Trial Outcomes & Findings for Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy (NCT NCT02065791)

NCT ID: NCT02065791

Last Updated: 2019-12-05

Results Overview

Primary composite endpoint is the composite of DoSC, ESKD, and renal or CV death. DoSC: from baseline average determination (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). ESKD: as initiation of maintenance dialysis for at least 30 days, or renal transplantation, or an estimated glomerular filtration rate (eGFR) value of less than (\<)15 milliliters per minute per 1.73 square meter (mL/min/1.73 m\^2) (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). Renal death: death in participants who had reached ESKD, died without initiating renal replacement therapy, and no other cause of death was determined via adjudication. Adjudication of these events by Endpoint Adjudication Committee (EAC) was performed in blinded fashion. Event rate estimated based on time to first occurrence of primary composite endpoint are presented.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 4401 participants
• Primary outcome timeframe: Up to 4.6 years
• Results posted on: 2019-12-05

Participant Flow

A total of 12900 participants were pre-screened, of those, 8932 were screened. A total of 4401 participants were randomized, with 2199 and 2202 participants assigned to placebo and canagliflozin 100 milligrams (mg), respectively.

Participant milestones

Measure	Placebo Participants received matching placebo orally once daily.	Canagliflozin 100 mg Participants received canagliflozin 100 milligram (mg) orally once daily.
Overall Study STARTED	2199	2202
Overall Study Treated	2197	2200
Overall Study COMPLETED	2174	2187
Overall Study NOT COMPLETED	25	15

Reasons for withdrawal

Measure	Placebo Participants received matching placebo orally once daily.	Canagliflozin 100 mg Participants received canagliflozin 100 milligram (mg) orally once daily.
Overall Study Closed Site	1	1
Overall Study Withdrawal by Subject	11	5
Overall Study Lost to Follow-up	13	9

Baseline Characteristics

Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy

Baseline characteristics by cohort

Measure	Placebo n=2199 Participants Participants received matching placebo orally once daily.	Canagliflozin 100 mg n=2202 Participants Participants received canagliflozin 100 milligram (mg) orally once daily.	Total n=4401 Participants Total of all reporting groups
Age, Continuous	63.2 years STANDARD_DEVIATION 9.23 • n=5 Participants	62.9 years STANDARD_DEVIATION 9.17 • n=7 Participants	63 years STANDARD_DEVIATION 9.2 • n=5 Participants
Sex: Female, Male Female	732 Participants n=5 Participants	762 Participants n=7 Participants	1494 Participants n=5 Participants
Sex: Female, Male Male	1467 Participants n=5 Participants	1440 Participants n=7 Participants	2907 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	706 Participants n=5 Participants	717 Participants n=7 Participants	1423 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1457 Participants n=5 Participants	1436 Participants n=7 Participants	2893 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	36 Participants n=5 Participants	49 Participants n=7 Participants	85 Participants n=5 Participants
Race/Ethnicity, Customized Asian	452 Participants n=5 Participants	425 Participants n=7 Participants	877 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	112 Participants n=5 Participants	112 Participants n=7 Participants	224 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	554 Participants n=5 Participants	567 Participants n=7 Participants	1121 Participants n=5 Participants
Race/Ethnicity, Customized Other	199 Participants n=5 Participants	189 Participants n=7 Participants	388 Participants n=5 Participants
Race/Ethnicity, Customized White Non-Hispanic	882 Participants n=5 Participants	909 Participants n=7 Participants	1791 Participants n=5 Participants
Region of Enrollment ARGENTINA	205 Participants n=5 Participants	221 Participants n=7 Participants	426 Participants n=5 Participants
Region of Enrollment AUSTRALIA	18 Participants n=5 Participants	20 Participants n=7 Participants	38 Participants n=5 Participants
Region of Enrollment BRAZIL	162 Participants n=5 Participants	152 Participants n=7 Participants	314 Participants n=5 Participants
Region of Enrollment BULGARIA	13 Participants n=5 Participants	16 Participants n=7 Participants	29 Participants n=5 Participants
Region of Enrollment CANADA	93 Participants n=5 Participants	79 Participants n=7 Participants	172 Participants n=5 Participants
Region of Enrollment CHILE	30 Participants n=5 Participants	22 Participants n=7 Participants	52 Participants n=5 Participants
Region of Enrollment CHINA	63 Participants n=5 Participants	66 Participants n=7 Participants	129 Participants n=5 Participants
Region of Enrollment COLOMBIA	42 Participants n=5 Participants	52 Participants n=7 Participants	94 Participants n=5 Participants
Region of Enrollment CZECH REPUBLIC	26 Participants n=5 Participants	31 Participants n=7 Participants	57 Participants n=5 Participants
Region of Enrollment FRANCE	33 Participants n=5 Participants	28 Participants n=7 Participants	61 Participants n=5 Participants
Region of Enrollment GERMANY	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment GUATEMALA	26 Participants n=5 Participants	29 Participants n=7 Participants	55 Participants n=5 Participants
Region of Enrollment HUNGARY	68 Participants n=5 Participants	67 Participants n=7 Participants	135 Participants n=5 Participants
Region of Enrollment INDIA	82 Participants n=5 Participants	62 Participants n=7 Participants	144 Participants n=5 Participants
Region of Enrollment ITALY	39 Participants n=5 Participants	51 Participants n=7 Participants	90 Participants n=5 Participants
Region of Enrollment JAPAN	53 Participants n=5 Participants	57 Participants n=7 Participants	110 Participants n=5 Participants
Region of Enrollment LITHUANIA	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment MALAYSIA	72 Participants n=5 Participants	63 Participants n=7 Participants	135 Participants n=5 Participants
Region of Enrollment MEXICO	152 Participants n=5 Participants	151 Participants n=7 Participants	303 Participants n=5 Participants
Region of Enrollment NEW ZEALAND	30 Participants n=5 Participants	31 Participants n=7 Participants	61 Participants n=5 Participants
Region of Enrollment PHILIPPINES	35 Participants n=5 Participants	36 Participants n=7 Participants	71 Participants n=5 Participants
Region of Enrollment POLAND	27 Participants n=5 Participants	23 Participants n=7 Participants	50 Participants n=5 Participants
Region of Enrollment ROMANIA	27 Participants n=5 Participants	32 Participants n=7 Participants	59 Participants n=5 Participants
Region of Enrollment RUSSIAN FEDERATION	76 Participants n=5 Participants	57 Participants n=7 Participants	133 Participants n=5 Participants
Region of Enrollment SERBIA	19 Participants n=5 Participants	21 Participants n=7 Participants	40 Participants n=5 Participants
Region of Enrollment SLOVAKIA	32 Participants n=5 Participants	34 Participants n=7 Participants	66 Participants n=5 Participants
Region of Enrollment SOUTH AFRICA	34 Participants n=5 Participants	28 Participants n=7 Participants	62 Participants n=5 Participants
Region of Enrollment SOUTH KOREA	58 Participants n=5 Participants	64 Participants n=7 Participants	122 Participants n=5 Participants
Region of Enrollment SPAIN	58 Participants n=5 Participants	83 Participants n=7 Participants	141 Participants n=5 Participants
Region of Enrollment TAIWAN	22 Participants n=5 Participants	15 Participants n=7 Participants	37 Participants n=5 Participants
Region of Enrollment UKRAINE	173 Participants n=5 Participants	198 Participants n=7 Participants	371 Participants n=5 Participants
Region of Enrollment UNITED ARAB EMIRATES	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment UNITED KINGDOM	59 Participants n=5 Participants	59 Participants n=7 Participants	118 Participants n=5 Participants
Region of Enrollment UNITED STATES	363 Participants n=5 Participants	344 Participants n=7 Participants	707 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 4.6 years

