Trial Outcomes & Findings for The VITAL Amyloidosis Study, a Global Phase 3, Efficacy and Safety Study of NEOD001 in Patients With AL Amyloidosis (NCT NCT02312206)

NCT ID: NCT02312206

Last Updated: 2023-11-14

Results Overview

Time to all-cause mortality death occurring after the first infusion of study drug or cardiac hospitalization as adjudicated by the CEC occurring at least 91 days after first infusion of study drug through last subject last visit, whichever came first

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 260 participants
• Primary outcome timeframe: Randomization until the date of death or cardiac hospitalization, up to 32 months
• Results posted on: 2023-11-14

Participant Flow

Participant milestones

Measure	NEOD001 (24 mg/kg) + Standard of Care NEOD001, 24 mg/kg IV every 28 days on top of standard of care until completion of 156 primary endpoints	Placebo + Standard of Care Placebo, 0.9% Saline IV every 28 days on top of standard of care until completion of 156 primary endpoints
Overall Study STARTED	130	130
Overall Study Informed Consent Obtained	130	130
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	130	130

Reasons for withdrawal

Measure	NEOD001 (24 mg/kg) + Standard of Care NEOD001, 24 mg/kg IV every 28 days on top of standard of care until completion of 156 primary endpoints	Placebo + Standard of Care Placebo, 0.9% Saline IV every 28 days on top of standard of care until completion of 156 primary endpoints
Overall Study Adverse Event	3	6
Overall Study Withdrawal by Subject	6	6
Overall Study Physician Decision	7	6
Overall Study Death	31	36
Overall Study Study Terminated by Sponsor	81	74
Overall Study Patient transferred to hospice	0	1
Overall Study Subject missed three consecutive treatment visits	0	1
Overall Study Patient progression and institution of a new therapy	1	0
Overall Study Disease Progression	1	0

Baseline Characteristics

The VITAL Amyloidosis Study, a Global Phase 3, Efficacy and Safety Study of NEOD001 in Patients With AL Amyloidosis

Baseline characteristics by cohort

Measure	NEOD001 (24 mg/kg) + Standard of Care n=130 Participants NEOD001, 24 mg/kg IV every 4 weeks on top of Standard of Care	Placebo + Standard of Care n=130 Participants Placebo 0.9% Saline IV every 4 weeks on top of Standard of Care	Total n=260 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	69 Participants n=5 Participants	70 Participants n=7 Participants	139 Participants n=5 Participants
Age, Categorical >=65 years	61 Participants n=5 Participants	60 Participants n=7 Participants	121 Participants n=5 Participants
Age, Continuous	63.69 years STANDARD_DEVIATION 9.478 • n=5 Participants	63.24 years STANDARD_DEVIATION 9.708 • n=7 Participants	63.46 years STANDARD_DEVIATION 9.578 • n=5 Participants
Sex: Female, Male Female	48 Participants n=5 Participants	40 Participants n=7 Participants	88 Participants n=5 Participants
Sex: Female, Male Male	82 Participants n=5 Participants	90 Participants n=7 Participants	172 Participants n=5 Participants
Race/Ethnicity, Customized White	118 Participants n=5 Participants	120 Participants n=7 Participants	238 Participants n=5 Participants
Race/Ethnicity, Customized Black Or African American	9 Participants n=5 Participants	3 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized Race not Reported	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic Or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic Or Latino	116 Participants n=5 Participants	122 Participants n=7 Participants	238 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity Not Reported	12 Participants n=5 Participants	6 Participants n=7 Participants	18 Participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization until the date of death or cardiac hospitalization, up to 32 months

Population: ITT Population

Time to all-cause mortality death occurring after the first infusion of study drug or cardiac hospitalization as adjudicated by the CEC occurring at least 91 days after first infusion of study drug through last subject last visit, whichever came first

Outcome measures

Measure	NEOD001 (24 mg/kg) + Standard of Care n=130 Participants NEOD001, 24 mg/kg IV every 4 weeks on top of Standard of Care	Placebo + Standard of Care n=130 Participants Placebo 0.9% Saline IV every 4 weeks on top of Standard of Care
Time to Composite of All-cause Mortality or Cardiac Hospitalization Number of Subjects Who Died or Experienced Cardiac Hospitalization	56 Participants	62 Participants
Time to Composite of All-cause Mortality or Cardiac Hospitalization Number of Subjects Censored	74 Participants	68 Participants

