Trial Outcomes & Findings for Dapagliflozin Effects on Cardiometabolic Outcomes in Patients With an Acute Heart Attack. (NCT NCT04564742)

NCT ID: NCT04564742

Last Updated: 2025-03-07

Results Overview

Study participants received dapagliflozin 10 mg or matching placebo, given once daily in addition to SoC. Overall, the mean study duration was 12.0 months (time in study until last visit) with an accumulated 4023.9 participant-years. The maximum study duration for any participant was 29 months. "Number of Events" for NYHA corresponds to the number of participants with a non-missing value for NYHA functional class at the last visit, and that all participants with a non-missing value take part in the analysis comparing their NYHA class value with all other participants with a NYHA value, according to the win-ratio method.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 4017 participants
• Primary outcome timeframe: 29 months
• Results posted on: 2025-03-07

Participant Flow

Participant milestones

Measure	Dapa 10 mg Active, Green, plain, diamond shaped, film coated tablet, 10 mg once daily	Placebo Control, Green, plain, diamond shaped, film coated tablets, once daily
Overall Study STARTED	2019	1998
Overall Study COMPLETED	2014	1994
Overall Study NOT COMPLETED	5	4

Reasons for withdrawal

Measure	Dapa 10 mg Active, Green, plain, diamond shaped, film coated tablet, 10 mg once daily	Placebo Control, Green, plain, diamond shaped, film coated tablets, once daily
Overall Study Lost to Follow-up	1	0
Overall Study Consent Withdrawal	4	4

Baseline Characteristics

The full analysis set population

Baseline characteristics by cohort

Measure	Dapa 10 mg n=2019 Participants Active, Green, plain, diamond shaped, film coated tablet, 10 mg once daily	Placebo n=1998 Participants Control, Green, plain, diamond shaped, film coated tablets, once daily	Total n=4017 Participants Total of all reporting groups
Age, Continuous Age (Years)	63.0 Years STANDARD_DEVIATION 11.06 • n=5 Participants	62.8 Years STANDARD_DEVIATION 10.64 • n=7 Participants	62.9 Years STANDARD_DEVIATION 10.85 • n=5 Participants
Age, Customized >65 years	831 Participants n=5 Participants	799 Participants n=7 Participants	1630 Participants n=5 Participants
Age, Customized <=65 years	1188 Participants n=5 Participants	1199 Participants n=7 Participants	2387 Participants n=5 Participants
Sex: Female, Male Female	388 Participants n=5 Participants • The full analysis set population	419 Participants n=7 Participants • The full analysis set population	807 Participants n=5 Participants • The full analysis set population
Sex: Female, Male Male	1631 Participants n=5 Participants • The full analysis set population	1579 Participants n=7 Participants • The full analysis set population	3210 Participants n=5 Participants • The full analysis set population
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants • The full analysis set population	0 Participants n=7 Participants • The full analysis set population	0 Participants n=5 Participants • The full analysis set population
Race/Ethnicity, Customized Asian	64 Participants n=5 Participants • The full analysis set population	52 Participants n=7 Participants • The full analysis set population	116 Participants n=5 Participants • The full analysis set population
Race/Ethnicity, Customized Black or African American	8 Participants n=5 Participants • The full analysis set population	15 Participants n=7 Participants • The full analysis set population	23 Participants n=5 Participants • The full analysis set population
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=5 Participants • The full analysis set population	0 Participants n=7 Participants • The full analysis set population	0 Participants n=5 Participants • The full analysis set population
Race/Ethnicity, Customized Other	40 Participants n=5 Participants • The full analysis set population	37 Participants n=7 Participants • The full analysis set population	77 Participants n=5 Participants • The full analysis set population
Race/Ethnicity, Customized White	1905 Participants n=5 Participants • The full analysis set population	1893 Participants n=7 Participants • The full analysis set population	3798 Participants n=5 Participants • The full analysis set population
Race/Ethnicity, Customized MISSING	2 Participants n=5 Participants • The full analysis set population	1 Participants n=7 Participants • The full analysis set population	3 Participants n=5 Participants • The full analysis set population

PRIMARY outcome

Timeframe: 29 months

Population: All participants are included in the analysis; Each row item displays the number of participants for the given event, and without preceding events defined in the hierarchical order.

Study participants received dapagliflozin 10 mg or matching placebo, given once daily in addition to SoC. Overall, the mean study duration was 12.0 months (time in study until last visit) with an accumulated 4023.9 participant-years. The maximum study duration for any participant was 29 months.

