Bioequivalence Study of Ferric Carboxymaltose Injection in Participants With Iron Deficiency Anaemia

NCT06080555 | Completed Phase 1

• 1 other identifier: 2023BE-SJMYTT
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 4

Brief Summary

The goal of this clinical trial is to compare the pharmacokinetic profile of the developed drug product and reference product in participants with iron deficiency anaemia 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 (10 mL: 500 mg \[calculated by iron\]) provided by Sichuan Huiyu Pharmaceutical Co., Ltd. and the ferric carboxymaltose injection (trade name: Ferinject®, strength: 10 mL: 500 mg \[calculated by iron\]) held by Vifor France?
• \[Question 2\] Is it safe for patient to take ferric carboxymaltose injection (10 mL: 500 mg \[calculated by iron\]) 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 patients 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

Conditions

Iron Deficiency; Anaemia

Keywords

Bioequivalence

Outcome Measures

Primary Outcomes (4)

• Pharmacokinetic parameter of total iron in serum: Cmax

  Cmax is the peak concentration of total iron in serum. It is directly obtained from observed blood drug concentration-time data.

  24hours,12hours,0hour before administration, and 5minutes,10minutes,15minutes,30minutes,45minutes,1hour,1.5hours,2hours,4hours,6hours,8hours,10hours,12hours,24hours,36hours,48hours,72hours,96hours,120hours and 144hours after administration.

• Pharmacokinetic parameter of total iron in serum: AUC0-t

  AUC0-t is the area under the concentration curve from dosing to the last measurable blood drug concentration.It is calculated using the linear trapezoidal rule.

  24hours,12hours,0hour before administration, and 5minutes,10minutes,15minutes,30minutes,45minutes,1hour,1.5hours,2hours,4hours,6hours,8hours,10hours,12hours,24hours,36hours,48hours,72hours,96hours,120hours and 144hours after administration.

• Pharmacokinetic parameter of transferrin bound iron in serum: Cmax

  Cmax is the peak concentration of transferrin bound iron in serum. It is directly obtained from observed blood drug concentration-time data.

  24hours,12hours,0hour before administration, and 5minutes,10minutes,15minutes,30minutes,45minutes,1hour,1.5hours,2hours,4hours,6hours,8hours,10hours,12hours,24hours,36hours,48hours,72hours,96hours,120hours and 144hours after administration.

• Pharmacokinetic parameter of transferrin bound iron in serum: AUC0-t

  AUC0-t is the area under the concentration curve from dosing to the last measurable blood drug concentration.It is calculated using the linear trapezoidal rule.

  24hours,12hours,0hour before administration, and 5minutes,10minutes,15minutes,30minutes,45minutes,1hour,1.5hours,2hours,4hours,6hours,8hours,10hours,12hours,24hours,36hours,48hours,72hours,96hours,120hours and 144hours after administration.

Secondary Outcomes (8)

• Pharmacokinetic parameter of total iron in serum: AUC0-∞

  24hours,12hours,0hour before administration, and 5minutes,10minutes,15minutes,30minutes,45minutes,1hour,1.5hours,2hours,4hours,6hours,8hours,10hours,12hours,24hours,36hours,48hours,72hours,96hours,120hours and 144hours after administration.

• Pharmacokinetic parameter of total iron in serum: Tmax

  24hours,12hours,0hour before administration, and 5minutes,10minutes,15minutes,30minutes,45minutes,1hour,1.5hours,2hours,4hours,6hours,8hours,10hours,12hours,24hours,36hours,48hours,72hours,96hours,120hours and 144hours after administration.

• Pharmacokinetic parameter of total iron in serum: t1/2

  24hours,12hours,0hour before administration, and 5minutes,10minutes,15minutes,30minutes,45minutes,1hour,1.5hours,2hours,4hours,6hours,8hours,10hours,12hours,24hours,36hours,48hours,72hours,96hours,120hours and 144hours after administration.

• Pharmacokinetic parameter of total iron in serum:λz

  24hours,12hours,0hour before administration, and 5minutes,10minutes,15minutes,30minutes,45minutes,1hour,1.5hours,2hours,4hours,6hours,8hours,10hours,12hours,24hours,36hours,48hours,72hours,96hours,120hours and 144hours after administration.

