Trial Outcomes & Findings for Open-label Extension Study to Evaluate Long-term Safety of Sacubitril/Valsartan in Pediatric Patients With HF (NCT NCT03785405)

NCT ID: NCT03785405

Last Updated: 2025-05-16

Results Overview

Number of participants with at least one Adverse Events (AEs)

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 216 participants
• Primary outcome timeframe: to end of study, up to 4,5 years
• Results posted on: 2025-05-16

Participant Flow

79 centers in 27 countries: Korea, Republic of(4), United States(15), Bulgaria(1), Italy(7), Thailand(2), Poland(2), Japan(8), Singapore(2), Israel(1), Turkey(3), Taiwan(2), South Africa(1), Portugal(3), Lebanon(2), Canada(2), Switzerland(1), Czech Republic(1), Croatia(1), Argentina(1), Hungary(1), India(4), Germany(5), France(1), Austria(1), Spain(5), Russia(2), Finland(1)

A 36-hour washout after the last dose of study medication taken in the PANORAMA-HF core study (Visit 416) was required for all participants before starting Open Label Extension study medication.

Participant milestones

Measure	Age Group 1 Patients 6 years and older receiving open label sacubitril/valsartan 3.1 mg/kg bid	Age Group 2 Patients 1 year to \< 6 years receiving open label sacubitril/valsartan 3.1 mg/kg bid
Overall Study STARTED	130	86
Overall Study Safety Set (SAF)	130	85
Overall Study COMPLETED	92	74
Overall Study NOT COMPLETED	38	12

Reasons for withdrawal

Measure	Age Group 1 Patients 6 years and older receiving open label sacubitril/valsartan 3.1 mg/kg bid	Age Group 2 Patients 1 year to \< 6 years receiving open label sacubitril/valsartan 3.1 mg/kg bid
Overall Study Adverse Event	16	1
Overall Study Death	6	4
Overall Study Guardian decision	4	1
Overall Study Lost to Follow-up	1	0
Overall Study Physician Decision	8	5
Overall Study Participant decision	2	0
Overall Study Other	1	0
Overall Study No treatment was received	0	1

Baseline Characteristics

Open-label Extension Study to Evaluate Long-term Safety of Sacubitril/Valsartan in Pediatric Patients With HF

Baseline characteristics by cohort

Measure	Age Group 1 n=130 Participants Patients 6 years and older receiving open label sacubitril/valsartan 3.1 mg/kg bid	Age Group 2 n=85 Participants Patients 1 year to \< 6 years receiving open label sacubitril/valsartan 3.1 mg/kg bid	Total n=215 Participants Total of all reporting groups
Age, Continuous	12.83 Years STANDARD_DEVIATION 3.864 • n=5 Participants	2.94 Years STANDARD_DEVIATION 1.149 • n=7 Participants	8.92 Years STANDARD_DEVIATION 5.747 • n=5 Participants
Sex: Female, Male Female	60 Participants n=5 Participants	49 Participants n=7 Participants	109 Participants n=5 Participants
Sex: Female, Male Male	70 Participants n=5 Participants	36 Participants n=7 Participants	106 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White	78 Participants n=5 Participants	41 Participants n=7 Participants	119 Participants n=5 Participants
Race/Ethnicity, Customized Asian	24 Participants n=5 Participants	23 Participants n=7 Participants	47 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	19 Participants n=5 Participants	10 Participants n=7 Participants	29 Participants n=5 Participants
Race/Ethnicity, Customized Multiple	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants

PRIMARY outcome

Timeframe: to end of study, up to 4,5 years

Population: Safety Set (SAF): All participants who received at least one dose of open-label study treatment during the extension open-label study.

Number of participants with at least one Adverse Events (AEs)

Outcome measures

Measure	Age Group 1 n=130 Participants Patients 6 years and older receiving open label sacubitril/valsartan 3.1 mg/kg bid	Age Group 2 n=85 Participants Patients 1 year to \< 6 years receiving open label sacubitril/valsartan 3.1 mg/kg bid
Number of Participants With Adverse Events	111 Participants	78 Participants

PRIMARY outcome

Timeframe: to end of study, up to 4.5 years

Population: Safety Set (SAF): All participants who received at least one dose of open-label study treatment during the extension open-label study.

Number of participants with at least one Serious Adverse Events (SAEs)

Outcome measures

Measure	Age Group 1 n=130 Participants Patients 6 years and older receiving open label sacubitril/valsartan 3.1 mg/kg bid	Age Group 2 n=85 Participants Patients 1 year to \< 6 years receiving open label sacubitril/valsartan 3.1 mg/kg bid
Number of Participants With Serious Adverse Events	59 Participants	25 Participants

PRIMARY outcome

Timeframe: Up to 4.5 years

Population: Safety Set (SAF): All participants who received at least one dose of open-label study treatment during the extension open-label study.

