaltose | Hb Concentration Increase of ≥1 g/dL From Baseline to Week 1, 2, 4, and 8 | Responder YES week 1 | 200 Participants |
| Iron Isomaltoside/Ferric Derisomaltose | Hb Concentration Increase of ≥1 g/dL From Baseline to Week 1, 2, 4, and 8 | Responder YES week 4 | 430 Participants |
| Iron Sucrose | Hb Concentration Increase of ≥1 g/dL From Baseline to Week 1, 2, 4, and 8 | Responder YES week 1 | 78 Participants |
| Iron Sucrose | Hb Concentration Increase of ≥1 g/dL From Baseline to Week 1, 2, 4, and 8 | Responder YES week 8 | 226 Participants |
| Iron Sucrose | Hb Concentration Increase of ≥1 g/dL From Baseline to Week 1, 2, 4, and 8 | Responder YES week 4 | 174 Participants |
| Iron Sucrose | Hb Concentration Increase of ≥1 g/dL From Baseline to Week 1, 2, 4, and 8 | Responder YES week 2 | 112 Participants |
Comparison: Week 1~Hb increase of ≥1 g/dL from baseline to week 1.~Proportion of Hb responders to each week was analysed using a repeated measures logistic regression model with treatment, visit, strata, and treatment by visit interaction as fixed effects and baseline value as covariate.p-value: 0.047895% CI: [1, 1.87]Repeated measures logistic regressioin
Comparison: Week 2~Hb increase of ≥1 g/dL from baseline to week 2.~Proportion of Hb responders to each week was analysed using a repeated measures logistic regression model with treatment, visit, strata, and treatment by visit interaction as fixed effects and baseline value as covariate.p-value: <0.000195% CI: [1.39, 2.36]Repeated measures logistic regressioin
Comparison: Week 4~Hb increase of ≥1 g/dL from baseline to week 4.~Proportion of Hb responders to each week was analysed using a repeated measures logistic regression model with treatment, visit, strata, and treatment by visit interaction as fixed effects and baseline value as covariate.p-value: 0.004895% CI: [1.11, 1.79]Repeated measures logistic regressioin
Comparison: Week 8~Hb increase of ≥1 g/dL from baseline to week 8.~Proportion of Hb responders to each week was analysed using a repeated measures logistic regression model with treatment, visit, strata, and treatment by visit interaction as fixed effects and baseline value as covariate.p-value: 0.94495% CI: [0.8, 1.27]Repeated measures logistic regressioin
Secondary
Hb Concentration Increase of ≥2 g/dL at Any Time From Week 1 to Week 8
Efficacy Results show the number of participants who achieved Hb concentration increase of ≥2 g/dL at any time from week 1 to week 8.
Time frame: Week 1 to week 8
Population: ITT. All randomised subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Hb Concentration Increase of ≥2 g/dL at Any Time From Week 1 to Week 8 | 307 Participants |
| Iron Sucrose | Hb Concentration Increase of ≥2 g/dL at Any Time From Week 1 to Week 8 | 133 Participants |
Comparison: The proportion of subjects who achieved an increase in Hb concentration ≥2 g/dL at any time from week 1 to week 8 was analysed using a logistic regression model with treatment and strata as fixed effects.~The estimated treatment ratio of iron isomaltoside/ferric derisomaltose versus iron sucrose was presented with 95% CI and corresponding p-value.p-value: 0.103595% CI: [0.96, 1.6]Regression, Logistic
Secondary
Hb Concentration of >12 g/dL at Any Time From Week 1 to Week 8
Efficacy Hb concentration of \>12 g/dL at any time from week 1 to week 8. Results show the number of participants who achieved Hb concentration of \>12 g/dL at any time from week 1 to week 8.
Time frame: Week 1 to week 8
Population: ITT. All randomised subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Hb Concentration of >12 g/dL at Any Time From Week 1 to Week 8 | 259 Participants |
| Iron Sucrose | Hb Concentration of >12 g/dL at Any Time From Week 1 to Week 8 | 121 Participants |
Comparison: The proportion of subjects who achieved a Hb level of \>12 g/dL at any time from week 1 to week 8 was analysed using a logistic regression model with treatment and strata as fixed effects. The estimated treatment ratio of iron isomaltoside/ferric derisomaltose versus iron sucrose is presented with 95% CI and corresponding p-value.p-value: 0.507495% CI: [0.83, 1.45]Regression, Logistic
Secondary
Health Care Resource Use Questionnaire
Pharmacoeconomics Resources used by the health care staff (per administration), measured by the health care resource use questionnaire. The questionnaire assessed the time used by the health care staff during administration of the investigational product and the administration time (including the observational time). The health care participants included in the evaluation were: investigator, pharmacist, physician, study coordinator, study nurse. The data for this endpoint show the responses at baseline for both treatment groups. The frequency of drug administration between the 2 treatment groups is different (i.e. up to a factor 5 more frequent in the iron sucrose treatment group).
