Trial Outcomes & Findings for A Pharmacokinetic Study Comparing MB02 And US And EU Avastin® In Healthy Male Volunteers (NCT NCT03293654)
NCT ID: NCT03293654
Last Updated: 2021-03-23
Results Overview
To compare the pharmacokinetic (PK) profiles of MB02, US Avastin® and EU Avastin® (in terms of Cmax) to establish bioequivalence between the 3 study arms. For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% confidence interval (CI) for the geometric LS means ratios are fully contained within the predefined bioequivalence limits of 0.80 to 1.25.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
114 participants
Primary outcome timeframe
Predose, 1.5 h after end of infusion, 2, 3, 4, 5, 6, 8, 12, 24 h post-dose on Day 1-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.
Results posted on
2021-03-23
Participant Flow
Participant milestones
| Measure |
MB02 (Bevacizumab Biosimilar)
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
MB02: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
US Licenced Avastin®
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
US licenced Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
EU Approved Avastin®
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
|---|---|---|---|
|
Overall Study
STARTED
|
38
|
38
|
38
|
|
Overall Study
COMPLETED
|
38
|
37
|
38
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
MB02 (Bevacizumab Biosimilar)
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
MB02: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
US Licenced Avastin®
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
US licenced Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
EU Approved Avastin®
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
0
|
Baseline Characteristics
A Pharmacokinetic Study Comparing MB02 And US And EU Avastin® In Healthy Male Volunteers
Baseline characteristics by cohort
| Measure |
MB02 (Bevacizumab Biosimilar)
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
MB02: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
US Licenced Avastin®
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
US licenced Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
EU Approved Avastin®
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
Total
n=114 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
38 Participants
n=93 Participants
|
38 Participants
n=4 Participants
|
38 Participants
n=27 Participants
|
114 Participants
n=483 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Age, Continuous
|
36 years
STANDARD_DEVIATION 10.8 • n=93 Participants
|
35 years
STANDARD_DEVIATION 9.1 • n=4 Participants
|
38 years
STANDARD_DEVIATION 9.9 • n=27 Participants
|
37 years
STANDARD_DEVIATION 9.9 • n=483 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
38 Participants
n=93 Participants
|
38 Participants
n=4 Participants
|
38 Participants
n=27 Participants
|
114 Participants
n=483 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
7 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
9 Participants
n=483 Participants
|
|
Race (NIH/OMB)
White
|
35 Participants
n=93 Participants
|
30 Participants
n=4 Participants
|
30 Participants
n=27 Participants
|
95 Participants
n=483 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Weight
|
76.9 kg
STANDARD_DEVIATION 9.38 • n=93 Participants
|
77.9 kg
STANDARD_DEVIATION 8.11 • n=4 Participants
|
77.8 kg
STANDARD_DEVIATION 8.29 • n=27 Participants
|
77.6 kg
STANDARD_DEVIATION 8.55 • n=483 Participants
|
|
BMI
|
24.3 kg/m^2
STANDARD_DEVIATION 2.66 • n=93 Participants
|
24.3 kg/m^2
STANDARD_DEVIATION 2.61 • n=4 Participants
|
25.0 kg/m^2
STANDARD_DEVIATION 2.07 • n=27 Participants
|
24.5 kg/m^2
STANDARD_DEVIATION 2.46 • n=483 Participants
|
PRIMARY outcome
Timeframe: Predose, 1.5 h after end of infusion, 2, 3, 4, 5, 6, 8, 12, 24 h post-dose on Day 1-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.Population: Overall number of participants analyzed equals to number of subjects who contributed to summary statistics.
To compare the pharmacokinetic (PK) profiles of MB02, US Avastin® and EU Avastin® (in terms of Cmax) to establish bioequivalence between the 3 study arms. For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% confidence interval (CI) for the geometric LS means ratios are fully contained within the predefined bioequivalence limits of 0.80 to 1.25.
