Pharmacokinetic, Safety, Tolerability, and Immunogenicity Study of SB8 in Healthy Male Subjects

Phase 1

Completed

Interventions: Biological: EU sourced Avastin®
Biological: US Sourced Avastin®
Biological: SB8

Brief Summary: Pharmacokinetics, Safety, Tolerability, and Immunogenicity of Three Formulations of Bevacizumab

Detailed Description: A Randomised, Double-blind, Three-arm, Parallel Group, Single-dose Study to Compare the Pharmacokinetics, Safety, Tolerability, and Immunogenicity of Three Formulations of Bevacizumab (SB8, EU Sourced Avastin®, and US Sourced Avastin®) in Healthy Male Subjects

Recruitment & Eligibility

Inclusion Criteria

Healthy male subjects
Have body weight between 65.0-90.0 kg (inclusive) and body mass index between 20.0-29.9 kg/m2 (inclusive)

Exclusion Criteria

Have a history of hypersensitivity or allergic reactions to bevacizumab or to any of the excipients
Have a history of and/or current clinically significant gastrointestinal, renal, hepatic, cardiovascular, haematological, pulmonary, neurologic, metabolic, psychiatric, or allergic disease excluding mild asymptomatic seasonal allergies
Have a history of arterial thromboembolic events including cerebrovascular accidents, transient ischaemic attacks, and myocardial infarction
Have a history of and/or current cardiac disease
Have previously been exposed to vascular endothelial growth factor (VEGF) antibody, any other antibody, or protein targeting the VEGF receptor
Have a history of cancer including lymphoma, leukaemia, and skin cancer.
Have received live vaccine(s) within 30 days prior to Screening visit or who will require a vaccine(s) between Screening and the end of study visit
Have taken medication with a half-life of > 24 hours within 30 days or 10 half-lives of the medication prior to the IP administration

Arm && Interventions

Group	Intervention	Description
EU Sourced Avastin®	EU sourced Avastin®	EU Sourced Avastin®, single dose of 3 mg/kg, IV infusion
US Sourced Avastin®	US Sourced Avastin®	US Sourced Avastin®, single dose of 3 mg/kg, IV infusion
SB8	SB8	SB8, single dose of 3 mg/kg, IV infusion

Primary Outcome Measures

Name	Time	Method
Maximum Serum Concentration (Cmax)	0 to 2016 hours after start of infusion	0 (pre-dose), 0.75, 1.5 (end of infusion), 3, 6, 12, 24, 48, and 96 hours, then at Day 8 (168 h), 15 (336 h), 22 (504 h), 29 (672 h), 43 (1008 h), 57 (1344 h), 71 (1680 h), and 85 (2016 h) after start of infusion.
Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf)	0 to 2016 hours after start of infusion	0 (pre-dose), 0.75, 1.5 (end of infusion), 3, 6, 12, 24, 48, and 96 hours, then at Day 8 (168 h), 15 (336 h), 22 (504 h), 29 (672 h), 43 (1008 h), 57 (1344 h), 71 (1680 h), and 85 (2016 h) after start of infusion.
Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast)	0 to 2016 hours after start of infusion	0 (pre-dose), 0.75, 1.5 (end of infusion), 3, 6, 12, 24, 48, and 96 hours, then at Day 8 (168 h), 15 (336 h), 22 (504 h), 29 (672 h), 43 (1008 h), 57 (1344 h), 71 (1680 h), and 85 (2016 h) after start of infusion.

Secondary Outcome Measures

Name	Time	Method
Time to Reach Cmax (Tmax)	0 to 2016 hours after start of infusion	0 (pre-dose), 0.75, 1.5 (end of infusion), 3, 6, 12, 24, 48, and 96 hours, then at Day 8 (168 h), 15 (336 h), 22 (504 h), 29 (672 h), 43 (1008 h), 57 (1344 h), 71 (1680 h), and 85 (2016 h) after start of infusion.