Time frame: Baseline
Population: ITT. All randomised subjects.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Health Care Resource Use Questionnaire | Time spent per site staff | 1.17 hours |
| Iron Isomaltoside/Ferric Derisomaltose | Health Care Resource Use Questionnaire | Time spent per subject | 2.58 hours |
| Iron Sucrose | Health Care Resource Use Questionnaire | Time spent per site staff | 1.00 hours |
| Iron Sucrose | Health Care Resource Use Questionnaire | Time spent per subject | 2.33 hours |
Secondary
Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Cost of Public Transport/Taxi And Parking
Pharmacoeconomics The Intervals in Screening for Diabetic Retinopathy (ISDR) questionnaire at the baseline visit assessed the resources used by subjects to receive treatment. Resources used on other trial activities were not included. ISDR responses were summarised using descriptive statistics. The data for this endpoint show the responses at baseline for both treatment groups. The frequency of drug administration between the 2 treatment groups is different, however, (i.e. up to a factor 5 in the iron sucrose treatment group).
Time frame: Baseline
Population: ITT. All randomised subjects.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Cost of Public Transport/Taxi And Parking | Cost of public transport/taxi | 0.0 US dollars ($) |
| Iron Isomaltoside/Ferric Derisomaltose | Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Cost of Public Transport/Taxi And Parking | Cost of parking | 0.0 US dollars ($) |
| Iron Sucrose | Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Cost of Public Transport/Taxi And Parking | Cost of public transport/taxi | 0.0 US dollars ($) |
| Iron Sucrose | Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Cost of Public Transport/Taxi And Parking | Cost of parking | 0.0 US dollars ($) |
Secondary
Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Participants/Others Who Took Time Off Work to Attend Visits
Pharmacoeconomics The Intervals in Screening for Diabetic Retinopathy (ISDR) questionnaire at the baseline visit assessed the resources used by subjects to receive treatment. Resources used on other trial activities were not included. ISDR responses were summarised using descriptive statistics. The data for this endpoint show the responses at baseline for both treatment groups. The frequency of drug administration between the 2 treatment groups is different, however, (i.e. up to a factor 5 in the iron sucrose treatment group).
Time frame: Baseline
Population: ITT. All randomised subjects.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Participants/Others Who Took Time Off Work to Attend Visits | In employment, YES | 152 Participants |
| Iron Isomaltoside/Ferric Derisomaltose | Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Participants/Others Who Took Time Off Work to Attend Visits | Took time off work to attend, YES | 70 Participants |
| Iron Isomaltoside/Ferric Derisomaltose | Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Participants/Others Who Took Time Off Work to Attend Visits | Assistance by others to attend visit, YES | 410 Participants |
| Iron Isomaltoside/Ferric Derisomaltose | Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Participants/Others Who Took Time Off Work to Attend Visits | Others took time off work to attend, YES | 82 Participants |
| Iron Sucrose | Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Participants/Others Who Took Time Off Work to Attend Visits | Others took time off work to attend, YES | 40 Participants |
| Iron Sucrose | Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Participants/Others Who Took Time Off Work to Attend Visits | In employment, YES | 57 Participants |
| Iron Sucrose | Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Participants/Others Who Took Time Off Work to Attend Visits | Assistance by others to attend visit, YES | 197 Participants |
| Iron Sucrose | Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Participants/Others Who Took Time Off Work to Attend Visits | Took time off work to attend, YES | 26 Participants |
Secondary
Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Return Journey by Car
Pharmacoeconomics The Intervals in Screening for Diabetic Retinopathy (ISDR) questionnaire at the baseline visit assessed the resources used by subjects to receive treatment. Resources used on other trial activities were not included. ISDR responses were summarised using descriptive statistics. The data for this endpoint show the responses at baseline for both treatment groups. The frequency of drug administration between the 2 treatment groups is different, however, (i.e. up to a factor 5 in the iron sucrose treatment group).
Time frame: Baseline
Population: ITT. All randomised subjects. The number of participants analyzed were less the number of participants starting the study since not all participants had data collected for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Return Journey by Car | 19.0 miles |
| Iron Sucrose | Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Return Journey by Car | 18.0 miles |
Secondary
Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Time Spent on Visit/Helping on Visit
Pharmacoeconomics The Intervals in Screening for Diabetic Retinopathy (ISDR) questionnaire at the baseline visit assessed the resources used by subjects to receive treatment. Resources used on other trial activities were not included. ISDR responses were summarised using descriptive statistics. The data for this endpoint show the responses at baseline for both treatment groups. The frequency of drug administration between the 2 treatment groups is different, however, (i.e. up to a factor 5 in the iron sucrose treatment group).