Median duration of exposure to sacubitril/valsartan (including temporary interruptions)

Outcome measures

Measure	Age Group 1 n=130 Participants Patients 6 years and older receiving open label sacubitril/valsartan 3.1 mg/kg bid	Age Group 2 n=85 Participants Patients 1 year to \< 6 years receiving open label sacubitril/valsartan 3.1 mg/kg bid
Duration of Drug Exposure	894 Days Interval 23.0 to 1612.0	951 Days Interval 62.0 to 1570.0

Adverse Events

Age Group 1

Serious events: 59 serious events

Other events: 90 other events

Deaths: 7 deaths

Age Group 2

Serious events: 25 serious events

Other events: 60 other events

Deaths: 4 deaths

Total

Serious events: 84 serious events

Other events: 150 other events

Deaths: 11 deaths

Serious adverse events

Measure	Age Group 1 n=130 participants at risk Patients 6 years and older receiving open label sacubitril/valsartan 3.1 mg/kg bid	Age Group 2 n=85 participants at risk Patients 1 year to \< 6 years receiving open label sacubitril/valsartan 3.1 mg/kg bid	Total n=215 participants at risk Total
Cardiac disorders Ventricular arrhythmia	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Cardiac disorders Ventricular dysfunction	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Cardiac disorders Ventricular fibrillation	1.5% 2/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.93% 2/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Cardiac disorders Ventricular tachycardia	1.5% 2/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.4% 3/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Gastrointestinal disorders Abdominal pain	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.93% 2/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Congenital, familial and genetic disorders Congenital epiblepharon	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Congenital, familial and genetic disorders Cryptorchism	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Gastrointestinal disorders Abdominal pain upper	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Gastrointestinal disorders Abdominal distension	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Blood and lymphatic system disorders Splenic cyst	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Cardiac disorders Arrhythmia	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Cardiac disorders Atrial fibrillation	1.5% 2/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.93% 2/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Cardiac disorders Atrial flutter	1.5% 2/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.93% 2/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Cardiac disorders Cardiac arrest	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Cardiac disorders Cardiac failure	11.5% 15/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	3.5% 3/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	8.4% 18/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Cardiac disorders Cardiac failure acute	1.5% 2/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	2.4% 2/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.9% 4/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Cardiac disorders Cardiac failure chronic	3.1% 4/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	2.4% 2/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	2.8% 6/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Cardiac disorders Cardiogenic shock	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Cardiac disorders Dilated cardiomyopathy	3.8% 5/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	2.3% 5/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Cardiac disorders Left ventricular dysfunction	1.5% 2/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.93% 2/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Cardiac disorders Mitral valve incompetence	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Cardiac disorders Pericardial effusion	1.5% 2/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.93% 2/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Cardiac disorders Pulmonary valve stenosis	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Cardiac disorders Tachycardia induced cardiomyopathy	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Cardiac disorders Torsade de pointes	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Gastrointestinal disorders Abdominal wall haemorrhage	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Gastrointestinal disorders Colitis	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Gastrointestinal disorders Dental caries	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Gastrointestinal disorders Diarrhoea	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.93% 2/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Gastrointestinal disorders Dysphagia	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Gastrointestinal disorders Gastritis	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Gastrointestinal disorders Haematemesis	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Gastrointestinal disorders Vomiting	2.3% 3/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	2.4% 2/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	2.3% 5/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
General disorders Chest pain	3.8% 5/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	2.3% 5/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
General disorders Complication associated with device	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.93% 2/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
General disorders Medical device site extravasation	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
General disorders Medical device site pain	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
General disorders Pyrexia	2.3% 3/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	3.5% 3/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	2.8% 6/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Hepatobiliary disorders Hepatitis	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.93% 2/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Immune system disorders Heart transplant rejection	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Bronchitis	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations COVID-19	3.1% 4/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	4.7% 4/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	3.7% 8/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations COVID-19 pneumonia	1.5% 2/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.93% 2/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Cytomegalovirus infection	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Gastroenteritis	3.1% 4/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	2.4% 2/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	2.8% 6/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Gastroenteritis norovirus	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Influenza	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Lower respiratory tract infection	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	2.4% 2/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.93% 2/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Lower respiratory tract infection viral	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Metapneumovirus infection	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Neutropenic infection	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Pharyngitis	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Pneumonia	3.8% 5/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	4.7% 4/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	4.2% 9/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Pneumonia aspiration	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.93% 2/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Pneumonia mycoplasmal	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Pneumonia respiratory syncytial viral	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Pneumonia viral	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Post procedural infection	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Postoperative wound infection	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Pseudomonas infection	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Respiratory syncytial virus infection	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.93% 2/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Respiratory tract infection	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Sepsis	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Septic shock	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Upper respiratory tract infection	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Vascular device infection	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Viral infection	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Viral upper respiratory tract infection	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Injury, poisoning and procedural complications Incorrect dose administered	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Injury, poisoning and procedural complications Seroma	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Investigations Alanine aminotransferase increased	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Investigations Aspartate aminotransferase increased	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Investigations Ejection fraction decreased	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Investigations International normalised ratio increased	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Investigations Respiratory syncytial virus test positive	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Investigations Staphylococcus test positive	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Metabolism and nutrition disorders Dehydration	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Metabolism and nutrition disorders Hyperkalaemia	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.93% 2/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Metabolism and nutrition disorders Hypernatraemia	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Metabolism and nutrition disorders Malnutrition	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Musculoskeletal and connective tissue disorders Gouty arthritis	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Musculoskeletal and connective tissue disorders Intervertebral disc space narrowing	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Musculoskeletal and connective tissue disorders Systemic lupus erythematosus	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Nervous system disorders Dizziness	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Nervous system disorders Epilepsy	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Nervous system disorders Febrile convulsion	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Nervous system disorders Loss of consciousness	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Nervous system disorders Posterior reversible encephalopathy syndrome	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Nervous system disorders Presyncope	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Nervous system disorders Status epilepticus	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Product Issues Device malfunction	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Product Issues Device power source issue	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Renal and urinary disorders Acute kidney injury	2.3% 3/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.4% 3/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Renal and urinary disorders Haematuria	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Renal and urinary disorders Prerenal failure	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Renal and urinary disorders Renal failure	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Renal and urinary disorders Renal impairment	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.93% 2/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Respiratory, thoracic and mediastinal disorders Asthma	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.3% 3/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.4% 3/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	1.5% 2/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.93% 2/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Skin and subcutaneous tissue disorders Dermal cyst	0.77% 1/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.47% 1/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Vascular disorders Hypotension	2.3% 3/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.9% 4/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.

