Trial Outcomes & Findings for Edoxaban Compared to Standard Care After Heart Valve Replacement Using a Catheter in Patients With Atrial Fibrillation (ENVISAGE-TAVI AF) (NCT NCT02943785)

NCT ID: NCT02943785

Last Updated: 2022-03-24

Results Overview

The composite endpoint net adverse clinical events (NACE) included all-cause death, myocardial infarction (MI), ischemic stroke, systemic embolic events (SEE), valve thrombosis, and major bleeding per definition of the International Society on Thrombosis and Haemostasis (ISTH\].

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1426 participants
• Primary outcome timeframe: Baseline through study completion, up to 36 months post-dose
• Results posted on: 2022-03-24

Participant Flow

A total of 1426 participants who met all inclusion criteria and no exclusion criteria were randomized to treatment at 173 clinic sites in Europe, Asia, and North America.

Participants in the study underwent successful transcatheter aortic valve implantation (TAVI) and had a pre-existing atrial fibrillation (AF) or new onset AF.

Participant milestones

Measure	Edoxaban Participants randomized to receive the Edoxaban-based regimen which included 60 mg and 30 mg film coated tablets for once-daily oral use, and 15 mg film coated tablet in case of transitioning at the end of treatment. Dosing followed the locally approved label.	Vitamin K Antagonist (VKA) Participants randomized to receive the VKA-based regimen which included oral VKA tablets as selected and provided by the site and used in accordance with the local label. The Investigator monitored the patient and adjusted the VKA dose to maintain the dose within target.
Overall Study STARTED	713	713
Overall Study COMPLETED	431	350
Overall Study NOT COMPLETED	282	363

Reasons for withdrawal

Measure	Edoxaban Participants randomized to receive the Edoxaban-based regimen which included 60 mg and 30 mg film coated tablets for once-daily oral use, and 15 mg film coated tablet in case of transitioning at the end of treatment. Dosing followed the locally approved label.	Vitamin K Antagonist (VKA) Participants randomized to receive the VKA-based regimen which included oral VKA tablets as selected and provided by the site and used in accordance with the local label. The Investigator monitored the patient and adjusted the VKA dose to maintain the dose within target.
Overall Study Adverse Event	112	97
Overall Study Withdrawal by Subject	63	126
Overall Study Physician Decision	23	47
Overall Study Death	46	46
Overall Study Lost to Follow-up	1	0
Overall Study Other	16	19
Overall Study Did not receive any study medication	21	28

Baseline Characteristics

Baseline characteristics are reported in participants with available baseline data.

