Clinical Trial Results:
A phase III, randomized, open-label study of intravenous iron isomaltoside 1000 (Monofer®) as mono therapy (without erythropoeisis stimulating agents) in comparison with oral iron sulfate in subjects with non-myeloid malignancies associated with Chemotherapy induced anaemia (CIA)
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Summary
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EudraCT number |
2009-016727-53 |
Trial protocol |
DK GB SE DE ES |
Global end of trial date |
23 Apr 2014
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Results information
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Results version number |
v2(current) |
This version publication date |
06 Apr 2016
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First version publication date |
16 Jul 2015
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
P-Monofer-CIA-01
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01145638 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Pharmacosmos A/S
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Sponsor organisation address |
Roervangsvej 30, Holbaek, Denmark, DK-4300
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Public contact |
Clinical trial disclosure desk, Pharmacosmos A/S, 45 59485935, trial@pharmacosmos.com
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Scientific contact |
Clinical trial disclosure desk, Pharmacosmos A/S, 45 59485935, trial@pharmacosmos.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
23 Apr 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
23 Apr 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
23 Apr 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To demonstrate that intravenous iron isomaltoside 1000 (Monofer®) is non-inferior to oral iron sulphate in the ability to increase haemoglobin (Hb) in subjects with chemotherapy induced anemia and either absolute or functional iron deficiency.
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Protection of trial subjects |
The protocol and amendments were approved by local ethics committees/Institutional Review Boards and competent authorities. The trial was conducted in accordance with good clinical practice and the Declaration of Helsinki. Informed consent was obtained in writing prior to any trial-related activities.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
19 Oct 2010
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Russian Federation: 47
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Country: Number of subjects enrolled |
United States: 18
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Country: Number of subjects enrolled |
India: 205
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Country: Number of subjects enrolled |
Poland: 56
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Country: Number of subjects enrolled |
Spain: 2
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Country: Number of subjects enrolled |
Sweden: 8
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Country: Number of subjects enrolled |
Denmark: 4
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Country: Number of subjects enrolled |
Germany: 10
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Worldwide total number of subjects |
350
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EEA total number of subjects |
80
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
288
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From 65 to 84 years |
61
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85 years and over |
1
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Recruitment
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Recruitment details |
Subjects were screened in the period 19 October 2010 to 30 October 2013. The trial took place at 47 sites (hospitals or private cancer clinics) in 3 continents: 18 in India, 9 in Russia, 7 in Poland, 4 in Germany, 3 in USA, 2 in Sweden and Spain, and 1 in Denmark and UK. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Patients who were ≥18 years of age, diagnosed with non-myeloid malignancies receiving chemotherapy at least 1 day prior to screening and who were going to receive at least 2 more chemotherapy cycles, Hb <12.0 g/dL, TSAT <50%, ferritin <800 μg/L, and with an eastern cooperative oncology group performance status of 0-2 were eligible to participate. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Group A, iron isomaltoside 1000 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Subjects treated with iron isomaltoside 1000 were randomised to either an IV infusion (group A1) of maximum 1000 mg (the maximum dose per infusion was 1000 mg for subjects with a weight >45 kg, 750 mg for subjects with a weight between 35 and 45 kg, and 500 mg for subjects with a weight <35 kg) iron isomaltoside 1000 as single doses over approximately 15 minutes (full iron replacement was achieved by 1 or up to 2 doses at a weekly interval) or IV bolus injections (group A2) of 500 mg iron isomaltoside 1000 administered over approximately 2 minutes once weekly until full replacement dose was achieved (a total of 1-4 doses at a weekly interval). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Iron isomaltoside 1000
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Investigational medicinal product code |
ATC code: B03AC
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Other name |
Monofer, Monover, Monofar, Monoferro
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Subjects treated with iron isomaltoside 1000 were randomised to either an IV infusion (group A1) of maximum 1000 mg (the maximum dose per infusion was 1000 mg for subjects with a weight >45 kg, 750 mg for subjects with a weight between 35 and 45 kg, and 500 mg for subjects with a weight <35 kg) iron isomaltoside 1000 as single doses over approximately 15 minutes (full iron replacement was achieved by 1 or up to 2 doses at a weekly interval) or IV bolus injections (group A2) of 500 mg iron isomaltoside 1000 administered over approximately 2 minutes once weekly until full replacement dose was achieved (a total of 1-4 doses at a weekly interval).
