A Double-blind, Randomized, Balanced, Parallel Group, Phase I Study Comparing Pharmacokinetics and Safety of Bevacizumab
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Pharmacokinetics
- Sponsor
- Laboratorios Richmond S.A.C.I.F.
- Enrollment
- 112
- Locations
- 1
- Primary Endpoint
- Peak Serum Concentration of Bevacizumab (Cmax)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Study subjects must be willing and able to provide written informed consent
- •Subjects of study, volunteers, adults, healthy.
- •Study subjects whose safety and complementary laboratory tests are within normal values or which, in the Investigator's opinion, do not have clinical relevance: blood count, erythrosedimentation, hepatogram, urea, creatinine, glucose, coagulogram, serology for HIV, hepatitis B , hepatitis C, complete urinalysis, detection of drugs of abuse in urine and electrocardiogram.
- •Sample taken for immunogenicity
- •Body mass index between 19 and 27 kg / m2 at the screening visit.
- •Subjects of study preferably non-smokers.
- •Men with a partner of childbearing age must agree that their partner uses an adequate contraceptive method before entering the study and for at least 3 months after the end of the study. It is understood as a contraceptive method suitable to any hormonal contraceptive method or intrauterine device (which should be established before the start of the study) and the use of a spermicide as a barrier method. The use of a barrier method alone or sexual abstinence is not considered adequate.
- •Subjects must agree not to donate sperm during the study and for 4 months after treatment.
Exclusion Criteria
- •History of pulmonary, gastrointestinal, hepatic, renal, hematological, endocrine-metabolic, neurological or psychiatric illnesses (depressive disorders, in particular) at the time of taking the anamnesis and the physical examination during the first visit of the Protocol of Clinical research.
- •History of gastrointestinal surgeries (except uncomplicated appendectomy, at least 3 months old).
- •History of major surgery, surgical biopsy and / or history of significant trauma within 1 month of the screening visit.
- •Specifically, pre-existing gastrointestinal conditions such as abdominal fistulas, gastrointestinal perforation within 6 months of the screening visit.
- •Specifically, preexisting gastrointestinal conditions such as acute or subacute intestinal occlusion.
- •Specifically, history of inflammatory bowel disease.
- •History of hemorrhagic diseases and / or coagulopathies and / or thromboembolic events.
- •History of heart and vascular diseases: specifically myocardial infarction, unstable angina, cerebrovascular accident, uncontrolled arterial hypertension and cardiac arrhythmias.
- •Background or current history of alcohol or drug abuse.
- •Blood donation within 3 months prior to selection.
Outcomes
Primary Outcomes
Peak Serum Concentration of Bevacizumab (Cmax)
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
Cmax will be obtained directly from the serum concentration-time curve
Area Under the Serum Concentration- Time Curve ob Bevacizumab (ABC0-∞)
Time Frame: Day 1 to Day 63
Area under the serum concentration- time curve from time zero to infinity
Area Under the Serum Concentration-time Curve of Bevacizumab (ABC0-t)
Time Frame: Day 1 to Day 63
Area under the serum concentration-time curve from time zero to the last experimental point, will be calculated by the trapezoidal rule
Secondary Outcomes
- Elimination Half Life (T1/2)(Day 1 to Day 63)
- Systemic Clearance (CL)(Day 1 to Day 63)
- Terminal Elimination Rate Constant (λz)(Day 1 to Day 63)
- Time to Reach the Peak Serum Concentration (Tmax)(Day 1 to Day 63)
- Distribution Volume(Day 1 to Day 63)
- Number of Participants With Positive Anti-bevacizumab Serum Antibodies Detection(Screening and end of study (Day 63))