A Pharmacokinetic Study Comparing MB02 And EU Avastin® In Healthy Male Volunteers

Inclusion Criteria

• Able to comprehend and willing to sign an informed consent form (ICF) and to abide by the study restrictions. Subjects must have signed an informed consent before any study-related procedure or evaluation is performed.
• Healthy Japanese males aged ≥20 to ≤55 years, inclusive, at Screening.
• Subjects with Body mass index (BMI) between ≥18.5 to ≤28 kg/m2 and total body weight between ≥50 and ≤100 kg, at Screening
• Subject must have no clinically relevant abnormalities identified by a detailed medical history.
• Systolic blood pressure ≤140 mm Hg and diastolic blood pressure ≤90 mm Hg.
• Computerized (12-lead) electrocardiogram (ECG) recording without signs of clinically relevant pathology.
• All other values for hematology, coagulation and for biochemistry and urinalysis tests of blood and urine within the normal range or showing no clinically relevant deviations as judged by the Investigator, according to the following laboratory values:

Adequate bone marrow function

• Absolute neutrophil count ≥1.5 × 109 L
• Platelet count ≥100 × 109 L
• Hemoglobin >10 g/dl

Adequate liver function:

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ ULN
• Alkaline phosphatase (ALP) ≤1.5 × ULN
• Total bilirubin 3.5 g/dL
• Low density lipoprotein cholesterol ≤139 mg/dL
• High density lipoprotein cholesterol ≥ 40 mg/dL
• Creatine kinase (CK) <2 ULN at D-1

Adequate coagulation:

• International normalised ratio (INR) 0.8 to 1.3

Adequate renal function:

• Blood urea nitrogen: ≤1.5 × ULN
• Creatinine: <1.5 mg/dL
• Urine dipstick for proteinuria <2+.
• All intermittent medications should have been stopped at least 30 days prior to admission to the clinical research center.
• Subjects agree to use contraception.
• Ability and willingness to abstain from alcoholic beverages (alcohol) 48 hours prior to admission to the clinical research center.

Exclusion Criteria

• History of relevant allergy/hypersensitivity (including allergy to drug or its excipients).
• Previous treatment with an anti VEGF antibody like bevacizumab or any other protein or antibody targeting the VEGF receptor.
• History of bleeding disorders or protein C, protein S, and/or factor V Leiden deficiency.
• Known history of clinically significant essential hypertension (subjects under any antihypertensive treatment included), orthostatic hypotension, fainting spells or blackouts for any reason, cardiac failure or history of thromboembolic conditions.
• History of GI perforation, ulcers, gastro oesophageal reflux, inflammatory bowel disease, diverticular disease, diverticular disease, any fistulae, pulmonary hemorrhage (hemoptysis) or reversible posterior leukoencephalopathy syndrome.
• Any out-of-range laboratory values considered clinically significant by the investigator.
• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, haematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee).
• Any current or recent history of active infections, including localized infections. (Within 2 months prior Screening Visit for any serious infection which requires hospitalization or intravenous anti-infective, and within 14 days prior Screening Visit for any active infection which requires oral treatment). A negative result for human immunodeficiency virus (HIV), Hepatitis B (Hep B), and hepatitis C (Hep C) is required for participation. If subject shows positive Hepatitis B test, but results are compatible with prior immunisation and not infection may be included at the discretion of the Investigator.
• Clinically relevant history of alcoholism, addiction or drug/chemical abuse prior to Check-in, and/or positive urinary drug test screen and/or positive breath alcohol test at Screening or Check in. Average intake of more than 24 units of alcohol / wk. (1 unit of alcoho