PharmacokineticsPhase 1NCT03919448
A Phase I Study Comparing Pharmacokinetics and Safety of Bevacizumab
A Phase 1 study testing Bevacizumab in people with Pharmacokinetics and Safety Issues, run by Laboratorios Richmond S.A.C.I.F. at 1 site in Argentina.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Pharmacokinetics, Safety Issues
- What is being tested?
- Bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 112 participants
- Where
- 1 siteArgentina
- Study dates
- 1 Apr 2019to 11 Sep 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 23Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Double-blind, Randomized, Balanced, Parallel Group, Phase I Study Comparing Pharmacokinetics and Safety of Bevacizumab
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.
Read the 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.
- Conditions
- Pharmacokinetics, Safety Issues
- Being tested
- Bevacizumab
- Keywords
- Bevacizumab, Biosimilar, Antineoplastic Agents, Bioequivalence, Immunogenicity, safety, healthy male volunteers
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabBiological
Single-dose infusion
| Study group | Role | What they receive |
|---|---|---|
| Zutrab® (Bevacizumab Richmond) | Active comparator | a single 1 mg/kg IV dose of Bevacizumab Receives: Biological: Bevacizumab |
| Avastin® | Active comparator | a single 1 mg/kg IV dose of Bevacizumab Receives: Biological: Bevacizumab |
| Cizumab® | Active comparator | a single 1 mg/kg IV dose of Bevacizumab Receives: Biological: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak Serum Concentration of Bevacizumab (Cmax)
Cmax will be obtained directly from the serum concentration-time curve
Measured: 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
Measured: 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
Measured: Day 1 to Day 63
Secondary outcomes (6)
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
Measured: 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
Measured: Day 1 to Day 63
Elimination Half Life (T1/2)
To assess pharmacokinetic parameters
Measured: Day 1 to Day 63
Systemic Clearance (CL)
To assess pharmacokinetic parameters
Measured: Day 1 to Day 63
Distribution Volume
To assess pharmacokinetic parameters
Measured: 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.
Measured: Screening and end of study (Day 63)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2019
- Study start1 Apr 2019
- Primary completion11 Sep 2019
- Study completion11 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for PharmacokineticsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 112 participants (actual)
Sponsor and investigators
- Lead sponsor
- Laboratorios Richmond S.A.C.I.F.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- FP Clinical Pharma S.R.L., Syngene
- Responsible party
- Sponsor
- Investigators
- Ethel C Feleder, MD, Principal investigator, FP Clinical Pharma S.R.L.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03919448
- Sponsor's protocol ID
- 0221
- Status last verified
- Aug 2022
- First submitted
- 15 Apr 2019
- Last updated
- 27 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Randomized, Balanced, Parallel Group, Phase I Study Comparing Pharmacokinetics and Safety of Bevacizumab
- ClinicalTrials.gov ID
- NCT03919448
- Acronym / sponsor ID
- 0221
- Conditions
- Pharmacokinetics, Safety Issues
- Keywords
- Bevacizumab, Biosimilar, Antineoplastic Agents, Bioequivalence, Immunogenicity, safety, healthy male volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 112 participants (actual)
- Lead sponsor
- Laboratorios Richmond S.A.C.I.F.Industry (pharma, biotech, devices)
- Collaborators
- FP Clinical Pharma S.R.L., Syngene
- Study start
- 1 Apr 2019 (actual)
- Primary completion
- 11 Sep 2019 (actual)
- Study completion
- 11 Sep 2019 (actual)
- First posted
- 18 Apr 2019 (actual)
- Results
- Posted 27 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Zutrab® (Bevacizumab Richmond) | Active comparator | Biological: Bevacizumaba single 1 mg/kg IV dose of Bevacizumab |
| Avastin® | Active comparator | Biological: Bevacizumaba single 1 mg/kg IV dose of Bevacizumab |
| Cizumab® | Active comparator | Biological: Bevacizumaba single 1 mg/kg IV dose of Bevacizumab |
Who may qualify
- Ages
- 21 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (23 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BevacizumabSingle-dose infusion | Biological | Avastin®, Cizumab®, Zutrab® (Bevacizumab Richmond) |
Primary outcome
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 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
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
6 secondary outcomes
Time to Reach the Peak Serum Concentration (Tmax)
Time frame: Day 1 to Day 63
Terminal Elimination Rate Constant (λz)
Time frame: Day 1 to Day 63
Elimination Half Life (T1/2)
Time frame: Day 1 to Day 63
Systemic Clearance (CL)
Time frame: Day 1 to Day 63
Distribution Volume
Time frame: Day 1 to Day 63
Number of Participants With Positive Anti-bevacizumab Serum Antibodies Detection
Time frame: Screening and end of study (Day 63)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ethel C Feleder, MD principal investigator
FP Clinical Pharma S.R.L.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Bevacizumab in people with Pharmacokinetics and Safety Issues, run by Laboratorios Richmond S.A.C.I.F. at 1 site in Argentina.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Argentina. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2023.