Outcome measures
| Measure |
MB02 (Bevacizumab Biosimilar)
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
MB02: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
US Licenced Avastin®
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
US licenced Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
EU Approved Avastin®
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
|---|---|---|---|
|
Cmax: Maximum Observed Serum Concentration
|
83000 (ng/mL)/(mg/mL)
Geometric Coefficient of Variation 22.4
|
65200 (ng/mL)/(mg/mL)
Geometric Coefficient of Variation 21.9
|
74400 (ng/mL)/(mg/mL)
Geometric Coefficient of Variation 25.3
|
PRIMARY outcome
Timeframe: Predose, 1.5 h after end of infusion, 2, 3, 4, 5, 6, 8, 12, 24 h post-dose on Day 1-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.Population: Overall number of participants analyzed equals to number of subjects who contributed to summary statistics.
To compare the pharmacokinetic (PK) profiles of MB02, US Avastin® and EU Avastin® (in terms of AUC\[0-∞\]) to establish bioequivalence between the 3 study arms. For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% confidence interval (CI) for the geometric least square means (GLSM) ratios are fully contained within the predefined bioequivalence limits of 0.80 to 1.25.
Outcome measures
| Measure |
MB02 (Bevacizumab Biosimilar)
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
MB02: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
US Licenced Avastin®
n=37 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
US licenced Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
EU Approved Avastin®
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
|---|---|---|---|
|
AUC(0-∞); Area Under the Serum Concentration-time Curve From Time Zero to Infinity
|
28200000 ng*h/mL
Geometric Coefficient of Variation 16.3
|
22900000 ng*h/mL
Geometric Coefficient of Variation 17.8
|
24500000 ng*h/mL
Geometric Coefficient of Variation 15.2
|
SECONDARY outcome
Timeframe: Predose, 1.5 h after end of infusion, 2, 3, 4, 5, 6, 8, 12, 24 h post-dose on Day 1-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.To evaluate the tmax of MB02, US Avastin® and EU Avastin® .
Outcome measures
| Measure |
MB02 (Bevacizumab Biosimilar)
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
MB02: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
US Licenced Avastin®
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
US licenced Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
EU Approved Avastin®
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
|---|---|---|---|
|
Tmax: Time of Maximum Observed Serum Concentration
|
2.51 h
Interval 1.62 to 71.98
|
4.00 h
Interval 1.62 to 11.98
|
3.00 h
Interval 1.57 to 12.0
|
SECONDARY outcome
Timeframe: Predose, 1.5 h after end of infusion, 2, 3, 4, 5, 6, 8, 12, 24 h post-dose on Day 1-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.To evaluate the AUC\[0-t\] of MB02, US Avastin® and EU Avastin®.
Outcome measures
| Measure |
MB02 (Bevacizumab Biosimilar)
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
MB02: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
US Licenced Avastin®
n=37 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
US licenced Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
EU Approved Avastin®
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
|---|---|---|---|
|
AUC(0-t) = Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Observable Concentration;
|
27400000 ng*h/mL
Geometric Coefficient of Variation 15.5
|
22300000 ng*h/mL
Geometric Coefficient of Variation 16.9
|
23700000 ng*h/mL
Geometric Coefficient of Variation 14.2
|
SECONDARY outcome
Timeframe: Predose, 1.5 h after end of infusion, 2, 3, 4, 5, 6, 8, 12, 24 h post-dose on Day 1-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.To evaluate the CL of MB02, US Avastin® and EU Avastin®
Outcome measures
| Measure |
MB02 (Bevacizumab Biosimilar)
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
MB02: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
US Licenced Avastin®
n=37 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
US licenced Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
EU Approved Avastin®
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
|---|---|---|---|
|
CL: Total Body Drug Clearance After IV Administration
|
0.00814 l/h
Geometric Coefficient of Variation 16.5
|
0.0101 l/h
Geometric Coefficient of Variation 17.9
|
0.00947 l/h
Geometric Coefficient of Variation 15.4
|
SECONDARY outcome
Timeframe: Predose, 1.5 h after end of infusion, 2, 3, 4, 5, 6, 8, 12, 24 h post-dose on Day 1-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.To evaluate the t1/2 of MB02, US Avastin® and EU Avastin®
Outcome measures
| Measure |
MB02 (Bevacizumab Biosimilar)
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
MB02: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
US Licenced Avastin®
n=37 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
US licenced Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
EU Approved Avastin®
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
|---|---|---|---|
|
t1/2: Apparent Serum Terminal Elimination Half-life
|
451 h
Geometric Coefficient of Variation 14.4
|
437 h
Geometric Coefficient of Variation 15.5
|
449 h
Geometric Coefficient of Variation 19.3
|
SECONDARY outcome
Timeframe: Day -1, Day 14, 28, 56, and 78Incidence of anti-bevacizumab antibodies (ADA), including neutralizing antibodies (Nab). Subjects who tested positive at baseline are not included here.