Iron isomaltoside 1000 is available as a dark brown, non-transparent aqueous solution for injection/infusion containing 100 mg iron/mL with pH between 5.0 and 7.0.
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Arm title
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Group B, iron sulphate | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Subjects receiving oral iron sulphate were treated daily for 12 weeks with 200 mg given as 100 mg twice a day. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Iron sulphate
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Investigational medicinal product code |
ATC code: B03AA07
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Other name |
Ferro Duretter
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects receiving oral iron sulphate were treated daily for 12 weeks with 200 mg given as 100 mg twice a day.
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Baseline characteristics reporting groups
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Reporting group title |
Group A, iron isomaltoside 1000
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Reporting group description |
Subjects treated with iron isomaltoside 1000 were randomised to either an IV infusion (group A1) of maximum 1000 mg (the maximum dose per infusion was 1000 mg for subjects with a weight >45 kg, 750 mg for subjects with a weight between 35 and 45 kg, and 500 mg for subjects with a weight <35 kg) iron isomaltoside 1000 as single doses over approximately 15 minutes (full iron replacement was achieved by 1 or up to 2 doses at a weekly interval) or IV bolus injections (group A2) of 500 mg iron isomaltoside 1000 administered over approximately 2 minutes once weekly until full replacement dose was achieved (a total of 1-4 doses at a weekly interval). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Group B, iron sulphate
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Reporting group description |
Subjects receiving oral iron sulphate were treated daily for 12 weeks with 200 mg given as 100 mg twice a day. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Safety analysis set
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The safety population (N=341) included all subjects who were randomised and received at least one dose of the trial drug.
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Subject analysis set title |
Full analysis set
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The full analysis set (N=337) included all subjects who were randomised into the trial, received at least one dose of the trial drug, and had at least one post-baseline Hb assessment.
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Subject analysis set title |
Per protocol analysis set
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The per protocol population (N=315) included all subjects in the FAS who did not have any major protocol deviation of clinical or statistical relevance.
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End points reporting groups
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Reporting group title |
Group A, iron isomaltoside 1000
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Reporting group description |
Subjects treated with iron isomaltoside 1000 were randomised to either an IV infusion (group A1) of maximum 1000 mg (the maximum dose per infusion was 1000 mg for subjects with a weight >45 kg, 750 mg for subjects with a weight between 35 and 45 kg, and 500 mg for subjects with a weight <35 kg) iron isomaltoside 1000 as single doses over approximately 15 minutes (full iron replacement was achieved by 1 or up to 2 doses at a weekly interval) or IV bolus injections (group A2) of 500 mg iron isomaltoside 1000 administered over approximately 2 minutes once weekly until full replacement dose was achieved (a total of 1-4 doses at a weekly interval). | ||
Reporting group title |
Group B, iron sulphate
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Reporting group description |
Subjects receiving oral iron sulphate were treated daily for 12 weeks with 200 mg given as 100 mg twice a day. | ||
Subject analysis set title |
Safety analysis set
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The safety population (N=341) included all subjects who were randomised and received at least one dose of the trial drug.
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Subject analysis set title |
Full analysis set
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The full analysis set (N=337) included all subjects who were randomised into the trial, received at least one dose of the trial drug, and had at least one post-baseline Hb assessment.
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Subject analysis set title |
Per protocol analysis set
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The per protocol population (N=315) included all subjects in the FAS who did not have any major protocol deviation of clinical or statistical relevance.
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End point title |
Change in Hb concentration from baseline to week 4, FAS | ||||||||||||
End point description |
Analysis performed on the FAS.
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End point type |
Primary
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End point timeframe |
Change in Hb concentration from baseline to week 4.
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Statistical analysis title |
Test for non-inferiority, MMRM | ||||||||||||
Statistical analysis description |
A mixed model for repeated measures (MMRM) was used to compare the average change in Hb concentration from baseline to week 4.