Other adverse events

Measure	Age Group 1 n=130 participants at risk Patients 6 years and older receiving open label sacubitril/valsartan 3.1 mg/kg bid	Age Group 2 n=85 participants at risk Patients 1 year to \< 6 years receiving open label sacubitril/valsartan 3.1 mg/kg bid	Total n=215 participants at risk Total
Gastrointestinal disorders Abdominal pain	7.7% 10/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	3.5% 3/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	6.0% 13/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Gastrointestinal disorders Diarrhoea	6.9% 9/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	10.6% 9/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	8.4% 18/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Gastrointestinal disorders Nausea	6.9% 9/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	4.7% 10/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Gastrointestinal disorders Vomiting	11.5% 15/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	14.1% 12/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	12.6% 27/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
General disorders Chest pain	6.2% 8/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	2.4% 2/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	4.7% 10/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
General disorders Pyrexia	11.5% 15/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	25.9% 22/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	17.2% 37/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations COVID-19	17.7% 23/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	28.2% 24/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	21.9% 47/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Conjunctivitis	2.3% 3/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	5.9% 5/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	3.7% 8/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Gastroenteritis	5.4% 7/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	8.2% 7/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	6.5% 14/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Influenza	4.6% 6/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	9.4% 8/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	6.5% 14/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Nasopharyngitis	9.2% 12/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	16.5% 14/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	12.1% 26/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Pharyngitis	4.6% 6/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	5.9% 5/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	5.1% 11/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Infections and infestations Upper respiratory tract infection	6.2% 8/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	25.9% 22/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	14.0% 30/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Investigations SARS-CoV-2 test positive	10.0% 13/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	1.2% 1/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	6.5% 14/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Musculoskeletal and connective tissue disorders Pain in extremity	6.2% 8/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	2.4% 2/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	4.7% 10/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Nervous system disorders Dizziness	10.8% 14/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	6.5% 14/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Nervous system disorders Headache	11.5% 15/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	3.5% 3/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	8.4% 18/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Respiratory, thoracic and mediastinal disorders Cough	15.4% 20/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	22.4% 19/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	18.1% 39/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.7% 10/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	0.00% 0/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	4.7% 10/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.4% 7/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	2.4% 2/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	4.2% 9/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	4.6% 6/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	7.1% 6/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	5.6% 12/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.
Vascular disorders Hypotension	13.8% 18/130 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	3.5% 3/85 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.	9.8% 21/215 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 4.5 years Adverse Events are assessed in the safety population.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

Email: Novartis.email@Novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER