Trial Outcomes & Findings for A Phase I Study Comparing Pharmacokinetics and Safety of Bevacizumab (NCT NCT03919448)

NCT ID: NCT03919448

Last Updated: 2023-07-27

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 112 participants
• Primary outcome timeframe: 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
• Results posted on: 2023-07-27

Participant Flow

Of 112 enrolled participants, 90 met inclusion criteria and were randomized to treatment.

Participant milestones

Measure	Zutrab® (Bevacizumab Richmond) a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Avastin® a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Cizumab® a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion
Overall Study STARTED	30	30	30
Overall Study COMPLETED	29	30	30
Overall Study NOT COMPLETED	1	0	0

Reasons for withdrawal

Measure	Zutrab® (Bevacizumab Richmond) a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Avastin® a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Cizumab® a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion
Overall Study Withdrawal by Subject	1	0	0

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Zutrab® (Bevacizumab Richmond) n=29 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Avastin® n=30 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Cizumab® n=30 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Total n=89 Participants Total of all reporting groups
Age, Customized 21 to 55 years	29 Participants n=29 Participants	30 Participants n=30 Participants	30 Participants n=30 Participants	89 Participants n=89 Participants
Sex: Female, Male Female	0 Participants n=29 Participants	0 Participants n=30 Participants	0 Participants n=30 Participants	0 Participants n=89 Participants
Sex: Female, Male Male	29 Participants n=29 Participants	30 Participants n=30 Participants	30 Participants n=30 Participants	89 Participants n=89 Participants
Race and Ethnicity Not Collected	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Body Mass Index (BMI)	24.05 kg/m^2 n=29 Participants	24.06 kg/m^2 n=30 Participants	24.85 kg/m^2 n=30 Participants	24.32 kg/m^2 n=89 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Measure	Zutrab® (Bevacizumab Richmond) n=29 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Avastin® n=30 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Cizumab® n=30 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion
Peak Serum Concentration of Bevacizumab (Cmax)	22144.83 ng/ml Standard Deviation 5550.07	21540 ng/ml Standard Deviation 4382	22566.67 ng/ml Standard Deviation 8368.14

PRIMARY outcome

Timeframe: 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

Outcome measures

Measure	Zutrab® (Bevacizumab Richmond) n=29 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Avastin® n=30 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Cizumab® n=30 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion
Area Under the Serum Concentration-time Curve of Bevacizumab (ABC0-t)	5153367.55 h*ng/ml Standard Deviation 1276468.14	5641733.72 h*ng/ml Standard Deviation 1160626.12	5500141.94 h*ng/ml Standard Deviation 1849362.76

PRIMARY outcome

Timeframe: Day 1 to Day 63

Area under the serum concentration- time curve from time zero to infinity

Outcome measures

Measure	Zutrab® (Bevacizumab Richmond) n=29 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Avastin® n=30 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Cizumab® n=30 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion
Area Under the Serum Concentration- Time Curve ob Bevacizumab (ABC0-∞)	5374225.878 h.ng/ml Standard Deviation 1340507.11	5919875.18 h.ng/ml Standard Deviation 1276082.30	5777584.241 h.ng/ml Standard Deviation 1951347.40

SECONDARY outcome

Timeframe: Day 1 to Day 63

Time to reach the peak serum concentration, which will be obtained directly from the serum concentration curve- time

Outcome measures

Measure	Zutrab® (Bevacizumab Richmond) n=29 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Avastin® n=30 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Cizumab® n=30 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion
Time to Reach the Peak Serum Concentration (Tmax)	9.34 h Standard Deviation 11.65	16.69 h Standard Deviation 22.79	5.64 h Standard Deviation 7.46

SECONDARY outcome

Timeframe: Day 1 to Day 63

Terminal elimination rate constant will be calculated by linear regression analysis of the semi-logarithmic curve

Outcome measures

Measure	Zutrab® (Bevacizumab Richmond) n=29 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Avastin® n=30 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Cizumab® n=30 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion
Terminal Elimination Rate Constant (λz)	0.002 1/h Standard Deviation 0.001	0.002 1/h Standard Deviation 0.001	0.002 1/h Standard Deviation 0.001

SECONDARY outcome

Timeframe: Day 1 to Day 63

To assess pharmacokinetic parameters

Outcome measures

Measure	Zutrab® (Bevacizumab Richmond) n=29 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Avastin® n=30 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Cizumab® n=30 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion
Elimination Half Life (T1/2)	352.19 h Standard Deviation 173.17	344.58 h Standard Deviation 82.04	371.86 h Standard Deviation 315.65