With a 2:1 randomisation, a two-sided significance level of 5%, and a non-inferiority margin of -0.5 g/dL, there was 80% power to demonstrate non-inferiority with 214 subjects in group A and 107 subjects in group B.
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Comparison groups |
Group B, iron sulphate v Group A, iron isomaltoside 1000
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Number of subjects included in analysis |
291
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [1] | ||||||||||||
P-value |
= 0.0002 [2] | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.0161
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.261 | ||||||||||||
upper limit |
0.293 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.1406
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| Notes [1] - Treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/No), and country were included as factors and baseline Hb were included as covariate. The treatment difference at week 4 was derived from the interaction between treatment and visit. The primary analysis was to assess non-inferiority and the non-inferiority margin was set as -0.5 g/dL. [2] - As the trial was designed to demonstrate non-inferiority, the analyses of FAS and PP population would lead to similar conclusions and therefore the analyses for both analysis sets needed to be powered properly. |
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Statistical analysis title |
Test for superiority, MMRM | ||||||||||||
Statistical analysis description |
From the primary analysis model, the p-value for the test of superiority of group A (iron isomaltoside 1000 group) versus group B (iron sulphate group) was derived.
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Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
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Number of subjects included in analysis |
291
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.9092 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.0161
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.261 | ||||||||||||
upper limit |
0.293 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.1406
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End point title |
Change in Hb concentration from baseline to week 4, PP | ||||||||||||
End point description |
Performed on the PP analysis set.
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End point type |
Primary
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End point timeframe |
Change in Hb concentration from baseline to week 4.
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Statistical analysis title |
Test for non-inferiority, MMRM | ||||||||||||
Statistical analysis description |
A mixed model for repeated measures (MMRM) was used to compare the average change in Hb concentration from baseline to week 4.
The number of subjects may differ from the analysis population if data is missing.
With a 2:1 randomisation, a two-sided significance level of 5%, and a non-inferiority margin of -0.5 g/dL, there was 80% power to demonstrate non-inferiority with 214 subjects in group A and 107 subjects in group B.
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Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
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Number of subjects included in analysis |
273
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [3] | ||||||||||||
P-value |
= 0.0006 [4] | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.0071
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.291 | ||||||||||||
upper limit |
0.276 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.1436
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| Notes [3] - Treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/No), and country were included as factors and baseline Hb were included as covariate. The treatment difference at week 4 was derived from the interaction between treatment and visit. The primary analysis was to assess non-inferiority and the non-inferiority margin was set as -0.5 g/dL. [4] - As the trial was designed to demonstrate non-inferiority, the analyses of FAS and PP population would lead to similar conclusions and therefore the analyses for both analysis sets needed to be powered properly. |
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Statistical analysis title |
Test for superiority, MMRM | ||||||||||||
Statistical analysis description |
In case the 95 % CI lay entirely above 0, this was evidence of superiority in terms of statistical significance at the 5 % level. In that case, the p-value associated with a test of superiority was calculated and evaluated whether this was sufficiently small to reject the hypothesis of no difference.
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Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
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Number of subjects included in analysis |
273
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.9609 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.0071
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.291 | ||||||||||||
upper limit |
0.276 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.1436
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End point title |
Proportion of subjects who achieved target limits of Hb (men 13-18 g/dL, women 12-16 g/dL) and had change in Hb concentration ≥ 1.0 g/dL at week 2, 4, 8, or 12 | |||||||||||||||
End point description |
The subjects needed to fulfill 2 criteria in order to be a responder:
1) achieved target limits of Hb (men 13-18 g/dL, women 12-16 g/dL)
2) have had a change in Hb concentration ≥ 1.0 g/dL at week 2, 4, 8, or 12
The analysis was performed on the FAS.
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End point type |
Secondary
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End point timeframe |
Proportion of subjects who achieved target limits of Hb (men 13-18 g/dL, women 12-16 g/dL) and had change in Hb concentration ≥ 1.0 g/dL at week 2, 4, 8, or 12.
