Bioequivalence Study Assessing Iron Sucrose or Venofer® in Healthy Adult Subjects

Study Overview
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Brief Summary
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This study evaluates the bioequivalence, pharmacokinetic (PK) profile, and safety and tolerability of Iron Sucrose (Test Product) relative to that of Venofer® in healthy subjects.

Official Title
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Bioequivalence Study Assessing a Single Dose of Iron Sucrose Injection (Baxter) or a Single Dose of Venofer® Injection in Healthy Adult Subjects

Conditions
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Bioequivalance

Intervention / Treatment
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* Drug: Iron Sucrose Injection
* Drug: Venofer Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males or non-pregnant, non-lactating healthy females Age 18 to 55 years of age (both inclusive) Must, in the opinion of the investigator, be in good health based upon medical history, physical examination (including vital signs and ECGs) and clinical laboratory tests assessed at the time of screening Body mass index (BMI) of 18.0 to 32.0 kg/m2 and a minimum body weight of 40 kg, or if outside the range, considered not clinically significant by the investigator Ferritin levels not less than the lower limit of normal as defined by clinical laboratory reference ranges for female and male subjects at screening only Transferrin Saturation (TSAT) not less than the lower limit of normal as defined by clinical laboratory reference ranges for female and male subjects at screening only Hemoglobin levels not less than the lower limit of normal as defined by clinical laboratory reference ranges for male and female subjects Must agree to use an adequate method of contraception: For male subjects: Subjects willing to follow approved birth control methods (a double barrier method) for the duration of the study as judged by the investigator(s), such as condom with spermicide, condom with diaphragm, or abstinence. Subjects should also not donate sperm during this time. For female subjects: Female subjects of childbearing potential, defined as a woman < 55 years of age who has not had a partial or full hysterectomy or oophorectomy, must have a negative urine pregnancy test at screening and a negative beta human chorionic gonadotropin (β-hCG) pregnancy test at admission. Subjects of childbearing potential must use a medically acceptable means of contraception during their participation in the study Non-smoker, defined as: Non-smoker for > 12 months (i.e., subject has not smoked or used any tobacco product, e-cigarettes, and nicotine replacement products for the 12 months prior to the start of the study) based on subject report. Must be willing and able to comply with all study requirements Must be able to understand a written informed consent, which must be obtained prior to initiation of study procedures Exclusion Criteria: Hypersensitivity to iron sucrose or iron products Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients Clinically significant abnormal biochemistry, hematology or urinalysis as judged by the investigator History of iron deficiency within 6 months prior to screening History of anemia within 6 months prior to screening Suspicion of iron overload as evidenced by both elevated serum TSAT and serum ferritin levels History of hemochromatosis Bleeding disorders, acute bleeding or recently documented hemorrhage Females with history of hypermenorrhea or menorrhagia History of cardiovascular, pulmonary, hepatic, renal, gastrointestinal, endocrine, immunological, dermatological, neurological or psychiatric disease or disorder, as judged by the investigator Must not have significant serious skin disease, including rash, food allergy, eczema, psoriasis, or urticaria Female subjects who are currently pregnant, lactating, or planning to become pregnant during the study period Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results Positive drugs of abuse test result or history of drug abuse in the past 6 months based on subject report Positive urinalysis test for alcohol at screening or history of alcoholism in the past 6 months based on subject report Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 Units = 125 mL glass of wine, depending on type) Administration of an injectable drug within 14 days prior to drug administration in this study Subjects who are taking, or have taken, any prescribed or over-the-counter drug (other than up to 4 g per day acetaminophen in the 14 days before IMP administration, hormonal contraceptives, or hormone replacement therapy. Exceptions may apply on a case by case basis, if considered not to interfere with the objectives of the study, as agreed by the PI and sponsor's medical monitor Use of iron supplements (including iron-containing multivitamins) within 3 months of the first dose IMP administration in the study Have poor venous access that limits phlebotomy Subjects who have donated blood (1 unit = 450 mL) within 3 months prior to the first dose of the study drug and plasma within 7 days prior to the first dose of the study drug. Subjects who have received any IMP in a clinical research study within 5 half-lives or within 30 days prior to first dose. However, in no event, shall the time between last receipt of IMP and first dose be less than 30 days Subjects who are study site employees, or immediate family members of a study site or sponsor employee Subjects who have previously been enrolled in this study Failure to satisfy the investigator of fitness to participate for any other reason