Population: The Intent-to-treat (ITT) population consisted of all randomized participants.

Primary composite endpoint is the composite of DoSC, ESKD, and renal or CV death. DoSC: from baseline average determination (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). ESKD: as initiation of maintenance dialysis for at least 30 days, or renal transplantation, or an estimated glomerular filtration rate (eGFR) value of less than (<)15 milliliters per minute per 1.73 square meter (mL/min/1.73 m^2) (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). Renal death: death in participants who had reached ESKD, died without initiating renal replacement therapy, and no other cause of death was determined via adjudication. Adjudication of these events by Endpoint Adjudication Committee (EAC) was performed in blinded fashion. Event rate estimated based on time to first occurrence of primary composite endpoint are presented.

Outcome measures

Measure	Placebo n=2199 Participants Participants received matching placebo orally once daily.	Canagliflozin 100 mg n=2202 Participants Participants received canagliflozin 100 milligram (mg) orally once daily.
Primary Composite Endpoint of Doubling of Serum Creatinine (DoSC), End-stage Kidney Disease (ESKD), and Renal or Cardiovascular (CV) Death	61.24 Event rate per 1000 participant-years	43.21 Event rate per 1000 participant-years

SECONDARY outcome

Timeframe: Up to 4.6 years

Population: The ITT population consisted of all randomized participants.

The composite endpoint included CV death and HHF. CV death included death due to myocardial infarction (MI), stroke, heart failure, sudden death, death during a CV procedure or as a result of procedure-related complications, or death due to other CV causes. For analytic purposes, undetermined causes of death were considered CV deaths. In determining whether a death event was CV in nature, the EAC took into consideration both the proximate and underlying causes. Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of the composite endpoint of CV death and HHF are presented.

Outcome measures

Measure	Placebo n=2199 Participants Participants received matching placebo orally once daily.	Canagliflozin 100 mg n=2202 Participants Participants received canagliflozin 100 milligram (mg) orally once daily.
Composite Endpoint of CV Death and Hospitalized Heart Failure (HHF)	45.44 Event rate per 1000 participant-years	31.47 Event rate per 1000 participant-years

SECONDARY outcome

Timeframe: Up to 4.6 years

Population: The ITT population consisted of all randomized participants.

The composite endpoint included CV death, non-fatal MI, and non-fatal stroke (that is, 3-point MACE). Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of MACE are presented.

Outcome measures

Measure	Placebo n=2199 Participants Participants received matching placebo orally once daily.	Canagliflozin 100 mg n=2202 Participants Participants received canagliflozin 100 milligram (mg) orally once daily.
Major Adverse Cardiac Event (MACE)	48.67 Event rate per 1000 participant-years	38.71 Event rate per 1000 participant-years

SECONDARY outcome

Timeframe: Up to 4.6 years

Population: The ITT population consisted of all randomized participants.