Baseline characteristics by cohort

Measure	Edoxaban n=713 Participants Participants randomized to receive the Edoxaban-based regimen which included 60 mg and 30 mg film coated tablets for once-daily oral use, and 15 mg film coated tablet in case of transitioning at the end of treatment. Dosing followed the locally approved label.	Vitamin K Antagonist (VKA) n=713 Participants Participants randomized to receive the VKA-based regimen which included oral VKA tablets as selected and provided by the site and used in accordance with the local label. The Investigator monitored the patient and adjusted the VKA dose to maintain the dose within target.	Total n=1426 Participants Total of all reporting groups
Age, Continuous	82.1 years STANDARD_DEVIATION 5.4 • n=713 Participants	82.1 years STANDARD_DEVIATION 5.5 • n=713 Participants	82.1 years STANDARD_DEVIATION 5.5 • n=1426 Participants
Age, Customized <65 years	5 Participants n=713 Participants	5 Participants n=713 Participants	10 Participants n=1426 Participants
Age, Customized ≥65 to <75 years	53 Participants n=713 Participants	55 Participants n=713 Participants	108 Participants n=1426 Participants
Age, Customized ≥75 to <80 years	131 Participants n=713 Participants	122 Participants n=713 Participants	253 Participants n=1426 Participants
Age, Customized ≥80 to <85 years	289 Participants n=713 Participants	298 Participants n=713 Participants	587 Participants n=1426 Participants
Age, Customized ≥85 to <90 years	191 Participants n=713 Participants	183 Participants n=713 Participants	374 Participants n=1426 Participants
Age, Customized ≥90 years	44 Participants n=713 Participants	50 Participants n=713 Participants	94 Participants n=1426 Participants
Sex: Female, Male Female	347 Participants n=713 Participants	331 Participants n=713 Participants	678 Participants n=1426 Participants
Sex: Female, Male Male	366 Participants n=713 Participants	382 Participants n=713 Participants	748 Participants n=1426 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=713 Participants	0 Participants n=713 Participants	0 Participants n=1426 Participants
Race (NIH/OMB) Asian	92 Participants n=713 Participants	89 Participants n=713 Participants	181 Participants n=1426 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=713 Participants	0 Participants n=713 Participants	0 Participants n=1426 Participants
Race (NIH/OMB) Black or African American	1 Participants n=713 Participants	4 Participants n=713 Participants	5 Participants n=1426 Participants
Race (NIH/OMB) White	593 Participants n=713 Participants	594 Participants n=713 Participants	1187 Participants n=1426 Participants
Race (NIH/OMB) More than one race	0 Participants n=713 Participants	0 Participants n=713 Participants	0 Participants n=1426 Participants
Race (NIH/OMB) Unknown or Not Reported	27 Participants n=713 Participants	26 Participants n=713 Participants	53 Participants n=1426 Participants
Region of Enrollment United States	77 participants n=713 Participants	77 participants n=713 Participants	154 participants n=1426 Participants
Region of Enrollment Japan	82 participants n=713 Participants	77 participants n=713 Participants	159 participants n=1426 Participants
Region of Enrollment United Kingdom	7 participants n=713 Participants	10 participants n=713 Participants	17 participants n=1426 Participants
Region of Enrollment Switzerland	17 participants n=713 Participants	17 participants n=713 Participants	34 participants n=1426 Participants
Region of Enrollment Spain	172 participants n=713 Participants	172 participants n=713 Participants	344 participants n=1426 Participants
Region of Enrollment Canada	8 participants n=713 Participants	6 participants n=713 Participants	14 participants n=1426 Participants
Region of Enrollment Austria	30 participants n=713 Participants	32 participants n=713 Participants	62 participants n=1426 Participants
Region of Enrollment Netherlands	28 participants n=713 Participants	27 participants n=713 Participants	55 participants n=1426 Participants
Region of Enrollment South Korea	9 participants n=713 Participants	10 participants n=713 Participants	19 participants n=1426 Participants
Region of Enrollment Belgium	17 participants n=713 Participants	17 participants n=713 Participants	34 participants n=1426 Participants
Region of Enrollment Poland	10 participants n=713 Participants	10 participants n=713 Participants	20 participants n=1426 Participants
Region of Enrollment Italy	65 participants n=713 Participants	67 participants n=713 Participants	132 participants n=1426 Participants
Region of Enrollment France	22 participants n=713 Participants	24 participants n=713 Participants	46 participants n=1426 Participants
Region of Enrollment Germany	169 participants n=713 Participants	167 participants n=713 Participants	336 participants n=1426 Participants
Weight	74.6 kg STANDARD_DEVIATION 17.9 • n=692 Participants • Baseline characteristics are reported in participants with available baseline data.	76.0 kg STANDARD_DEVIATION 17.3 • n=685 Participants • Baseline characteristics are reported in participants with available baseline data.	75.3 kg STANDARD_DEVIATION 17.6 • n=1377 Participants • Baseline characteristics are reported in participants with available baseline data.
Body mass index	27.5 kg/m^2 STANDARD_DEVIATION 5.7 • n=691 Participants • Baseline characteristics are reported in participants with available baseline data.	27.9 kg/m^2 STANDARD_DEVIATION 5.4 • n=680 Participants • Baseline characteristics are reported in participants with available baseline data.	27.7 kg/m^2 STANDARD_DEVIATION 5.5 • n=1371 Participants • Baseline characteristics are reported in participants with available baseline data.
Creatinine Clearance (Cockcroft-Gault formula)	57.9 mL/min STANDARD_DEVIATION 24.0 • n=692 Participants • Baseline characteristics are reported in participants with available data.	58.6 mL/min STANDARD_DEVIATION 24.3 • n=681 Participants • Baseline characteristics are reported in participants with available data.	58.2 mL/min STANDARD_DEVIATION 24.1 • n=1373 Participants • Baseline characteristics are reported in participants with available data.
Hypertension	647 Participants n=713 Participants	657 Participants n=713 Participants	1304 Participants n=1426 Participants
Diabetes mellitus	270 Participants n=713 Participants	257 Participants n=713 Participants	527 Participants n=1426 Participants
Congestive heart failure Congestive heart failure	591 Participants n=713 Participants	619 Participants n=713 Participants	1210 Participants n=1426 Participants
Congestive heart failure NYHA class III or IV status	314 Participants n=713 Participants	328 Participants n=713 Participants	642 Participants n=1426 Participants
Mitral valve disease	57 Participants n=713 Participants	60 Participants n=713 Participants	117 Participants n=1426 Participants
History of stroke or transient ischemic attack	123 Participants n=713 Participants	116 Participants n=713 Participants	239 Participants n=1426 Participants
Coronary artery disease History of coronary artery disease	293 Participants n=713 Participants	297 Participants n=713 Participants	590 Participants n=1426 Participants
Coronary artery disease Prior coronary bypass surgery	67 Participants n=713 Participants	60 Participants n=713 Participants	127 Participants n=1426 Participants
Coronary artery disease Prior percutaneous coronary intervention	176 Participants n=713 Participants	192 Participants n=713 Participants	368 Participants n=1426 Participants
Coronary artery disease Prior myocardial infarction	97 Participants n=713 Participants	101 Participants n=713 Participants	198 Participants n=1426 Participants

PRIMARY outcome

Timeframe: Baseline through study completion, up to 36 months post-dose

Population: Net adverse clinical events were assessed in the Intent-to-Treat (ITT) Analysis Set.

The composite endpoint net adverse clinical events (NACE) included all-cause death, myocardial infarction (MI), ischemic stroke, systemic embolic events (SEE), valve thrombosis, and major bleeding per definition of the International Society on Thrombosis and Haemostasis (ISTH].

Outcome measures

Measure	Edoxaban n=713 Participants Participants randomized to receive the Edoxaban-based regimen which included 60 mg and 30 mg film coated tablets for once-daily oral use, and 15 mg film coated tablet in case of transitioning at the end of treatment. Dosing followed the locally approved label.	Vitamin K Antagonist (VKA) n=713 Participants Participants randomized to receive the VKA-based regimen which included oral VKA tablets as selected and provided by the site and used in accordance with the local label. The Investigator monitored the patient and adjusted the VKA dose to maintain the dose within target.
Number of Participants Who Experienced Net Adverse Clinical Events (Adjudicated Data) Based on ISTH Criteria in Participants Taking Edoxaban vs VKA	170 Participants	157 Participants

PRIMARY outcome

Timeframe: Baseline through study completion, up to 36 months post-dose

Population: Bleeding events were assessed in the ITT Analysis Set.

ISTH Bleeding Criteria for Major Bleeding are defined as clinically overt bleeding that is associated with: a fall in hemoglobin of 2 g/dL (1.24 mmol/L) or more, or a transfusion of 2 or more units of whole blood or packed red blood cells, or symptomatic bleeding into a critical site or organ such as intracranial, intraspinal, intraocular, retroperitoneal, pericardial, intra-articular, or intramuscular with compartment syndrome, or a fatal outcome.

Outcome measures

Measure	Edoxaban n=713 Participants Participants randomized to receive the Edoxaban-based regimen which included 60 mg and 30 mg film coated tablets for once-daily oral use, and 15 mg film coated tablet in case of transitioning at the end of treatment. Dosing followed the locally approved label.	Vitamin K Antagonist (VKA) n=713 Participants Participants randomized to receive the VKA-based regimen which included oral VKA tablets as selected and provided by the site and used in accordance with the local label. The Investigator monitored the patient and adjusted the VKA dose to maintain the dose within target.
Number of Participants Who Experienced Major Bleeding (Adjudicated Data) Based on ISTH Criteria in Participants Taking Edoxaban vs VKA	98 Participants	68 Participants

SECONDARY outcome

Timeframe: Baseline through study completion, up to 36 months post-dose

Population: Net adverse clinical events were assessed in the ITT Analysis Set.

The composite endpoint of net adverse event clinical events (NACE) included all-cause death, myocardial infarction (MI), ischemic stroke, systemic embolic events (SEE), valve thrombosis, and major bleeding based on Thrombolysis in Myocardial Infarction (TIMI) criteria. Bleeding by TIMI criteria was defined as the following: (1) Major, any intracranial hemorrhage or any clinically overt bleeding, (including bleeding evident in imaging studies) associated with a fall of hemoglobin (Hb) of ≥ 5g/dL or fatal bleeding and (2) Minor, any clinically overt bleeding associated with a fall in Hb ≥ 3g/dL but < 5 g/dL.

Outcome measures

Measure	Edoxaban n=713 Participants Participants randomized to receive the Edoxaban-based regimen which included 60 mg and 30 mg film coated tablets for once-daily oral use, and 15 mg film coated tablet in case of transitioning at the end of treatment. Dosing followed the locally approved label.	Vitamin K Antagonist (VKA) n=713 Participants Participants randomized to receive the VKA-based regimen which included oral VKA tablets as selected and provided by the site and used in accordance with the local label. The Investigator monitored the patient and adjusted the VKA dose to maintain the dose within target.
Number of Participants Who Experienced Net Adverse Clinical Events (Adjudicated Data) Based on TIMI Criteria in Participants Taking Edoxaban vs VKA Composite endpoint NACE (TIMI)	154 Participants	141 Participants
Number of Participants Who Experienced Net Adverse Clinical Events (Adjudicated Data) Based on TIMI Criteria in Participants Taking Edoxaban vs VKA Composite of major and minor bleeding (TIMI)	72 Participants	42 Participants

SECONDARY outcome

Timeframe: Baseline through study completion, up to 36 months post-dose

Population: Net adverse clinical events were assessed in the ITT Analysis Set.

The composite endpoint of net adverse event clinical events (NACE) included all-cause death, MI, ischemic stroke, SEE, valve thrombosis, and major bleeding based on Bleeding Academic Research Consortium (BARC) Type 3 or 5 criteria. Major bleeding by BARC criteria was defined as Type 3: clinical, laboratory, and/or imaging evidence of bleeding with provider responses; Type 3a: any transfusion with overt bleeding; overt bleeding plus Hb drop of 3 to < 5 g/dL; Type 3b: overt bleeding plus Hb drop ≥ 5 g/dL; cardiac tamponade; bleeding requiring surgical intervention; bleeding requiring intravenous vasoactive drugs; Type 3c: intracranial hemorrhage; subcategories confirmed by autopsy, imaging, or lumbar puncture; intraocular bleed compromising vision; Type 5: fatal bleeding; Type 5a: probable fatal bleeding; no autopsy or imaging confirmation but clinically suspicious; Type 5b: definite fatal bleeding; overt bleeding or autopsy or imaging confirmation

Outcome measures

Measure	Edoxaban n=713 Participants Participants randomized to receive the Edoxaban-based regimen which included 60 mg and 30 mg film coated tablets for once-daily oral use, and 15 mg film coated tablet in case of transitioning at the end of treatment. Dosing followed the locally approved label.	Vitamin K Antagonist (VKA) n=713 Participants Participants randomized to receive the VKA-based regimen which included oral VKA tablets as selected and provided by the site and used in accordance with the local label. The Investigator monitored the patient and adjusted the VKA dose to maintain the dose within target.
Number of Participants Who Experienced Net Adverse Clinical Events (Adjudicated Data) Based on BARC Type 3 or 5 Criteria in Participants Taking Edoxaban vs VKA Composite endpoint NACE (BARC Type 3 or 5)	164 Participants	151 Participants
Number of Participants Who Experienced Net Adverse Clinical Events (Adjudicated Data) Based on BARC Type 3 or 5 Criteria in Participants Taking Edoxaban vs VKA Major bleeding (BARC Type 3 or 5)	89 Participants	57 Participants

SECONDARY outcome

Timeframe: Baseline through study completion, up to 36 months post-dose

Population: Net adverse clinical events were assessed in the ITT Analysis Set.

The composite endpoint of net adverse event clinical events (NACE) included all-cause death, MI, ischemic stroke, SEE, valve thrombosis, and major bleeding based on Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO). GUSTO criteria was defined as the following: severe or life threatening: intracerebral hemorrhage or resulting in substantial hemodynamic compromise requiring treatment and moderate: requiring blood transfusion but not resulting in hemodynamic compromise.

Outcome measures

Measure	Edoxaban n=713 Participants Participants randomized to receive the Edoxaban-based regimen which included 60 mg and 30 mg film coated tablets for once-daily oral use, and 15 mg film coated tablet in case of transitioning at the end of treatment. Dosing followed the locally approved label.	Vitamin K Antagonist (VKA) n=713 Participants Participants randomized to receive the VKA-based regimen which included oral VKA tablets as selected and provided by the site and used in accordance with the local label. The Investigator monitored the patient and adjusted the VKA dose to maintain the dose within target.
Number of Participants Who Experienced Net Adverse Clinical Events (Adjudicated Data) Based on GUSTO Criteria in Participants Taking Edoxaban vs VKA Composite endpoint NACE (GUSTO)	160 Participants	146 Participants
Number of Participants Who Experienced Net Adverse Clinical Events (Adjudicated Data) Based on GUSTO Criteria in Participants Taking Edoxaban vs VKA Severe or life threatening and moderate bleeding (GUSTO)	82 Participants	51 Participants

SECONDARY outcome

Timeframe: Baseline through study completion, up to 36 months post-dose

Population: MACE were assessed in the ITT Analysis Set.

