Bioequivalence Study of Ferric Carboxymaltose Injection in Healthy Chinese Participants Under Fasting Conditions

A Randomized, Open-label, Two-treatment, Two-period, Two-cross-over Bioequivalence Study of Ferric Carboxymaltose Injection in Healthy Chinese Participants Under Fasting Conditions

The goal of this clinical trial is to compare the pharmacokinetic profile of the developed drug product and reference product in healthy participants under fasting condition. The main questions it aims to answer are:

• [Question 1] Is there significant difference in the pharmacokinetic profile between the ferric carboxymaltose injection 750 mg iron/15 mL provided by Sichuan Huiyu Pharmaceutical Co., Ltd. and the ferric carboxymaltose injection licensed by American Regent, Inc. (trade name: Injectafer®, strength:750 mg iron/15 mL )?
• [Question 2] Is it safe for healthy participants to take ferric carboxymaltose injection (750 mg iron/15 mL [calculated by iron]) provided by Sichuan Huiyu Pharmaceutical Co., Ltd. under fasting condition? Participants will be randomly divided into two groups by stratified blocked randomization, with equal number of healthy participants in each group, to receive test product or reference product according to the protocol below.
• Dosing on D1: Group T (Test product) Group R (Reference product)
• PK blood sample collection
• Safety evaluation

Inclusion Criteria:

1. Participants must fully understand the purpose, nature, procedures, and potential adverse reactions of the study. They must voluntarily agree to participate in the trial, comply with all study requirements, and provide written informed consent before the initiation of any study procedures.
2. Healthy male or female participants aged 18 to 55 years (inclusive).
3. Participants must have a body weight of ≥ 50.0 kg; Body Mass Index(BMI) must range from 19.0 to 26.0 kg/m² (inclusive).
4. Participants have been using effective contraception for 14 days prior to screening. Participants must agree to use highly effective contraceptive measures from screening until 3 months after the last administration. They must have no plans for pregnancy, sperm donation, or egg donation during this period.

Exclusion Criteria:

1. Participants with allergic conditions, such as a known history of hypersensitivity to two or more medications; known allergies to iron, maltose, or its analogues/ metabolites; or a history/presence of severe asthma, eczema, or other atopic allergic disorders.

2. History/presence of iron storage diseases (e.g., hemochromatosis), iron utilization disorders (e.g., iron-refractory iron deficiency anemia), hemoglobinopathies (e.g., thalassemia), hemolytic anemia, symptomatic anemia requiring red blood cell infusion, or undergoing hemodialysis.

3. History of iron deficiency or anemia within 6 months prior to screening.

4. History of clinically significant chronic or severe conditions affecting the respiratory, cardiovascular, gastrointestinal, renal, hematological, lymphatic, endocrine, immune, psychiatric, or nervous systems; past or current diagnosis of porphyria cutanea tarda; or other conditions deemed by the investigator to be unsuitable for participation.

5. Acute conditions (e.g., acute infection, acute gastrointestinal disorders such as nausea, vomiting, diarrhea, or constipation, etc.) within 2 weeks prior to the first dose.

6. Participants with clinically significant abnormalities in vital signs, physical examination, laboratory tests (e.g., hematology, urinalysis, blood chemistry, coagulation function tests, iron metabolism assessments), infectious disease testing, or 12-lead Electrocardiogram (ECG), as determined by the investigator (special requirement: calcium and phosphorus values in blood chemistry tests are in the abnormal range). Hepatic enzyme levels exceeding 1.5 times the upper limit of normal (ULN) during screening. Serious arrhythmias shown in ECG at screening, such as recurrent or symptomatic ventricular tachycardia, atrial fibrillation accompanied by rapid ventricular response, or supraventricular tachycardia.

7. History of hypersensitivity or intolerance to intravenous iron administration.

8. Receiving parenteral iron treatment within 6 months prior to screening, erythropoiesis-stimulating agent (ESA) therapy and/or blood transfusion within 4 weeks prior to screening.

9. Use of any medication that may affect iron absorption iron absorption within 28 days prior to dosing, such as antacids (e.g., omeprazole), tetracycline antibiotics, calcium supplements, or lipid-lowering agents (e.g., cholestyramine).

10. Use of any medications (prescription, over-the-counter, herbal remedies, or dietary supplements) and healthcare products within 2 weeks prior to screening.

11. History of smoking an average of more than 5 cigarettes per day within 3 months prior to screening or unwillingness to abstain from smoking from 48 hours prior to dosing until the completion of blood sampling in each treatment period.

12. Participants who have undergone surgeries within 6 months prior to screening that might affect drug absorption, distribution, metabolism and excretion, or planning to undergo surgeries during the study.

13. Participants who have enrolled in other clinical trials and received investigational products or devices within 3 months prior to screening.

14. Blood donation or significant blood loss due to other reasons within 3 months prior to screening (> 400 mL, excluding menstrual blood loss in female participants), or donated platelets in an amount equal to or exceeding 2 therapeutic doses (1 therapeutic dose = 12 units of platelets) within 1 month prior to screening, or plan to donate blood during the study.

15. Participants with drug abuse history (including the use of various anesthetic and psychotropic drugs for non-medical purposes) within 1 year prior to screening or have a positive drug abuse screening result.

16. Participants with history of alcohol abuse within 1 year prior to screening, defined as average daily alcohol consume over 2 units (1 unit = 360 mL beer, 45 mL spirits with 40% alcohol, or 150 mL wine), or are unwilling to abstain from alcohol or alcohol-containing products from 48 hours prior to dosing until the completion of blood sampling in each treatment period, or have positive breath alcohol test result.

17. Participants who have special diet: xanthine-rich foods (e.g., coffee, chocolate, tea or cocoa beverages), iron-rich foods including animal organs, animal blood, spinach, as well as calcium/phosphorus-rich seafood, shellfish, crab, and nuts such as peanuts and sunflower seeds, dragon fruit, mango, grapefruit or grapefruit-containing products, or taking strenuous exercise, or other factors affecting drug absorption, distribution, metabolism, and excretion, within 48 hours before receiving the first dose of investigational product.

18. Participants who received a live vaccine within 14 days prior to screening, or plan to receive vaccination during the study.

19. Inability to tolerate venipuncture or history of fear of needles or hemophobia.

20. Participants with special dietary requirements, and participants who cannot accept the study standardized diet.

21. Any other condition deemed by the investigator to be unsuitable for enrollment.

    In addition to the aforementioned requirements, females who meet the following conditions should also be excluded:

22. Use of oral contraceptives within 30 days prior to screening.

23. Use of long-acting estrogen or progestin injections (progestin-based intrauterine devices), or implants within 6 months prior to screening.

24. Pregnancy, breastfeeding, or positive pregnancy test at screening.