Outcome measures
| Measure |
MB02 (Bevacizumab Biosimilar)
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
MB02: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
US Licenced Avastin®
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
US licenced Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
EU Approved Avastin®
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
|---|---|---|---|
|
Immunogenicity
ADA positive
|
2 Participants
|
2 Participants
|
1 Participants
|
|
Immunogenicity
nAb positive
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Immunogenicity
NO seroconversion
|
35 Participants
|
36 Participants
|
37 Participants
|
SECONDARY outcome
Timeframe: Day 1 - Day 100Compare the incidence of TEAEs reported in each treatment arm.
Outcome measures
| Measure |
MB02 (Bevacizumab Biosimilar)
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
MB02: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
US Licenced Avastin®
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
US licenced Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
EU Approved Avastin®
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
|---|---|---|---|
|
Safety (Incidence of Treatment-related Adverse Events Using CTCAE v4.03)
TEAEs of moderate severity
|
4 participants
|
10 participants
|
5 participants
|
|
Safety (Incidence of Treatment-related Adverse Events Using CTCAE v4.03)
TEAEs of severe severity
|
0 participants
|
1 participants
|
0 participants
|
|
Safety (Incidence of Treatment-related Adverse Events Using CTCAE v4.03)
Subjects with TEAEs
|
24 participants
|
28 participants
|
25 participants
|
|
Safety (Incidence of Treatment-related Adverse Events Using CTCAE v4.03)
Subjects with SAEs
|
0 participants
|
1 participants
|
0 participants
|
|
Safety (Incidence of Treatment-related Adverse Events Using CTCAE v4.03)
Subjects discontinued due to TEAEs
|
0 participants
|
0 participants
|
0 participants
|
|
Safety (Incidence of Treatment-related Adverse Events Using CTCAE v4.03)
Related TEAEs
|
6 participants
|
3 participants
|
8 participants
|
|
Safety (Incidence of Treatment-related Adverse Events Using CTCAE v4.03)
TEAEs of mild severity
|
24 participants
|
25 participants
|
24 participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Predose, 1.5 h after end of infusion, 2, 3, 4, 5, 6, 8, 12, 24 h post-dose on Day 1-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.Due to variability in the actual protein content between the study drugs and study drug batches which had the potential to influence the study results (as AUC is a dose-dependent PK parameter), protein-adjusted AUC(0-∞) was also derived for each individual by dividing each parameter by the actual protein content of the product batch that the individual subjects received. The 3 mg/kg IV dose of MB02 and US Avastin®, MB02 and EU Avastin®, and EU and US Avastin® were all considered bioequivalent in terms of the protein-adjusted AUCs and Cmax as the 90% CI for the geometric LS means ratios were fully contained within the predefined bioequivalence limits of 0.80 to 1.25 for all 3 comparisons. In general, as assessed from the geometric CV%, between-subject variability remained similar following protein adjustment compared to the unadjusted AUCs and Cmax.
