An Study to Compare Single-dose Pharmacokinetic and Pharmacodynamic Characteristics of Epogen® and Epoetin Alfas (Eprex® and Binocrit®) in Healthy Subjects.

Study identifier:D5740C00003

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

An Open-label, Randomized, Cross-over, Single-center Study to Compare Single-dose Pharmacokinetic and Pharmacodynamic Characteristics of US-marketed (Epogen®) and Two European-marketed Epoetin Alfas (Eprex® and Binocrit®) in Healthy Subjects.

Medical condition

Anemia

Phase

Phase 1

Healthy volunteers

Yes

Study drug

Binocrit®, Eprex®, Epogen® Batch 1, Epogen® Batch 2

Sex

Male

Actual Enrollment

Study type

Interventional

Age

18 Years - 50 Years

Date

Study Start Date: 13 Jun 2018

Primary Completion Date: 22 Nov 2018

Study Completion Date: 22 Nov 2018

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Crossover Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Oct 2019 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

1. Provision of signed and dated, written informed consent before any study specific procedures.
2. Subject is a healthy male between 18 to 50 years of age, inclusive, at the Screening Visit.
3. Subject has a body mass index (BMI) range of 18.5 to 30.0 kg/m2, inclusive and weighs between 50 kg to 100 kg at the Screening Visit.
4. Subject has hemoglobin concentrations between 130 and 155 g/L and percentage of reticulocytes ≤ 3.0% at the Screening Visit.
5. Subject has a ferritin level 20 to 275 ng/mL, and transferrin saturation 20% to 50% at the Screening Visit.
6. Subject has an aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBL) ≤ the upper limit of normal (ULN) of the central laboratory reference range at the Screening Visit.
7. Subject has screening vitamin B12 and folate values ≥ the lower limit of normal (LLN) of the central laboratory reference range at the Screening Visit.
8. Subject has serum creatinine levels ≤ the ULN of the central laboratory reference range at the Screening Visit.
9. Subject and their female spouse/partner who are of childbearing potential must be using 2 highly-effective forms of birth control (1 of which must be a barrier method) starting at the Screening Visit and continuing throughout the clinical study period and for 28 days after the final IMP administration.
10. Subject agrees not to participate in another interventional study while participating in the present study, defined as signing the ICF until completion of the last study visit.

Exclusion Criteria

1. Subject has a known or suspected hypersensitivity to recombinant human EPO-α, or any components of the formulations used.
2. Subject has had exposure to any erythropoietic agents, such as EPO-α, darbepoetin-alfa, methoxy polyethylene glycol-epoetin beta, peginesatide or hypoxia-inducible factor prolyl hydroxylase within 6 months before Day -1 of Treatment Period 1.
3. Subject has, in the opinion of the PI, any clinically significant history of allergic conditions (including drug allergies, asthma, eczema or anaphylactic reactions; but excluding seasonal allergies that are untreated and asymptomatic).
4. Subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy, as judged by the Investigator.
5. Subject has known hereditary hematologic disease including, but not limited to thalassemia, sickle cell anemia and/or hemoglobinopathy.
6. Subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection), or fungal (noncutaneous) infection within 1 week before Day -1 of Treatment Period 1.
7. Subject has/had an arterial and/or venous thrombosis or any history of thrombosis-promoting disease such as but not limited to evidence of peripheral arterial stenosis, cerebrovascular disorders including carotid artery stenosis, coagulation dysfunction.
8. Subject has any clinically significant abnormality following the Investigator’s review of the physical examination, ECG and CSP defined clinical laboratory tests at the Screening Visit or Day -1 of Treatment Period 1.
9. Subject has a mean pulse < 50 or > 90 beats per minute (bpm); mean SBP ≥ 140 mmHg; mean DBP ≥ 90 mmHg (measurements taken in triplicate after subject has been resting in supine position for 5 minutes; pulse will be measured automatically) at the Screening Visit or Day -1 of Treatment Period 1.
10. Subject has a medical history of cardiovascular disorders, particularly hypertension and/or any intake of anti-hypertensive medication, cardiomyopathy, coronary heart disease, arrhythmia, or valvular disorders.
11. Subject has a mean QT interval corrected for heart rate using Fridericia’s formula (QTcF) interval of > 450 ms at the Screening Visit. If the mean QTcF exceeds the limits above, 1 additional triplicate ECG can be taken on the same day.
12. Subject has used any prescribed or non-prescribed drugs (including vitamins, iron supplements, natural and herbal remedies, e.g., St. John’s Wort) in the 2 weeks before IMP administration, except for occasional use of paracetamol (up to 2 g per day).
13. Subject has smoked or has used tobacco-containing products and nicotine or nicotine-containing products in the past 6 months before the Screening Visit.
14. Subject has a history of drinking more than 21 units of alcohol per week (1 unit = 10 g pure alcohol = 250 mL of beer [5%] or 35 mL of spirits [35%] or 100 mL of wine [12%]) within 3 months before Day -1 of Treatment Period 1.
15. Subject has used any drugs of abuse within 3 months before Day -1 of Treatment Period 1.
16. Subject has had significant blood loss, donated 1 unit (450 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days before Day -1 of Treatment Period 1.
17. Subject has a positive serology test for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus antibody (anti-HCV), hepatitis B core antibody (anti-HBc) or positive screening test for immunodeficiency virus (HIV) type 1 or 2 at the Screening Visit.
18. Subject has participated in any clinical study or has been treated with any investigational drugs within 28 days or 5 x t½ whichever is longer, before the Screening Visit.
19. Subject has any condition, which, in the Investigator’s opinion, makes the subject unsuitable for study participation.
20. Subject is an employee of AstraZeneca or the Clinical Research Organization (CRO).
21. Vulnerable subjects, e.g., subjects kept in detention, protected adults under guardianship, trusteeship and soldiers or subjects committed to an institution by governmental or juridical order.
22. Subject has positive result for anti-epoetin antibodies.

Location

Research Site

Berlin, Germany, 14050

Arms	Assigned Interventions
Experimental: Cohort 1 13 participants receive Binocrit®	Drug: Binocrit® Participants will receive Binocrit® 100 IU/kg Intravenously
Experimental: Cohort 2 13 participants will receive Eprex®	Drug: Eprex® Participants will receive Eprex® 100 IU/kg Intravenously.
Active Comparator: Cohort 3 13 participants will receive Epogen® Batch 1.	Drug: Epogen® Batch 1 Participants will receive Epogen® Batch 1 100 IU/kg Intravenously.
Active Comparator: Cohort 4 13 participants will receive Epogen® Batch 2.	Drug: Epogen® Batch 2 Participants will receive Epogen® Batch 2 100 IU/kg Intravenously.

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Thomas Körnicke

PAREXEL Early Phase Clinical Unit

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Trial Results Summaries