Time frame: Baseline
Population: ITT. All randomised subjects.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Time Spent on Visit/Helping on Visit | Time spent on visit | 2.00 Hours |
| Iron Isomaltoside/Ferric Derisomaltose | Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Time Spent on Visit/Helping on Visit | Total time spent helping on visit | 2.00 Hours |
| Iron Sucrose | Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Time Spent on Visit/Helping on Visit | Time spent on visit | 2.00 Hours |
| Iron Sucrose | Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Time Spent on Visit/Helping on Visit | Total time spent helping on visit | 2.00 Hours |
Secondary
S-Ferritin Concentration of ≥100 ng/mL and Transferrin Saturation (TSAT) of 20-50% at Any Time From Week 1 to Week 8
Efficacy Proportion of subjects reaching the composite endpoint of s-ferritin concentration ≥100 ng/mL and TSAT of 20-50% at any time from week 1 to 8.
Time frame: Week 1 to week 8
Population: ITT. All randomised subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | S-Ferritin Concentration of ≥100 ng/mL and Transferrin Saturation (TSAT) of 20-50% at Any Time From Week 1 to Week 8 | 873 Participants |
| Iron Sucrose | S-Ferritin Concentration of ≥100 ng/mL and Transferrin Saturation (TSAT) of 20-50% at Any Time From Week 1 to Week 8 | 388 Participants |
Comparison: Proportion of subject who achieved a s-ferritin level of ≥100 ng/mL AND a TSAT of 20-50% at any time from week 1 to week 8 was analysed using a logistic regression model with treatment and strata as fixed effects.~The estimated treatment ratio of iron isomaltoside/ferric derisomaltose versus iron sucrose is presented with 95% CI and corresponding p-value.p-value: <0.000195% CI: [1.38, 2.4]Regression, Logistic
Secondary
S-phosphate <2 mg/dL at Any Time From Baseline to Week 1, 2, 4, and 8
Safety Results show the number of participants who had s-phosphate \<2 mg/dL at any time from baseline to week 1, 2, 4, or 8.
Time frame: Baseline, week 1, 2, 4, and 8
Population: Safety analysis set. All randomised subjects who received at least one dose of the investigational product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | S-phosphate <2 mg/dL at Any Time From Baseline to Week 1, 2, 4, and 8 | 32 Participants |
| Iron Sucrose | S-phosphate <2 mg/dL at Any Time From Baseline to Week 1, 2, 4, and 8 | 4 Participants |
Secondary
Time to Change in Hb Concentration ≥1 g/dL
Efficacy Time to change in Hb concentration ≥1 g/dL. Subjects who showed Hb concentration increase of ≥1 g/dL (from baseline to week 1, 2, 4, and 8). For responders, time to Hb response was defined as the scheduled time from baseline until the visit where the first Hb response was measured.
Time frame: Baseline, week 1, 2, 4, and 8
Population: ITT. All randomised subjects.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Time to Change in Hb Concentration ≥1 g/dL | 56 Days |
| Iron Sucrose | Time to Change in Hb Concentration ≥1 g/dL | 56 Days |
Comparison: Time to Hb response was estimated using the Kaplan-Meier method and the hypothesis of no treatment difference was assessed by a 2-sided log-rank test.p-value: 0.0174Log Rank
Secondary
Time to First Composite Cardiovascular Safety AE
Safety Time to first composite cardiovascular AE was defined as the actual time in days from first dose of treatment until the date of the composite cardiovascular AE. For subjects not reporting a composite cardiovascular AE, the time was censored at the date of the last attended visit. Only the adjudicated and confirmed composite cardiovascular safety AEs, as judged by the CEAC, were considered for this endpoint. Time to first composite cardiovascular AE was defined as the actual time in days from first dose of treatment until the date of the composite cardiovascular AE. For subjects not reporting a composite cardiovascular AE, the time was censored at the date of the last attended visit.
Time frame: Baseline, week 1, 2, 4, and 8
Population: Safety analysis set. All randomised subjects who received at least one dose of the investigational product.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Iron Isomaltoside/Ferric Derisomaltose | Time to First Composite Cardiovascular Safety AE | NA Week |
| Iron Sucrose | Time to First Composite Cardiovascular Safety AE | NA Week |
Comparison: The time to first adjudicated and confirmed composite cardiovascular AEs was estimated using the Kaplan-Meier method and the hypothesis of no treatment difference was assessed by a log-rank test.p-value: 0.0185Log Rank