• Pharmacokinetic parameter of transferrin bound iron in serum: AUC0-∞

  24hours,12hours,0hour before administration, and 5minutes,10minutes,15minutes,30minutes,45minutes,1hour,1.5hours,2hours,4hours,6hours,8hours,10hours,12hours,24hours,36hours,48hours,72hours,96hours,120hours and 144hours after administration.

Study Arms (2)

Test product-Ferric carboxymaltose Injection provided by SichuanHuiyuPharma

EXPERIMENTAL

Drug: Ferric Carboxymaltose Injection

Reference product-marketed by Vifor France

ACTIVE COMPARATOR

Drug: Ferric Carboxymaltose Injection [Ferinject]

Interventions

Ferric Carboxymaltose Injection DRUG

For the T group, participants will have a standardized dinner on the night before the trial, followed by a fasting period of at least 10 h before receiving the test product (T, 10 mL: 500 mg elemental iron) via intravenous injection in the single upper limb, at a continuous rate for 5 min, with a speed of 2 mL/min.

Test product-Ferric carboxymaltose Injection provided by SichuanHuiyuPharma

Ferric Carboxymaltose Injection [Ferinject] DRUG

For the R group, participants will have a standardized dinner on the night before the trial, followed by a fasting period of at least 10 h before receiving the reference product (trade name: Ferinject®) (R, 10 mL: 500 mg elemental iron) via intravenous injection on an empty stomach, at a continuous rate for 5 min, with a speed of 2 mL/min.

Reference product-marketed by Vifor France

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participants with a thorough understanding of the content, process, and potential adverse reactions of the study, who have signed Informed Consent Form;
• Those able to complete the study as per the study protocol;
• Participants (including their partners) having no planning for pregnancy from the screening through 3 months after the last administration, and willing to take effective contraceptive measures;
• Male and/or female participants aged 18-60 (including those aged 18 and 60);
• Male participants weighing not less than 50 kilograms and female participants weighing not less than 45 kilograms. Body mass index (BMI) = weight (kg)/height 2 (m2), with a body mass index ranging from 18 to 30 kg/m2 (including both boundaries);
• Diagnosis of iron-deficiency anemia is confirmed during the screening process based on the following criteria (both criteria must be met): ①Hemoglobin (Hb) \< 110 g/L (for females) or Hb \< 120 g/L (for males). ②Serum ferritin ≤ 100 ng/mL, or when the serum transferrin saturation (TSAT) is ≤ 30%, serum ferritin ≤ 300 ng/mL.

You may not qualify if:

• Participants with an allergic constitution, such as asthma and eczema, or having known hypersensitivity to iron, maltose or its analogues, metabolites;
• In addition to iron-deficiency anemia, participants will be excluded from the screening process if they have had any of the following conditions within the past 6 months: cardiovascular, digestive, respiratory, urinary, hematological, metabolic, immune, or neurological system diseases, or any active malignancies as determined by the investigator;
• Individuals with acute infection in previous 2 weeks prior to the screening visit;
• laboratory tests: alanine aminotransferase (ALT) \> 1.5 times the upper limit of the normal range (× ULN); aspartate transaminase (AST) \> 1.5 × ULN; total serum bilirubin (TBiL) \> 1.5 × ULN; albumin \< 30 g/L; platelet count \< 90 × 109/L; neutrophil absolute count \< 1.3 × 109/L; glomerular filtration rate \< 60 mL/min/1.73 m2 (estimated based on simplified Modification of Diet in Renal Disease (MDRD) formula);
• Serious arrhythmias showed in ECG at screening period, such as recurrent and highly symptomatic ventricular tachycardia, atrial fibrillation accompanied by rapid ventricular response or supraventricular tachycardia, and are not suitable for the trial at the investigator's discretion;
• With history of iron storage diseases such as haemochromatosis; history of iron utilisation disorders such as sideroachrestic anaemia; history of haemoglobinopathy (such as Thalassemia); having symptomatic anemia requiring red blood cell infusion;
• Receiving IV iron therapy in previous 3 months prior to the screening visit, erythropoiesis stimulating agent (ESA) therapy and/or blood transfusion in previous 4 weeks prior to the screening visit, and oral iron or iron-containing products in previous 7 days prior to the screening visit;
• Receiving any prescription drugs that affect PK results in previous 14 days prior to the screening visit;
• Receiving any non-prescription drugs, traditional Chinese medicine, or healthcare products that affect PK results in previous 7 days prior to the screening visit;
• Individuals who consume an average of more than 5 cigarettes per day in previous 3 months prior to the screening visit;
• Individuals who have undergone surgeries within the past 3 months that might affect drug absorption, distribution, metabolism, or excretion, or those who are planning to undergo surgeries during the study period, will also be deemed ineligible to participate;
• Received investigational drug or participated in other clinical trials within the preceding 3 months;
• Blood donation or significant blood loss in previous 3 months prior to the screening visit (\> 400 mL, excluding menstrual blood loss in female participants);
• Female participants who are currently breastfeeding or have positive pregnancy test results during the screening period or clinical trials;
• People having viral hepatitis, such as hepatitis B or C, HIV antibody positive, treponema pallidum antibody positive and rapid plasma reaction (RPR) positive; (patients with positive hepatitis B surface antigen alone can be subjected to additional test for HBV DNA, patients with positive hepatitis C antibody alone can be subjected to additional test for HCV RNA, and those with positive Treponema pallidum antibody alone can be subjected to additional test for RPR);