Adverse Events

NEOD001 (24 mg/kg) + Standard of Care

Serious events: 88 serious events

Other events: 124 other events

Deaths: 41 deaths

Placebo + Standard of Care

Serious events: 91 serious events

Other events: 125 other events

Deaths: 42 deaths

Serious adverse events

Measure	NEOD001 (24 mg/kg) + Standard of Care n=130 participants at risk NEOD001, 24 mg/kg IV every 4 weeks on top of Standard of Care	Placebo + Standard of Care n=130 participants at risk Placebo 0.9% Saline IV every 4 weeks on top of Standard of Care
Cardiac disorders Cardiac failure	13.1% 17/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	21.5% 28/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Cardiac failure congestive	11.5% 15/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	6.9% 9/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Cardiac arrest	6.9% 9/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	7.7% 10/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Atrial fibrillation	4.6% 6/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	4.6% 6/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Cardiac failure acute	3.8% 5/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	3.8% 5/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Ventricular tachycardia	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	3.8% 5/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Acute myocardial infarction	2.3% 3/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Cardiogenic shock	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Arrhythmia	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Atrial flutter	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Cardiac amyloidosis	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Atrioventricular block	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Atrioventricular block complete	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Bradycardia	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Cardiac failure chronic	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Cardiac ventricular thrombosis	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Cardio-respiratory arrest	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Cardiopulmonary failure	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Conduction disorder	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Coronary artery disease	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Left ventricular dysfunction	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Pericardial effusion	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Sinus bradycardia	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Ventricular arrhythmia	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Ventricular fibrillation	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Pneumonia	10.0% 13/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	9.2% 12/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Sepsis	2.3% 3/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Septic shock	3.1% 4/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Gastroenteritis	2.3% 3/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Upper respiratory tract infection	3.1% 4/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Bronchitis	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	2.3% 3/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Lower respiratory tract infection	2.3% 3/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Influenza	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Urinary tract infection	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Viral infection	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Abdominal abscess	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Bacteraemia	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Bacterial infection	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Bronchiolitis	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Cellulitis	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Herpes zoster	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Infection	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Injection site cellulitis	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Parainfluenzae virus infection	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Pasteurella infection	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Peritonitis bacterial	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Pneumococcal sepsis	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Pneumonia viral	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Pyelonephritis	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Respiratory syncytial virus infection	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Soft tissue infection	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Urosepsis	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Abdominal Pain	3.1% 4/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Diarrhoea	2.3% 3/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Gastrointestinal haemorrhage	2.3% 3/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Ileus	2.3% 3/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Vomiting	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Constipation	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	2.3% 3/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Colitis	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Ascites	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Colitis ulcerative	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Intestinal pseudo-obstruction	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Diverticular perforation	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Haematochezia	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Haemorrhoids	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Incarcerated umbilical hernia	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Mesenteric artery thrombosis	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Nausea	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Oesophagitis	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Pancreatitis	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Metabolism and nutrition disorders Fluid overload	3.1% 4/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	3.1% 4/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Metabolism and nutrition disorders Hyponatraemia	3.1% 4/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	2.3% 3/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Metabolism and nutrition disorders Dehydration	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	2.3% 3/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Metabolism and nutrition disorders Hyperkalaemia	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Metabolism and nutrition disorders Hypervolaemia	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Metabolism and nutrition disorders Failure to thrive	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Metabolism and nutrition disorders Hypovolaemia	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Metabolism and nutrition disorders Cell death	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Metabolism and nutrition disorders Fluid retention	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Nervous system disorders Syncope	8.5% 11/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	5.4% 7/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Nervous system disorders Cerebrovascular accident	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Nervous system disorders Seizure	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Nervous system disorders Brain injury	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Nervous system disorders Dizziness	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Nervous system disorders Encephalopathy	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Nervous system disorders Bell's palsy	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Nervous system disorders Haemorrhagic stroke	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Nervous system disorders Ischaemic stroke	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Nervous system disorders Partial seizures	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Renal and urinary disorders Acute kidney injury	5.4% 7/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	6.9% 9/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Renal and urinary disorders Renal failure	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	3.1% 4/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Renal and urinary disorders Chronic kidney disease	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Renal and urinary disorders Haematuria	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Renal and urinary disorders Renal impairment	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Renal and urinary disorders Anuria	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Renal and urinary disorders Dysuria	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Hydronephrosis	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Renal and urinary disorders Nephrolithiasis	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Renal and urinary disorders Nephrotic syndrome	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Renal and urinary disorders Urinary retention	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	4.6% 6/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Respiratory, thoracic and mediastinal disorders Lung disorder	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	2.3% 3/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.3% 3/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Respiratory, thoracic and mediastinal disorders Hypoxia	2.3% 3/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Respiratory, thoracic and mediastinal disorders Lung infiltration	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Respiratory, thoracic and mediastinal disorders Pulmonary amyloidosis	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Respiratory, thoracic and mediastinal disorders Pulmonary mass	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
General disorders Sudden death	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	2.3% 3/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
General disorders Death	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
General disorders Generalised oedema	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
General disorders Oedema peripheral	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
General disorders Malaise	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
General disorders Sudden cardiac death	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
General disorders Non-cardiac Chest pain	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
General disorders General physical health deterioration	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
General disorders Multiple organ dysfunction syndrome	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
General disorders Oedema	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
General disorders Pyrexia	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Vascular disorders Hypotension	2.3% 3/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	4.6% 6/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Vascular disorders Orthostatic hypotension	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	2.3% 3/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Vascular disorders Deep vein thrombosis	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Vascular disorders Haematoma	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Vascular disorders Peripheral artery thrombosis	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Injury, poisoning and procedural complications Toxicity to various agents	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Injury, poisoning and procedural complications Facial bones fracture	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Injury, poisoning and procedural complications Femur fracture	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Injury, poisoning and procedural complications Spinal fracture	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Injury, poisoning and procedural complications Hip fracture	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Injury, poisoning and procedural complications Infusion related reaction	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Injury, poisoning and procedural complications Procedural haemorrhage	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Blood and lymphatic system disorders Anaemia	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Blood and lymphatic system disorders Acquired factor VIII deficiency	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Blood and lymphatic system disorders Lymphopenia	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Hepatobiliary disorders Cholecystitis	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Hepatobiliary disorders Hepatic failure	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Hepatobiliary disorders Haemorrhagic hepatic cyst	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Hepatobiliary disorders Hepatic haematoma	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Hepatobiliary disorders Hepatosplenomegaly	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Investigations Blood creatinine increased	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Investigations Anticoagulation drug level above therapeutic	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Investigations Myocardial necrosis marker increased	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Investigations Neutrophil count decreased	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Investigations Troponin T increased	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Investigations White blood cell count decreased	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Psychiatric disorders Mania	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Psychiatric disorders Confusional state	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Psychiatric disorders Delirium	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Psychiatric disorders Schizophrenia	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Musculoskeletal and connective tissue disorders Pain in extremity	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Musculoskeletal and connective tissue disorders Polymyalgia rheumatica	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pericardial effusion malignant	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Immune system disorders Amyloidosis	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Immune system disorders Hypersensitivity	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Sinus tachycardia	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Pneumonia parainfluenzae viral	0.00% 0/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months