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Statistical analysis title |
Test for superiority, logistic regression | |||||||||||||||
Statistical analysis description |
The p-value is calculated by logistic regression with treatment and platinum based chemotherapy (Yes/ No) as factors and baseline values as covariates using PROC LOGISTIC Procedure.
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Comparison groups |
Group B, iron sulphate v Group A, iron isomaltoside 1000
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Number of subjects included in analysis |
319
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||
P-value |
= 0.7772 | |||||||||||||||
Method |
Regression, Logistic | |||||||||||||||
Confidence interval |
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End point title |
Proportion of subjects who had a change in Hb concentration ≥ 2.0 g/dL at week 2 or 4 | |||||||||||||||
End point description |
The subjects had to have an increase in Hb ≥ 2.0 g/dL at either week 2 or week 4 in order to be a responder.
The analysis was performed on the FAS.
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End point type |
Secondary
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End point timeframe |
Proportion of subjects who had a change in Hb concentration ≥ 2.0 g/dL at week 2 or 4.
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Statistical analysis title |
Superiority test, logistic regression | |||||||||||||||
Statistical analysis description |
The p-value is calculated by logistic regression with treatment and platinum based chemotherapy (Yes/ No) as factors and baseline values as covariates.
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Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
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Number of subjects included in analysis |
318
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Analysis specification |
Pre-specified
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|||||||||||||||
Analysis type |
superiority | |||||||||||||||
P-value |
= 0.1193 | |||||||||||||||
Method |
Regression, Logistic | |||||||||||||||
Confidence interval |
||||||||||||||||
|
||||||||||||||||
End point title |
Proportion of subjects who had a change in Hb concentration ≥ 2.0 g/dL at week 2, 4, 8, or 12 | |||||||||||||||
End point description |
The subjects had to have an increase in Hb ≥ 2.0 g/dL at either week 2, 4, 8 or 12 in order to be a responder.
The analysis was performed on the FAS.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Proportion of subjects who had a change in Hb concentration ≥ 2.0 g/dL at week 2, 4, 8, or 12.
|
|||||||||||||||
|
||||||||||||||||
Statistical analysis title |
Superiority tested by logistic regression | |||||||||||||||
Statistical analysis description |
The p-value is calculated by Logistic Regression with treatment and platinum based chemotherapy (Yes/ No) as factors and baseline values as covariates.
|
|||||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
|||||||||||||||
Number of subjects included in analysis |
319
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
superiority | |||||||||||||||
P-value |
= 0.8372 | |||||||||||||||
Method |
Regression, Logistic | |||||||||||||||
Confidence interval |
||||||||||||||||
|
||||||||||||||||
End point title |
Number of subjects receiving transfusions | |||||||||||||||
End point description |
Number of subjects receiving transfusions.
The analysis was performed on the FAS.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
The endpoint covers the complete trial period.
|
|||||||||||||||
|
||||||||||||||||
Statistical analysis title |
Superiority tested by chi-squared | |||||||||||||||
Statistical analysis description |
The p-value was calculated by using chi-squared.
