Trial Outcomes & Findings for Safety and Efficacy of Nerinetide (NA-1) in Subjects Undergoing Endovascular Thrombectomy for Stroke (NCT NCT02930018)

Last Updated: 2022-10-10

Results Overview

Overall number of subjects experiencing a favorable functional outcome 90 days post-randomization, defined as 0 to 2 on the mRS. The modified Rankin Scale (mRS) is a valid and reliable clinician-reported measure of global disability that has been widely applied for evaluating recovery from stroke. It is a scale used to measure functional recovery (the degree of disability or dependence in daily activities) of people who have suffered a stroke. mRS scores range from 0 (best outcome) to 6 (worst outcome), with 0 indicating no residual symptoms; 5 indicating bedbound, requiring constant care; and 6 indicating death.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1105 participants

Primary outcome timeframe

90 Days

Results posted on

2022-10-10

Participant Flow

Patients with acute ischaemic stroke who were selected to undergo EVT (endovascular thrombectomy) were enrolled. The trial was done at acute care hospitals. Patients were randomly assigned (1:1) to receive a single intravenous dose of nerinetide (NA-1) or placebo. All patients underwent endovascular thrombectomy and received alteplase in usual care when indicated.

The trial drug was administered as soon as possible after randomisation.

Participant milestones

Participant milestones
Measure	Placebo Drug vehicle only Placebo: Placebo Comparator: Placebo	Nerinetide (NA-1), 2.6 mg/kg Single intravenous infusion of nerinetide over 10 ± 1 minutes
Overall Study STARTED	556	549
Overall Study COMPLETED	550	546
Overall Study NOT COMPLETED	6	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Drug vehicle only Placebo: Placebo Comparator: Placebo	Nerinetide (NA-1), 2.6 mg/kg Single intravenous infusion of nerinetide over 10 ± 1 minutes
Overall Study Lost to Follow-up	1	1
Overall Study Withdrawal by Subject	5	2

Baseline Characteristics

Safety and Efficacy of Nerinetide (NA-1) in Subjects Undergoing Endovascular Thrombectomy for Stroke

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=556 Participants Drug vehicle only Placebo: Placebo Comparator: Placebo	Nerinetide (NA-1), 2.6 mg/kg n=549 Participants Single intravenous infusion of nerinetide over 10 ± 1 minutes	Total n=1105 Participants Total of all reporting groups
Age, Continuous	70.0 years n=99 Participants	71.0 years n=107 Participants	70.0 years n=206 Participants
Sex: Female, Male Female	281 Participants n=99 Participants	268 Participants n=107 Participants	549 Participants n=206 Participants
Sex: Female, Male Male	275 Participants n=99 Participants	281 Participants n=107 Participants	556 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=99 Participants	8 Participants n=107 Participants	23 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	540 Participants n=99 Participants	541 Participants n=107 Participants	1081 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=99 Participants	2 Participants n=107 Participants	4 Participants n=206 Participants
Race (NIH/OMB) Asian	52 Participants n=99 Participants	55 Participants n=107 Participants	107 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	3 Participants n=99 Participants	0 Participants n=107 Participants	3 Participants n=206 Participants
Race (NIH/OMB) Black or African American	31 Participants n=99 Participants	45 Participants n=107 Participants	76 Participants n=206 Participants
Race (NIH/OMB) White	453 Participants n=99 Participants	436 Participants n=107 Participants	889 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	15 Participants n=99 Participants	11 Participants n=107 Participants	26 Participants n=206 Participants
Region of Enrollment Canada	252 Participants n=99 Participants	253 Participants n=107 Participants	505 Participants n=206 Participants
Region of Enrollment South Korea	20 Participants n=99 Participants	22 Participants n=107 Participants	42 Participants n=206 Participants
Region of Enrollment Sweden	8 Participants n=99 Participants	6 Participants n=107 Participants	14 Participants n=206 Participants
Region of Enrollment United States	203 Participants n=99 Participants	211 Participants n=107 Participants	414 Participants n=206 Participants
Region of Enrollment Ireland	5 Participants n=99 Participants	4 Participants n=107 Participants	9 Participants n=206 Participants
Region of Enrollment United Kingdom	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
Region of Enrollment Australia	25 Participants n=99 Participants	18 Participants n=107 Participants	43 Participants n=206 Participants
Region of Enrollment Germany	42 Participants n=99 Participants	34 Participants n=107 Participants	76 Participants n=206 Participants
Alteplase Treatment Participants treated with alteplase	329 Participants n=99 Participants	330 Participants n=107 Participants	659 Participants n=206 Participants
Alteplase Treatment Participants not treated with alteplase	227 Participants n=99 Participants	219 Participants n=107 Participants	446 Participants n=206 Participants

