A Phase I Study Comparing Pharmacokinetics and Safety of Bevacizumab

NCT03919448 | Completed Phase 1 Results

• 1 other identifier: 0221
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

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.

Conditions

Pharmacokinetics; Safety Issues

Keywords

Bevacizumab; Biosimilar; Antineoplastic Agents; Bioequivalence; Immunogenicity; safety; healthy male volunteers

Outcome Measures

Primary Outcomes (3)

• Peak Serum Concentration of Bevacizumab (Cmax)

  Cmax will be obtained directly from the serum concentration-time curve

  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

  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

  Day 1 to Day 63

Secondary Outcomes (6)

• Time to Reach the Peak Serum Concentration (Tmax)

  Day 1 to Day 63

• Terminal Elimination Rate Constant (λz)

  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

Study Arms (3)

Zutrab® (Bevacizumab Richmond)

ACTIVE COMPARATOR

a single 1 mg/kg IV dose of Bevacizumab

Biological: Bevacizumab

Avastin®

ACTIVE COMPARATOR

a single 1 mg/kg IV dose of Bevacizumab

Biological: Bevacizumab

Cizumab®

ACTIVE COMPARATOR

a single 1 mg/kg IV dose of Bevacizumab

Biological: Bevacizumab

Interventions

Bevacizumab BIOLOGICAL

Single-dose infusion

Avastin®; Cizumab®; Zutrab® (Bevacizumab Richmond)

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Laboratorios Richmond S.A.C.I.F.: lead
• FP Clinical Pharma S.R.L.: collaborator
• Syngene: collaborator

Study Sites (1)

FP Clinical Pharma S.R.L.

Buenos Aires, C1425BAA, Argentina

Location

MeSH Terms

Interventions

Bevacizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Regulatory Affairs Department
• Organization: Laboratorios Richmond

info@richmondlab.com

(+54 11) 5555 - 1600

Study Officials

• Ethel C Feleder, MD

  FP Clinical Pharma S.R.L.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2019
• First Posted: April 18, 2019
• Study Start: April 1, 2019
• Primary Completion: September 11, 2019
• Study Completion: September 11, 2019
• Last Updated: July 27, 2023
• Results First Posted: July 27, 2023

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

AR (1)