|
|||||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
|||||||||||||||
Number of subjects included in analysis |
337
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
superiority | |||||||||||||||
P-value |
= 0.4509 | |||||||||||||||
Method |
Chi-squared | |||||||||||||||
Confidence interval |
||||||||||||||||
|
|||||||||||||
End point title |
Change in Hb from baseline to week 1 | ||||||||||||
End point description |
Change in Hb from baseline to week 1.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in Hb from baseline to week 1.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/ No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
325
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0799 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.2006
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.024 | ||||||||||||
upper limit |
0.425 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.1139
|
||||||||||||
|
|||||||||||||
End point title |
Change in Hb from baseline to week 2 | ||||||||||||
End point description |
Change in Hb from baseline to week 2.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in Hb from baseline to week 2.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
310
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.2448 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.1502
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.104 | ||||||||||||
upper limit |
0.404 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.1287
|
||||||||||||
|
|||||||||||||
End point title |
Change in Hb from baseline to week 8 | ||||||||||||
End point description |
Change in Hb from baseline to week 8.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in Hb from baseline to week 8.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
265
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.881 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.0268
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.326 | ||||||||||||
upper limit |
0.379 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.1788
|
||||||||||||
|
|||||||||||||
End point title |
Change in Hb from baseline to week 12 | ||||||||||||
End point description |
Change in Hb from baseline to week 12.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in Hb from baseline to week 12.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
245
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.5786 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.1152
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.294 | ||||||||||||
upper limit |
0.524 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.2071
|
||||||||||||
|
|||||||||||||
End point title |
Change in Hb from baseline to week 24 | ||||||||||||
End point description |
Change in Hb from baseline to week 24.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in Hb from baseline to week 24.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
229
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.8495 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.0526
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.599 | ||||||||||||
upper limit |
0.494 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.2766
|
||||||||||||
|
|||||||||||||
End point title |
Change in total iron binding capacity (TIBC) from baseline to week 1 | ||||||||||||
End point description |
Change in total iron binding capacity (TIBC) from baseline to week 1.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in total iron binding capacity (TIBC) from baseline to week 1.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
325
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.003 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-2.5652
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-4.252 | ||||||||||||
upper limit |
-0.878 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.856
|
||||||||||||
|
|||||||||||||
End point title |
Change in total iron binding capacity (TIBC) from baseline to week 2 | ||||||||||||
End point description |
Change in total iron binding capacity (TIBC) from baseline to week 2.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in total iron binding capacity (TIBC) from baseline to week 2.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
310
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-3.7922
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-5.599 | ||||||||||||
upper limit |
-1.985 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.9164
|
||||||||||||
|
|||||||||||||
End point title |
Change in total iron binding capacity (TIBC) from baseline to week 4 | ||||||||||||
End point description |
Change in total iron binding capacity (TIBC) from baseline to week 4.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in total iron binding capacity (TIBC) from baseline to week 4.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
292
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-4.6663
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-6.901 | ||||||||||||
upper limit |
-2.432 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
1.1327
|
||||||||||||
|
|||||||||||||
End point title |
Change in total iron binding capacity (TIBC) from baseline to week 8 | ||||||||||||
End point description |
Change in total iron binding capacity (TIBC) from baseline to week 8.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in total iron binding capacity (TIBC) from baseline to week 8.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
266
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0278 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-3.1772
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-6.002 | ||||||||||||
upper limit |
-0.352 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.0278
|
||||||||||||
|
|||||||||||||
End point title |
Change in total iron binding capacity (TIBC) from baseline to week 12 | ||||||||||||
End point description |
Change in total iron binding capacity (TIBC) from baseline to week 12.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in total iron binding capacity (TIBC) from baseline to week 12.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
244
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.1662 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-1.8274
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-4.421 | ||||||||||||
upper limit |
0.766 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
1.3151
|
||||||||||||
|
|||||||||||||
End point title |
Change in total iron binding capacity (TIBC) from baseline to week 24 | ||||||||||||
End point description |
Change in total iron binding capacity (TIBC) from baseline to week 24.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in total iron binding capacity (TIBC) from baseline to week 24.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
227
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0396 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-3.2405
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-6.325 | ||||||||||||
upper limit |
-0.156 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
1.5614
|
||||||||||||
