The purpose of this study is to compare the pharmacokinetics, as well as to evaluate the safety, tolerability and immunogenicity of HD204, US-Avastin and EU-Avastin in healthy male subjects after intravenous administration of a single dose..
This is a double-blind, randomized, three-arm, parallel-group, single-dose study. A total of 120 evaluable subjects are required.
Inclusion Criteria:
* Non-smoking healthy male subjects, 18-50 years old inclusive
* Body Mass index is between 19 to 30 kg/m2, inclusive
* NO history of hypersensitivity or allergic reaction to the active ingredient, murine proteins, or excipients, spontaneous or following drug administration.
* For subjects with female partners of child-bearing potential, an adequate form of contraception must be adhered to prior to entry into the study and for a further 3 months after the end of study. Adequate contraception is defined as the usage by the female partner of any form of hormonal contraception or intra-uterine device (which should be established prior to the start of study) plus usage by one of the partners of an additional spermicide-containing barrier method of contraception. The use of a barrier method alone or reliance on abstinence is not considered adequate.
* Subjects must agree not to donate sperm during the study and for 4 months following treatment with the study medication or until scheduled End Of Study (EOS), whichever is longer.
* Subjects must be able to communicate well with the investigator, to understand and comply with the requirements of the study, and understand and sign the written informed consent.
Exclusion Criteria:
* Clinically significant abnormalities in physical examination, laboratory test results or electrocardiogram (ECG)
* Systolic blood pressure \> 140 mmHg or \< 90 mmHg , or diastolic blood pressure \> 90 mmHg or \<50 mmHg
* Proteinuria (with a urine dipstick value of 2+ or above)
* Coagulation abnormalities ( i.e., INR \> 2x ULN)
* Bleeding diathesis, history of duodenal ulcers, concomitant use of anticoagulants, or any hemorrhage within 6 months prior to study enrollment.
* Surgical procedure within 2 months of screening, or planned surgical procedure within 2 months of EOS
* Positive test result for drugs of abuse or alcohol breathing test.
* Positive test result for hepatitis B surface antigen (HBsAg), hepatitis C (HCV), or human immunodeficiency virus (HIV) 1 or 2.
* Donated or lost \> 500ml of blood in the previous 3 months
* Taken an investigational drug within 3 months (or 5 half-lives), whichever is longer.
* Taken any prescription medications within 14 days or 5 half-lives (whichever is longer) of the first dose of study drug or non-prescription drugs (with the exception of paracetamol, which is allowed).
* Previously received bevacizumab or any product considered to be biosimilar to bevacizumab, or any other antibody or protein targeting VEGF or VEGFR.
* Unwillingness or inability to comply with the study protocol for any reason.
* Male subject whose partner is pregnant.
* History or evidence of a clinically significant disorder (including cardiovascular, cerebrovascular, endocrine or psychiatric), or immunocompromised condition, or disease that, in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
* History of alcohol and/or drug abuse within 12 months of screening.
Locations (2)
Auckland Clinical Studies
Auckland, New Zealand
Christchurch Clinical Studies Trust Ltd
Christchurch, New Zealand
Outcomes
Primary Outcomes
Bevacizumab PK Parameter (AUC0-inf)
PK blood samples were collected from subjects to determine the AUC0-inf of bevacizumab. Samples were collected from 0 (pre-dose) to 1680 (post-dose) on days 1-74.
Time frame: 71 Days
Serum Concentration of Bevacizumab (AUC0-last)
PK blood samples were collected from subjects to determine the serum concentration of bevacizumab to evaluate the PK similarity across the three study drugs.
Time frame: 71 days
Serum Concentration of Bevacizumab (Cmax)
PK blood samples were collected from subjects to determine the serum concentration of bevacizumab to evaluate the PK similarity across the three study drugs.