PRIMARY outcome

Timeframe: 90 Days

Population: Intent-to-Treat Population

Outcome measures

Outcome measures
Measure	Placebo n=556 Participants Drug vehicle only Placebo: Placebo Comparator: Placebo	Nerinetide, 2.6 mg/kg n=549 Participants Single intravenous infusion of nerinetide over 10 ± 1 minutes
Number of Subjects With mRS Score of 0 to 2	329 Participants	337 Participants

SECONDARY outcome

Timeframe: 90 Days or the last rating

Number of subjects with good neurological outcome, as defined by a score of 0 to 2 on the NIHSS at Day 90 or the last rating. The National Institutes of Health Stroke Scale (NIHSS) is a standardized neurological examination score that is a valid and reliable measure of disability and recovery after acute stroke. Scores range from 0 to 42, with higher scores indicating increasing severity.

Outcome measures

Outcome measures
Measure	Placebo n=556 Participants Drug vehicle only Placebo: Placebo Comparator: Placebo	Nerinetide, 2.6 mg/kg n=549 Participants Single intravenous infusion of nerinetide over 10 ± 1 minutes
Number of Subjects With NIHSS Score of 0 to 2	320 Participants	320 Participants

SECONDARY outcome

Timeframe: 90 Days

Mortality rate, as defined by event rate (%) for mortality over the 90-day study period

Outcome measures

Outcome measures
Measure	Placebo n=556 Participants Drug vehicle only Placebo: Placebo Comparator: Placebo	Nerinetide, 2.6 mg/kg n=549 Participants Single intravenous infusion of nerinetide over 10 ± 1 minutes
Mortality Rate	74 Participants	64 Participants

POST_HOC outcome

Timeframe: 90 days

Overall number of subjects experiencing a favorable functional outcome 90 days post-randomization, defined as 0 to 2 on the mRS in the sub-group of participants not treated with alteplase as part of standard-of-care. The modified Rankin Scale (mRS) is a valid and reliable clinician-reported measure of global disability that has been widely applied for evaluating recovery from stroke. It is a scale used to measure functional recovery (the degree of disability or dependence in daily activities) of people who have suffered a stroke. mRS scores range from 0 (best outcome) to 6 (worst outcome), with 0 indicating no residual symptoms; 5 indicating bedbound, requiring constant care; and 6 indicating death.

Outcome measures

Outcome measures
Measure	Placebo n=227 Participants Drug vehicle only Placebo: Placebo Comparator: Placebo	Nerinetide, 2.6 mg/kg n=219 Participants Single intravenous infusion of nerinetide over 10 ± 1 minutes
Number of Subjects With mRS Score of 0 to 2 in the No-alteplase Sub-group	113 Participants	130 Participants

POST_HOC outcome

Timeframe: 90 days or last rating

Number of subjects with good neurological outcome, as defined by a score of 0 to 2 on the NIHSS at Day 90 or the last rating in the sub-group of participants not treated with alteplase as part of standard-of-care. The National Institutes of Health Stroke Scale (NIHSS) is a standardized neurological examination score that is a valid and reliable measure of disability and recovery after acute stroke. Scores range from 0 to 42, with higher scores indicating increasing severity.

Outcome measures

Outcome measures
Measure	Placebo n=227 Participants Drug vehicle only Placebo: Placebo Comparator: Placebo	Nerinetide, 2.6 mg/kg n=219 Participants Single intravenous infusion of nerinetide over 10 ± 1 minutes
Number of Subjects With NIHSS Score of 0 to 2 in the No-Alteplase Sub-group	113 Participants	129 Participants

POST_HOC outcome

Timeframe: 90 days

Mortality rate, as defined by event rate (%) for mortality over the 90-day study period in the sub-group of participants not treated with alteplase as part of standard-of-care

Outcome measures

Outcome measures
Measure	Placebo n=227 Participants Drug vehicle only Placebo: Placebo Comparator: Placebo	Nerinetide, 2.6 mg/kg n=219 Participants Single intravenous infusion of nerinetide over 10 ± 1 minutes
Mortality Rate in the No-Alteplase Sub-group	43 Participants	25 Participants