Adjudication of these events by the Endpoint Adjudication Committee (EAC) was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of hospitalized heart failure are presented.

Outcome measures

Measure	Placebo n=2199 Participants Participants received matching placebo orally once daily.	Canagliflozin 100 mg n=2202 Participants Participants received canagliflozin 100 milligram (mg) orally once daily.
Hospitalized Heart Failure (HHF)	25.33 Event rate per 1000 participant-years	15.65 Event rate per 1000 participant-years

SECONDARY outcome

Timeframe: Up to 4.6 years

Population: The ITT population consisted of all randomized participant.

The renal composite endpoint included composite of DoSC, ESKD and Renal death. DoSC: from the baseline average determination (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). ESKD: initiation of maintenance dialysis for at least 30 days, or renal transplantation, or an eGFR value of <15 mL/min/1.73 m^2 (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). Renal death: death in participants who have reached ESKD, died without initiating renal replacement therapy, and no other cause of death was determined via adjudication. Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of the renal composite endpoint are presented.

Outcome measures

Measure	Placebo n=2199 Participants Participants received matching placebo orally once daily.	Canagliflozin 100 mg n=2202 Participants Participants received canagliflozin 100 milligram (mg) orally once daily.
Renal Composite Endpoint	40.36 Event rate per 1000 participant-years	26.99 Event rate per 1000 participant-years

SECONDARY outcome

Timeframe: Up to 4.6 years

Population: The ITT population consisted of all randomized participants.

CV death included death due to MI, stroke, heart failure, sudden death, death during a CV procedure or as a result of procedure-related complications, or death due to other CV causes. For analytic purposes, undetermined causes of death were considered CV deaths. In determining whether a death event was a CV in nature, the EAC took into consideration both the proximate and underlying causes. Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of CV death are presented.

Outcome measures

Measure	Placebo n=2199 Participants Participants received matching placebo orally once daily.	Canagliflozin 100 mg n=2202 Participants Participants received canagliflozin 100 milligram (mg) orally once daily.
Cardiovascular (CV) Death	24.38 Event rate per 1000 participant-years	19.01 Event rate per 1000 participant-years

SECONDARY outcome

Timeframe: Up to 4.6 years

Population: The ITT population consisted of all randomized participants.

Adjudication of these events by Endpoint Adjudication Committee (EAC) was performed in a blinded fashion. Event rate estimated based on time to first occurrence of all-cause mortality are presented.

Outcome measures

Measure	Placebo n=2199 Participants Participants received matching placebo orally once daily.	Canagliflozin 100 mg n=2202 Participants Participants received canagliflozin 100 milligram (mg) orally once daily.
All-cause Mortality	35.00 Event rate per 1000 participant-years	29.04 Event rate per 1000 participant-years

SECONDARY outcome

Timeframe: Up to 4.6 years

Population: The ITT population consisted of all randomized participant.

The CV composite endpoint included the CV death, non-fatal MI, non-fatal stroke, hospitalized heart failure, and hospitalized unstable angina. CV death included death due to MI, stroke, heart failure, sudden death, death during a CV procedure or as a result of procedure-related complications, or death due to other CV causes. For analytic purposes, undetermined causes of death were considered CV deaths. In determining whether a death event was a CV in nature, the EAC took into consideration both the proximate and underlying causes. Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of the CV composite endpoint are presented.

Outcome measures

Measure	Placebo n=2199 Participants Participants received matching placebo orally once daily.	Canagliflozin 100 mg n=2202 Participants Participants received canagliflozin 100 milligram (mg) orally once daily.
CV Composite Endpoint	66.95 Event rate per 1000 participant-years	49.35 Event rate per 1000 participant-years