Major adverse cardiac events (MACE) is defined as the composite of all-cause death (excluding adjudicated non-cardiac death), MI, or repeat coronary revascularization of the target lesion.

Outcome measures

Measure	Edoxaban n=713 Participants Participants randomized to receive the Edoxaban-based regimen which included 60 mg and 30 mg film coated tablets for once-daily oral use, and 15 mg film coated tablet in case of transitioning at the end of treatment. Dosing followed the locally approved label.	Vitamin K Antagonist (VKA) n=713 Participants Participants randomized to receive the VKA-based regimen which included oral VKA tablets as selected and provided by the site and used in accordance with the local label. The Investigator monitored the patient and adjusted the VKA dose to maintain the dose within target.
Number of Participants Who Experienced Major Adverse Cardiac Events (MACE) in Participants Taking Edoxaban vs VKA (Adjudicated Data)	61 Participants	53 Participants

SECONDARY outcome

Timeframe: Baseline through study completion, up to 36 months post-dose

Population: MACE were assessed in the ITT Analysis Set.

Major adverse cardiac and cerebrovascular events (MACCE) is defined as the composite of all-cause death (excluding adjudicated non-cardiac death), MI, stroke (ischemic, hemorrhagic, or undetermined), or repeat coronary revascularization of the target lesion

Outcome measures

Measure	Edoxaban n=713 Participants Participants randomized to receive the Edoxaban-based regimen which included 60 mg and 30 mg film coated tablets for once-daily oral use, and 15 mg film coated tablet in case of transitioning at the end of treatment. Dosing followed the locally approved label.	Vitamin K Antagonist (VKA) n=713 Participants Participants randomized to receive the VKA-based regimen which included oral VKA tablets as selected and provided by the site and used in accordance with the local label. The Investigator monitored the patient and adjusted the VKA dose to maintain the dose within target.
Number of Participants Who Experienced Major Adverse Cardiac and Cerebrovascular Events (MACCE) in Participants Taking Edoxaban vs VKA (Adjudicated Data)	86 Participants	80 Participants

SECONDARY outcome

Timeframe: Baseline through study completion, up to 36 months post-dose

Population: A composite of adverse events was assessed in the ITT Analysis Set.

A composite of clinical adverse events included cardiovascular death, MI ischemic stroke, SEE, valve thrombosis, and major bleeding as defined by ISTH criteria.

Outcome measures

Measure	Edoxaban n=713 Participants Participants randomized to receive the Edoxaban-based regimen which included 60 mg and 30 mg film coated tablets for once-daily oral use, and 15 mg film coated tablet in case of transitioning at the end of treatment. Dosing followed the locally approved label.	Vitamin K Antagonist (VKA) n=713 Participants Participants randomized to receive the VKA-based regimen which included oral VKA tablets as selected and provided by the site and used in accordance with the local label. The Investigator monitored the patient and adjusted the VKA dose to maintain the dose within target.
Number of Participants Who Experienced a Composite of Adverse Events in Participants Taking Edoxaban vs VKA (Adjudicated Data)	151 Participants	123 Participants

SECONDARY outcome

Timeframe: Baseline through study completion, up to 36 months post-dose

Population: Stroke events were assessed in the ITT Analysis Set.

Stroke events are categorized as any stroke, fatal stroke, and non-fatal stroke.

Outcome measures

Measure	Edoxaban n=713 Participants Participants randomized to receive the Edoxaban-based regimen which included 60 mg and 30 mg film coated tablets for once-daily oral use, and 15 mg film coated tablet in case of transitioning at the end of treatment. Dosing followed the locally approved label.	Vitamin K Antagonist (VKA) n=713 Participants Participants randomized to receive the VKA-based regimen which included oral VKA tablets as selected and provided by the site and used in accordance with the local label. The Investigator monitored the patient and adjusted the VKA dose to maintain the dose within target.
Number of Participants Who Experienced Stroke Events (Ischemic, Hemorrhagic, Undetermined) in Participants Taking Edoxaban vs VKA (Adjudicated Data) Any stroke (ischemic, hemorrhagic, or undetermined)	29 Participants	35 Participants
Number of Participants Who Experienced Stroke Events (Ischemic, Hemorrhagic, Undetermined) in Participants Taking Edoxaban vs VKA (Adjudicated Data) Fatal stroke (ischemic, hemorrhagic, or undetermined)	4 Participants	3 Participants
Number of Participants Who Experienced Stroke Events (Ischemic, Hemorrhagic, Undetermined) in Participants Taking Edoxaban vs VKA (Adjudicated Data) Non-fatal stroke (ischemic, hemorrhagic, or undetermined)	25 Participants	32 Participants

SECONDARY outcome

Timeframe: Baseline through study completion, up to 36 months post-dose

Population: Systemic embolic events (SEE) were assessed in the ITT Analysis Set.

Systemic thromboembolism [non-central nervous system] is defined as abrupt vascular insufficiency of an extremity or organ associated with clinical or radiological evidence of arterial occlusion in the absence of other likely mechanisms, (e.g., trauma, atherosclerosis, instrumentation).