POST_HOC outcome

Timeframe: 90 days

Overall proportion of subjects experiencing a favorable functional outcome 90 days post-randomization, defined as 0 to 2 on the mRS in the sub-group of participants treated with alteplase as part of standard-of-care. The modified Rankin Scale (mRS) is a valid and reliable clinician-reported measure of global disability that has been widely applied for evaluating recovery from stroke. It is a scale used to measure functional recovery (the degree of disability or dependence in daily activities) of people who have suffered a stroke. mRS scores range from 0 (best outcome) to 6 (worst outcome), with 0 indicating no residual symptoms; 5 indicating bedbound, requiring constant care; and 6 indicating death.

Outcome measures

Outcome measures
Measure	Placebo n=329 Participants Drug vehicle only Placebo: Placebo Comparator: Placebo	Nerinetide, 2.6 mg/kg n=330 Participants Single intravenous infusion of nerinetide over 10 ± 1 minutes
Number of Subjects With mRS Score of 0 to 2 in the Alteplase Sub-group	216 Participants	207 Participants

POST_HOC outcome

Timeframe: 90 days or last rating

Number of subjects with good neurological outcome, as defined by a score of 0 to 2 on the NIHSS at Day 90 or the last rating in the sub-group of participants treated with alteplase as part of standard-of-care. The National Institutes of Health Stroke Scale (NIHSS) is a standardized neurological examination score that is a valid and reliable measure of disability and recovery after acute stroke. Scores range from 0 to 42, with higher scores indicating increasing severity.

Outcome measures

Outcome measures
Measure	Placebo n=329 Participants Drug vehicle only Placebo: Placebo Comparator: Placebo	Nerinetide, 2.6 mg/kg n=330 Participants Single intravenous infusion of nerinetide over 10 ± 1 minutes
Number of Subjects With NIHSS Score of 0 to 2 in the Alteplase Sub-group	207 Participants	191 Participants

POST_HOC outcome

Timeframe: 90 days

Mortality rate, as defined by event rate (%) for mortality over the 90-day study period in the sub-group of participants treated with alteplase as part of standard-of-care

Outcome measures

Outcome measures
Measure	Placebo n=329 Participants Drug vehicle only Placebo: Placebo Comparator: Placebo	Nerinetide, 2.6 mg/kg n=330 Participants Single intravenous infusion of nerinetide over 10 ± 1 minutes
Mortality Rate in the Alteplase Sub-group	31 Participants	39 Participants

Adverse Events

Placebo

Serious events: 198 serious events

Other events: 472 other events

Deaths: 74 deaths

Nerinetide, 2.6 mg/kg

Serious events: 181 serious events

Other events: 474 other events

Deaths: 64 deaths

Serious adverse events

Other adverse events

Additional Information

Michael Tymianski, MD PhD

NoNO Inc.

