Study to Test the Hypothesis of Non-inferior Efficacy and Safety of Ferrum Lek® (Iron (III) Hydroxide Polymaltosate), 100 mg Chewable Tablets (Lek d.d., Slovenia), as Compared With MALTOFER® (Vifor S.A., Switzerland), in Subjects With Mild and Moderate Iron Deficiency Anemia.

The purpose of this study was to evaluate non-inferiority for efficacy and safety of Ferrum Lek® (iron (III) hydroxide polymaltosate), 100 mg chewable tablets (Lek d.d., Slovenia), compared to MALTOFER® (Vifor S.A., Switzerland), in the treatment of patients with mild and moderate iron-deficiency anaemia.

This was a multi-centric, open-label, randomized, prospective, comparative, parallel-group, active-controlled, phase III clinical trial (in the Russian Federation).

The purpose of this study was to evaluate non-inferiority for efficacy and safety of Ferrum Lek® (iron (III) hydroxide polymaltosate), compared to MALTOFER®, in the treatment of patients with mild and moderate iron-deficiency anaemia.

Participants underwent screening for up to 7 days. Eligible participants were randomized in 1:1 ratio to two treatment arms.

Subjects in Group 1 received 2 tablets per day (200 mg) of chewable tablets Ferrum Lek® during or immediately after meals; once daily.

Subjects in Group 2 (reference product) received 2 tablets per day (200 mg) of chewable tablets Maltofer® during or immediately after meals; once daily.

The subjects received the medicinal products daily for 12 weeks. After the last scheduled study site visit, a follow-up visit (by phone) was scheduled 14 days after the completion of the active treatment period (day 98±2) to record any delayed adverse events.

Eligibility Criteria:
Inclusion Criteria:

1. The signed and dated written informed consent prior to participation in the study.
2. Men and women aged 18 and older (by the time of screening).
3. Outpatients.
4. Diagnosed iron-deficiency anemia, based on two criteria:

   1. hemoglobin level below 110 g/L (in men and women), but above 80 g/L,
   2. serum ferritin levels below 30 µg/L.

Exclusion Criteria:

1. Administration of any iron-containing drugs during the last 3 months.
2. History of erythropoietin drugs administration.
3. Hypersensitivity to iron therapy (both Oral and/or IV administration) and other components of the study drugs.
4. Hormone therapy (including the use of androgens/anabolic steroids) or administration of drugs that inhibit blood formation, less than 3 months before the start of the study.
5. History of severe allergic reactions or drug intolerance.
6. Fructose intolerance, glucose-galactose malabsorption syndrome, and sucrase-isomaltase deficiency.
7. Pregnant or lactating women, or women intending to become pregnant during the study.
8. Failure of iron therapy for iron-deficiency anaemia in a subject's past medical history.
9. Heme metabolism disorders (e.g., sideroachrestic anaemia, lead anaemia, thalassaemia).
10. Iron overload including haemochromatosis and hemosiderosis
11. Other causes of anemia, apart from iron deficiency, including:

    1. Haemolysis (determined as per analyses results at screening, or as per anamnestic data),
    2. Vitamin B12 and folic acid deficiency (as per the screening data),
    3. Chronic kidney disease (creatinine clearance at screening is below 90 ml/min (based on Cockcroft-Gault Formula)),
    4. Systemic connective tissue diseases, chronic infectious diseases requiring regular therapy (as per the past medical history), and other conditions which may, in the investigator's opinion, be accompanied by anaemia of chronic diseases.
12. Dysfunction of the thyroid gland (based on the data obtained at screening).
13. Laboratory and clinical signs of an active inflammatory process for 10 days before screening.
14. AST, ALT, and total bilirubin levels exceeding the upper limit of normal 1.5 times and more.
15. Clinically apparent hypothyroidism, in the investigator's opinion.
16. Malignant diseases, including blood and lymphoid tissue disorders (leukemia, Hodgkin disease, myelodysplastic syndrome, myeloma, etc.) at screening or in the past medical history, provided that the remission was less than 5 years before screening.
17. Signs of bone marrow aplasia at screening or history of bone marrow aplasia.
18. The necessity of parenteral iron therapy, i.e. the following cases:

    1. impaired absorption in case of an intestinal pathology (enteritis, coeliac disease, malabsorption, small intestinal resection, stomach resection, including the duodenum);
    2. exacerbation of gastric or duodenal ulcer;
    3. the necessity of quick iron saturation, e.g. in patients with iron-deficiency anaemia with upcoming surgery;
    4. continuous vast blood loss and other causes, at the discretion of the investigator.
19. Known presence of an active infection caused by Helicobacter pylori. In case of presence of Helicobacter pylori, a subject may be enrolled after eradicative therapy.
20. Concomitant diseases and conditions, which, in the investigator's opinion, pose risk to a subject's safety in case of his/her participation in the study, or able to affect the safety data analysis in case of exacerbation of this disease/condition during the study, including:

    1. Myocardial infarction or stroke within 6 months before screening.
    2. Unstable angina;
    3. Severe arrhythmia, not controlled by drug therapy;
    4. Decompensated diabetes mellitus;
    5. Nephrological disorders;
    6. Other significant diseases, at the discretion of the investigator.
21. HIV infection (as per the screening data or the results of analysis performed within 6 months before screening).
22. Known or suspected drug or alcohol abuse for the last 2 years.
23. Suspected poor adherence of a subject (e.g., due to mental disorders).
24. Participation in any clinical drug studies less than 3 months before the study.
25. Blood donation / blood transfusion within 30 days prior to screening or planned blood transfusion at time of screening.
26. History of smoking, unless leave off smoking \> 6 months.