Outcome measures

Measure	Edoxaban n=713 Participants Participants randomized to receive the Edoxaban-based regimen which included 60 mg and 30 mg film coated tablets for once-daily oral use, and 15 mg film coated tablet in case of transitioning at the end of treatment. Dosing followed the locally approved label.	Vitamin K Antagonist (VKA) n=713 Participants Participants randomized to receive the VKA-based regimen which included oral VKA tablets as selected and provided by the site and used in accordance with the local label. The Investigator monitored the patient and adjusted the VKA dose to maintain the dose within target.
Number of Participants Who Experienced Systemic Embolic Events in Participants Taking Edoxaban vs VKA (Adjudicated Data)	2 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline through study completion, up to 36 months post-dose

Population: Myocardial infarctions were assessed in the ITT Analysis Set.

Peri-procedural MI was defined as new ischemic symptoms or signs and elevated cardiac biomarkers within 72 hours after index procedure, consisting of at least one sample post-procedure with a peak value exceeding 15x as the upper reference limit (URL) for troponin or 5x for CK-MB. Spontaneous MI is defined as any one of the following: Detection of rise and/or fall of cardiac biomarkers with at least one value above the 99th percentile URL, together with the evidence of myocardial ischemia with at least one of the following: Symptoms of ischemia; ECG changes indicative of new ischemia; New pathological Q-waves in at least two contiguous leads; Imaging evidence of a new loss of viable myocardium or new wall motion abnormality; Sudden, unexpected cardiac death, involving cardiac arrest, often with symptoms suggestive of myocardial ischemia, and accompanied by new ST elevation or new left bundle branch block, and/or evidence of fresh thrombus; Pathological findings of an acute MI.

Outcome measures

Measure	Edoxaban n=713 Participants Participants randomized to receive the Edoxaban-based regimen which included 60 mg and 30 mg film coated tablets for once-daily oral use, and 15 mg film coated tablet in case of transitioning at the end of treatment. Dosing followed the locally approved label.	Vitamin K Antagonist (VKA) n=713 Participants Participants randomized to receive the VKA-based regimen which included oral VKA tablets as selected and provided by the site and used in accordance with the local label. The Investigator monitored the patient and adjusted the VKA dose to maintain the dose within target.
Number of Participants Who Experienced Myocardial Infarctions (MI) in Participants Taking Edoxaban vs VKA (Adjudicated Data)	12 Participants	7 Participants

SECONDARY outcome

Timeframe: Baseline through study completion, up to 36 months post-dose

Population: Valve thrombosis were assessed in the ITT Analysis Set.

Valve thrombosis was defined as any thrombus attached to or near an implanted valve that occludes part of the blood flow path, interferes with valve function, or is sufficiently large to warrant treatment.

Outcome measures

Measure	Edoxaban n=713 Participants Participants randomized to receive the Edoxaban-based regimen which included 60 mg and 30 mg film coated tablets for once-daily oral use, and 15 mg film coated tablet in case of transitioning at the end of treatment. Dosing followed the locally approved label.	Vitamin K Antagonist (VKA) n=713 Participants Participants randomized to receive the VKA-based regimen which included oral VKA tablets as selected and provided by the site and used in accordance with the local label. The Investigator monitored the patient and adjusted the VKA dose to maintain the dose within target.
Number of Participants Who Experienced Valve Thrombosis in Participants Taking Edoxaban vs VKA (Adjudicated Data)	0 Participants	0 Participants

Adverse Events

Edoxaban

Serious events: 388 serious events

Other events: 522 other events

Deaths: 83 deaths

Vitamin K Antagonist (VKA)

