E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with iron deficiency anaemia (IDA) caused by different aetiologies such as abnormal uterine bleeding, gastrointestinal diseases (e.g. inflammatory bowel disease), cancer, preoperative anaemia (e.g. orthopaedic surgery), and other conditions leading to IDA and with a documented history of intolerance or unresponsiveness to oral iron therapy. |
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E.1.1.1 | Medical condition in easily understood language |
Iron deficiency anaemia and documented history of intolerance or unresponsiveness to oral iron therapy. |
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E.1.1.2 | Therapeutic area | Not possible to specify |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10022972 |
E.1.2 | Term | Iron deficiency anaemia |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to evaluate and compare the effect of iron isomaltoside 1000 to placebo in its ability to increase haemoglobin (Hb) in subjects with IDA when oral iron preparations are ineffective or cannot be used. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to compare the effect of iron isomaltoside 1000 and placebo on:
• Other relevant iron related biochemical parameters
• Fatigue symptoms
• Restless leg syndrome (RLS) symptoms
• QoL
The safety objective of the study is to evaluate the safety of iron isomaltoside 1000 compared to placebo.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
A subject will be eligible for inclusion in the study if he/she fulfils the following criteria:
1. Men or women ≥ 18 years having IDA caused by different aetiologies* such as ab-normal uterine bleeding, gastrointestinal diseases (e.g. inflammatory bowel disease), cancer, preoperative anaemia (e.g. orthopaedic surgery), and other conditions leading to IDA and with a documented history of intolerance or unresponsiveness to oral iron therapy** for at least one month*** prior to study enrolment
2. Hb < 11 g/dL
3. TSAT < 20 %
4. S-ferritin < 100 ng/mL
5. Willingness to participate and signing the informed consent form (ICF)
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E.4 | Principal exclusion criteria |
A subject will not be eligible for inclusion in this study if he/she fulfils any of the following criteria:
1. Hb < 6 g/dL
2. Anaemia predominantly caused by factors other than IDA (e.g. anaemia with untreat-ed vitamin B12 or folate deficiency, haemolytic anaemia)
3. Iron overload or disturbances in utilisation of iron (e.g. haemochromatosis and haemosiderosis)
4. Decompensated liver cirrhosis or active hepatitis (ALAT > 3 times upper limit of normal)
5. Active acute or chronic infections (assessed by clinical judgement supplied with white blood cells (WBC) and C-reactive protein (CRP))
6. Body weight < 50 kg
7. Pregnant or nursing women. In order to avoid pregnancy, women of childbearing po-tential have to use adequate contraception (e.g. intrauterine devices, hormonal contra-ceptives, or double barrier method) during the whole study period and 7 days after the last dosing
8. History of multiple allergies
9. Known hypersensitivity to parenteral iron or any excipients in the investigational drug products
10. Erythropoietin treatment within 8 weeks prior to the screening visit
11. Other intravenous (IV) iron treatment or blood transfusion within 4 weeks prior to the screening visit
12. Participation in any other interventional clinical study within 3 months prior to the screening visit
13. Any other medical condition that, in the opinion of Investigator, may cause the subject to be unsuitable for the completion of the study or place the subject at potential risk from being in the study, e.g. uncontrolled hypertension, unstable ischaemic heart dis-ease, or uncontrolled diabetes mellitus |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Proportion of subjects with an Hb increase of ≥ 2 g/dL from baseline at any time from week 1 to week 5 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Any time between week 1 and week 5 |
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E.5.2 | Secondary end point(s) |
• Time to Hb ≥ 2 g/dL
• Number of subjects who achieve Hb levels of > 12 g/dL
• Number of subjects who achieve a serum (s-) ferritin increase of at least 100 ng/mL; or achieve a transferrin saturation (TSAT) of 20-50 % at week 2, 4, or 5
• Change in Hb concentration from baseline to week 2, 4, and 5
• Change in concentrations of s-ferritin, TSAT, and s-iron from baseline to week 1, 2, 4, and 5
• Change in fatigue symptoms from baseline to week 2 and 5 measured by the Func-tional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale
• Change in RLS symptoms from baseline to week 5 measured by the Cambridge-Hopkins RLS questionnaire (CH-RLSq)
• Change in QoL from baseline to week 2 and 5 measured by Short Form (SF)-36 ques-tionnaires
• Type and incidence of adverse drug reactions (ADRs)
• Number of adverse events (AEs) of special interest (i.e. hypersensitivity symptoms such as: urticaria, oedema, bronchospasm, hypotension, cardiorespiratory arrest, syn-cope, unresponsiveness, or loss of consciousness at pre-specified time points in rela-tion to administration of study drug)
• Change in haematology parameters, s-sodium, s-potassium, s-calcium, s-phosphate, s-urea, s-creatinine, s-albumin, s-bilirubin, aspartate aminotransferase (ASAT), and alanine aminotransferase (ALAT) from baseline to week 1, 2, 3, 4, and 5
• Change in vital signs (heart rate and blood pressure) from baseline to each visit
• Change in electrocardiogram (ECG) from baseline to peri-infusion and week 5 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Please see secondary end points for details. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Germany |
Russian Federation |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |