E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with iron deficiency anemia and heart failure carrying left ventricular assist devices (LVAD) |
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E.1.1.1 | Medical condition in easily understood language |
Patients with iron deficiency anemia and heart failure carrying left ventricular assist devices |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022974 |
E.1.2 | Term | Iron deficiency anemia |
E.1.2 | System Organ Class | 100000004851 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008908 |
E.1.2 | Term | Chronic heart failure |
E.1.2 | System Organ Class | 100000004849 |
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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 |
To detect AEs and SAEs with a relative frequency of at least 11.5% in LVAD patients with iron deficiency anemia treated with oral ferric maltol for 12 weeks |
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E.2.2 | Secondary objectives of the trial |
To assess the effects of oral ferric maltol on hemoglobin levels in LVAD patients with iron deficiency anemia
To assess the effects of oral ferric maltol on hemoglobin level, serum ferritin, transferrin saturation, 6 min walking distance, serum NT-proBNP, right and left ventricular function (determined by echocardiography), liver and renal function and NYHA class in LVAD patients with iron deficiency anemia |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed written informed consent prior to any study-related procedure and willingness to comply with treatment and follow-up procedures 2. Male and female patients ≥18 years at day of inclusion 3. Patients capable of understanding the investigational nature, potential risks and benefits of the clinical trial 4. Patients that have an LVAD implanted for chronic heart failure and which are clinically stable for at least 6 months after LVAD implantation in the opinion of the investigator 5. 6 min walk distance >50 m 6. Mild-to-moderate iron-deficiency anemia as defined by a hemoglobin concentration ≥7 g/dl and <12 g/dl in females or ≥8 g/dl and <13 g/dl in males, and serum ferritin <100 µg/l, or 100-300 µg/l and transferrin saturation <20% at screening 7. Prevention of pregnancy: Women without childbearing potential defined as follows: • at least 6 weeks after surgical sterilization by bilateral tubal ligation or bilateral oophorectomy or • hysterectomy or uterine agenesis or • ≥ 50 years and in postmenopausal state ≥ 1 year or • < 50 years and in postmenopausal state ≥ 1 year with serum FSH > 40 IU/l and serum oestrogen < 30 ng/l or a negative oestrogen test or Women of childbearing potential with a negative ß-HCG pregnancy test at screening who agree to meet one of the following criteria from the time of screening, during the study and for a period of four weeks following the last administration of study medication: • correct use of contraception methods. The following are acceptable: hormonal contraceptives (combined oral contraceptives and oestrogen-free pills with desogestrel, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release), intrauterine device (IUD), intrauterine system (IUS) or a barrier method, e.g. condom or occlusive cap (diaphragm or cervical/vault caps) with spermicide (foam, gel, film, cream or suppository) • true abstinence (periodic abstinence and withdrawal are not acceptable methods of contraception) • sexual relationship only with female partners and/or sterile male partners
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E.4 | Principal exclusion criteria |
1. Active hematological disorders other than iron-deficiency anemia 2. Other medical condition that according to the investigator’s assessment is causing or contributing to anemia 3. Active malignancy 4. Active infectious disease 5. Active bleeding 6. Severe renal insufficiency (requiring dialysis) 7. Severe liver injury as indicated by serum aminotransferases >3 x upper limit of normal or bilirubin levels >50 µmol/l 8. Ongoing oral or intravenous iron supplementation 9. Concomitant erythropoietin medication 10. Pregnancy or lactation period 11. Subject has received any investigational medication or any investigational devices within 30 days prior to the first dose of study medication or is actively participating in any investigational drug/ devices trial, or is scheduled to receive investigational drug/devices during the course of the study. 12. Known or suspected hypersensitivity to any of the active substances or any excipients of the investigational medicinal product 13. Known haemochromatosis or other iron overload syndromes 14. Patients who have been receiving repeated (>1) blood transfusions during the past 6 months
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E.5 End points |
E.5.1 | Primary end point(s) |
Relative and absolute frequency of AEs and SAEs |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
from baseline Day 0 to week 16 |
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E.5.2 | Secondary end point(s) |
Change in hemoglobin level from baseline to week 12 Change in hemoglobin level from baseline to week 6 Change in serum ferritin levels and transferrin saturation from baseline to week 6 and 12 Change in 6 min walking distance from baseline to week 12 Change in serum NT-proBNP from baseline to weeks 6 and 12 Change in echocardiographic markers of right ventricular function (right atrial area, right ventricular diameter, fractional area change, tricuspid annular plane systolic excursion) and left ventricular function (left ventricular ejection fraction, left atrial area, left ventricular diameter, fractional area change, tricuspid annular plane systolic excursion), change from baseline to week 12. • Liver: Change in Albumin, ALT, AST and Bilirubin from baseline to week 6 and 12 • Kidney: Change in Creatinine (+GFR) and Urea from baseline to week 6 and 12 • Change in NYHA from baseline to week 12
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 12 Week 6 Week 6 and 12 Week 12 Weeks 6 and 12 Week 12 Week 6 and 12 Week 6 and 12 Week 12
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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 | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 4 |
E.8.9.1 | In the Member State concerned days | |