The aim of the Clinical study is to evaluate the pharmacokinetic and safety profile of a new formulation of Bevacizumab (Zutrab®, Argentinian origin) when compared to two already marketed formulations of Bevacizumab Avastin® (reference product) and Cizumab® (Indian origin), to establish similarity.
Three-way bridge phase 1 trial. It is conducted in healthy, male adult subjects, it is single-dose, double-blind, parallel groups, randomized and balanced. Blood samples are collected for up to 90 days, to determine serum drug concentration and anti-drug antibodies. Safety and tolerability are also assessed.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
QUADRUPLE
Enrollment
112
Single-dose infusion
FP Clinical Pharma S.R.L.
Buenos Aires, Argentina
Peak Serum Concentration of Bevacizumab (Cmax)
Cmax will be obtained directly from the serum concentration-time curve
Time frame: 0, 0.33, 0.5, 1, 1.5 hours during infusion, 0.33, 0.66, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512 hours post-infusion
Area Under the Serum Concentration-time Curve of Bevacizumab (ABC0-t)
Area under the serum concentration-time curve from time zero to the last experimental point, will be calculated by the trapezoidal rule
Time frame: Day 1 to Day 63
Area Under the Serum Concentration- Time Curve ob Bevacizumab (ABC0-∞)
Area under the serum concentration- time curve from time zero to infinity
Time frame: Day 1 to Day 63
Time to Reach the Peak Serum Concentration (Tmax)
Time to reach the peak serum concentration, which will be obtained directly from the serum concentration curve- time
Time frame: Day 1 to Day 63
Terminal Elimination Rate Constant (λz)
Terminal elimination rate constant will be calculated by linear regression analysis of the semi-logarithmic curve
Time frame: Day 1 to Day 63
Elimination Half Life (T1/2)
To assess pharmacokinetic parameters
Time frame: Day 1 to Day 63
Systemic Clearance (CL)
To assess pharmacokinetic parameters
Time frame: Day 1 to Day 63
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Distribution Volume
To assess pharmacokinetic parameters
Time frame: Day 1 to Day 63
Number of Participants With Positive Anti-bevacizumab Serum Antibodies Detection
To assess the immunogenic potential of the products under investigation, samples were taken for the determination of anti-bevacizumab serum antibodies for each randomized volunteer subject.
Time frame: Screening and end of study (Day 63)