Sponsors & Collaborators

• Sichuan Huiyu Pharmaceutical Co., Ltd: lead
• The First Hospital of Jilin University: collaborator
• Suzhou Guochen Biotek Co., Ltd.: collaborator
• Boji Data Technology (Beijing) Co., Ltd.: collaborator
• Boji Medical Technology Co., Ltd.: collaborator

Study Sites (4)

Boji medical technology (Beijing) co., Ltd

Beijing, Beijing Municipality, China

Location

Boji Medical Technology Co., Ltd

Guangzhou, Guangdong, China

Location

Suzhou Guochen Biotek Co., Ltd

Suzhou, Jiangsu, China

Location

Phase I Clinical Trial Department, The First Hospital of Jilin University

Changchun, Jilin, China

Location

Related Publications (4)

• Ikuta K, Shimura A, Terauchi M, Yoshii K, Kawabata Y. Pharmacokinetics, pharmacodynamics, safety, and tolerability of intravenous ferric carboxymaltose: a dose-escalation study in Japanese volunteers with iron-deficiency anemia. Int J Hematol. 2018 May;107(5):519-527. doi: 10.1007/s12185-018-2400-z. Epub 2018 Jan 22.

  PMID: 29357079 BACKGROUND

• Ding Y, Zhu X, Li X, Zhang H, Wu M, Liu J, Palmen M, Roubert B, Li C. Pharmacokinetic, Pharmacodynamic, and Safety Profiles of Ferric Carboxymaltose in Chinese Patients with Iron-deficiency Anemia. Clin Ther. 2020 Feb;42(2):276-285. doi: 10.1016/j.clinthera.2019.12.010. Epub 2020 Jan 11.

  PMID: 31937462 BACKGROUND

• Ferric Carboxymaltose Injection Package Insert. Vifor (International) Inc

  BACKGROUND

• Multidisciplinary Expert Consensus on Diagnosis, Treatment, and Prevention of Iron Deficiency and Iron-Deficiency Anemia by the Hematology Branch of the Chinese Medical Association (Anemia Group) [J]. Chinese Medical Journal, 2022, 102(41):3246-3256

  BACKGROUND

Related Links

• EMA Guideline on the investigation of bioequivalence
• EMA Reflection paper on the data requirements for intravenous iron-based nano-colloidal products developed with reference to an innovator medicinal product

MeSH Terms

Conditions

Iron Deficiencies; Anemia

Interventions

ferric carboxymaltose

Condition Hierarchy (Ancestors)

Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Li Xiang

  Sichuan Huiyu Pharmaceutical Co., Ltd

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2023
• First Posted: October 12, 2023
• Study Start: October 9, 2023
• Primary Completion: January 22, 2024
• Study Completion: March 22, 2024
• Last Updated: April 18, 2024

Record last verified: 2023-11

Locations

CN (4)