A Study to Evaluate the Safety and Pharmacokinetics of Bevacizumab After a Single Dose in Healthy Males

Exclusion Criteria28

• Any clinically significant abnormality at physical examination at screening or on Day -1.
• Positive test for hepatitis B, hepatitis C, or HIV at screening.
• Positive urine drug screen, alcohol test or cotinine test at screening or on Day -1.
• History of allergic reactions to bevacizumab, CHO cell products, other recombinant human or humanized antibodies, other related drugs, or to any excipients of the drug products.
• History of anaphylaxis, angioedema, hypertensive crisis or infusion-related reactions following i.v. administration of a drug.
• Any reason which, in the opinion of the Investigator, would prevent the subject from participating in the study.
• Clinically significant ECG abnormalities (e.g., QTcF greater than 450 ms) or vital sign abnormalities (sustained systolic blood pressure lower than 90 or over 140 mmHg, diastolic blood pressure lower than 50 or over 90 mmHg, or heart rate less than 45 or over 100 bpm) at screening.
• History of significant alcohol abuse within one year prior to screening or regular use of alcohol within 6 months prior to the screening visit (more than 21 units of alcohol per week [1 unit is equal to 150 mL of wine, 360 mL of beer, or 45 mL of 40 percent alcohol]).
• History of significant drug abuse within one year prior to screening or use of soft drugs (such as marijuana) within 3 months prior to the screening visit or hard drugs (such as cocaine, phencyclidine [PCP], crack, opioid derivatives including heroin, and amphetamine derivatives) within 1 year prior to screening.
• Previous exposure to bevacizumab or biphosphonates for a medical condition or in the context of another clinical trial.
• Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to dosing or administration of a biological product in the context of a clinical research study within 90 days prior to dosing.
• Use of medication other than topical products without significant systemic absorption:
• a) prescription medication within 14 days prior to dosing;
• b) over-the-counter products and herbal remedies, such as St. John’s wort, homeopathic and traditional medicines, within 7 days prior to dosing, with the exception of the occasional use of acetaminophen (up to 4 g daily). Vitamins, minerals and nutritional supplements may be taken at the discretion of the Investigator;
• c) a depot injection or an implant of any drug within 3 months prior to dosing.
• d) use of immunosuppressive drug within 6 weeks prior to dosing.
• Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding volume drawn at screening) of 50 mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to dosing.
• Administration of immunoglobulin or blood products within 6 weeks prior to dosing.
• History of gastrointestinal perforation or bleeding, gall bladder perforation, intra-abdominal abscess, internal fistula, hemorrhage, frequent epistaxis, clinically significant history of hemoptysis or evidence of bleeding diathesis or coagulopathy.
• Clinically significant history of arterial or venous thromboembolic events or clinically significant peripheral vascular disease.
• Current or past history of hypertension.
• History or presence of any clinically significant nervous system disease including, but not restricted to any stroke, transient ischemic attack, seizures, migraine headaches or migrainous aura (scotoma with zig-zag lines or blinking lights).
• Presence of serious, non-healing wound, or recent wound for which the healing process is not completed or surgical wound 28 days or less before dosing.
• Elective surgery or invasive dental procedure planned over the course of the study.
• Body temperature > 38.0ºC prior to dosing on Day 1.
• Evidence of chronic or significant active infection, as judged by the Investigator, prior to dosing on Day 1.
• Live virus vaccination within 3 months prior to dosing on Day 1 or live virus vaccine planned over the course of the study.
• Family history of coagulopathy.