"Number of Events" for NYHA corresponds to the number of participants with a non-missing value for NYHA functional class at the last visit, and that all participants with a non-missing value take part in the analysis comparing their NYHA class value with all other participants with a NYHA value, according to the win-ratio method.

Outcome measures

Measure	Dapa 10 mg n=2019 Participants Active, Green, plain, diamond shaped, film coated tablet, 10 mg once daily	Placebo n=1998 Participants Control, Green, plain, diamond shaped, film coated tablets, once daily
Analysis of the Hierarchical Primary Composite Endpoint (Full Analysis Set) The hierachical composite endpoint of all components	1990 Participants	1970 Participants
Analysis of the Hierarchical Primary Composite Endpoint (Full Analysis Set) Death, adjudicated	41 Participants	33 Participants
Analysis of the Hierarchical Primary Composite Endpoint (Full Analysis Set) Hospitalisation due to HF	32 Participants	41 Participants
Analysis of the Hierarchical Primary Composite Endpoint (Full Analysis Set) Non-fatal MI	29 Participants	32 Participants
Analysis of the Hierarchical Primary Composite Endpoint (Full Analysis Set) AF/Flutter event	8 Participants	15 Participants
Analysis of the Hierarchical Primary Composite Endpoint (Full Analysis Set) New onset of T2DM	40 Participants	74 Participants
Analysis of the Hierarchical Primary Composite Endpoint (Full Analysis Set) NYHA Classification at last visit, measuring limitations of physical activity	1839 Participants	1773 Participants
Analysis of the Hierarchical Primary Composite Endpoint (Full Analysis Set) Body Weight decrease of at least 5% at last visit	684 Participants	468 Participants

