Trial Outcomes & Findings for A Study to Compare Pharmacokinetic and Safety of TRS003 to China-approved Bevacizumab and US-licensed Avastin® (NCT NCT03882424)

Last Updated: 2020-06-16

Results Overview

The primary assessment of PK similarity will be based upon a 90 percentage CI for the ratio of the geometric means (TRS003, China-approved bevacizumab and US-licensed Avastin®) for AUC0-inf on PK analysis set. If the 90 percentage CI of the ratio of the geometric means for AUC0-inf is within the range of 80-125 percentage, then PK similarity will be concluded.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

114 participants

Primary outcome timeframe

Pre-dose, 0 hour (End of infusion, EOI), 0.5 hour, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours, 336 hours, 672 hours, 1008 hours, 1344 hours, 1680 hours, and 2016 hours post EOI

Results posted on

2020-06-16

Participant Flow

Participant milestones

Participant milestones
Measure	TRS003 Proposed biosimilar of bevacizumab，Intravenous administration TRS003: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes	China-approved Bevacizumab Intravenous administration China-approved Bevacizumab: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes	US-licensed Avastin Intravenous administration US-licensed Avastin: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes
Overall Study STARTED	38	38	38
Overall Study COMPLETED	34	38	38
Overall Study NOT COMPLETED	4	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	TRS003 Proposed biosimilar of bevacizumab，Intravenous administration TRS003: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes	China-approved Bevacizumab Intravenous administration China-approved Bevacizumab: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes	US-licensed Avastin Intravenous administration US-licensed Avastin: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes
Overall Study Lost to Follow-up	3	0	0
Overall Study schedule conflict	1	0	0

Baseline Characteristics

A Study to Compare Pharmacokinetic and Safety of TRS003 to China-approved Bevacizumab and US-licensed Avastin®

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TRS003 n=38 Participants Proposed biosimilar of bevacizumab，Intravenous administration TRS003: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes	China-approved Bevacizumab n=38 Participants Intravenous administration China-approved Bevacizumab: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes	US-licensed Avastin n=38 Participants Intravenous administration US-licensed Avastin: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes	Total n=114 Participants Total of all reporting groups
Age, Customized Safety Population · <18	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Customized Safety Population · 18-40	26 Participants n=93 Participants	30 Participants n=4 Participants	25 Participants n=27 Participants	81 Participants n=483 Participants
Age, Customized Safety Population · >40	12 Participants n=93 Participants	8 Participants n=4 Participants	13 Participants n=27 Participants	33 Participants n=483 Participants
Age, Customized Pharmacokinetic Population · <18	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Customized Pharmacokinetic Population · 18-40	26 Participants n=93 Participants	30 Participants n=4 Participants	25 Participants n=27 Participants	81 Participants n=483 Participants
Age, Customized Pharmacokinetic Population · >40	12 Participants n=93 Participants	8 Participants n=4 Participants	13 Participants n=27 Participants	33 Participants 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
Ethnicity (NIH/OMB) Hispanic or Latino	27 Participants n=93 Participants	27 Participants n=4 Participants	25 Participants n=27 Participants	79 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=93 Participants	11 Participants n=4 Participants	13 Participants n=27 Participants	35 Participants n=483 Participants
Ethnicity (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
Race/Ethnicity, Customized Race · White	15 Participants n=93 Participants	22 Participants n=4 Participants	25 Participants n=27 Participants	62 Participants n=483 Participants
Race/Ethnicity, Customized Race · Black	18 Participants n=93 Participants	8 Participants n=4 Participants	9 Participants n=27 Participants	35 Participants n=483 Participants
Race/Ethnicity, Customized Race · Asian	4 Participants n=93 Participants	6 Participants n=4 Participants	4 Participants n=27 Participants	14 Participants n=483 Participants
Race/Ethnicity, Customized Race · Am Indian	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants
Race/Ethnicity, Customized Race · Hawaiian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race/Ethnicity, Customized Race · Multi-racial	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race/Ethnicity, Customized Race · Other	0 Participants n=93 Participants	2 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants
Height	175.37 cm n=93 Participants	173.09 cm n=4 Participants	174.62 cm n=27 Participants	174.36 cm n=483 Participants
Weight	80.16 kg n=93 Participants	78.55 kg n=4 Participants	78.82 kg n=27 Participants	79.18 kg n=483 Participants
BMI	26.09 kg/m^2 n=93 Participants	26.21 kg/m^2 n=4 Participants	25.84 kg/m^2 n=27 Participants	26.05 kg/m^2 n=483 Participants

PRIMARY outcome

Timeframe: Pre-dose, 0 hour (End of infusion, EOI), 0.5 hour, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours, 336 hours, 672 hours, 1008 hours, 1344 hours, 1680 hours, and 2016 hours post EOI