Serious events: 372 serious events

Other events: 429 other events

Deaths: 78 deaths

Serious adverse events

Measure	Edoxaban n=693 participants at risk Participants randomized to receive the Edoxaban-based regimen which included 60 mg and 30 mg film coated tablet for once-daily oral use, and 15 mg film coated tablet in case of transitioning at the end of treatment. Dosing followed the locally approved label.	Vitamin K Antagonist (VKA) n=684 participants at risk Participants randomized to receive the VKA-based regimen which included oral VKA tablets as selected and provided by the site and used in accordance with the local label. The Investigator monitored the patient and adjusted the VKA dose to maintain the dose within target.
General disorders Inflammatory marker increased	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
General disorders Myocardial necrosis marker increased	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
General disorders Weight increased	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Vascular pseudoaneurysm	0.87% 6/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	1.2% 8/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Fall	1.3% 9/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.58% 4/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Femur fracture	0.72% 5/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.88% 6/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Subdural haematoma	0.43% 3/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.73% 5/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Femoral neck fracture	0.58% 4/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.44% 3/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Head injury	0.43% 3/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.44% 3/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Hip fracture	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.58% 4/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Pelvic fracture	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.58% 4/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Humerus fracture	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.44% 3/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.58% 4/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Spinal compression fracture	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Traumatic intracranial haemorrhage	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Anaemia postoperative	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.44% 3/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Ankle fracture	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Cervical vertebral fracture	0.43% 3/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Overdose	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.44% 3/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Fibula fracture	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Radius fracture	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Skin laceration	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Subcutaneous haematoma	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Toxicity to various agents	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Vascular access site pseduoaneurysm	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Acetabulum fracture	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Bone contusion	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Chest injury	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Clavicle fracture	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Colon injury	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Concussion	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Contusion	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Craniocerebral injury	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Extradural haematoma	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Face injury	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Facial bones fracture	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Foreign body in gastrointestinal tract	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Fracture	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Fractured sacrum	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Hand fracture	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Heat illness	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Heat stroke	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Joint dislocation	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Open globe injury	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Patella fracture	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Post procedural complication	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Post procedural fever	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Post procedural haematoma	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Postoperative delirium	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Rib fracture	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Road traffic accident	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Seroma	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Tendon rupture	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Vascular access site haematoma	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Wound	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Wound dehiscence	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Wound haemorrhage	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Product Issues Device leakage	0.43% 3/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Product Issues Device malfunction	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Product Issues Device power source issue	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Pneumonia	5.6% 39/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	5.4% 37/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Urinary tract infection	3.0% 21/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	2.5% 17/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Endocarditis	2.0% 14/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	1.0% 7/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Respiratory tract infection	1.0% 7/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	1.9% 13/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Sepsis	0.87% 6/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	1.0% 7/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Bronchitis	0.58% 4/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.73% 5/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations COVID-19	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.88% 6/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Septic shock	0.72% 5/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.44% 3/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Urosepsis	0.87% 6/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Cellulitis	0.43% 3/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.58% 4/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Gastroenteritis	0.43% 3/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.44% 3/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Bacteraemia	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.44% 3/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations COVID-19 pneumonia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.58% 4/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Influenza	0.58% 4/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Enterococcal sepsis	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Lower respiratory tract infection	0.43% 3/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Appendicitis	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.44% 3/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Cystitis	0.43% 3/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Erysipelas	0.43% 3/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Infection	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Intervertebral discitis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Staphylococcal bacteraemia	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Staphylococcal sepsis	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Streptococcal endocarditis	0.43% 3/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Clostridium difficile infection	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Endocarditis staphylococcal	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Enterococcal bacteraemia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Enterococcal infection	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Epididymitis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Escherichia sepsis	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Gangrene	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Herpes zoster	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Klebsiella infection	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Pulmonary sepsis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Pyelonephritis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Streptococcal bacteraemia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Abscess soft tissue	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Acinetobacter bacteraemia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Alveolar osteitis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Anal abscess	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Aspergilloma	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Bacterial sepsis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Citrobacter sepsis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Clostridium difficile colitis	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Cystitis klebsiella	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Device-related sepsis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Diverticulitis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Endocarditis enterococcal	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Escherichia bacteraemia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Escherichia infection	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Escherichia urinary tract infection	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Fracture infection	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Fungal tracheitis	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Gastric infection	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Groin infection	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Herpes zoster oticus	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Infected lymphocele	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Infective aneurysm	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Klebsiella bacteraemia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Klebsiella sepsis	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Medical device site infection	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Mycotic corneal ulcer	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Nosocomial infection	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Oesophageal candidiasis	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Osteomyelitis	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Peritonitis	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Pneumococcal bacteraemia	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Pneumococcal sepsis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Pneumonia pneumococcal	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Pneumonia streptococcal	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Postoperative wound infection	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Pseudomonal sepsis	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Pyelonephritis acute	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Respiratory tract infection viral	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Rhinovirus infection	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Salmonellosis	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Sinusitis	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Streptococcal sepsis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Upper respiratory tract infection	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Viral infection	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Wound infection	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute leukaemia	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma gastric	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Anogenital warts	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cholangiocarcinoma	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic lymphocytic leukaemia	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myelomonocytic leukaemia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal tract adenoma	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leukaemia	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to pelvis	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myeloproliferative neoplasm	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm prostate	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm skin	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine carcinoma of the skin	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal adenocarcinoma	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary thyroid cancer	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer metastatic	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal adenocarcinoma	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Refractory cytopenia with unilineage dysplasia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ureteric cancer	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Blood and lymphatic system disorders Anemia	4.5% 31/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	1.6% 11/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Blood and lymphatic system disorders Blood loss anaemia	0.72% 5/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Blood and lymphatic system disorders Iron deficiency anaemia	0.43% 3/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.44% 3/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.88% 6/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Blood and lymphatic system disorders Anaemia folate deficiency	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Blood and lymphatic system disorders Hypochromic anaemia	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Blood and lymphatic system disorders Normocytic anaemia	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Blood and lymphatic system disorders Coagulopathy	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Blood and lymphatic system disorders Heparin-induced thrombocytopenia	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Blood and lymphatic system disorders Leukocytosis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Blood and lymphatic system disorders Lymphadenopathy mediastinal	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Blood and lymphatic system disorders Microcytic anaemia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Blood and lymphatic system disorders Nephrogenic anaemia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Blood and lymphatic system disorders Normochromic anaemia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Blood and lymphatic system disorders Normochromic normocytic anaemia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Blood and lymphatic system disorders Splenic infarction	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Blood and lymphatic system disorders Spontaneous haematoma	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Immune system disorders Anaphylatic shock	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Endocrine disorders Hyperthyroidism	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Metabolism and nutrition disorders Dehydration	0.43% 3/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.44% 3/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Metabolism and nutrition disorders Hyponatraemia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.44% 3/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Metabolism and nutrition disorders Fluid overload	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Metabolism and nutrition disorders Hypokalaemia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Metabolism and nutrition disorders Cachexia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Metabolism and nutrition disorders Decreased appetite	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Metabolism and nutrition disorders Hypoglycaemia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Metabolism and nutrition disorders Malnutrition	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Metabolism and nutrition disorders Metabolic acidosis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Metabolism and nutrition disorders Acidosis	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Metabolism and nutrition disorders Diabetic metabolic decompensation	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Metabolism and nutrition disorders Fluid retention	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Metabolism and nutrition disorders Fructose intolerance	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Metabolism and nutrition disorders Gout	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Psychiatric disorders Confusional state	0.58% 4/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Psychiatric disorders Anxiety	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Psychiatric disorders Depression	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Psychiatric disorders Drug dependence	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Psychiatric disorders Mental status changes	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Psychiatric disorders Stress	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Syncope	1.9% 13/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	1.8% 12/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Ischaemic stroke	1.3% 9/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	1.5% 10/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Transient ischaemic attack	1.0% 7/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	1.2% 8/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Dizziness	0.87% 6/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.73% 5/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Cerebral haemorrhage	0.72% 5/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Cerebral infarction	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.58% 4/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Embolic stroke	0.58% 4/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Cognitive disorder	0.43% 3/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Haemorrhage intracranial	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.44% 3/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Haemorrhage stroke	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.44% 3/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Chorea	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Epilepsy	0.43% 3/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Loss of consciousness	0.43% 3/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Presyncope	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Cerebral ischaemia	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Cerebrovascular accident	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Dementia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Embolic cerebral infarction	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Lacunar infarction	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Subarachnoid haemorrhage	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Altered state of consciousness	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Amnesia	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Carotid artery stenosis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Carpal tunnel syndrome	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Central nervous system lesion	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Cerebellar infarction	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Cerebral microangiopathy	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Cerebrovascular disorder	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Choreoathetosis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Cubital tunnel syndrome	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Dementia Alzheimer's type	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Dysaesthesia	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Dysarthria	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Generalised tonic-clonic seizure	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Headache	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Hypertensive encephalopathy	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Intraventricular haemorrhage	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Lacunar stroke	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Metabolic encephalopathy	