Adverse Events

Dapa 10 mg

Serious events: 449 serious events

Other events: 0 other events

Deaths: 41 deaths

Placebo

Serious events: 404 serious events

Other events: 0 other events

Deaths: 33 deaths

Serious adverse events

Measure	Dapa 10 mg n=2019 participants at risk Description (Arm-group)	Placebo n=1998 participants at risk Description (Arm-group)
Nervous system disorders Dizziness	0.25% 5/2019 • Number of events 5 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Nervous system disorders Embolic stroke	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Blood and lymphatic system disorders Normocytic anaemia	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Upper gastrointestinal perforation	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
General disorders Adverse drug reaction	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
General disorders Cardiac death	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
General disorders Chest discomfort	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
General disorders Chest pain	0.79% 16/2019 • Number of events 16 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	1.2% 24/1998 • Number of events 24 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
General disorders Death	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
General disorders Fatigue	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
General disorders General physical health deterioration	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
General disorders Hernia	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Blood and lymphatic system disorders Pancytopenia	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
General disorders Inflammation	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
General disorders Non-cardiac chest pain	1.9% 39/2019 • Number of events 43 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	1.5% 30/1998 • Number of events 34 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
General disorders Peripheral swelling	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
General disorders Strangulated hernia	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
General disorders Sudden cardiac death	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
General disorders Vascular stent stenosis	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
General disorders Vascular stent thrombosis	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Hepatobiliary disorders Biliary colic	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Hepatobiliary disorders Cholecystitis	0.20% 4/2019 • Number of events 4 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.40% 8/1998 • Number of events 8 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Hepatobiliary disorders Cholecystitis acute	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 3 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Acute coronary syndrome	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Hepatobiliary disorders Cholelithiasis	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Hepatobiliary disorders Congestive hepatopathy	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Hepatobiliary disorders Drug-induced liver injury	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Hepatobiliary disorders Hepatic cirrhosis	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Hepatobiliary disorders Hepatic steatosis	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Hepatobiliary disorders Hypertransaminasaemia	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Hepatobiliary disorders Primary biliary cholangitis	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Immune system disorders Anaphylactic reaction	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Immune system disorders Hypersensitivity	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Anal abscess	0.05% 1/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Acute myocardial infarction	1.8% 36/2019 • Number of events 39 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	1.8% 36/1998 • Number of events 40 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Appendicitis	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.15% 3/1998 • Number of events 3 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Biliary tract infection	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Bronchitis viral	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Covid-19	0.15% 3/2019 • Number of events 3 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.15% 3/1998 • Number of events 3 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Covid-19 pneumonia	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Campylobacter infection	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Catheter site infection	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Cellulitis	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Clostridium difficile infection	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Diverticulitis	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Angina pectoris	1.6% 33/2019 • Number of events 35 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	1.6% 32/1998 • Number of events 34 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Epiglottitis	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Erysipelas	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Escherichia bacteraemia	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Fascial infection	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Gastroenteritis	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Gastroenteritis viral	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Genitourinary tract infection	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Haemophilus infection	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Infection	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Infective exacerbation of bronchiectasis	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Angina unstable	0.99% 20/2019 • Number of events 21 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.85% 17/1998 • Number of events 21 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Infective myositis	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Influenza	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Kidney infection	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Localised infection	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Lower respiratory tract infection	0.50% 10/2019 • Number of events 11 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.25% 5/1998 • Number of events 5 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Neutropenic sepsis	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Orchitis	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Osteomyelitis	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Parapharyngeal space infection	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Pelvic abscess	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Aortic valve incompetence	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Pneumonia	1.1% 22/2019 • Number of events 24 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.75% 15/1998 • Number of events 16 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Pneumonia pneumococcal	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Post procedural pneumonia	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Postoperative wound infection	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.15% 3/1998 • Number of events 4 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Pseudomonal sepsis	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Pyelonephritis	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Pyonephrosis	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Rectal abscess	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Respiratory syncytial virus infection	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Salpingitis	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Arrhythmia	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Scrotal infection	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Sepsis	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Staphylococcal sepsis	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Streptococcal infection	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Streptococcal sepsis	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Tonsillitis	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Upper respiratory tract infection	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Urinary tract infection	0.40% 8/2019 • Number of events 9 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.35% 7/1998 • Number of events 7 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Urosepsis	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.15% 3/1998 • Number of events 3 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Infections and infestations Viral infection	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Arteriospasm coronary	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Anaemia postoperative	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Contusion	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Coronary artery dissection	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Craniocerebral injury	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Delayed recovery from anaesthesia	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Fall	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Forearm fracture	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Gastrointestinal stoma complication	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Head injury	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Atrial fibrillation	0.54% 11/2019 • Number of events 11 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.90% 18/1998 • Number of events 21 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Heat exhaustion	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Hip fracture	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Humerus fracture	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Intentional overdose	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Multiple fractures	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Periprocedural myocardial infarction	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Periprosthetic fracture	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Post procedural haematoma	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Post procedural haematuria	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Blood and lymphatic system disorders