Outcome measures

Outcome measures
Measure	TRS003 n=34 Participants Proposed biosimilar of bevacizumab，Intravenous administration TRS003: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes	China-approved Bevacizumab n=38 Participants Intravenous administration China-approved Bevacizumab: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes	US-licensed Avastin n=38 Participants Intravenous administration US-licensed Avastin: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes
AUC0-inf，Area Under the Serum Concentration Versus Time Curve，Time 0 to Infinity	30308695.01 hr*ng/mL Standard Deviation 4780171.58	28449241.04 hr*ng/mL Standard Deviation 5232124.54	29050169.73 hr*ng/mL Standard Deviation 4476342.82

SECONDARY outcome

To assess other PK parameters such as Cmax, following a single dose of TRS003, China-approved bevacizumab and US-licensed Avastin® in healthy male participants. If the 90 percentage CI of the ratio of the geometric means for Cmax is within the range of 80-125 percentage, then PK similarity will be concluded.

Outcome measures

Outcome measures
Measure	TRS003 n=38 Participants Proposed biosimilar of bevacizumab，Intravenous administration TRS003: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes	China-approved Bevacizumab n=38 Participants Intravenous administration China-approved Bevacizumab: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes	US-licensed Avastin n=38 Participants Intravenous administration US-licensed Avastin: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes
Cmax, Maximum Drug Concentration	86051.02 ng/mL Standard Deviation 14888.99	84748.14 ng/mL Standard Deviation 12592.56	82509.03 ng/mL Standard Deviation 13197.95

SECONDARY outcome

To assess other PK parameters such as AUClast, following a single dose of TRS003, China-approved bevacizumab and US-licensed Avastin® in healthy male participants. If the 90 percentage CI of the ratio of the geometric means for AUC0-last is within the range of 80-125 percentage, then PK similarity will be concluded.

Outcome measures

Outcome measures
Measure	TRS003 n=34 Participants Proposed biosimilar of bevacizumab，Intravenous administration TRS003: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes	China-approved Bevacizumab n=38 Participants Intravenous administration China-approved Bevacizumab: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes	US-licensed Avastin n=38 Participants Intravenous administration US-licensed Avastin: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes
AUC0-last, Area Under the Serum Concentration-time Curve，Time 0 to Last	29146948.37 hr*ng/mL Standard Deviation 4383124.30	27446018.92 hr*ng/mL Standard Deviation 4716128.56	27951588.98 hr*ng/mL Standard Deviation 4089884.99

SECONDARY outcome

Timeframe: Pre-dose, 336 hours, 672 hours, 1344 hours and 2016 hours after EOI (End of infusion)

Population: In TRS003, four subjects were lost to follow-up and one subject elected to withdraw due to schedule conflict, resulting in 13 samples missing. In China-approved bevacizumab, three subjects were lost to follow-up, resulting in 4 samples missing. In US-licensed Avastin, two subjects were lost to follow-up, resulting in 2 sample missing.

To determine the number of participants with immunogenicity against TRS003, China-approved bevacizumab, and US-licensed Avastin® in healthy male participants, blood samples will be collected for ADA analyses.

Outcome measures

Outcome measures
Measure	TRS003 n=38 Participants Proposed biosimilar of bevacizumab，Intravenous administration TRS003: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes	China-approved Bevacizumab n=38 Participants Intravenous administration China-approved Bevacizumab: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes	US-licensed Avastin n=38 Participants Intravenous administration US-licensed Avastin: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes
Number of Participants Who Develop Detectable Anti-drug Antibody (ADA) 0 hour · Negative	37 Participants	37 Participants	38 Participants
Number of Participants Who Develop Detectable Anti-drug Antibody (ADA) 0 hour · Positive	1 Participants	1 Participants	0 Participants
Number of Participants Who Develop Detectable Anti-drug Antibody (ADA) 336 hour · Negative	36 Participants	37 Participants	37 Participants
Number of Participants Who Develop Detectable Anti-drug Antibody (ADA) 336 hour · Positive	0 Participants	0 Participants	0 Participants
Number of Participants Who Develop Detectable Anti-drug Antibody (ADA) 672 hour · Negative	35 Participants	37 Participants	37 Participants
Number of Participants Who Develop Detectable Anti-drug Antibody (ADA) 672 hour · Positive	0 Participants	0 Participants	0 Participants
Number of Participants Who Develop Detectable Anti-drug Antibody (ADA) 1344 hour · Negative	33 Participants	34 Participants	38 Participants
Number of Participants Who Develop Detectable Anti-drug Antibody (ADA) 1344 hour · Positive	0 Participants	2 Participants	0 Participants
Number of Participants Who Develop Detectable Anti-drug Antibody (ADA) 2016 hour · Negative	35 Participants	35 Participants	38 Participants
Number of Participants Who Develop Detectable Anti-drug Antibody (ADA) 2016 hour · Positive	0 Participants	3 Participants	0 Participants

SECONDARY outcome

Timeframe: Within 85 days following the drug administration

Population: 110 subjects completed the study. Three subjects who received Treatment A (Subject Nos. Subject Nos. 1-119, 1-120, and 1-177) were lost to follow-up and 1 subject (Subject No. 1-138) who received Treatment A was withdrawn from the study due to other reason (schedule conflict).