Outcome measures
| Measure |
MB02 (Bevacizumab Biosimilar)
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
MB02: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
US Licenced Avastin®
n=37 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
US licenced Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
EU Approved Avastin®
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
|---|---|---|---|
|
AUC(0-∞) Adjusted: Protein-adjusted Area Under the Serum Concentration-time Curve From Time Zero to Infinity
|
1040000 ng*h/mL
Geometric Coefficient of Variation 16.3
|
981000 ng*h/mL
Geometric Coefficient of Variation 18.1
|
1020000 ng*h/mL
Geometric Coefficient of Variation 14.5
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Predose, 1.5 h after end of infusion, 2, 3, 4, 5, 6, 8, 12, 24 h post-dose on Day 1-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.Due to variability in the actual protein content between the study drugs and study drug batches which had the potential to influence the study results (as AUC is a dose-dependent PK parameters), protein-adjusted AUC(0-t) was also derived for each individual by dividing each parameter by the actual protein content of the product batch that the individual subjects received. The 3 mg/kg IV dose of MB02 and US Avastin®, MB02 and EU Avastin®, and EU and US Avastin® were all considered bioequivalent in terms of the protein-adjusted AUCs and Cmax as the 90% CI for the geometric LS means ratios were fully contained within the predefined bioequivalence limits of 0.80 to 1.25 for all 3 comparisons. In general, as assessed from the geometric CV%, between-subject variability remained similar following protein adjustment compared to the unadjusted AUCs and Cmax.
Outcome measures
| Measure |
MB02 (Bevacizumab Biosimilar)
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
MB02: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
US Licenced Avastin®
n=37 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
US licenced Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
EU Approved Avastin®
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
|---|---|---|---|
|
AUC(0-t) Adjusted: Protein Adjusted Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Observable Concentration
|
1010000 ng*h/mL
Geometric Coefficient of Variation 15.5
|
955000 ng*h/mL
Geometric Coefficient of Variation 17.2
|
991000 ng*h/mL
Geometric Coefficient of Variation 13.6
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Predose, 1.5 h after end of infusion, 2, 3, 4, 5, 6, 8, 12, 24 h post-dose on Day 1-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.Due to variability in the actual protein content between the study drugs and study drug batches which had the potential to influence the study results (as Cmax is a dose-dependent PK parameters), protein-adjusted Cmax was also derived for each individual by dividing each parameter by the actual protein content of the product batch that the individual subjects received. The 3 mg/kg IV dose of MB02 and US Avastin®, MB02 and EU Avastin®, and EU and US Avastin® were all considered bioequivalent in terms of the protein-adjusted AUCs and Cmax as the 90% CI for the geometric LS means ratios were fully contained within the predefined bioequivalence limits of 0.80 to 1.25 for all 3 comparisons. In general, as assessed from the geometric CV%, between-subject variability remained similar following protein adjustment compared to the unadjusted AUCs and Cmax.
Outcome measures
| Measure |
MB02 (Bevacizumab Biosimilar)
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
MB02: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
US Licenced Avastin®
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
US licenced Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
EU Approved Avastin®
n=38 Participants
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
|---|---|---|---|
|
Cmax Adjusted: Protein Adjusted Maximum Observed Serum Concentration
|
3050 (ng/mL)/(mg/mL)
Geometric Coefficient of Variation 22.4
|
2790 (ng/mL)/(mg/mL)
Geometric Coefficient of Variation 22.1
|
3110 (ng/mL)/(mg/mL)
Geometric Coefficient of Variation 25.2
|
Adverse Events
MB02 (Bevacizumab Biosimilar)
Serious events: 0 serious events
Other events: 24 other events
Deaths: 0 deaths
US Licenced Avastin®
Serious events: 1 serious events
Other events: 28 other events
Deaths: 0 deaths
EU Approved Avastin®
Serious events: 0 serious events
Other events: 25 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
MB02 (Bevacizumab Biosimilar)
n=38 participants at risk
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
MB02: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
US Licenced Avastin®
n=38 participants at risk
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
US licenced Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
EU Approved Avastin®
n=38 participants at risk
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Purpura
|
0.00%
0/38 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
2.6%
1/38 • Number of events 1 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
0.00%
0/38 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
Other adverse events
| Measure |
MB02 (Bevacizumab Biosimilar)
n=38 participants at risk
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
MB02: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
US Licenced Avastin®
n=38 participants at risk
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
US licenced Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
EU Approved Avastin®
n=38 participants at risk
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.