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Paraesthesia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Parkinson's disease	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Partial seizures	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Sciatica	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Seizure	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Status epileticus	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Vascular encephalopathy	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Eye disorders Cataract	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Eye disorders Retinal artery occlusion	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Eye disorders Amaurosis fugax	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Eye disorders Choroidal detachment	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Eye disorders Retinal haemorrhage	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Eye disorders Vitreous detachment	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Ear and labyrinth disorders Tympanic membrane perforation	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Ear and labyrinth disorders Vestibular disorder	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Ear and labyrinth disorders Vestibular paroxysmia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Cardiac failure	8.2% 57/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	9.4% 64/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Atrial fibrillation	2.5% 17/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	2.6% 18/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Cardiac failure congestive	3.3% 23/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	1.8% 12/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Cardiac failure acute	1.2% 8/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	1.6% 11/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Atrioventricular block complete	1.3% 9/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.88% 6/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Mitral valve incompetence	0.87% 6/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	1.2% 8/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Bradycardia	0.87% 6/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.44% 3/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Cardiac arrest	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	1.0% 7/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Atrial flutter	0.87% 6/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Acute myocardial infarction	0.58% 4/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Angina pectoris	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.58% 4/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Sinus node dysfunction	0.58% 4/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Pericardial effusion	0.58% 4/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Tachyarrhythmia	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.44% 3/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Atrioventricular block	0.43% 3/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.58% 4/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Ventricular tachycardia	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Bundle branch block left	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Cardiac failure chronic	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Coronary artery disease	0.43% 3/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Aortic valve stenosis	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Arrhythmia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Cardiac asthma	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Cardiac tamponade	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Cardiopulmonary failure	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Left ventricular failure	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Myocardial infarction	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Sinus arrest	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Acute coronary syndrome	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Acute left ventricular failure	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Angina unstable	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Aortic valve disease	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Aortic valve incompetence	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Atrial tachycardia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Atrioventricular block first degree	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Atrioventricular block second degree	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Bifascicular block	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Bradyarrhythmia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Cardiogenic shock	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Cardiorenal syndrome	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Chronic left ventricular failure	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Conduction disorder	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Cor pulmonale	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Coronary artery stenosis	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Intracardiac thrombus	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Ischaemic cardiomyopathy	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Mitral valve disease	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Pericarditis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Prosthetic cardiac valve thrombosis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Right ventricular failure	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Stress cardiomyopathy	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Supraventricular tachycardia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Ventricular dysfunction	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Ventricular extrasystoles	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Peripheral arterial occlusive disease	1.0% 7/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.73% 5/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Haematoma	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	1.3% 9/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Hypertensive crisis	1.2% 8/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Orthostatic hypotension	0.43% 3/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Hypertension	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Aortic dissection	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Circulatory collapse	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Hypotension	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Iliac artery stenosis	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Peripheral ischaemia	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Phlebitis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Aortic aneurysm	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Aortic occlusion	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Aortic perforation	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Aortic thrombosis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Arterial haemorrhage	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Arterial occlusive disease	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Arteriovenous fistula	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Blue toe syndrome	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Diabetic vascular disorder	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Extremity necrosis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Femoral artery embolism	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Haemorrhage	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Hypovolaemic shock	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Peripheral artery aneurysm	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Peripheral artery thrombosis	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Peripheral embolism	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Peripheral vascular disorder	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Peripheral venous disease	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Shock haemorrhagic	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Subclavian vein thrombosis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Varicose vein	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.6% 11/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	1.2% 8/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.0% 7/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	1.2% 8/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.72% 5/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	1.0% 7/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.0% 7/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.44% 3/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.72% 5/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.44% 3/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.72% 5/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.44% 3/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.43% 3/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Asthma	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Bronchial hyperreactivity	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Emphysema	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Haemothorax	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Pharyngeal haematoma	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Pharyngeal haemorrhage	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Pickwickian syndrome	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Respiratory acidosis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	2.3% 16/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	1.0% 7/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	1.2% 8/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.58% 4/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Diarrhoea	1.0% 7/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.72% 5/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.44% 3/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Inguinal hernia	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.88% 6/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Rectal haemorrhage	0.58% 4/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Abdominal pain	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Anal haemorrhage	0.43% 3/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Intestinal ischaemia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Intestinal obstruction	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Melaena	0.43% 3/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Constipation	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Diverticulum intestinal hemorrhagic	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Gastric ulcer	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Vomiting	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Abdominal hernia	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Anal fissure	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Chronic gastritis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Colitis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Diverticulum intestinal	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Enterocele	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Gastric haemorrhage	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Gastric perforation	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Gastric polyps	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Gastritis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Gastroduodenal ulcer	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Gastrointestinal disorder	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Haematemesis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Haematochezia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Haemorrhoids	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Ileus	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Intestinal haemorrhage	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Intestinal polyp	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Mallory-Weiss syndrome	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Mechanical ileus	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Oesophageal ulcer	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Pancreatic failure	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Pancreatitis	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Pancreatitis necrotising	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Subileus	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Ulcerative duodenitis	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Gastrointestinal disorders Umbilical hernia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Hepatobiliary disorders Bile duct stone	0.58% 4/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Hepatobiliary disorders Cholelithiasis	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Hepatobiliary disorders Cholangitis	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Hepatobiliary disorders Cholangitis acute	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Hepatobiliary disorders Cholecystitis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Skin and subcutaneous tissue disorders Skin ulcer	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.44% 3/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Skin and subcutaneous tissue disorders Diabetic foot	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Skin and subcutaneous tissue disorders Dermal cyst	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Skin and subcutaneous tissue disorders Rash	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Skin and subcutaneous tissue disorders Skin ulcer haemorrhage	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.72% 5/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.44% 3/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Musculoskeletal and connective tissue disorders Haemarthrosis	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.44% 3/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.44% 3/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Musculoskeletal and connective tissue disorders Arthralgia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Musculoskeletal and connective tissue disorders Arthritis	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Musculoskeletal and connective tissue disorders Back pain	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Musculoskeletal and connective tissue disorders Muscular weakness	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Musculoskeletal and connective tissue disorders Arthropathy	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Musculoskeletal and connective tissue disorders Bursitis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Musculoskeletal and connective tissue disorders Chest wall haematoma	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Musculoskeletal and connective tissue disorders Chondrocalcinosis pyrophosphate	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Musculoskeletal and connective tissue disorders Haematoma muscle	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Musculoskeletal and connective tissue disorders Osteonecrosis of jaw	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Musculoskeletal and connective tissue disorders Polymyalgia rheumatica	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Musculoskeletal and connective tissue disorders Soft tissue disorder	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Musculoskeletal and connective tissue disorders Spinal stenosis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Musculoskeletal and connective tissue disorders Tendonitis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Renal and urinary disorders Acute kidney injury	2.6% 18/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	2.5% 17/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Renal and urinary disorders Haematuria	1.6% 11/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.44% 3/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Renal and urinary disorders Chronic kidney disease	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.73% 5/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Renal and urinary disorders Renal failure	0.58% 4/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Renal and urinary disorders Urinary retention	0.58% 4/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Renal and urinary disorders End stage renal disease	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Renal and urinary disorders Nephrolithiasis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Renal and urinary disorders Renal impairment	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Renal and urinary disorders Calculus bladder	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Renal and urinary disorders Renal haematoma	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Renal and urinary disorders Renal infarct	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Renal and urinary disorders Ureterolithiasis	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Renal and urinary disorders Urethral haemorrhage	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Renal and urinary disorders Urethral stenosis	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Reproductive system and breast disorders Female genital tract fistula	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Reproductive system and breast disorders Pelvic haematoma	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Reproductive system and breast disorders Prostatitis	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Reproductive system and breast disorders Rectocele	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Reproductive system and breast disorders Vaginal haemorrhage	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
General disorders Death	1.2% 8/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.44% 3/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
General disorders General physical health deterioration	0.43% 3/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.88% 6/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
General disorders Asthenia	0.58% 4/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.58% 4/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
General disorders Multiple organ dysfunction syndrome	0.72% 5/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
General disorders Non-cardiac chest pain	0.58% 4/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
General disorders Sudden death	0.58% 4/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
General disorders Impaired healing	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.29% 2/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
General disorders Pyrexia	0.43% 3/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
General disorders Malaise	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
General disorders Oedema peripheral	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
General disorders Pacemaker generated arrhythmia	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
General disorders Chest discomfort	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
General disorders Chest pain	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
General disorders Fatigue	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
General disorders Injection site haematoma	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
General disorders Peripheral swelling	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
General disorders Stent-graft endoleak	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
General disorders Sudden cardiac death	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
General disorders Systemic inflammatory response syndrome	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Investigations International normalised ratio increased	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.73% 5/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Investigations Haemoglobin decreased	0.29% 2/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Investigations Troponin increased	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Investigations Anticoagulation drug level above therapeutic	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Investigations Blood lactic acid increased	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Investigations Coronavirus test positive	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Investigations Ejection fraction decreased	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Investigations General physical condition normal	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
General disorders Heart rate irregular	0.00% 0/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.15% 1/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
General disorders Hepatic enzyme increased	0.14% 1/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	0.00% 0/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.