|
|||||||||||||
End point title |
Change in s-iron from baseline to week 1 | ||||||||||||
End point description |
Change in s-iron from baseline to week 1.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in s-iron from baseline to week 1.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
325
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.013 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
3.3255
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.708 | ||||||||||||
upper limit |
5.943 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
1.33
|
||||||||||||
|
|||||||||||||
End point title |
Change in s-iron from baseline to week 2 | ||||||||||||
End point description |
Change in s-iron from baseline to week 2.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in s-iron from baseline to week 2.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
310
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.9993 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.0014
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-2.91 | ||||||||||||
upper limit |
2.908 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
1.474
|
||||||||||||
|
|||||||||||||
End point title |
Change in s-iron from baseline to week 4 | ||||||||||||
End point description |
Change in s-iron from baseline to week 4.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in s-iron from baseline to week 4.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group B, iron sulphate v Group A, iron isomaltoside 1000
|
||||||||||||
Number of subjects included in analysis |
292
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.9473 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.0801
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-2.463 | ||||||||||||
upper limit |
2.303 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
1.2092
|
||||||||||||
|
|||||||||||||
End point title |
Change in s-iron from baseline to week 8 | ||||||||||||
End point description |
Change in s-iron from baseline to week 8.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in s-iron from baseline to week 8.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
266
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.3829 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-1.0612
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-3.457 | ||||||||||||
upper limit |
1.335 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
1.2126
|
||||||||||||
|
|||||||||||||
End point title |
Change in s-iron from baseline to week 12 | ||||||||||||
End point description |
Change in s-iron from baseline to week 12.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in s-iron from baseline to week 12.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
244
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.1239 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-2.053
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-4.676 | ||||||||||||
upper limit |
0.57 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
1.3251
|
||||||||||||
|
|||||||||||||
End point title |
Change in s-iron from baseline to week 24 | ||||||||||||
End point description |
Change in s-iron from baseline to week 24.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in s-iron from baseline to week 24.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
228
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.7693 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.3722
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-2.879 | ||||||||||||
upper limit |
2.135 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
1.2656
|
||||||||||||
|
|||||||||||||
End point title |
Change in s-ferritin from baseline to week 1. | ||||||||||||
End point description |
Change in s-ferritin from baseline to week 1.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in s-ferritin from baseline to week 1.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
325
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
434.9819
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
377.818 | ||||||||||||
upper limit |
492.146 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
29.0261
|
||||||||||||
|
|||||||||||||
End point title |
Change in s-ferritin from baseline to week 2 | ||||||||||||
End point description |
Change in s-ferritin from baseline to week 2.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in s-ferritin from baseline to week 2.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
309
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
477.6825
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
373.581 | ||||||||||||
upper limit |
581.785 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
51.1129
|
||||||||||||
|
|||||||||||||
End point title |
Change in s-ferritin from baseline to week 4 | ||||||||||||
End point description |
Change in s-ferritin from baseline to week 4.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in s-ferritin from baseline to week 4.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
291
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
324.0235
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
253.896 | ||||||||||||
upper limit |
394.151 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
35.6293
|
||||||||||||
|
|||||||||||||
End point title |
Change in s-ferritin from baseline to week 8 | ||||||||||||
End point description |
Change in s-ferritin from baseline to week 8.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in s-ferritin from baseline to week 8.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
266
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
234.8969
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
174.5 | ||||||||||||
upper limit |
295.294 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
30.6672
|
||||||||||||
|
|||||||||||||
End point title |
Change in s-ferritin from baseline to week 12 | ||||||||||||
End point description |
Change in s-ferritin from baseline to week 12.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in s-ferritin from baseline to week 12.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
245
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
179.2712
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
112.44 | ||||||||||||
upper limit |
246.102 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
33.8524
|
||||||||||||
|
|||||||||||||
End point title |
Change in s-ferritin from baseline to week 24 | ||||||||||||
End point description |
Change in s-ferritin from baseline to week 24.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in s-ferritin from baseline to week 24.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
228
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0003 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
224.8656
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
102.9 | ||||||||||||
upper limit |
346.831 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
61.9284
|
||||||||||||
|
|||||||||||||
End point title |
Change in transferrin saturation (TSAT) from baseline to week 1 | ||||||||||||
End point description |