Anaemia	0.20% 4/2019 • Number of events 4 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.15% 3/1998 • Number of events 5 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Atrial flutter	0.25% 5/2019 • Number of events 5 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Post procedural hypotension	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Post procedural myocardial infarction	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Postoperative delirium	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Postoperative respiratory failure	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Postoperative wound complication	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Procedural complication	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Procedural pain	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Rib fracture	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Skin injury	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Tendon rupture	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Atrial tachycardia	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Traumatic haematoma	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Traumatic intracranial haemorrhage	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Vascular pseudoaneurysm	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Injury, poisoning and procedural complications Wound secretion	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Investigations Blood potassium increased	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Investigations Ejection fraction decreased	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Investigations Liver function test abnormal	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Investigations Sars-cov-2 test positive	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Atrioventricular block complete	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.20% 4/1998 • Number of events 4 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Metabolism and nutrition disorders Hypermagnesaemia	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Metabolism and nutrition disorders Hypokalaemia	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Metabolism and nutrition disorders Iron deficiency	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Musculoskeletal and connective tissue disorders Arthritis reactive	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Musculoskeletal and connective tissue disorders Back pain	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Musculoskeletal and connective tissue disorders Costochondritis	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Musculoskeletal and connective tissue disorders Crystal arthropathy	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Atrioventricular block second degree	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Musculoskeletal and connective tissue disorders Mobility decreased	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.20% 4/2019 • Number of events 4 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.15% 3/1998 • Number of events 3 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.35% 7/1998 • Number of events 7 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Musculoskeletal and connective tissue disorders Myalgia	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Musculoskeletal and connective tissue disorders Myopathy	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Musculoskeletal and connective tissue disorders Pain in extremity	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Musculoskeletal and connective tissue disorders Polyarthritis	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Bradycardia	0.35% 7/2019 • Number of events 7 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.20% 4/1998 • Number of events 4 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Musculoskeletal and connective tissue disorders Spinal stenosis	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.15% 3/2019 • Number of events 3 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer metastatic	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brenner tumour	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Cardiac aneurysm	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic lymphocytic leukaemia	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial cancer	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Essential thrombocythaemia	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal carcinoma	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal stromal tumour	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Glioblastoma	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intestinal adenocarcinoma	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Cardiac arrest	0.25% 5/2019 • Number of events 5 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.40% 8/1998 • Number of events 8 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Large intestine polyp	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Laryngeal cancer	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung cancer metastatic	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm papilla of vater	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mesothelioma	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oropharyngeal cancer stage iv	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma metastatic	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Cardiac failure	2.0% 40/2019 • Number of events 55 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	2.0% 39/1998 • Number of events 43 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer metastatic	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal adenocarcinoma	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectosigmoid cancer	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tongue neoplasm malignant stage unspecified	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma recurrent	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine cancer	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Nervous system disorders Brain injury	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Cardiac failure acute	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.20% 4/1998 • Number of events 4 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Nervous system disorders Cauda equina syndrome	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Nervous system disorders Cerebellar infarction	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Nervous system disorders Cerebral infarction	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Nervous system disorders Cerebrovascular accident	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Nervous system disorders Cervical radiculopathy	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Nervous system disorders Cognitive disorder	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Nervous system disorders Haemorrhage intracranial	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Nervous system disorders Ischaemic stroke	0.30% 6/2019 • Number of events 6 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.45% 9/1998 • Number of events 9 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Cardiac failure chronic	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Nervous system disorders Lacunar stroke	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Nervous system disorders Loss of consciousness	0.15% 3/2019 • Number of events 3 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Nervous system disorders Presyncope	0.15% 3/2019 • Number of events 3 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Nervous system disorders Spinal cord compression	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Nervous system disorders Status epilepticus	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Nervous system disorders Subarachnoid haemorrhage	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Nervous system disorders Syncope	0.69% 14/2019 • Number of events 14 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.50% 10/1998 • Number of events 10 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Nervous system disorders Transient ischaemic attack	0.20% 4/2019 • Number of events 5 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.20% 4/1998 • Number of events 4 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Nervous system disorders Vertebrobasilar insufficiency	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Product Issues Device dislocation	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Blood and lymphatic system disorders Blood loss anaemia	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Cardiac failure congestive	0.15% 3/2019 • Number of events 4 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 3 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Psychiatric disorders Anxiety	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Psychiatric disorders Completed suicide	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Psychiatric disorders Confusional state	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Psychiatric disorders Conversion disorder	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Psychiatric disorders Mental disorder	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Psychiatric disorders Mixed anxiety and depressive disorder	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Psychiatric disorders Panic attack	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Renal and urinary disorders Acute kidney injury	0.69% 14/2019 • Number of events 15 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.80% 16/1998 • Number of events 16 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Renal and urinary disorders Calculus urinary	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Renal and urinary disorders Haematuria	0.35% 7/2019 • Number of events 8 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Cardiac pseudoaneurysm	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Renal and urinary disorders Hydronephrosis	0.05% 1/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Renal and urinary disorders Nephrolithiasis	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Renal and urinary disorders Renal failure	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Renal and urinary disorders Renal infarct	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Renal and urinary disorders Ureterolithiasis	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Renal and urinary disorders Urinary bladder haemorrhage	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Renal