NCT03919448CompletedPhase 1
A Double-blind, Randomized, Balanced, Parallel Group, Phase I Study Comparing Pharmacokinetics and Safety of Bevacizumab
Laboratorios Richmond S.A.C.I.F.1 site in 1 country112 target enrollmentStarted: April 1, 2019Last updated:
Conditions
Interventions
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 112
- Locations
- 1
- Primary Endpoint
- Peak Serum Concentration of Bevacizumab (Cmax)
Study 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Other
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 21 Years to 55 Years (Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- Yes
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.
- •Administration of any other drug under investigation or participation in a clinical research trial within 3 months prior to the planned participation in this Clinical Research Protocol.
- •History of clinically significant diseases or disorders that, in the opinion of the Investigator, may impede the participation of the study subject for safety reasons or that may influence the results of the same as well as the ability of the study subject to participate in the Clinical Research Protocol.
- •History of hypersensitivity to bevacizumab and / or any of the excipients.
- •Study subjects who present contraindications to therapy
- •Study subjects who have received (2 weeks before) or are receiving aspirin or clopidogrel
- •The study subjects must have suspended any pharmacological treatments at least 2 weeks before the initiation of this Clinical Research Protocol.
- •Non-cooperative study subjects
- •Study subjects employed by the Researcher or the Clinical-Pharmacokinetic Research Unit, with direct participation in the Clinical Research Protocol or other clinical protocols under the Direction of the Researcher or the Clinical-Pharmacokinetic Research Unit
- •Physical findings and laboratory analyses:
- •Cardiac, pulmonary, gastrointestinal, hepatic, renal, hematological, endocrine-metabolic, neurological disease or psychiatric disorder (depressive disorders, in particular)
- •Evidence of ulcers, unhealed wounds or bone fractures.
- •Clinically significant abnormalities in any laboratory analysis, and electrocardiogram
- •Positive serology for HIV, hepatitis B, hepatitis C
Arms & Interventions
Zutrab® (Bevacizumab Richmond)
Active Comparator
a single 1 mg/kg IV dose of Bevacizumab
Intervention: Bevacizumab (Biological)
Cizumab®
Active Comparator
a single 1 mg/kg IV dose of Bevacizumab
Intervention: Bevacizumab (Biological)
Avastin®
Active Comparator
a single 1 mg/kg IV dose of Bevacizumab
Intervention: Bevacizumab (Biological)
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
- Terminal Elimination Rate Constant (λz)(Day 1 to Day 63)
- Time to Reach the Peak Serum Concentration (Tmax)(Day 1 to Day 63)
- Elimination Half Life (T1/2)(Day 1 to Day 63)
- Systemic Clearance (CL)(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))
Investigators
Study Sites (1)
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