Other adverse events

Measure	NEOD001 (24 mg/kg) + Standard of Care n=130 participants at risk NEOD001, 24 mg/kg IV every 4 weeks on top of Standard of Care	Placebo + Standard of Care n=130 participants at risk Placebo 0.9% Saline IV every 4 weeks on top of Standard of Care
Gastrointestinal disorders Constipation	41.5% 54/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	42.3% 55/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Diarrhoea	39.2% 51/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	41.5% 54/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Nausea	43.1% 56/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	33.1% 43/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Vomiting	19.2% 25/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	15.4% 20/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Abdominal distension	11.5% 15/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	11.5% 15/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Abdominal pain	10.8% 14/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	10.8% 14/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Stomatitis	5.4% 7/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	6.2% 8/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Abdominal pain upper	4.6% 6/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	6.2% 8/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Dry mouth	4.6% 6/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	5.4% 7/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Gastrointestinal disorders Dysphagia	5.4% 7/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	3.8% 5/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
General disorders Oedema peripheral	42.3% 55/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	43.1% 56/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
General disorders Fatigue	43.8% 57/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	40.0% 52/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
General disorders Pyrexia	9.2% 12/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	8.5% 11/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
General disorders Asthenia	6.2% 8/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	6.2% 8/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
General disorders Chills	6.9% 9/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	3.1% 4/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Nervous system disorders Dizziness	19.2% 25/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	29.2% 38/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Nervous system disorders Neuropathy peripheral	22.3% 29/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	13.8% 18/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Nervous system disorders Headache	13.1% 17/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	12.3% 16/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Nervous system disorders Peripheral sensory neuropathy	10.8% 14/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	10.0% 13/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Nervous system disorders Paraesthesia	7.7% 10/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	10.0% 13/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Nervous system disorders Dysgeusia	6.2% 8/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	6.9% 9/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Nervous system disorders Syncope	5.4% 7/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	8.5% 11/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Nervous system disorders Hypoaesthesia	6.2% 8/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	3.1% 4/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Upper respiratory tract infection	17.7% 23/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	19.2% 25/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Urinary tract infection	10.8% 14/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	4.6% 6/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Nasopharyngitis	6.2% 8/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	7.7% 10/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Pneumonia	7.7% 10/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	6.2% 8/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Infections and infestations Respiratory tract infection	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	5.4% 7/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Respiratory, thoracic and mediastinal disorders Dyspnoea	30.0% 39/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	31.5% 41/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Respiratory, thoracic and mediastinal disorders Cough	23.8% 31/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	20.8% 27/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Respiratory, thoracic and mediastinal disorders Pleural effusion	6.2% 8/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	9.2% 12/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	8.5% 11/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	4.6% 6/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Respiratory, thoracic and mediastinal disorders Epistaxis	6.2% 8/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	5.4% 7/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Metabolism and nutrition disorders Hypokalaemia	20.0% 26/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	20.0% 26/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Metabolism and nutrition disorders Decreased appetite	20.0% 26/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	15.4% 20/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Metabolism and nutrition disorders Hyponatraemia	12.3% 16/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	13.1% 17/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Metabolism and nutrition disorders Hyperuricaemia	6.9% 9/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	9.2% 12/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Metabolism and nutrition disorders Hyperkalaemia	6.2% 8/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	6.2% 8/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Metabolism and nutrition disorders Hyperglycaemia	6.2% 8/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	6.2% 8/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Metabolism and nutrition disorders Hypocalcaemia	5.4% 7/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	3.1% 4/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Investigations Weight decreased	14.6% 19/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	12.3% 16/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Investigations