Change in transferrin saturation (TSAT) from baseline to week 1.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in transferrin saturation (TSAT) from baseline to week 1.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
325
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0025 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
6.1406
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
2.179 | ||||||||||||
upper limit |
10.102 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
2.0124
|
||||||||||||
|
|||||||||||||
End point title |
Change in transferrin saturation (TSAT) from baseline to week 2 | ||||||||||||
End point description |
Change in transferrin saturation (TSAT) from baseline to week 2.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in transferrin saturation (TSAT) from baseline to week 2.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
310
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.4567 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
1.7931
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-2.951 | ||||||||||||
upper limit |
6.537 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
2.4038
|
||||||||||||
|
|||||||||||||
End point title |
Change in transferrin saturation (TSAT) from baseline to week 4 | ||||||||||||
End point description |
Change in transferrin saturation (TSAT) from baseline to week 4.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in transferrin saturation (TSAT) from baseline to week 4.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
292
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.4655 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
1.4872
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-2.522 | ||||||||||||
upper limit |
5.496 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
2.034
|
||||||||||||
|
|||||||||||||
End point title |
Change in transferrin saturation (TSAT) from baseline to week 8 | ||||||||||||
End point description |
Change in transferrin saturation (TSAT) from baseline to week 8.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in transferrin saturation (TSAT) from baseline to week 8.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
266
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.9401 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.1555
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-4.235 | ||||||||||||
upper limit |
3.924 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
2.0659
|
||||||||||||
|
|||||||||||||
End point title |
Change in transferrin saturation (TSAT) from baseline to week 12 | ||||||||||||
End point description |
Change in transferrin saturation (TSAT) from baseline to week 12.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in transferrin saturation (TSAT) from baseline to week 12.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
244
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.4541 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-1.5555
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-5.651 | ||||||||||||
upper limit |
2.54 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
2.0722
|
||||||||||||
|
|||||||||||||
End point title |
Change in transferrin saturation (TSAT) from baseline to week 24 | ||||||||||||
End point description |
Change in transferrin saturation (TSAT) from baseline to week 24.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in transferrin saturation (TSAT) from baseline to week 24.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
227
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.7359 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.7721
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-3.752 | ||||||||||||
upper limit |
5.296 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
2.2839
|
||||||||||||
|
||||||||||||||||
End point title |
Number of subjects in each randomisation group who discontinued study because of lack of response or intolerance of investigational drugs | |||||||||||||||
End point description |
Number of subjects in each randomisation group who discontinued study because of lack of response or intolerance of investigational drugs.
The analysis was performed on the safety population.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
The endpoint covers the complete trial period.
|
|||||||||||||||
|
||||||||||||||||
Statistical analysis title |
Superiority tested by Fisher Exact | |||||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
|||||||||||||||
Number of subjects included in analysis |
139
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
superiority | |||||||||||||||
P-value |
= 0.0007 | |||||||||||||||
Method |
Fisher exact | |||||||||||||||
Confidence interval |
||||||||||||||||
|
|||||||||||||
End point title |
Change in quality of life (QoL) from baseline to week 4 | ||||||||||||
End point description |
Change in quality of life (QoL) from baseline to week 4.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in quality of life (QoL) from baseline to week 4.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
279
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.9224 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.09428
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.81 | ||||||||||||
upper limit |
2 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.9668
|
||||||||||||
|
|||||||||||||
End point title |
Change in quality of life (QoL) from baseline to week 12 | ||||||||||||
End point description |
Change in quality of life (QoL) from baseline to week 12.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in quality of life (QoL) from baseline to week 12.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Superiority tested by MMRM | ||||||||||||
Statistical analysis description |
The MMRM included treatment, visit, treatment*visit interactions, platinum based chemotherapy (Yes/
No), and country as factors and baseline value as covariate.
|
||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
||||||||||||
Number of subjects included in analysis |
231
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.2527 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.9777
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-2.66 | ||||||||||||
upper limit |
0.7 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.8515
|
||||||||||||
|
|||||||||||||
End point title |
Change in restless legs syndrome (RLS) symptoms (RLS score) from baseline to week 12 in subjects with RLS symptoms at baseline | ||||||||||||
End point description |
Change in restless legs syndrome (RLS) symptoms (RLS score) from baseline to week 12 in subjects with RLS symptoms at baseline.
The analysis was performed on the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change in restless legs syndrome (RLS) symptoms (RLS score) from baseline to week 12.
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
||||||||||||||||
End point title |
Impact of study drug on ability to complete chemotherapy assessed as yes or no response at 24 weeks | |||||||||||||||
End point description |
Impact of study drug on ability to complete chemotherapy assessed as yes or no response at 24 weeks.