Phone: 4165831687

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Placebo n=554 participants at risk Drug vehicle only Placebo: Placebo Comparator: Placebo	Nerinetide, 2.6 mg/kg n=547 participants at risk Single intravenous infusion of nerinetide over 10 ± 1 minutes
Blood and lymphatic system disorders Anaemia	0.72% 4/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.18% 1/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.18% 1/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Cardiac disorders Acute coronary syndrome	0.00% 0/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.55% 3/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Cardiac disorders Angina pectoris	0.00% 0/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.18% 1/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Cardiac disorders Arrhythmia	0.18% 1/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.00% 0/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Cardiac disorders Atrial fibrillation	0.90% 5/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	1.1% 6/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Cardiac disorders Atrial flutter	0.18% 1/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.18% 1/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Cardiac disorders Atrial tachycardia	0.00% 0/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.18% 1/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Cardiac disorders Atrioventricular block	0.00% 0/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.18% 1/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Cardiac disorders Bradycardia	0.54% 3/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.00% 0/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Cardiac disorders Cardiac arrest	0.36% 2/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.55% 3/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Cardiac disorders Cardiac failure congestive	0.72% 4/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	1.6% 9/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Cardiac disorders Cardiac ventricular thrombosis	0.18% 1/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.00% 0/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Cardiac disorders Cardiogenic shock	0.18% 1/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.00% 0/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Cardiac disorders Intracardiac thrombus	0.36% 2/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.00% 0/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Cardiac disorders Mitral valve stenosis	0.00% 0/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.18% 1/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Cardiac disorders Myocardial infarction	0.54% 3/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	1.1% 6/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Cardiac disorders Sinus arrest	0.18% 1/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.00% 0/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Cardiac disorders Stress cardiomyopathy	0.00% 0/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.18% 1/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Cardiac disorders Supraventricular tachycardia	0.00% 0/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.18% 1/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Cardiac disorders Ventricular tachycardia	0.00% 0/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.18% 1/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Congenital, familial and genetic disorders Atrial septal defect	0.36% 2/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.18% 1/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Endocrine disorders Hyperparathyroidism	0.00% 0/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.18% 1/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Eye disorders Retinal artery occlusion	0.18% 1/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.55% 3/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Eye disorders Retinal detachment	0.18% 1/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.00% 0/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Eye disorders Visual impairment	0.18% 1/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.00% 0/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Gastrointestinal disorders Abdominal distension	0.18% 1/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.00% 0/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Gastrointestinal disorders Ascites	0.00% 0/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.18% 1/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Gastrointestinal disorders Colitis ischaemic	0.00% 0/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.18% 1/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Gastrointestinal disorders Diarrhoea	0.00% 0/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.18% 1/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Gastrointestinal disorders Dysphagia	0.00% 0/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.37% 2/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Gastrointestinal disorders Gastric ulcer haemorrhage	0.18% 1/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.18% 1/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Gastrointestinal disorders Gastrointestinal haemorrhage	0.72% 4/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	1.1% 6/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Gastrointestinal disorders Intestinal ischaemia	0.18% 1/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.00% 0/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Gastrointestinal disorders Melaena	0.00% 0/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.18% 1/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Gastrointestinal disorders Mouth haemorrhage	0.00% 0/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.18% 1/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Gastrointestinal disorders Oesophagitis	0.00% 0/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.18% 1/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Gastrointestinal disorders Pancreatitis	0.18% 1/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.00% 0/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Gastrointestinal disorders Peritoneal haemorrhage	0.18% 1/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.00% 0/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Gastrointestinal disorders Vomiting	0.18% 1/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	0.18% 1/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".

Other adverse events
Measure	Placebo n=554 participants at risk Drug vehicle only Placebo: Placebo Comparator: Placebo	Nerinetide, 2.6 mg/kg n=547 participants at risk Single intravenous infusion of nerinetide over 10 ± 1 minutes
Nervous system disorders Headache	15.9% 88/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	14.4% 79/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Nervous system disorders Hemorrhagic Transformation Stroke	11.9% 66/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	11.0% 60/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Vascular disorders Hypotension	9.7% 54/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	11.0% 60/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Infections and infestations Urinary tract infection	12.3% 68/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	9.5% 52/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Injury, poisoning and procedural complications Vascular procedure complication	9.7% 54/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	9.0% 49/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Cardiac disorders Atrial fibrillation	8.1% 45/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	8.8% 48/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
General disorders Pyrexia	8.5% 47/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	7.3% 40/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Gastrointestinal disorders Nausea	5.6% 31/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	6.8% 37/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	5.1% 28/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	6.4% 35/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Gastrointestinal disorders Constipation	8.1% 45/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	6.2% 34/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Blood and lymphatic system disorders Anemia	7.6% 42/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	6.0% 33/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Metabolism and nutrition disorders Hypokalaemia	6.1% 34/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	6.0% 33/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
General disorders Vessel puncture site hematoma	5.1% 28/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	5.9% 32/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Gastrointestinal disorders Vomiting	6.5% 36/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	5.7% 31/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Cardiac disorders Bradycardia	5.8% 32/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	3.3% 18/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".
Nervous system disorders Stroke In Evolution	9.7% 54/554 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".	8.8% 48/547 • Adverse Events occurring within 30 days of randomization and all Serious Adverse Events up to the end of study visit (Day 90 visit or death) or until the subject was deemed "lost to follow-up" were reported. All Adverse Events (Serious and Non-Serious) were monitored for the Safety Population, which included all subjects who received any amount of study drug (total of 1101 subjects). Adverse Events of Special Interest (AESI) were also collected, and included any Adverse Event which occurred within 2 hours of end of drug infusion and which fall under the standardized MedDRA queries of "Angioedema", "Anaphylactic reaction", "Anaphylactic shock" and terms relating to "hypotension".