Adverse Events

Placebo

Serious events: 806 serious events

Other events: 1447 other events

Deaths: 193 deaths

Canagliflozin 100 mg

Serious events: 737 serious events

Other events: 1320 other events

Deaths: 164 deaths

Serious adverse events

Measure	Placebo n=2197 participants at risk Participants received matching placebo orally once daily.	Canagliflozin 100 mg n=2200 participants at risk Participants received canagliflozin 100 milligram (mg) orally once daily.
Gastrointestinal disorders Epulis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Faeces Discoloured	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Food Poisoning	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Gastric Ulcer	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant Neoplasm of Unknown Primary Site	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma Malignant	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Appendicitis Perforated	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Investigations Blood Urea Increased	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Anaemia	0.46% 10/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.32% 7/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Anaemia Vitamin B12 Deficiency	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Bicytopenia	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Disseminated Intravascular Coagulation	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Haemorrhagic Anaemia	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Hypochromic Anaemia	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Iron Deficiency Anaemia	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Nephrogenic Anaemia	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Normochromic Normocytic Anaemia	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Normocytic Anaemia	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Acute Coronary Syndrome	0.36% 8/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.55% 12/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Acute Left Ventricular Failure	0.18% 4/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Acute Myocardial Infarction	1.7% 38/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	1.7% 38/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Angina Pectoris	0.64% 14/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.95% 21/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Angina Unstable	1.3% 29/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.77% 17/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Arrhythmia	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Arteriosclerosis Coronary Artery	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.18% 4/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Atrial Fibrillation	0.86% 19/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.73% 16/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Atrial Flutter	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Atrioventricular Block	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Atrioventricular Block Complete	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Atrioventricular Block First Degree	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Bradycardia	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Brugada Syndrome	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Cardiac Arrest	0.32% 7/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.23% 5/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Cardiac Asthma	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Cardiac Disorder	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Cardiac Failure	2.3% 50/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	1.5% 34/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Cardiac Failure Acute	0.27% 6/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.27% 6/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Cardiac Failure Chronic	0.18% 4/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Cardiac Failure Congestive	2.2% 48/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	1.1% 24/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Cardiac Fibrillation	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Cardiac Tamponade	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Cardio-Respiratory Arrest	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.18% 4/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Cardiogenic Shock	0.36% 8/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Cardiomyopathy	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Cardiorenal Syndrome	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Chronic Left Ventricular Failure	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Chronic Right Ventricular Failure	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Cor Pulmonale	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Coronary Artery Disease	1.0% 23/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.41% 9/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Coronary Artery Insufficiency	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Coronary Artery Occlusion	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Coronary Artery Stenosis	0.23% 5/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Hypertensive Heart Disease	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Ischaemic Cardiomyopathy	0.27% 6/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.18% 4/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Left Ventricular Failure	0.23% 5/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Mitral Valve Incompetence	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Myocardial Infarction	1.2% 27/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	1.0% 22/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Myocardial Ischaemia	0.36% 8/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.36% 8/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Myocarditis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Pericardial Effusion	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Pericardial Haemorrhage	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Pericarditis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Pulseless Electrical Activity	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Right Ventricular Failure	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Sinus Node Dysfunction	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Supraventricular Tachycardia	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Tricuspid Valve Incompetence	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Ventricular Arrhythmia	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Ventricular Extrasystoles	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Ventricular Fibrillation	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Ventricular Tachycardia	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Ear and labyrinth disorders Vertigo	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Ear and labyrinth disorders Vertigo Positional	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Endocrine disorders Goitre	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Endocrine disorders Hyperparathyroidism	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Endocrine disorders Hyperthyroidism	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Endocrine disorders Hypothyroidism	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Endocrine disorders Inappropriate Antidiuretic Hormone Secretion	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Endocrine disorders Thyroid Mass	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Eye disorders Amaurosis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Eye disorders Angle Closure Glaucoma	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Eye disorders Cataract	0.41% 9/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.36% 8/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Eye disorders Cataract Subcapsular	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Eye disorders Diabetic Retinopathy	0.18% 4/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.32% 7/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Eye disorders Eye Haemorrhage	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Eye disorders Eyelid Ptosis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Eye disorders Glaucoma	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Eye disorders Keratitis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Eye disorders Maculopathy	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Eye disorders Neovascular Age-Related Macular Degeneration	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Eye disorders Optic Ischaemic Neuropathy	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Eye disorders Retinal Detachment	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Eye disorders Rhegmatogenous Retinal Detachment	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Eye disorders Tractional Retinal Detachment	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Eye disorders Uveitis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Eye disorders Vision Blurred	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Eye disorders Visual Impairment	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Eye disorders Vitreous Adhesions	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Eye disorders Vitreous Haemorrhage	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.18% 4/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal Fat Apron	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal Incarcerated Hernia	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal Pain	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal Pain Lower	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal Pain Upper	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Anal Fistula	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Anal Haemorrhage	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Chronic Gastritis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Colitis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Colitis Ischaemic	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Diabetic Gastroparesis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Diverticulum	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Diverticulum Intestinal	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Diverticulum Intestinal Haemorrhagic	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Duodenal Ulcer	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Duodenal Ulcer Haemorrhage	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Duodenitis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Enteritis	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Enterocolitis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Enterovesical Fistula	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Gastritis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Gastrointestinal Haemorrhage	0.27% 6/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.18% 4/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Gastrooesophageal Reflux Disease	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Haematemesis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Haemorrhoidal Haemorrhage	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Ileus	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Incarcerated Inguinal Hernia	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Inguinal Hernia	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.18% 4/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Intestinal Obstruction	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.32% 7/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Intestinal Perforation	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Large Intestine Polyp	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Leukoplakia Oral	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Lower Gastrointestinal Haemorrhage	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Melaena	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Obstructive Pancreatitis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Pancreatitis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.18% 4/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Pancreatitis Acute	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Peptic Ulcer	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Peptic Ulcer Haemorrhage	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Rectal Haemorrhage	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Rectal Polyp	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Small Intestinal Haemorrhage	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Small Intestinal Obstruction	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Subileus	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Swollen Tongue	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Umbilical Hernia	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Upper Gastrointestinal Haemorrhage	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.18% 4/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	0.18% 4/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Asthenia	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Atrophy	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Cardiac Death	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Chest Discomfort	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Chest Pain	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Complication Associated with Device	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Critical Illness	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Cyst	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Death	0.27% 6/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.32% 7/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Drowning	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Gait Disturbance	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders General Physical Health Deterioration	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Generalised Oedema	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Incarcerated Hernia	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Influenza Like Illness	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Localised Oedema	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Multiple