SECONDARY outcome

Timeframe: Day 1 to Day 63

Population: To asses pharmacokinetic parameters

To assess pharmacokinetic parameters

Outcome measures

Measure	Zutrab® (Bevacizumab Richmond) n=29 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Avastin® n=30 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Cizumab® n=30 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion
Systemic Clearance (CL)	0.20 ml/h/kg Standard Deviation 0.05	0.18 ml/h/kg Standard Deviation 0.04	0.19 ml/h/kg Standard Deviation 0.06

SECONDARY outcome

Timeframe: Day 1 to Day 63

To assess pharmacokinetic parameters

Outcome measures

Measure	Zutrab® (Bevacizumab Richmond) n=29 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Avastin® n=30 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Cizumab® n=30 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion
Distribution Volume	99.10 ml/kg Standard Deviation 51.39	85.35 ml/kg Standard Deviation 17.62	97.91 ml/kg Standard Deviation 67.17

SECONDARY outcome

Timeframe: Screening and end of study (Day 63)

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.

Outcome measures

Measure	Zutrab® (Bevacizumab Richmond) n=29 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Avastin® n=30 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Cizumab® n=30 Participants a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion
Number of Participants With Positive Anti-bevacizumab Serum Antibodies Detection Screening	0 participants tested positive for ADA	0 participants tested positive for ADA	1 participants tested positive for ADA
Number of Participants With Positive Anti-bevacizumab Serum Antibodies Detection End of study	0 participants tested positive for ADA	0 participants tested positive for ADA	0 participants tested positive for ADA

Adverse Events

Zutrab® (Bevacizumab Richmond)

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Avastin®

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Cizumab®

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Zutrab® (Bevacizumab Richmond) n=29 participants at risk a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Avastin® n=30 participants at risk a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion	Cizumab® n=30 participants at risk a single 1 mg/kg IV dose of Bevacizumab Bevacizumab: Single-dose infusion
Gastrointestinal disorders Abdominal pain	20.7% 6/29 • Number of events 6 • Adverse events were evaluated and recorded during the 63 days of the clinical study.	16.7% 5/30 • Number of events 6 • Adverse events were evaluated and recorded during the 63 days of the clinical study.	13.3% 4/30 • Number of events 4 • Adverse events were evaluated and recorded during the 63 days of the clinical study.
Eye disorders Blurry vision	0.00% 0/29 • Adverse events were evaluated and recorded during the 63 days of the clinical study.	6.7% 2/30 • Number of events 2 • Adverse events were evaluated and recorded during the 63 days of the clinical study.	0.00% 0/30 • Adverse events were evaluated and recorded during the 63 days of the clinical study.
Nervous system disorders Headache	13.8% 4/29 • Number of events 5 • Adverse events were evaluated and recorded during the 63 days of the clinical study.	3.3% 1/30 • Number of events 1 • Adverse events were evaluated and recorded during the 63 days of the clinical study.	10.0% 3/30 • Number of events 3 • Adverse events were evaluated and recorded during the 63 days of the clinical study.
Gastrointestinal disorders Diarrhea	24.1% 7/29 • Number of events 7 • Adverse events were evaluated and recorded during the 63 days of the clinical study.	20.0% 6/30 • Number of events 6 • Adverse events were evaluated and recorded during the 63 days of the clinical study.	10.0% 3/30 • Number of events 3 • Adverse events were evaluated and recorded during the 63 days of the clinical study.
Gastrointestinal disorders Vomiting	13.8% 4/29 • Number of events 4 • Adverse events were evaluated and recorded during the 63 days of the clinical study.	6.7% 2/30 • Number of events 2 • Adverse events were evaluated and recorded during the 63 days of the clinical study.	3.3% 1/30 • Number of events 1 • Adverse events were evaluated and recorded during the 63 days of the clinical study.
Gastrointestinal disorders Nausea	6.9% 2/29 • Number of events 2 • Adverse events were evaluated and recorded during the 63 days of the clinical study.	0.00% 0/30 • Adverse events were evaluated and recorded during the 63 days of the clinical study.	3.3% 1/30 • Number of events 1 • Adverse events were evaluated and recorded during the 63 days of the clinical study.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/29 • Adverse events were evaluated and recorded during the 63 days of the clinical study.	0.00% 0/30 • Adverse events were evaluated and recorded during the 63 days of the clinical study.	3.3% 1/30 • Number of events 1 • Adverse events were evaluated and recorded during the 63 days of the clinical study.

Additional Information

Regulatory Affairs Department

Laboratorios Richmond

Phone: (+54 11) 5555 - 1600

Email: info@richmondlab.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place