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Iron Sucrose Injection<br>IV injection (5 mL), delivered over 5 minutes to subjects that have been fasted for a minimum of 10 hours. | Drug: Iron Sucrose Injection<br>* USP 100 mg/5 mL (20 mg/mL), solution for IV injection, 100 mg unit dose strength<br>|
| Active Comparator: Venofer Injection<br>IV injection (5 mL), delivered over 5 minutes to subjects that have been fasted for a minimum of 10 hours. | Drug: Venofer Injection<br>* (Iron Sucrose 20 mg/mL), solution for IV injection, 100 mg unit dose strength<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax(delta) | Maximum concentration (Cmax) across all time points for the delta difference between Total Iron (TI) and Transferrin Bound Iron (TBI). This is a PK test parameter to compare bioequivalence of two drug products. | Hours before injection (24, 12, 0.25); Minutes after end of injection (1, 5, 10, 15, 30, 45); Hours after end of injection (1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36) | 
| AUC0-t(delta) | Area under the concentration curve (AUC) from time zero to last time of quantifiable concentration (Tlast) for the delta difference in AUC0-t between TI and TBI. This is a PK test parameter to compare bioequivalence of two plasma drug products. | Hours before injection (24, 12, 0.25); Minutes after end of injection (1, 5, 10, 15, 30, 45); Hours after end of injection (1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum concentration (Cmax) across all time points for both TI and TBI. This is a PK test parameter to compare bioequivalence of two plasma drug products. | Hours before injection (24, 12, 0.25); Minutes after end of injection (1, 5, 10, 15, 30, 45); Hours after end of injection (1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36) | 
| AUC0-t | Area under the concentration-time curve (AUC) from time zero to last sample time for both TI and TBI. This is a PK test parameter to compare bioequivalence of two drug products. | Hours before injection (24, 12, 0.25); Minutes after end of injection (1, 5, 10, 15, 30, 45); Hours after end of injection (1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36) | 
| AUC0-inf | Area under the concentration-time curve (AUC) from time zero extrapolated to infinity for both TI and TBI. This is a PK test parameter to compare bioequivalence of two drug products. | Hours before injection (24, 12, 0.25); Minutes after end of injection (1, 5, 10, 15, 30, 45); Hours after end of injection (1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36) | 
| Tmax | Time of occurrence of Cmax (Tmax) for both TI and TBI. This is a PK test parameter to compare bioequivalence of two drug products. | Hours before injection (24, 12, 0.25); Minutes after end of injection (1, 5, 10, 15, 30, 45); Hours after end of injection (1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36) | 
| t1/2 | Terminal phase half-life (t1/2) for both TI and TBI. This is a PK test parameter to compare bioequivalence of two drug products. | Hours before injection (24, 12, 0.25); Minutes after end of injection (1, 5, 10, 15, 30, 45); Hours after end of injection (1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36) | 
| Vz | Volume of distribution (Vz) for both TI and TBI. This is a PK test parameter to compare bioequivalence of two drug products. | Hours before injection (24, 12, 0.25); Minutes after end of injection (1, 5, 10, 15, 30, 45); Hours after end of injection (1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36) | 
| CL | Total body clearance (CL) for extravascular administration calculated by Dose/AUC for both TI and TBI. This is a PK test parameter to compare bioequivalence of two drug products. | Hours before injection (24, 12, 0.25); Minutes after end of injection (1, 5, 10, 15, 30, 45); Hours after end of injection (1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36) | 
| Percentage of AUCex | AUC0-inf due to extrapolation (AUCex) from Tlast to infinity calculated by: 100 × (AUC0-inf-AUC0-t)/AUC0-inf (%AUCex) for both TI and TBI. This is a PK test parameter to compare bioequivalence of two drug products. | Hours before injection (24, 12, 0.25); Minutes after end of injection (1, 5, 10, 15, 30, 45); Hours after end of injection (1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36) | 
| Number of participants with clinically significant laboratory abnormalities | Any clinically significant abnormality will also be reported as an AE. | Day -28 (Screening) through Day 10 (Follow-up) | 
| Number of participants with clinically significant findings on physical examinations | Any clinically significant abnormality will also be reported as an AE. | Day -28 (Screening) through Day 10 (Follow-up) | 
| Number of participants with clinically significant changes to ECG parameters | Any clinically significant abnormality will also be reported as an AE. | Day -28 (Screening), Day -2, 0.25 hours before injection, and 6, 24 and 36 hours after end of injection | 
| Number of participants with occurrence of adverse events (AEs) | An AE is any untoward medical occurrence in a subject that occurs either before dosing (referred to as a pre-dose AE) or once a medicinal product has been administered, including occurrences which are not necessarily caused by or related to that product. | Day -28 (Screening) through Day 30 | 
| Number of participants with occurrence of adverse events of special interest | Special interest items includes hypersensitivity reactions including anaphylactic/anaphylactoid reactions. | Day -28 (Screening) through Day 30 |