Blood creatinine increased	16.9% 22/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	8.5% 11/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Investigations Aspartate aminotransferase increased	8.5% 11/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	6.2% 8/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Investigations Weight increased	4.6% 6/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	8.5% 11/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Investigations Platelet count decreased	3.1% 4/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	7.7% 10/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Investigations Alanine aminotransferase increased	3.8% 5/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	6.2% 8/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Investigations Lymphocyte count decreased	2.3% 3/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	5.4% 7/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Musculoskeletal and connective tissue disorders Back pain	10.0% 13/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	8.5% 11/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Musculoskeletal and connective tissue disorders Muscle spasms	11.5% 15/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	5.4% 7/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Musculoskeletal and connective tissue disorders Pain in extremity	10.8% 14/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	6.9% 9/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Musculoskeletal and connective tissue disorders Arthralgia	10.0% 13/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	6.9% 9/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Musculoskeletal and connective tissue disorders Muscular weakness	6.9% 9/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	4.6% 6/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Musculoskeletal and connective tissue disorders Myalgia	6.2% 8/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	3.1% 4/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Psychiatric disorders Insomnia	30.0% 39/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	23.1% 30/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Psychiatric disorders Depression	8.5% 11/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	5.4% 7/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Psychiatric disorders Anxiety	8.5% 11/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	2.3% 3/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Skin and subcutaneous tissue disorders Rash	10.8% 14/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	10.8% 14/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Skin and subcutaneous tissue disorders Pruritus	10.8% 14/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	10.8% 14/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Skin and subcutaneous tissue disorders Ecchymosis	5.4% 7/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	3.8% 5/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Skin and subcutaneous tissue disorders Dry Skin	5.4% 7/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	5.4% 7/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Vascular disorders Hypotension	14.6% 19/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	22.3% 29/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Vascular disorders Orthostatic hypotension	6.9% 9/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	10.0% 13/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Injury, poisoning and procedural complications Fall	10.8% 14/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	8.5% 11/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Injury, poisoning and procedural complications Contusion	6.2% 8/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	6.9% 9/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Blood and lymphatic system disorders Anaemia	15.4% 20/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	20.8% 27/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Blood and lymphatic system disorders Thrombocytopenia	7.7% 10/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	6.2% 8/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Blood and lymphatic system disorders Lymphopenia	4.6% 6/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	5.4% 7/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Atrial fibrillation	6.2% 8/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	7.7% 10/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Cardiac failure	7.7% 10/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	4.6% 6/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Cardiac disorders Palpitations	2.3% 3/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	8.5% 11/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Renal and urinary disorders Acute kidney injury	6.2% 8/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	3.1% 4/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Renal and urinary disorders Chronic kidney disease	5.4% 7/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	4.6% 6/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Renal and urinary disorders Haematuria	1.5% 2/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	5.4% 7/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Eye disorders Dry eye	3.1% 4/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	5.4% 7/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Eye disorders Vision blurred	6.2% 8/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	0.77% 1/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months
Investigations Blood alkaline phosphatase increased	9.2% 12/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months	3.8% 5/130 • Initiation of study drug through the last study visit or up to 30 days after last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30 days after date of last dose, whichever is later up to 32 months

Additional Information

Wendy Curlin

Prothena Biosciences

Phone: (650) 837-8550

Email: clinicaltrials@prothena.com

Results disclosure agreements

• Principal investigator is a sponsor employee The PI, institution and the sponsor have agreed that the PI and institution may publish or disclose study results from their site after the earlier of (a) publication of the complete multicenter study results or (b) 18 months after database lock for the multicenter study. The sponsor has at least 45 days to review a proposed publication and may request deletion of confidential information and up to 60 days additional delay to obtain patent protection.
• Publication restrictions are in place

Restriction type: OTHER