Organ Dysfunction Syndrome	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Necrobiosis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Non-Cardiac Chest Pain	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.36% 8/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Oedema Peripheral	0.18% 4/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Peripheral Swelling	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Pyrexia	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Sudden Cardiac Death	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Sudden Death	0.36% 8/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Systemic Inflammatory Response Syndrome	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Hepatobiliary disorders Bile Duct Obstruction	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Hepatobiliary disorders Bile Duct Stone	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Hepatobiliary disorders Cholangitis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Hepatobiliary disorders Cholangitis Acute	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Hepatobiliary disorders Cholangitis Sclerosing	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Hepatobiliary disorders Cholecystitis	0.23% 5/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Hepatobiliary disorders Cholecystitis Acute	0.18% 4/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.23% 5/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Hepatobiliary disorders Cholecystitis Chronic	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Hepatobiliary disorders Cholelithiasis	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.23% 5/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Hepatobiliary disorders Hepatic Cirrhosis	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Hepatobiliary disorders Hepatic Function Abnormal	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Hepatobiliary disorders Ischaemic Hepatitis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Immune system disorders Anaphylactic Reaction	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Immune system disorders Drug Hypersensitivity	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Abdominal Abscess	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Abdominal Sepsis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Abdominal Wall Abscess	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Abscess Limb	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Acute Hepatitis B	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Appendicitis	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Arteriovenous Fistula Site Infection	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Arthritis Bacterial	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Atypical Pneumonia	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Bacteraemia	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Bacterial Pyelonephritis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Bacterial Sepsis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Bronchiolitis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Bronchitis	0.32% 7/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.23% 5/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Bronchitis Viral	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Campylobacter Colitis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Cellulitis	1.2% 26/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.82% 18/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Cellulitis Staphylococcal	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Chronic Sinusitis	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Clostridium Difficile Colitis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Clostridium Difficile Infection	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Cystitis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Dengue Fever	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Device Related Infection	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Diabetic Foot Infection	0.18% 4/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Diabetic Gangrene	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.23% 5/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Diverticulitis	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.18% 4/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Dysentery	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Ear Infection	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Empyema	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Endocarditis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Endophthalmitis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Enteritis Infectious	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Enterobacter Infection	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Enterocolitis Bacterial	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Epididymitis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Erysipelas	0.23% 5/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Escherichia Sepsis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Furuncle	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Gangrene	0.68% 15/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.45% 10/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Gas Gangrene	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Gastroenteritis	0.86% 19/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.27% 6/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Gastroenteritis Bacterial	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Gastroenteritis Viral	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Gastrointestinal Bacterial Infection	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Giardiasis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Graft Infection	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Groin Abscess	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Haemophilus Infection	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Hepatic Echinococciasis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Herpes Zoster	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Infected Skin Ulcer	0.27% 6/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.23% 5/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Infection in An Immunocompromised Host	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Infective Exacerbation of Chronic Obstructive Airways Disease	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Influenza	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Intervertebral Discitis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Keratitis Fungal	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Laryngitis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Liver Abscess	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Localised Infection	0.27% 6/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.27% 6/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Lower Respiratory Tract Infection	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Lung Infection	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Mediastinitis	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Meningitis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Meningitis Bacterial	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Necrotising Fasciitis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Onychomycosis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Opisthorchiasis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Orchitis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Osteomyelitis	0.50% 11/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.50% 11/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Osteomyelitis Acute	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Osteomyelitis Chronic	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Perineal Abscess	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Periodontitis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Pharyngeal Abscess	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia	3.9% 86/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	2.9% 63/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia Bacterial	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia Influenzal	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia Pneumococcal	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia Staphylococcal	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia Streptococcal	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia Viral	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Postoperative Wound Infection	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Pseudomonas Bronchitis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Pulmonary Sepsis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Pyelonephritis	0.23% 5/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Pyelonephritis Acute	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.18% 4/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Pyelonephritis Chronic	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Rectal Abscess	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Respiratory Syncytial Virus Bronchiolitis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Respiratory Tract Infection	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Respiratory Tract Infection Viral	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Rhinitis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Scrotal Abscess	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Scrub Typhus	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Sepsis	0.55% 12/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.50% 11/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Septic Shock	0.55% 12/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.23% 5/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Investigations Ejection Fraction Decreased	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Investigations Glomerular Filtration Rate Decreased	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.23% 5/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Soft Tissue Infection	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Staphylococcal Bacteraemia	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Staphylococcal Infection	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Staphylococcal Sepsis	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Streptococcal Infection	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Subcutaneous Abscess	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Tonsillitis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Tooth Abscess	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Tracheobronchitis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Upper Respiratory Tract Infection	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Urinary Tract Infection	0.96% 21/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	1.1% 25/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Urinary Tract Infection Fungal	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Investigations Haemoglobin Decreased	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Urosepsis	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Viral Infection	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Viral Upper Respiratory Tract Infection	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Wound Infection	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.27% 6/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Anaesthetic Complication	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Ankle Fracture	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Investigations International Normalised Ratio Increased	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Cervical Vertebral Fracture	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Chest Injury	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Clavicle Fracture	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Concussion	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Contusion	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Coronary Artery Reocclusion	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Coronary Vascular Graft Occlusion	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Craniocerebral Injury	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Expired Product Administered	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Facial Bones Fracture	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Fall	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Investigations Troponin Increased	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Femoral Neck Fracture	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.18% 4/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Femur Fracture	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.23% 5/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Fibula Fracture	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Investigations Weight Decreased	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Cachexia	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Foot Fracture	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Foreign Body in Eye	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Fracture Displacement	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Head Injury	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Hip Fracture	0.23% 5/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Humerus Fracture	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.18% 4/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Joint Dislocation	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Dehydration	0.36% 8/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.18% 4/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Joint Injury	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Ligament Rupture	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Ligament Sprain	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Limb Injury	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Meniscus Injury	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Muscle Injury	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Muscle Strain	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Overdose	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Patella Fracture	