Adverse events will be classified using the MedDRA classification system. The severity of the toxicities will be graded according to the NCI CTCAE version 4.03.

Outcome measures

Outcome measures
Measure	TRS003 n=38 Participants Proposed biosimilar of bevacizumab，Intravenous administration TRS003: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes	China-approved Bevacizumab n=38 Participants Intravenous administration China-approved Bevacizumab: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes	US-licensed Avastin n=38 Participants Intravenous administration US-licensed Avastin: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes
Number of Participants With Adverse Events (AEs)	6 Participants	12 Participants	11 Participants

Adverse Events

TRS003

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

China-approved Bevacizumab

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

US-licensed Avastin

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Yilin Li, Medical Director

Zhejiang Teruisi Pharmaceutical Inc.

Phone: 13601247168

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	TRS003 n=38 participants at risk Proposed biosimilar of bevacizumab，Intravenous administration TRS003: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes	China-approved Bevacizumab n=38 participants at risk Intravenous administration China-approved Bevacizumab: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes	US-licensed Avastin n=38 participants at risk Intravenous administration US-licensed Avastin: 25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes
Nervous system disorders Headache	2.6% 1/38 • Number of events 1 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	5.3% 2/38 • Number of events 2 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	7.9% 3/38 • Number of events 3 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.
Nervous system disorders Hypoaesthesia	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	2.6% 1/38 • Number of events 2 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	2.6% 1/38 • Number of events 1 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.
Nervous system disorders Dizziness	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	2.6% 1/38 • Number of events 1 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.
Nervous system disorders Somnolence	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	2.6% 1/38 • Number of events 1 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.
Nervous system disorders Syncope	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	2.6% 1/38 • Number of events 1 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.
Infections and infestations Pharyngitis	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	10.5% 4/38 • Number of events 4 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.
Infections and infestations Gingivitis	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	2.6% 1/38 • Number of events 1 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.
Infections and infestations Rhinitis	2.6% 1/38 • Number of events 1 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.
Infections and infestations Sinusitis	2.6% 1/38 • Number of events 1 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.
Infections and infestations Upper Respiratory Tract Infection	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	2.6% 1/38 • Number of events 1 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.
Infections and infestations Viral Infection	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	2.6% 1/38 • Number of events 1 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.
Musculoskeletal and connective tissue disorders Arthralgia	2.6% 1/38 • Number of events 1 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	2.6% 1/38 • Number of events 1 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	2.6% 1/38 • Number of events 1 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	2.6% 1/38 • Number of events 1 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.
Musculoskeletal and connective tissue disorders Tendonitis	2.6% 1/38 • Number of events 1 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.
Skin and subcutaneous tissue disorders Rash	2.6% 1/38 • Number of events 1 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	2.6% 1/38 • Number of events 1 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	2.6% 1/38 • Number of events 1 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.
Skin and subcutaneous tissue disorders Skin Exfoliation	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	2.6% 1/38 • Number of events 1 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.
Investigations Alanine Aminotransferase Increased	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	5.3% 2/38 • Number of events 3 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.
Investigations Aspartate Aminotransferase Increased	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	5.3% 2/38 • Number of events 2 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.
Gastrointestinal disorders Constipation	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	2.6% 1/38 • Number of events 1 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.
Gastrointestinal disorders Diarrhoea	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	2.6% 1/38 • Number of events 1 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.
Injury, poisoning and procedural complications Ligament Sprain	2.6% 1/38 • Number of events 1 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.
Injury, poisoning and procedural complications Muscle Strain	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	2.6% 1/38 • Number of events 1 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.
General disorders Infusion Site Pain	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	2.6% 1/38 • Number of events 1 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.
Psychiatric disorders Insomnia	2.6% 1/38 • Number of events 1 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.	0.00% 0/38 • Throughout the study, subjects were monitored for AEs. All AEs, including those reported within 85 days following the last dose of drug administration, were recorded. AEs were followed-up until complete resolution, or until the Medical Sub-Investigator judged safe to discontinue follow-up. Any subjects who were withdrawn from the study due to an AE were followed until the outcome of the AE was determined.