The analysis was performed on the FAS.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Impact of study drug on ability to complete chemotherapy assessed as yes or no response at 24 weeks.
|
|||||||||||||||
|
||||||||||||||||
Statistical analysis title |
Superiority tested by Chi squared | |||||||||||||||
Comparison groups |
Group B, iron sulphate v Group A, iron isomaltoside 1000
|
|||||||||||||||
Number of subjects included in analysis |
231
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
superiority | |||||||||||||||
P-value |
= 0.9112 | |||||||||||||||
Method |
Chi-squared | |||||||||||||||
Confidence interval |
||||||||||||||||
|
||||||||||||||||||||||
End point title |
Impact of study drug on response to chemotherapy, assessed as complete remission, partial remission, stable remission, and progressive disease as per the investigator discretion at 24 weeks. | |||||||||||||||||||||
End point description |
Impact of study drug on response to chemotherapy, assessed as complete remission, partial remission, stable remission, and progressive disease as per the investigator discretion at 24 weeks.
The analysis was performed on the FAS.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Impact of study drug on response to chemotherapy, assessed as complete remission, partial remission, stable remission, and progressive disease as per the investigator discretion at 24 weeks.
|
|||||||||||||||||||||
|
||||||||||||||||||||||
Statistical analysis title |
Superiority tested by Chi squared | |||||||||||||||||||||
Comparison groups |
Group A, iron isomaltoside 1000 v Group B, iron sulphate
|
|||||||||||||||||||||
Number of subjects included in analysis |
231
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||
P-value |
= 0.3909 | |||||||||||||||||||||
Method |
Chi-squared | |||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
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Timeframe for reporting adverse events |
From the time a subject had signed the ICF and until he/she had completed the trial, all AEs/SAEs were collected in the CRF. The SAEs occurring after study termination were reported if considered related to the trial treatment.
|
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Adverse event reporting additional description |
The investigator was responsible for ensuring that all AEs observed by the investigator or reported by the subjects were properly collected and recorded in the subject’s medical record as well as on the AE form.
|
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.0
|
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Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Group A, iron isomaltoside 1000
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects treated with iron isomaltoside 1000 were randomised to either an IV infusion (group A1) of maximum 1000 mg (the maximum dose per infusion was 1000 mg for subjects with a weight >45 kg, 750 mg for subjects with a weight between 35 and 45 kg, and 500 mg for subjects with a weight <35 kg) iron isomaltoside 1000 as single doses over approximately 15 minutes (full iron replacement was achieved by 1 or up to 2 doses at a weekly interval) or IV bolus injections (group A2) of 500 mg iron isomaltoside 1000 administered over approximately 2 minutes once weekly until full replacement dose was achieved (a total of 1-4 doses at a weekly interval). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Group B, oral iron sulphate
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects receiving oral iron sulphate were treated daily for 12 weeks with 200 mg given as 100 mg twice a day. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
19 May 2010 |
• Primary objective was changed to demonstrate that iron isomaltoside 1000 is non-inferior to iron sulphate
• Endpoints were better defined to evaluate change in Hb and other iron parameters at defined time points during the study
• An additional visit was added at 24 weeks
• Iron dosage was increased to 2000 mg for subjects with body weight ≥ 100 kg
|
||
27 Jul 2010 |
• Duration of individual subject participation was clarified to be 24-26 weeks
• Stratification criteria for Hb and s-ferritin was modified
• The inclusion criteria was modified to clarify the types of non-myeloid malignancies
|
||
20 Mar 2013 |
• The primary objective was re-phrased to “ability to maintain haemoglobin concentration”
• Measurement of TIBC was added as a secondary objective
• The primary endpoint was modified from “change in Hb concentration from baseline to week 12” to “change in Hb concentration from baseline to week 4”
• Additional secondary endpoint “Number of AEs of special interest (i.e. hypersensitivity reactions or hypotension at pre-specified time points in relation to administration of study drug)” was added
• High grade lymphoma was added to inclusion criterion 2
• Exclusion criterion 10 was clarified and exclusion criterion 11 was deleted
• Clarifications in drug dosage and formulation, study flowchart, study assessments, recording of vital signs, prohibited medications, protocol deviations, and reporting of AEs
• Definition of non-smokers, statement on provision of study drug, storage temperature of study drug, description of overdose, and interim analyses were added
• Changes in the statistical analyses were made as per changes in endpoints. MMRM was used instead of LOCF to account for missing values
• Change in frequency of safety review meeting to once in 4 months
|
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