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Post Procedural Complication	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Post Procedural Haematoma	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Post Procedural Haemorrhage	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Postoperative Thrombosis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Postoperative Wound Complication	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Procedural Intestinal Perforation	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Procedural Pain	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Pubis Fracture	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Radius Fracture	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Rib Fracture	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Road Traffic Accident	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Soft Tissue Injury	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Spinal Compression Fracture	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Spinal Fracture	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Sternal Fracture	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Stress Fracture	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Subarachnoid Haemorrhage	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Subdural Haematoma	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Subdural Haemorrhage	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Thermal Burn	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Thoracic Vertebral Fracture	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Tibia Fracture	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Traumatic Intracranial Haemorrhage	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Ulna Fracture	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Vascular Graft Occlusion	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Wound	0.23% 5/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Wound Dehiscence	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Wound Haemorrhage	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Wrist Fracture	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Investigations Aspiration Bronchial	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Investigations Biopsy Kidney	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Investigations Blood Creatine Phosphokinase Increased	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Investigations Blood Creatinine Increased	0.91% 20/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.32% 7/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Investigations Blood Glucose Increased	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Investigations Blood Osmolarity Decreased	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Diabetes Mellitus	0.46% 10/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.23% 5/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Diabetes Mellitus Inadequate Control	0.55% 12/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.32% 7/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Diabetic Ketoacidosis	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.41% 9/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Diabetic Ketosis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Diabetic Metabolic Decompensation	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Electrolyte Imbalance	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Fluid Overload	0.18% 4/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Fluid Retention	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypercalcaemia	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hyperglycaemia	0.50% 11/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hyperglycaemic Hyperosmolar Nonketotic Syndrome	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hyperkalaemia	0.46% 10/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.45% 10/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hyperlipidaemia	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypoglycaemia	0.50% 11/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.77% 17/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hyponatraemia	0.18% 4/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypophagia	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypoproteinaemia	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Ketoacidosis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Lactic Acidosis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Metabolic Acidosis	0.27% 6/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Metabolic Disorder	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Obesity	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Type 2 Diabetes Mellitus	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Back Pain	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Cervical Spinal Stenosis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Chest Wall Haematoma	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Gouty Arthritis	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Haemarthrosis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Intervertebral Disc Degeneration	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Intervertebral Disc Displacement	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Intervertebral Disc Protrusion	0.23% 5/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Lumbar Spinal Stenosis	0.23% 5/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Muscular Weakness	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Neuropathic Arthropathy	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Osteitis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Osteitis Deformans	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.50% 11/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.45% 10/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Osteochondrosis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Pain in Extremity	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Periarthritis	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Rotator Cuff Syndrome	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Spinal Column Stenosis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Spinal Disorder	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Spinal Osteoarthritis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.18% 4/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Spondylolisthesis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Symphysiolysis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Systemic Lupus Erythematosus	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Trigger Finger	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Vertebral Foraminal Stenosis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute Leukaemia	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma Gastric	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of Colon	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-Cell Lymphoma	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal Cell Carcinoma	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign Neoplasm of Bladder	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder Cancer	0.18% 4/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.23% 5/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder Neoplasm	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder Transitional Cell Carcinoma	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain Cancer Metastatic	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain Neoplasm	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast Cancer	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cholangiocarcinoma	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic Lymphocytic Leukaemia	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon Adenoma	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon Cancer	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.27% 6/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon Neoplasm	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse Large B-Cell Lymphoma	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial Adenocarcinoma	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial Cancer	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric Cancer	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric Neoplasm	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic Neoplasm	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular Carcinoma	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive Breast Carcinoma	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive Ductal Breast Carcinoma	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive Lobular Breast Carcinoma	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Large Intestine Benign Neoplasm	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Laryngeal Cancer	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung Adenocarcinoma	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung Cancer Metastatic	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung Neoplasm	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung Neoplasm Malignant	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant Melanoma	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to Bone	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to Liver	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic Renal Cell Carcinoma	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic Syndrome	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine Tumour	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkin's Lymphoma Stage Ii	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal Adenocarcinoma	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oropharyngeal Squamous Cell Carcinoma	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian Cancer	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian Endometrioid Carcinoma	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic Carcinoma	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic Carcinoma Metastatic	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic Neoplasm	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary Thyroid Cancer	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Peritoneal Carcinoma Metastatic	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pituitary Tumour Benign	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma Cell Myeloma	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate Cancer	0.18% 4/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.36% 8/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostatic Adenoma	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal Adenocarcinoma	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal Adenoma	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal Cancer	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectosigmoid Cancer	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal Cell Carcinoma	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal Cell Carcinoma Stage I	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal Neoplasm	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal Oncocytoma	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Salivary Gland Neoplasm	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous Cell Carcinoma	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous Cell Carcinoma of Lung	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous Cell Carcinoma of Skin	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous Cell Carcinoma of the Vulva	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tongue Neoplasm Malignant Stage Unspecified	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional Cell Cancer of Renal Pelvis and Ureter Metastatic	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional Cell Cancer of the Renal Pelvis and Ureter	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional Cell Carcinoma	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine Cancer	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine Leiomyoma	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Amputation Stump Pain	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Basilar Migraine	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Brain Injury	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Brain Oedema	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Carotid Artery Occlusion	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Carotid Artery Stenosis	0.36% 8/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.18% 4/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Carpal Tunnel Syndrome	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Cauda Equina Syndrome	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Cerebellar Haemorrhage	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Cerebellar Infarction	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Cerebellar Stroke	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Cerebral Haematoma	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Cerebral Haemorrhage	0.18% 4/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Cerebral Hypoperfusion	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Cerebral Infarction	0.32% 7/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.27% 6/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Cerebral Ischaemia	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Cerebrovascular Accident	1.6% 36/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	1.4% 30/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Cervical Radiculopathy	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Chronic Inflammatory Demyelinating Polyradiculoneuropathy	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Clonus	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Dementia	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Depressed Level of Consciousness	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Diabetic Autonomic Neuropathy	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Diabetic Hyperosmolar Coma	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Diabetic Neuropathy	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Dizziness	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Dural Arteriovenous Fistula	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Embolic Cerebral Infarction	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Embolic