ORal IrON Supplementation With Ferric Maltol in Patients With Pulmonary Hypertension (ORION-PH-1)

A Pilot Study to Explore Preliminary Safety, Tolerability and Efficacy of ORal IrON Supplementation With Ferric Maltol in Treating Iron Deficiency in Patients With Pulmonary Hypertension and Iron Deficiency Anemia

This is an explorative, open-label, uncontrolled, single center study to explore the preliminary safety, tolerability and efficacy of oral ferric maltol in treating iron deficiency in patients with pulmonary hypertension and iron deficiency anemia.

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 with a diagnosis of PH confirmed by a (historical) right heart catheterization showing a mean pulmonary artery pressure ≥25 mmHg at rest and stable PH medication for at least 3 months.
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 (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

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 (glomerular filtration rate <30 ml/min)
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. Hemoglobin <7 g/dl in females or <8 g/dl in males at screening
10. Concomitant erythropoietin medication
11. Pregnancy or lactation period
12. Subject has received any investigational medication or any investigational device 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 an investigational drug/device during the course of the study.
13. Known or suspected hypersensitivity to any of the active substances or any excipients of the investigational medicinal product
14. Known haemochromatosis or other iron overload syndromes
15. Patients who have been receiving repeated (>1) blood transfusions during the past 6 months