Other adverse events

Measure	Edoxaban n=693 participants at risk Participants randomized to receive the Edoxaban-based regimen which included 60 mg and 30 mg film coated tablet for once-daily oral use, and 15 mg film coated tablet in case of transitioning at the end of treatment. Dosing followed the locally approved label.	Vitamin K Antagonist (VKA) n=684 participants at risk Participants randomized to receive the VKA-based regimen which included oral VKA tablets as selected and provided by the site and used in accordance with the local label. The Investigator monitored the patient and adjusted the VKA dose to maintain the dose within target.
Infections and infestations Urinary tract infection	9.1% 63/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	6.6% 45/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Infections and infestations Pneumonia	6.5% 45/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	6.3% 43/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Blood and lymphatic system disorders Anaemia	8.9% 62/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	5.8% 40/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Nervous system disorders Dizziness	6.8% 47/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	4.8% 33/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Cardiac failure	11.3% 78/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	12.4% 85/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Cardiac disorders Atrial fibrillation	3.3% 23/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	5.3% 36/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Vascular disorders Haematoma	3.8% 26/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	6.0% 41/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Epistaxis	9.2% 64/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	4.4% 30/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.6% 39/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	5.1% 35/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Renal and urinary disorders Haematuria	5.8% 40/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	2.6% 18/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
Injury, poisoning and procedural complications Fall	5.1% 35/693 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.	3.4% 23/684 • Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment or through study completion, up to 36 months post-dose. Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.

Additional Information

Contact for Clinical Trial Information

Daiichi Sankyo

Phone: + 1 908-992-6400

Email: CTRinfo@dsi.com

Results disclosure agreements

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