Stroke	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Encephalopathy	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Epilepsy	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Facial Paralysis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Generalised Tonic-Clonic Seizure	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Haemorrhage Intracranial	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Haemorrhagic Stroke	0.18% 4/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Haemorrhagic Transformation Stroke	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Headache	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Hemiparesis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Hypoglycaemic Coma	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Hypoglycaemic Encephalopathy	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Hypoxic-Ischaemic Encephalopathy	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Intracranial Mass	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Ischaemic Cerebral Infarction	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Ischaemic Neuropathy	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Ischaemic Stroke	0.77% 17/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.64% 14/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Lacunar Infarction	0.18% 4/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.18% 4/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Language Disorder	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Lumbar Radiculopathy	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Lumbosacral Radiculopathy	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Metabolic Encephalopathy	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Myelopathy	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Paraesthesia	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Paraparesis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Parkinson's Disease	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Peripheral Sensorimotor Neuropathy	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Piriformis Syndrome	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Polyneuropathy	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Presyncope	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Progressive Supranuclear Palsy	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Radicular Syndrome	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Radiculopathy	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Sciatica	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Seizure	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Somnolence	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Spinal Cord Compression	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Status Epilepticus	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Syncope	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.18% 4/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Tension Headache	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Thalamic Infarction	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Transient Ischaemic Attack	0.18% 4/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.45% 10/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Vascular Encephalopathy	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Vasculitis Cerebral	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Vertebral Artery Stenosis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Vith Nerve Paralysis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Pregnancy, puerperium and perinatal conditions Abortion Spontaneous	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Pregnancy, puerperium and perinatal conditions Retained Products of Conception	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Product Issues Device Malfunction	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Psychiatric disorders Affective Disorder	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Psychiatric disorders Completed Suicide	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Psychiatric disorders Confusional State	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Psychiatric disorders Delirium	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Psychiatric disorders Disorientation	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Psychiatric disorders Mental Status Changes	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Psychiatric disorders Substance-Induced Psychotic Disorder	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Psychiatric disorders Suicide Attempt	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Acute Kidney Injury	2.3% 50/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	1.9% 41/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Anuria	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Azotaemia	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Bladder Cyst	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Calculus Urinary	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Chronic Kidney Disease	0.55% 12/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.55% 12/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Diabetic Nephropathy	0.46% 10/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.55% 12/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders End Stage Renal Disease	1.0% 23/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.73% 16/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Glomerulonephritis Chronic	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Haematuria	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Hydronephrosis	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Nephrolithiasis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Nephropathy	0.18% 4/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Nephrotic Syndrome	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Neurogenic Bladder	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Renal Artery Stenosis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Renal Colic	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Renal Failure	0.41% 9/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.23% 5/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Renal Impairment	0.32% 7/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.45% 10/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Renal Injury	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Renal Tubular Necrosis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Stress Urinary Incontinence	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Ureterolithiasis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Urethral Stenosis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Urinary Retention	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Urinary Tract Obstruction	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Acquired Phimosis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Adenomyosis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Benign Prostatic Hyperplasia	0.18% 4/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Cervix Disorder	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Cystocele	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Erectile Dysfunction	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Genital Swelling	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Ovarian Cyst	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Postmenopausal Haemorrhage	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Prostatitis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Rectocele	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Uterine Prolapse	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Uterovaginal Prolapse	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Vaginal Prolapse	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Acute Pulmonary Oedema	0.36% 8/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.27% 6/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Acute Respiratory Distress Syndrome	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Acute Respiratory Failure	0.27% 6/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.23% 5/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Apnoeic Attack	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Bronchiectasis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Bronchitis Chronic	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	0.73% 16/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.41% 9/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Chronic Respiratory Failure	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea at Rest	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Emphysema	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Hiccups	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Hydrothorax	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Laryngeal Haematoma	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Nasal Polyps	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Nasal Septum Perforation	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pickwickian Syndrome	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.27% 6/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pleuritic Pain	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pneumonia Aspiration	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary Arterial Hypertension	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary Congestion	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.32% 7/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary Fibrosis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.18% 4/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary Infarction	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary Mass	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary Oedema	0.32% 7/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory Depression	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory Distress	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.46% 10/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.45% 10/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Sleep Apnoea Syndrome	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Vocal Cord Leukoplakia	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Angioedema	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Diabetic Foot	0.46% 10/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.68% 15/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Diabetic Ulcer	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Drug Eruption	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Eczema	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Idiopathic Angioedema	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Neuropathic Ulcer	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Psoriasis	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Rash Generalised	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Skin Ulcer	0.36% 8/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.82% 18/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Surgical and medical procedures Hospitalisation	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Accelerated Hypertension	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Aortic Dissection	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Aortic Stenosis	0.23% 5/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Arterial Disorder	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Arterial Insufficiency	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Arteriosclerosis	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Circulatory Collapse	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Deep Vein Thrombosis	0.32% 7/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Diabetic Vascular Disorder	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Embolism	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Embolism Arterial	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Extremity Necrosis	0.36% 8/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.41% 9/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Haematoma	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Hypertension	0.32% 7/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.32% 7/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Hypertensive Crisis	0.41% 9/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.41% 9/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Hypertensive Emergency	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Hypotension	0.14% 3/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.18% 4/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Intermittent Claudication	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Leriche Syndrome	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Lymphoedema	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Necrosis Ischaemic	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Orthostatic Hypotension	0.23% 5/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Peripheral Arterial Occlusive Disease	0.50% 11/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.45% 10/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Peripheral Artery Occlusion	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Peripheral Ischaemia	0.23% 5/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.14% 3/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Peripheral Vascular Disorder	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.23% 5/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Peripheral Venous Disease	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Post Thrombotic Syndrome	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Shock Haemorrhagic	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Subclavian Artery Stenosis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Thrombophlebitis Superficial	0.09% 2/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.09% 2/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Thrombosis	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Vascular Occlusion	0.00% 0/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.05% 1/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Venous Haemorrhage	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Venous Thrombosis Limb	0.05% 1/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.