|
|---|---|---|---|
|
Immune system disorders
Seasonal allergy
|
0.00%
0/38 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
0.00%
0/38 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
5.3%
2/38 • Number of events 2 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
|
General disorders
Influenza like illness
|
2.6%
1/38 • Number of events 1 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
5.3%
2/38 • Number of events 2 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
0.00%
0/38 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
|
Injury, poisoning and procedural complications
Contusion
|
5.3%
2/38 • Number of events 2 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
2.6%
1/38 • Number of events 1 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
0.00%
0/38 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
2.6%
1/38 • Number of events 1 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
10.5%
4/38 • Number of events 5 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
13.2%
5/38 • Number of events 5 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.5%
4/38 • Number of events 4 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
5.3%
2/38 • Number of events 2 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
2.6%
1/38 • Number of events 1 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/38 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
0.00%
0/38 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
7.9%
3/38 • Number of events 3 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/38 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
0.00%
0/38 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
5.3%
2/38 • Number of events 2 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
|
Nervous system disorders
Headache
|
15.8%
6/38 • Number of events 9 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
21.1%
8/38 • Number of events 10 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
21.1%
8/38 • Number of events 10 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
|
Nervous system disorders
Dizziness
|
5.3%
2/38 • Number of events 2 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
2.6%
1/38 • Number of events 1 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
0.00%
0/38 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
|
Gastrointestinal disorders
Nausea
|
10.5%
4/38 • Number of events 5 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
0.00%
0/38 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
2.6%
1/38 • Number of events 2 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
|
Gastrointestinal disorders
Vomiting
|
5.3%
2/38 • Number of events 5 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
2.6%
1/38 • Number of events 1 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
0.00%
0/38 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
|
Gastrointestinal disorders
Toothache
|
2.6%
1/38 • Number of events 1 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
5.3%
2/38 • Number of events 2 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
5.3%
2/38 • Number of events 2 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
|
Gastrointestinal disorders
Diarrhoea
|
7.9%
3/38 • Number of events 3 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
2.6%
1/38 • Number of events 1 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
0.00%
0/38 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/38 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
2.6%
1/38 • Number of events 1 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
7.9%
3/38 • Number of events 3 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
|
Gastrointestinal disorders
Gingival pain
|
0.00%
0/38 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
7.9%
3/38 • Number of events 3 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
0.00%
0/38 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.6%
1/38 • Number of events 1 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
18.4%
7/38 • Number of events 8 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
10.5%
4/38 • Number of events 4 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/38 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
10.5%
4/38 • Number of events 4 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
7.9%
3/38 • Number of events 3 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
5.3%
2/38 • Number of events 2 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
5.3%
2/38 • Number of events 2 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
0.00%
0/38 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
5.3%
2/38 • Number of events 2 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
2.6%
1/38 • Number of events 1 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
0.00%
0/38 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/38 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
5.3%
2/38 • Number of events 2 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
0.00%
0/38 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
|
Infections and infestations
Upper respiratory tract infection
|
10.5%
4/38 • Number of events 4 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
28.9%
11/38 • Number of events 12 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
15.8%
6/38 • Number of events 7 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
|
Infections and infestations
Nasophyringitis
|
5.3%
2/38 • Number of events 2 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
10.5%
4/38 • Number of events 6 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
13.2%
5/38 • Number of events 6 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
|
Infections and infestations
Conjunctivitis
|
5.3%
2/38 • Number of events 2 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
2.6%
1/38 • Number of events 1 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
0.00%
0/38 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
|
Infections and infestations
Gingivitis
|
0.00%
0/38 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
2.6%
1/38 • Number of events 1 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
5.3%
2/38 • Number of events 2 • Study duration (Day 1 - Day 100)
Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Following a request from the Medicines and Healthcare products Regulatory Authority (MHRA) all serious adverse reactions were considered unexpected and reported as SUSARs, for the purpose of safety reporting in healthy volunteers.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place