and urinary disorders Urinary retention	0.20% 4/2019 • Number of events 4 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Reproductive system and breast disorders Epididymitis	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Reproductive system and breast disorders Prostatic haemorrhage	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Reproductive system and breast disorders Prostatitis	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Cardiac sarcoidosis	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Reproductive system and breast disorders Vaginal haemorrhage	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Respiratory, thoracic and mediastinal disorders Acute lung injury	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Respiratory, thoracic and mediastinal disorders Asthma	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Respiratory, thoracic and mediastinal disorders Bronchiectasis	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.25% 5/1998 • Number of events 9 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Respiratory, thoracic and mediastinal disorders Chronic respiratory failure	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.64% 13/2019 • Number of events 13 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.15% 3/1998 • Number of events 3 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.40% 8/2019 • Number of events 10 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.25% 5/1998 • Number of events 7 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Cardiac ventricular thrombosis	0.35% 7/2019 • Number of events 7 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.20% 4/1998 • Number of events 4 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.20% 4/2019 • Number of events 5 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.30% 6/1998 • Number of events 6 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Respiratory, thoracic and mediastinal disorders Pulmonary haematoma	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Skin and subcutaneous tissue disorders Rash	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Skin and subcutaneous tissue disorders Skin ulcer	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Cardiogenic shock	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Surgical and medical procedures Cholecystectomy	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Surgical and medical procedures Elective procedure	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Surgical and medical procedures Knee arthroplasty	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Vascular disorders Aortic aneurysm	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Vascular disorders Aortic aneurysm rupture	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Vascular disorders Aortic stenosis	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Vascular disorders Circulatory collapse	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Vascular disorders Embolism venous	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Vascular disorders Hypertension	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Cardiomyopathy	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Coronary artery disease	0.15% 3/2019 • Number of events 3 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.15% 3/1998 • Number of events 3 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Coronary artery dissection	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Dressler's syndrome	0.45% 9/2019 • Number of events 10 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.40% 8/1998 • Number of events 8 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Extrasystoles	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Blood and lymphatic system disorders Febrile neutropenia	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Haemorrhage coronary artery	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Intracardiac thrombus	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Ischaemic cardiomyopathy	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Left ventricular dysfunction	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Left ventricular hypertrophy	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Mitral valve prolapse	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Myocardial infarction	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Myocardial ischaemia	0.20% 4/2019 • Number of events 4 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Palpitations	0.20% 4/2019 • Number of events 4 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.20% 4/1998 • Number of events 4 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Pericardial effusion	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Blood and lymphatic system disorders Iron deficiency anaemia	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Pericarditis	0.54% 11/2019 • Number of events 11 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.25% 5/1998 • Number of events 5 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Postinfarction angina	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Right ventricular failure	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Sinus arrest	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Sinus bradycardia	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Sinus node dysfunction	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Supraventricular tachycardia	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Tachycardia	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Ventricular extrasystoles	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Ventricular fibrillation	0.15% 3/2019 • Number of events 3 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Blood and lymphatic system disorders Lymphadenitis	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Cardiac disorders Ventricular tachycardia	0.15% 3/2019 • Number of events 5 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.20% 4/1998 • Number of events 5 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Congenital, familial and genetic disorders Atrial septal defect	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Ear and labyrinth disorders Vertigo	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Ear and labyrinth disorders Vertigo positional	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Eye disorders Retinal artery occlusion	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Eye disorders Retinal detachment	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Abdominal pain	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Abdominal pain upper	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Anal fistula	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Ascites	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Blood and lymphatic system disorders Microcytic anaemia	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Barrett's oesophagus	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Colitis ulcerative	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Constipation	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Diarrhoea	0.15% 3/2019 • Number of events 3 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Diarrhoea haemorrhagic	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Diverticulum intestinal haemorrhagic	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Duodenal ulcer	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Duodenitis	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Dyspepsia	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Dysphagia	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Blood and lymphatic system disorders Nephrogenic anaemia	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Faecaloma	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Gastric perforation	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Gastric ulcer	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Gastritis	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Gastrointestinal angiectasia	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Gastrointestinal disorder	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.15% 3/2019 • Number of events 3 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 4 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.15% 3/2019 • Number of events 4 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.25% 5/1998 • Number of events 5 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Ileus	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Blood and lymphatic system disorders Neutropenia	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Inguinal hernia	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Intestinal ischaemia	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Large intestinal obstruction	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Mallory-weiss syndrome	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Oesophagitis	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Pancreatitis	0.20% 4/2019 • Number of events 5 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Pancreatitis acute	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Rectal haemorrhage	0.10% 2/2019 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Gastrointestinal disorders Small intestinal obstruction	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.10% 2/1998 • Number of events 2 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Vascular disorders Hypertensive crisis	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Vascular disorders Hypotension	0.30% 6/2019 • Number of events 6 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.25% 5/1998 • Number of events 5 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Vascular disorders Hypovolaemic shock	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Vascular disorders Orthostatic hypotension	0.20% 4/2019 • Number of events 4 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.25% 5/1998 • Number of events 5 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/2019 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.05% 1/1998 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Vascular disorders Peripheral ischaemia	0.05% 1/2019 • Number of events 1 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.	0.00% 0/1998 • Time frame was from date of randomization and up to and including last day in study, up to 29 months.

Other adverse events

Adverse event data not reported

Additional Information

Global Clinical Lead

AstraZeneca

Phone: 1-877-240-9479

Email: information.center@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place