Other adverse events

Measure	Placebo n=2197 participants at risk Participants received matching placebo orally once daily.	Canagliflozin 100 mg n=2200 participants at risk Participants received canagliflozin 100 milligram (mg) orally once daily.
Blood and lymphatic system disorders Anaemia	6.2% 136/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	3.5% 77/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Ear and labyrinth disorders Vertigo	2.3% 50/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	2.1% 46/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Eye disorders Cataract	3.6% 80/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	2.6% 58/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Eye disorders Diabetic Retinopathy	2.5% 55/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	3.0% 65/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	3.7% 82/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	3.6% 80/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	4.8% 105/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	4.1% 91/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	2.4% 52/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	2.5% 54/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	2.2% 48/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	1.9% 41/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Oedema Peripheral	9.1% 199/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	5.4% 119/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Bronchitis	3.9% 86/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	3.8% 83/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Gastroenteritis	2.3% 51/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	2.2% 49/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Influenza	4.0% 88/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	4.0% 87/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Nasopharyngitis	6.1% 133/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	5.9% 130/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Onychomycosis	1.5% 33/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	2.0% 45/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia	2.4% 52/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	1.9% 41/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Respiratory Tract Infection	2.0% 44/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.86% 19/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Upper Respiratory Tract Infection	5.3% 117/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	4.1% 90/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Urinary Tract Infection	8.4% 185/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	9.2% 202/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Limb Injury	2.0% 45/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	2.0% 43/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Investigations Blood Creatinine Increased	8.4% 185/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	6.4% 140/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Investigations Glomerular Filtration Rate Decreased	3.6% 80/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	2.9% 63/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Diabetes Mellitus	2.0% 44/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	1.1% 24/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hyperglycaemia	3.4% 74/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	2.5% 54/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hyperkalaemia	6.9% 152/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	5.9% 129/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hyperuricaemia	3.4% 75/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	2.9% 64/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypoglycaemia	10.3% 227/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	9.7% 213/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	3.8% 83/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	3.7% 81/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Back Pain	4.5% 99/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	4.3% 94/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Pain in Extremity	2.5% 54/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	2.5% 56/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Diabetic Neuropathy	3.1% 69/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	2.5% 56/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Headache	3.0% 65/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	3.1% 69/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Acute Kidney Injury	2.3% 51/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	2.3% 50/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders End Stage Renal Disease	2.4% 52/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	1.4% 30/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Renal Impairment	2.8% 61/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	1.9% 42/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	3.7% 81/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	3.6% 80/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.1% 46/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	1.6% 35/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Skin Ulcer	3.2% 70/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	3.9% 85/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Hypertension	8.8% 193/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	6.5% 144/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Hypotension	1.4% 30/2197 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.	2.6% 57/2200 • Up to 4.6 years Safety population included all randomized participants who received at least 1 dose of study drug.

Additional Information

Senior Director

Janssen Research & Development, LLC

Phone: 844-434-4210

Email: ClinicalTrialDisclosure@its.jnj.com

Results disclosure agreements

• Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
• Publication restrictions are in place

Restriction type: OTHER